Steven M. Gordon, MD

With dramatically increasing costs of healthcare, it has become increasingly necessary for healthcare providers to demonstrate value in the delivery of care. Porter and Teisberg have strongly advocated that healthcare reform efforts should focus on improving value rather than limiting cost, with value being defined as quality per unit cost.1 However, it has been pointed out that value means different things to different people.2 The biggest challenge in defining value stems mainly from the difficulty in defining quality, because it, too, means vastly different things to different people. Modern medicine is increasingly characterized by multidisciplinary care. With limited or shrinking resources, it will become necessary for individual specialists to describe and articulate, in quantitative terms, their specific contributions to the overall outcome of individual patients.

Previous publications have provided broad descriptions of the value provided by infectious disease (ID) specialists in the domains of sepsis, infection control, outpatient antibiotic therapy, antimicrobial stewardship, and directive care and teaching.3, 4 Studies have also shown the value of ID physicians in specific disease conditions. ID consultation is associated with lower mortality5, 6 and lower relapse rates7 in hospitalized patients with Staphylococcus aureus bacteremia. In another study evaluating the impact of ID consultants, patients seen by ID consultants had longer lengths of hospital stay, longer intensive care unit lengths of stay, and higher antibiotic costs than matched controls not seen by ID consultants.8 It can be argued that a major limitation of the study was that controls were not matched for the ID diagnosis, nor for the causative microorganisms, but it is clear that ID physicians are challenged to demonstrate their contribution to the care of patients.

A unique activity of ID physicians is the management of community‐based parenteral anti‐infective therapy (CoPAT). At Baystate Medical Center, a policy of mandatory ID consultation was instituted for patients leaving hospital on parenteral antibiotics. A study was conducted on the impact of predischarge ID consultation for 44 patients who were not already being followed by the ID service. The study documented change from intravenous (IV) to oral formulation, change of antibiotic choice, and change of dose/duration of treatment in a substantial proportion of patients.9 These are significant changes, but ID consultation contributes more than the themes explored in the study.

The purpose of this study was to evaluate the contribution of ID consultation when consulted for CoPAT, an activity specific to ID practice, in a different institution, and using an expanded definition of medical contribution.

METHODS

The Cleveland Clinic's Department of Infectious Disease has 24 staff physicians and 11 inpatient ID consultative services. These include: 2 solid organ transplant services; a bone marrow transplant and oncologic service; 2 infective endocarditis/cardiac device infection services; an intensive care unit (ICU) service; a bone and joint infection service; a neuroinfection service; and 3 general ID consult services. Consultative services are provided 7 days a week. At the Cleveland Clinic, ID consultation is required prior to discharge on parenteral antibiotic therapy.10, 11 ID consultation for CoPAT usually occurs when the primary service deems the patient is close to being discharged from hospital. This circumstance allows for assessing the specific contribution of ID physicians beyond that of the primary service and other consulting services.

RESULTS

In the time period studied, there were 1326 CPOE requests for ID consultation. The response to the question, CoPAT consult? was Yes for 304, No for 507, and Not sure for 515 requests. Of the 304 consultation requests marked Yes, 41 were excluded. Reasons for exclusion were: no ID consultation note (21), wrong service consulted (8), consultation request placed while the ID service was already following the patient (7), and duplicate consultation request (5). The remaining 263 consultation requests corresponded to 1 or more CoPAT consultation requests for 249 patients (across different hospitalizations). Of the 263 consultation requests, 172 were initial consultations, while the remaining 91 were reconsultations (patients not actively being followed by the ID service, but previously seen during the same hospitalization).

Consultation characteristics are outlined in Table 2. The most common group of infections for which CoPAT was sought was bone and joint infections, accounting for over 20% of the consultation requests. CoPAT consultations were requested a median of 4 days after hospitalization. Patients were discharged from hospital a median of 3 days after they were seen by the ID service. ID consultation did not delay discharge. The ID service usually saw the patient the same day, and followed the patient in hospital for a median of 1 day. There was no difference in hospital days after consult for patients who did not need antibiotics versus those who did.

ID consultation provided value in at least 1 domain in 260 of the 263 consultations. This included optimization of antimicrobial treatment in 84%, significant alteration of patient assessment in 52%, and additional medical care contribution in 71% of consultations. Substantial contributions were made in all domains in both initial consultations and in reconsultations. Specific ID contributions within each of the domains are shown in Figure 1. There was wide overlap of contributions across the 3 domains for individual consultations (Figure 2), with contributions in all domains occurring in 34% of consultations. CoPAT was deemed not to be necessary in 27% of consultations. Among patients who did not require CoPAT, 60% received oral antibiotics and 40% were deemed not to need any antibiotics at hospital discharge. Among the patients discharged on CoPAT, a follow‐up appointment with a Cleveland Clinic ID physician familiar with the patient was set up 86% of the time; the rest either followed up with another physician or it was deemed that a scheduled follow‐up ID visit was not necessary.0

Figure 1

Figure 2

DISCUSSION

Physicians practicing in the specialty of infectious diseases face challenges and opportunities, as they adapt to changing demands within hospital practice in regard to reimbursement in an Accountable Care environment. Other challenges include emerging infections, antimicrobial resistance, need for antimicrobial stewardship, and increasing numbers of immunocompromised patients.12 From a health systems perspective, the overall value of care provided by the entire organization, and overall outcomes, are ultimately what matter. However, healthcare administrators need an appreciation of contributions of individual providers and specialties to fairly allocate resources and compensation for care provided. Articulating unique contributions is particularly challenging for individuals or services that provide purely cognitive input. Shrinking healthcare resources makes it critically important for cognitive specialists to be able to define their unique role in the care of patients with complex problems.

Our study found that a major contribution of ID consultation for CoPAT is that the process identifies a large number of patients who do not need CoPAT, thus effecting a powerful antimicrobial stewardship function. In our study, CoPAT was deemed unnecessary 27% of the time. The Infectious Diseases Society of America practice guidelines on outpatient parenteral antimicrobial therapy emphasize the importance of careful evaluation of patients considered for parenteral antibiotics outside the hospital setting.13 The focus on careful selection of appropriate patients for CoPAT has been a cornerstone of the Cleveland Clinic model of care. Nearly 30 years ago, we found that outpatient parenteral antibiotic therapy was unnecessary or not feasible in 40% of the patients referred for evaluation.10 If we adjust the numbers with the assumption that reimbursement issues present at that time are now less of an issue, the proportion of patients who were referred for CoPAT but not discharged on it was 29%, a figure remarkably similar to that found in the current study.

Another major contribution of ID consultation is the provision of effective transition of care from the inpatient to the outpatient setting. Frequent occurrence of postdischarge adverse events has been recognized as a problem in clinical practice.14 Primary care physicians are rarely involved in discussions about hospital discharge.15 A consensus conference including the American College of Physicians, Society of Hospital Medicine, and Society of General Internal Medicine, convened in July 2007 to address quality gaps in transitions of care between inpatient and outpatient settings. It identified 5 principles for effective care transitions: accountability, communication, timeliness, patient and family involvement, and respect for the hub of coordination of care.16 Recognizing gaps in care transition, hospitalists in a hospital‐based infusion program developed a model of care that successfully bridged the hospital‐to‐home care transition for patients who could return to hospital for daily antimicrobial infusions.17 In our system, ID physicians take ownership for directing parenteral antibiotic therapy for the episode of illness, specifying the physician, date, and time of follow‐up before the patient is discharged from hospital, thereby essentially satisfying the principles of effective care transitions identified. The purpose of the ID follow‐up is not to replace other follow‐up care for patients but to ensure safe transition of care while treating an episode of infection.

Attribution of identified contributions to the ID consultation could be done because our study was limited to CoPAT consultations. Such consultations typically occur when patients are deemed close to hospital discharge by the primary service. There should be little controversy about attribution of cognitive input in such consultations, because from the primary service's perspective, the patient is ready or almost ready to be discharged from hospital. It would be fair to state that most of the identified contributions in the study would not have occurred had it not been for the ID consultation.

We acknowledge that the study suffers from many limitations. The biggest limitation is that the contribution elements are defined by ID physicians and sought in the medical record by physicians from the same specialty. This arrangement certainly has potential for significant bias. To limit this bias, data collection was performed by physicians who had not participated in the care of the patient. In addition, we only could assess what was documented in the electronic health record. Our study found that alteration of antibiotic therapy was a substantial contribution, however, documentation of recommendation to change antibiotics in the medical record rarely specified exactly why the change was recommended. Reasons for antibiotic change recommendations included bug‐drug mismatch, minimum inhibitory concentration (MIC) considerations, pharmacokinetic considerations, adverse effects, convenience of dosing, drug interactions, and insurance coverage. However, it is not possible to quantify the specific contribution of each of these reasons, in a retrospective study, without making assumptions about why specific ID physicians made specific antibiotic change recommendations. There may have been more contributions that might not have been apparent on a retrospective chart review. The lack of a control group also lessens the impact of our findings. We could not have a control group, because no patient is discharged from the Cleveland Clinic on CoPAT without having been seen by an ID physician. Mandatory ID consultation for CoPAT has previously been shown to reduce costs,9 however, our study was not designed to evaluate cost.

The perceived value of ID consultation in our institution can be appreciated when one considers the longstanding institutional policy of requiring ID consultation for CoPAT.10, 11 The perpetuation of this tradition in the hospital is testament to the presumption that mandatory ID consultation is seen to be of value by the institution.

In summary, ID consultation in our institution contributes to the care of inpatients being considered for CoPAT by substantially reducing unnecessary parenteral antibiotic use, optimizing antibiotic therapy, recognizing need for additional testing before discharge from hospital, and by providing effective transition of care from the inpatient to the outpatient setting.

With dramatically increasing costs of healthcare, it has become increasingly necessary for healthcare providers to demonstrate value in the delivery of care. Porter and Teisberg have strongly advocated that healthcare reform efforts should focus on improving value rather than limiting cost, with value being defined as quality per unit cost.1 However, it has been pointed out that value means different things to different people.2 The biggest challenge in defining value stems mainly from the difficulty in defining quality, because it, too, means vastly different things to different people. Modern medicine is increasingly characterized by multidisciplinary care. With limited or shrinking resources, it will become necessary for individual specialists to describe and articulate, in quantitative terms, their specific contributions to the overall outcome of individual patients.

Previous publications have provided broad descriptions of the value provided by infectious disease (ID) specialists in the domains of sepsis, infection control, outpatient antibiotic therapy, antimicrobial stewardship, and directive care and teaching.3, 4 Studies have also shown the value of ID physicians in specific disease conditions. ID consultation is associated with lower mortality5, 6 and lower relapse rates7 in hospitalized patients with Staphylococcus aureus bacteremia. In another study evaluating the impact of ID consultants, patients seen by ID consultants had longer lengths of hospital stay, longer intensive care unit lengths of stay, and higher antibiotic costs than matched controls not seen by ID consultants.8 It can be argued that a major limitation of the study was that controls were not matched for the ID diagnosis, nor for the causative microorganisms, but it is clear that ID physicians are challenged to demonstrate their contribution to the care of patients.

A unique activity of ID physicians is the management of community‐based parenteral anti‐infective therapy (CoPAT). At Baystate Medical Center, a policy of mandatory ID consultation was instituted for patients leaving hospital on parenteral antibiotics. A study was conducted on the impact of predischarge ID consultation for 44 patients who were not already being followed by the ID service. The study documented change from intravenous (IV) to oral formulation, change of antibiotic choice, and change of dose/duration of treatment in a substantial proportion of patients.9 These are significant changes, but ID consultation contributes more than the themes explored in the study.

The purpose of this study was to evaluate the contribution of ID consultation when consulted for CoPAT, an activity specific to ID practice, in a different institution, and using an expanded definition of medical contribution.

METHODS

The Cleveland Clinic's Department of Infectious Disease has 24 staff physicians and 11 inpatient ID consultative services. These include: 2 solid organ transplant services; a bone marrow transplant and oncologic service; 2 infective endocarditis/cardiac device infection services; an intensive care unit (ICU) service; a bone and joint infection service; a neuroinfection service; and 3 general ID consult services. Consultative services are provided 7 days a week. At the Cleveland Clinic, ID consultation is required prior to discharge on parenteral antibiotic therapy.10, 11 ID consultation for CoPAT usually occurs when the primary service deems the patient is close to being discharged from hospital. This circumstance allows for assessing the specific contribution of ID physicians beyond that of the primary service and other consulting services.

RESULTS

In the time period studied, there were 1326 CPOE requests for ID consultation. The response to the question, CoPAT consult? was Yes for 304, No for 507, and Not sure for 515 requests. Of the 304 consultation requests marked Yes, 41 were excluded. Reasons for exclusion were: no ID consultation note (21), wrong service consulted (8), consultation request placed while the ID service was already following the patient (7), and duplicate consultation request (5). The remaining 263 consultation requests corresponded to 1 or more CoPAT consultation requests for 249 patients (across different hospitalizations). Of the 263 consultation requests, 172 were initial consultations, while the remaining 91 were reconsultations (patients not actively being followed by the ID service, but previously seen during the same hospitalization).

Consultation characteristics are outlined in Table 2. The most common group of infections for which CoPAT was sought was bone and joint infections, accounting for over 20% of the consultation requests. CoPAT consultations were requested a median of 4 days after hospitalization. Patients were discharged from hospital a median of 3 days after they were seen by the ID service. ID consultation did not delay discharge. The ID service usually saw the patient the same day, and followed the patient in hospital for a median of 1 day. There was no difference in hospital days after consult for patients who did not need antibiotics versus those who did.

ID consultation provided value in at least 1 domain in 260 of the 263 consultations. This included optimization of antimicrobial treatment in 84%, significant alteration of patient assessment in 52%, and additional medical care contribution in 71% of consultations. Substantial contributions were made in all domains in both initial consultations and in reconsultations. Specific ID contributions within each of the domains are shown in Figure 1. There was wide overlap of contributions across the 3 domains for individual consultations (Figure 2), with contributions in all domains occurring in 34% of consultations. CoPAT was deemed not to be necessary in 27% of consultations. Among patients who did not require CoPAT, 60% received oral antibiotics and 40% were deemed not to need any antibiotics at hospital discharge. Among the patients discharged on CoPAT, a follow‐up appointment with a Cleveland Clinic ID physician familiar with the patient was set up 86% of the time; the rest either followed up with another physician or it was deemed that a scheduled follow‐up ID visit was not necessary.0

Figure 1

Figure 2

DISCUSSION

Physicians practicing in the specialty of infectious diseases face challenges and opportunities, as they adapt to changing demands within hospital practice in regard to reimbursement in an Accountable Care environment. Other challenges include emerging infections, antimicrobial resistance, need for antimicrobial stewardship, and increasing numbers of immunocompromised patients.12 From a health systems perspective, the overall value of care provided by the entire organization, and overall outcomes, are ultimately what matter. However, healthcare administrators need an appreciation of contributions of individual providers and specialties to fairly allocate resources and compensation for care provided. Articulating unique contributions is particularly challenging for individuals or services that provide purely cognitive input. Shrinking healthcare resources makes it critically important for cognitive specialists to be able to define their unique role in the care of patients with complex problems.

Our study found that a major contribution of ID consultation for CoPAT is that the process identifies a large number of patients who do not need CoPAT, thus effecting a powerful antimicrobial stewardship function. In our study, CoPAT was deemed unnecessary 27% of the time. The Infectious Diseases Society of America practice guidelines on outpatient parenteral antimicrobial therapy emphasize the importance of careful evaluation of patients considered for parenteral antibiotics outside the hospital setting.13 The focus on careful selection of appropriate patients for CoPAT has been a cornerstone of the Cleveland Clinic model of care. Nearly 30 years ago, we found that outpatient parenteral antibiotic therapy was unnecessary or not feasible in 40% of the patients referred for evaluation.10 If we adjust the numbers with the assumption that reimbursement issues present at that time are now less of an issue, the proportion of patients who were referred for CoPAT but not discharged on it was 29%, a figure remarkably similar to that found in the current study.

Another major contribution of ID consultation is the provision of effective transition of care from the inpatient to the outpatient setting. Frequent occurrence of postdischarge adverse events has been recognized as a problem in clinical practice.14 Primary care physicians are rarely involved in discussions about hospital discharge.15 A consensus conference including the American College of Physicians, Society of Hospital Medicine, and Society of General Internal Medicine, convened in July 2007 to address quality gaps in transitions of care between inpatient and outpatient settings. It identified 5 principles for effective care transitions: accountability, communication, timeliness, patient and family involvement, and respect for the hub of coordination of care.16 Recognizing gaps in care transition, hospitalists in a hospital‐based infusion program developed a model of care that successfully bridged the hospital‐to‐home care transition for patients who could return to hospital for daily antimicrobial infusions.17 In our system, ID physicians take ownership for directing parenteral antibiotic therapy for the episode of illness, specifying the physician, date, and time of follow‐up before the patient is discharged from hospital, thereby essentially satisfying the principles of effective care transitions identified. The purpose of the ID follow‐up is not to replace other follow‐up care for patients but to ensure safe transition of care while treating an episode of infection.

Attribution of identified contributions to the ID consultation could be done because our study was limited to CoPAT consultations. Such consultations typically occur when patients are deemed close to hospital discharge by the primary service. There should be little controversy about attribution of cognitive input in such consultations, because from the primary service's perspective, the patient is ready or almost ready to be discharged from hospital. It would be fair to state that most of the identified contributions in the study would not have occurred had it not been for the ID consultation.

We acknowledge that the study suffers from many limitations. The biggest limitation is that the contribution elements are defined by ID physicians and sought in the medical record by physicians from the same specialty. This arrangement certainly has potential for significant bias. To limit this bias, data collection was performed by physicians who had not participated in the care of the patient. In addition, we only could assess what was documented in the electronic health record. Our study found that alteration of antibiotic therapy was a substantial contribution, however, documentation of recommendation to change antibiotics in the medical record rarely specified exactly why the change was recommended. Reasons for antibiotic change recommendations included bug‐drug mismatch, minimum inhibitory concentration (MIC) considerations, pharmacokinetic considerations, adverse effects, convenience of dosing, drug interactions, and insurance coverage. However, it is not possible to quantify the specific contribution of each of these reasons, in a retrospective study, without making assumptions about why specific ID physicians made specific antibiotic change recommendations. There may have been more contributions that might not have been apparent on a retrospective chart review. The lack of a control group also lessens the impact of our findings. We could not have a control group, because no patient is discharged from the Cleveland Clinic on CoPAT without having been seen by an ID physician. Mandatory ID consultation for CoPAT has previously been shown to reduce costs,9 however, our study was not designed to evaluate cost.

The perceived value of ID consultation in our institution can be appreciated when one considers the longstanding institutional policy of requiring ID consultation for CoPAT.10, 11 The perpetuation of this tradition in the hospital is testament to the presumption that mandatory ID consultation is seen to be of value by the institution.

In summary, ID consultation in our institution contributes to the care of inpatients being considered for CoPAT by substantially reducing unnecessary parenteral antibiotic use, optimizing antibiotic therapy, recognizing need for additional testing before discharge from hospital, and by providing effective transition of care from the inpatient to the outpatient setting.

With dramatically increasing costs of healthcare, it has become increasingly necessary for healthcare providers to demonstrate value in the delivery of care. Porter and Teisberg have strongly advocated that healthcare reform efforts should focus on improving value rather than limiting cost, with value being defined as quality per unit cost.1 However, it has been pointed out that value means different things to different people.2 The biggest challenge in defining value stems mainly from the difficulty in defining quality, because it, too, means vastly different things to different people. Modern medicine is increasingly characterized by multidisciplinary care. With limited or shrinking resources, it will become necessary for individual specialists to describe and articulate, in quantitative terms, their specific contributions to the overall outcome of individual patients.

Previous publications have provided broad descriptions of the value provided by infectious disease (ID) specialists in the domains of sepsis, infection control, outpatient antibiotic therapy, antimicrobial stewardship, and directive care and teaching.3, 4 Studies have also shown the value of ID physicians in specific disease conditions. ID consultation is associated with lower mortality5, 6 and lower relapse rates7 in hospitalized patients with Staphylococcus aureus bacteremia. In another study evaluating the impact of ID consultants, patients seen by ID consultants had longer lengths of hospital stay, longer intensive care unit lengths of stay, and higher antibiotic costs than matched controls not seen by ID consultants.8 It can be argued that a major limitation of the study was that controls were not matched for the ID diagnosis, nor for the causative microorganisms, but it is clear that ID physicians are challenged to demonstrate their contribution to the care of patients.

A unique activity of ID physicians is the management of community‐based parenteral anti‐infective therapy (CoPAT). At Baystate Medical Center, a policy of mandatory ID consultation was instituted for patients leaving hospital on parenteral antibiotics. A study was conducted on the impact of predischarge ID consultation for 44 patients who were not already being followed by the ID service. The study documented change from intravenous (IV) to oral formulation, change of antibiotic choice, and change of dose/duration of treatment in a substantial proportion of patients.9 These are significant changes, but ID consultation contributes more than the themes explored in the study.

The purpose of this study was to evaluate the contribution of ID consultation when consulted for CoPAT, an activity specific to ID practice, in a different institution, and using an expanded definition of medical contribution.

METHODS

The Cleveland Clinic's Department of Infectious Disease has 24 staff physicians and 11 inpatient ID consultative services. These include: 2 solid organ transplant services; a bone marrow transplant and oncologic service; 2 infective endocarditis/cardiac device infection services; an intensive care unit (ICU) service; a bone and joint infection service; a neuroinfection service; and 3 general ID consult services. Consultative services are provided 7 days a week. At the Cleveland Clinic, ID consultation is required prior to discharge on parenteral antibiotic therapy.10, 11 ID consultation for CoPAT usually occurs when the primary service deems the patient is close to being discharged from hospital. This circumstance allows for assessing the specific contribution of ID physicians beyond that of the primary service and other consulting services.

RESULTS

In the time period studied, there were 1326 CPOE requests for ID consultation. The response to the question, CoPAT consult? was Yes for 304, No for 507, and Not sure for 515 requests. Of the 304 consultation requests marked Yes, 41 were excluded. Reasons for exclusion were: no ID consultation note (21), wrong service consulted (8), consultation request placed while the ID service was already following the patient (7), and duplicate consultation request (5). The remaining 263 consultation requests corresponded to 1 or more CoPAT consultation requests for 249 patients (across different hospitalizations). Of the 263 consultation requests, 172 were initial consultations, while the remaining 91 were reconsultations (patients not actively being followed by the ID service, but previously seen during the same hospitalization).

Consultation characteristics are outlined in Table 2. The most common group of infections for which CoPAT was sought was bone and joint infections, accounting for over 20% of the consultation requests. CoPAT consultations were requested a median of 4 days after hospitalization. Patients were discharged from hospital a median of 3 days after they were seen by the ID service. ID consultation did not delay discharge. The ID service usually saw the patient the same day, and followed the patient in hospital for a median of 1 day. There was no difference in hospital days after consult for patients who did not need antibiotics versus those who did.

ID consultation provided value in at least 1 domain in 260 of the 263 consultations. This included optimization of antimicrobial treatment in 84%, significant alteration of patient assessment in 52%, and additional medical care contribution in 71% of consultations. Substantial contributions were made in all domains in both initial consultations and in reconsultations. Specific ID contributions within each of the domains are shown in Figure 1. There was wide overlap of contributions across the 3 domains for individual consultations (Figure 2), with contributions in all domains occurring in 34% of consultations. CoPAT was deemed not to be necessary in 27% of consultations. Among patients who did not require CoPAT, 60% received oral antibiotics and 40% were deemed not to need any antibiotics at hospital discharge. Among the patients discharged on CoPAT, a follow‐up appointment with a Cleveland Clinic ID physician familiar with the patient was set up 86% of the time; the rest either followed up with another physician or it was deemed that a scheduled follow‐up ID visit was not necessary.0

Figure 1

Figure 2

DISCUSSION

Physicians practicing in the specialty of infectious diseases face challenges and opportunities, as they adapt to changing demands within hospital practice in regard to reimbursement in an Accountable Care environment. Other challenges include emerging infections, antimicrobial resistance, need for antimicrobial stewardship, and increasing numbers of immunocompromised patients.12 From a health systems perspective, the overall value of care provided by the entire organization, and overall outcomes, are ultimately what matter. However, healthcare administrators need an appreciation of contributions of individual providers and specialties to fairly allocate resources and compensation for care provided. Articulating unique contributions is particularly challenging for individuals or services that provide purely cognitive input. Shrinking healthcare resources makes it critically important for cognitive specialists to be able to define their unique role in the care of patients with complex problems.

Our study found that a major contribution of ID consultation for CoPAT is that the process identifies a large number of patients who do not need CoPAT, thus effecting a powerful antimicrobial stewardship function. In our study, CoPAT was deemed unnecessary 27% of the time. The Infectious Diseases Society of America practice guidelines on outpatient parenteral antimicrobial therapy emphasize the importance of careful evaluation of patients considered for parenteral antibiotics outside the hospital setting.13 The focus on careful selection of appropriate patients for CoPAT has been a cornerstone of the Cleveland Clinic model of care. Nearly 30 years ago, we found that outpatient parenteral antibiotic therapy was unnecessary or not feasible in 40% of the patients referred for evaluation.10 If we adjust the numbers with the assumption that reimbursement issues present at that time are now less of an issue, the proportion of patients who were referred for CoPAT but not discharged on it was 29%, a figure remarkably similar to that found in the current study.

Another major contribution of ID consultation is the provision of effective transition of care from the inpatient to the outpatient setting. Frequent occurrence of postdischarge adverse events has been recognized as a problem in clinical practice.14 Primary care physicians are rarely involved in discussions about hospital discharge.15 A consensus conference including the American College of Physicians, Society of Hospital Medicine, and Society of General Internal Medicine, convened in July 2007 to address quality gaps in transitions of care between inpatient and outpatient settings. It identified 5 principles for effective care transitions: accountability, communication, timeliness, patient and family involvement, and respect for the hub of coordination of care.16 Recognizing gaps in care transition, hospitalists in a hospital‐based infusion program developed a model of care that successfully bridged the hospital‐to‐home care transition for patients who could return to hospital for daily antimicrobial infusions.17 In our system, ID physicians take ownership for directing parenteral antibiotic therapy for the episode of illness, specifying the physician, date, and time of follow‐up before the patient is discharged from hospital, thereby essentially satisfying the principles of effective care transitions identified. The purpose of the ID follow‐up is not to replace other follow‐up care for patients but to ensure safe transition of care while treating an episode of infection.

Attribution of identified contributions to the ID consultation could be done because our study was limited to CoPAT consultations. Such consultations typically occur when patients are deemed close to hospital discharge by the primary service. There should be little controversy about attribution of cognitive input in such consultations, because from the primary service's perspective, the patient is ready or almost ready to be discharged from hospital. It would be fair to state that most of the identified contributions in the study would not have occurred had it not been for the ID consultation.

We acknowledge that the study suffers from many limitations. The biggest limitation is that the contribution elements are defined by ID physicians and sought in the medical record by physicians from the same specialty. This arrangement certainly has potential for significant bias. To limit this bias, data collection was performed by physicians who had not participated in the care of the patient. In addition, we only could assess what was documented in the electronic health record. Our study found that alteration of antibiotic therapy was a substantial contribution, however, documentation of recommendation to change antibiotics in the medical record rarely specified exactly why the change was recommended. Reasons for antibiotic change recommendations included bug‐drug mismatch, minimum inhibitory concentration (MIC) considerations, pharmacokinetic considerations, adverse effects, convenience of dosing, drug interactions, and insurance coverage. However, it is not possible to quantify the specific contribution of each of these reasons, in a retrospective study, without making assumptions about why specific ID physicians made specific antibiotic change recommendations. There may have been more contributions that might not have been apparent on a retrospective chart review. The lack of a control group also lessens the impact of our findings. We could not have a control group, because no patient is discharged from the Cleveland Clinic on CoPAT without having been seen by an ID physician. Mandatory ID consultation for CoPAT has previously been shown to reduce costs,9 however, our study was not designed to evaluate cost.

The perceived value of ID consultation in our institution can be appreciated when one considers the longstanding institutional policy of requiring ID consultation for CoPAT.10, 11 The perpetuation of this tradition in the hospital is testament to the presumption that mandatory ID consultation is seen to be of value by the institution.

In summary, ID consultation in our institution contributes to the care of inpatients being considered for CoPAT by substantially reducing unnecessary parenteral antibiotic use, optimizing antibiotic therapy, recognizing need for additional testing before discharge from hospital, and by providing effective transition of care from the inpatient to the outpatient setting.

Collaboration between members of a multidisciplinary team is a key component of an effective institutional antimicrobial stewardship program, which itself is a key component of optimizing the care of hospitalized patients being treated with antimicrobial agents for proven or suspected infectious diseases. However, patient care does not and should not end once the patient is discharged from the hospital. In fact, high‐quality, value‐based health care across the full range of a medical condition depends on planning for optimization of care within the hospital as well as transitions of care to the outpatient setting. This extended care plan includes collaboration with multiple members of the health care community, both inside and outside the institution. The current review examines 3 aspects of patient care across the full cycle of an infectious disease condition: (1) value‐based health care, (2) stewardship of antimicrobials, and (3) community‐based parenteral anti‐infective therapy (CoPAT) as a model for antimicrobial stewardship outside the institutional setting.

Value‐Based Health Care

Patients first want to know that the health care professionals treating them actually care about them as individuals, and only then are patients concerned about how much the medical team knows. Patient‐centered care is a critical component of value‐based health care, a term that was bandied about quite a bit during the recent and ongoing health care debate in the United States. But what exactly does it mean? First, value in health care is defined by health care outcomes as a function of or divided by the cost of delivery of care. As Dr. Michael Porter and Dr. Elizabeth Olmsted Teisberg delineated in their 2007 article in the Journal of the American Medical Association,2 as well as in the 2006 book Redefining Health Care,3 The purpose of the healthcare system is not to minimize costs but to deliver value to patients, that is, better health per dollar spent. As they discuss value, it is a patient‐centric measure, and is focused on individual patient (not just diagnosis‐related group) outcomes and the cost of care across the full cycle. In this way of looking at things, an episode of care goes beyond the treatment provided during the acute admission to also include the transition of care to the outpatient or posthospital setting.

The reforms proposed by Porter and Teisberg are best achieved when the participating health care institutions have developed an information technology platform able to integrate and fully measure care across the full cycle of a medical condition. Furthermore, there is strong evidence that patient value increases with physician and team experience and volume for a particular condition.2 High volumes tend to correlate with the development of better information technology, as well as the formation of dedicated teams with tailored facilities, and with a greater capacity for constructive feedback to improve patient outcomes. The more experience a physician and team have with the management of a particular medical condition, the greater is the opportunity to learn and refine practices to provide greater value to the patient.

The Institute of Medicine has recommended that all healthcare professionals should be educated to deliver patient‐centered care as members of an interdisciplinary team emphasizing evidence‐based practice, quality improvement, and informatics.4 As has been demonstrated for patients with congestive heart failure59 and other conditions,10, 11 outcomes improve when components of care are integrated (often by nurse‐directed teams), preparing for the transition of care from the hospital to the home.12 This concept is the basis for the community‐based parenteral anti‐infective therapy program (CoPAT) at the Cleveland Clinic as a model for antimicrobial stewardship for patients requiring parenteral antimicrobial therapy at the time of discharge from the inpatient setting.

Community‐Based Parenteral Anti‐Infective Therapy as a Systems‐Based Approach to Antimicrobial Stewardship

A systems‐based approach for antimicrobial stewardship, CoPAT has been in operation at the Cleveland Clinic, a 1200‐bed hospital in downtown Cleveland, Ohio, since November 1979. The experiences of the authors and their colleagues demonstrate it to be a value‐based proposition for the patient that uses an antimicrobial stewardship platform. Also known as outpatient parenteral antimicrobial therapy (OPAT), CoPAT refers to the practice of administering antimicrobial therapy in the home or other outpatient settings, first introduced by Rucker and Harrison in 1974 in the context of outpatient management of cystic fibrosis.16 In the United States, CoPAT is a common practice today, and the IDSA has created practice guidelines for it.17

In 1983, Rehm and Weinstein coauthored an article describing their experiences at the Cleveland Clinic, in which selected patients were trained for home‐based antimicrobial therapy.12 Figure 1 illustrates the astronomical growth that has occurred over the years at the Cleveland Clinic in the number of patients discharged from the acute care center undergoing CoPAT (Gordon, unpublished data). It is anticipated that this growth will continue and in large part reflects the complexity of patients being seen and the desire to reduce length of stay. Evaluating the quality of any medical care is difficult, but there are 3 general approaches to assessing or measuring the quality of medical care: assessing the structure of care, assessing processes of care, and assessing outcomes.18 The quality of the CoPAT program at the Cleveland Clinic can be examined in the context of these 3 areas of assessment.

Figure 1

Settings or the Structure of Care

In a 1966 publication on quality of medical care evaluations, Donabedian described assessment of the structure of care as one of the primary approaches to measuring the quality of care.18 By structure, Donabedian meant the settings in which medical care takes place, including the adequacy of facilities and equipment, qualifications or expertise of medical staff and their organization, the administrative structure of the institution or institutional program of interest, and other administrative and related processes supporting and directing the delivery of care. Although the structure of care has the advantage of being concrete and relatively easy to assess, to be most meaningful, it ultimately needs to be related to the processes and outcomes of care.

With respect to the CoPAT program at the Cleveland Clinic main hospital, infectious diseases consultation is required for every patient being considered for discharge with parenteral antibiotics, whether the patient is going home or to another facility, including the clinic's own skilled nursing facility (SNF). Arrangements are then made for the delivery of antibiotics at home or in SNFs or long‐term acute care (LTAC) centers. The Cleveland Clinic CoPAT program does not use an outpatient infusion center.

The Cleveland Clinic uses a mandatory infectious diseases consultation for CoPAT because there are a number of important issues that need to be addressed before the patient is discharged, and for our system this is best accomplished by an infectious diseases specialist.12 For example, is antimicrobial therapy actually required in the first place? If it is, what is the optimal type, route, and duration of therapy? Are there other medical issues that need to be addressed? Decisions also need to be made about optimal vascular access and antimicrobial selection and administration, as well as arrangements being made for monitoring clinical and laboratory aspects. It is important that there is a smooth transition of care and prescheduled follow‐up in the outpatient clinic. The identification and use of an infectious diseases clinician directing the process leads to accountability. Notably, mandatory infectious disease consultation for outpatient parenteral antibiotic therapy has been used at Baystate Medical Center with improvement in reducing costs.19

The Process of Care

Assessments of the process of care involve examination of the particulars of medical care delivery, or whether what is recognized or accepted as good medical care has been applied. As discussed by Donabedian, process of care deals with issues such as the appropriateness and completeness of information obtained through clinical history, physical examination, and diagnostic tests; justification of diagnosis and therapy; technical competence in the performance of diagnostic and therapeutic procedures; and coordination and continuity of care.18

The CoPAT initiation process at the Cleveland Clinic is illustrated in Figure 2. It is a bundled process. As already mentioned, an infectious diseases consultation and evaluation is scheduled for all patients considered for CoPAT, after which a CoPAT form is completed and a follow‐up appointment made before the patient is discharged. In addition, the vascular access team is consulted and an appropriate vascular access device is placed in the patient prior to discharge. Likewise, a case manager is enlisted to identify a health care agency or SNF for patient placement or to determine whether the patient will receive home treatment. Once the appropriate setting is identified, the case manager transmits a completed CoPAT form to the health care agency or SNF, while forwarding a copy to the CoPAT nurse coordinator in the infectious disease department.

Figure 2

An electronic health record system is used at the Cleveland Clinic to provide real‐time information relevant for patient management. In 2007, a structured data form for CoPAT start‐of‐care was created within the Cleveland Clinic hospital electronic health record (EHR). This form contains a number of elements relevant for setting up patients for transition to CoPAT. In particular, the electronic CoPAT form contains information about the infection(s) and microorganism(s) being treated, intravenous antibiotic(s) prescribed (including treatment stop date), concurrent oral antibiotics, premedication recommendations (if appropriate), and recommended monitoring of laboratory tests. In addition, the form contains the telephone and fax numbers of the CoPAT coordinator and the name of the responsible physician, including a scheduled appointment for follow‐up (Fig. 3). The staff physician is responsible for completing the electronic CoPAT form or prescription. This CoPAT prescription then becomes part of the patient's electronic record and is transmissible and viewable by anyone with access to the EHR. This is important in terms of follow‐up and care accountability: an infectious disease staff clinician is identified as the contact person for clinical issues when a patient is on CoPAT.

Figure 3

After the patient is discharged, the CoPAT coordinator in the infectious disease department becomes responsible, together with the clinic's outpatient pharmacy, for reviewing laboratory results and notifying clinicians of potential problems that need to be addressed. These issues can pertain to laboratory findings, vascular access, or new symptoms or signs observed by the home nurse or patient. All this information is communicated via electronic health record messaging and/or through direct calls to the physician, when needed.

The CoPAT program has been widely accepted by internal customers of the Cleveland Clinic, which include hospitalists. This is probably because there is autonomy and accountability with the infectious diseases staff, the program or team is available 7 days per week, and the EHR facilitates communication. In addition, the use of infectious disease‐specific subspecialty groups (eg, bone marrow and solid‐organ transplant, bone and joint, and infective endocarditis groups) increases clinical credibility, as well as value received by patients of the clinic. Furthermore, the electronic CoPAT script facilitates discharge planning. CoPATs constitute approximately 25% of all ID consultation requests at the Cleveland Clinic and help to justify the 20 clinical ID clinical FTEs.

Outcomes of Medical Care

Assessment of medical care outcomes is another frequently used approach for measuring the quality of medical care.18 Medical care outcomes that have been examined as measures of quality of care include survival, number of hospital readmissions, time between discharge and readmissions, length of initial hospital stay and subsequent readmissions, quality of life, and health care costs. As has often been said, If you cannot measure it, you cannot manage it. The CoPAT program using the EHR has facilitated retrieval of structured reports in a format that provides clinicians with real‐time data enabling assessment of outcomes. By examining this data, the CoPAT team is in a better position to contemplate potential interventions for improving outpatient care and the value patients receive.

A 36‐month review of Cleveland Clinic CoPAT patient demographics from July 2007 to June 2010 demonstrated 6287 patients (56% male) had been prescribed 9471 courses of CoPAT (Gordon, unpublished data). Seventy‐nine percent of the patients were white, 16% African American, and 5% of other races. Most patients received 1 antibiotic per CoPAT course (79.1%), whereas 18.2%, 2.5%, and 0.2% received 2, 3, and 4 antibiotics per CoPAT course, respectively. Figure 4 highlights CoPAT distribution by source for anatomic site of infection. Bone and joint infections were the most common diagnoses associated with CoPAT at the Cleveland Clinic, followed by abdominal, cardiovascular, primary disseminated disease (eg, catheter‐associated bloodstream infections), and skin and soft‐tissue infection.

Figure 4

Figure 5 highlights the top‐10 pathogenic microorganisms in patients being discharged from the Cleveland Clinic with CoPAT, and the top‐10 antimicrobials prescribed for these patients. As can be seen, Staphylococcus aureus (methicillin susceptible and methicillin resistant) was the number one pathogen identified for patients undergoing CoPAT, followed by coagulase‐negative Staphylococcus and Enterococcus species. The most commonly identified gram‐negative bacteria among discharged patients was Pseudomonas aeruginosa. Only 2 of the top 10 pathogens were nonbacterial: Candida species and cytomegalovirus (CMV), the latter being the result of the high volume of transplantations performed at the clinic. With respect to the intravenous antimicrobials prescribed for patients undergoing CoPAT, the most commonly prescribed agent was vancomycin, followed by piperacillin/tazobactam. Of the 10 agents, only micafungin and ganciclovir were not antibacterial agents, indicating that the vast majority of patients discharged from the Cleveland Clinic with CoPAT had had bacterial, rather than fungal or viral, infections.

Figure 5

Of particular note, data collected from July 2007 through December 2008 demonstrated that more than 80% of patients discharged from the hospital with CoPAT did so with a prescheduled follow‐up visit. This patient‐centric measure is important because patients may not follow through with establishing appointments for follow‐up visits once discharge has already occurred. The Cleveland Clinic prides itself on making sure that a follow‐up appointment is actually made before the time of discharge for the vast majority of patients. The process also facilitates continuity of care with a specific infectious disease physician.

The various outcomes data collected by the Cleveland Clinic CoPAT Registry puts it in the position of being able to use the data to identify areas for improvement. Some of the projects made possible by the CoPAT Registry include analysis of: (1) outcomes of CoPAT in patients with bone and joint infections, (2) intensity of care in patients with cardiac and cardiac device infections while undergoing CoPAT, (3) C. difficile infections in patients undergoing CoPAT, and (4) emergency department (ED) visits or unanticipated readmissions in patients undergoing CoPAT. With respect to the last point, a 2009 article by Jencks and colleagues reported that 19.6% of the approximately 12 million Medicare beneficiaries who had been discharged from a hospital were rehospitalized within 30 days.20 Moreover, more than a third (34%) were rehospitalized within 90 days of discharge. It was estimated that no more than 10% of these readmissions were scheduled. More than 50% of patients with a medical condition who were rehospitalized within 30 days of discharge had not been billed for a physician visit between the time of discharge and hospitalization.20 This suggests that scheduling a follow‐up visit at the time of discharge might have reduced the need for many of these rehospitalizations. Unplanned rehospitalizations among the Medicare patients examined were not only relatively common but were also costly, resulting in an estimated $17.4 billion in additional Medicare costs.20 A New York Times editorial accompanying publication of the Jencks article noted that rehospitalizations and accompanying costs might be reduced by better discharge planning and closer cooperation between hospitals and physicians to ensure follow‐up care.21

At the Cleveland Clinic, data have recently been collected on the reasons for ED visits or hospital readmissions for patients receiving CoPAT at home through the Cleveland Clinic home care program. As illustrated in Figure 6, 24% of ED visits22 and 41% of hospital readmissions (Gordon, unpublished data) were for the infection being treated. Vascular access complications accounted for 23% of ED visits but only 2% of hospital readmissions. Nearly 50% of ED visits and 60% of hospital readmissions were for a reason unrelated to the infection being treated or CoPAT. It is hoped that closer examination of the data and perhaps additional analyses will suggest interventions to further reduce preventable readmissions or ED visits among patients discharged from the Cleveland Clinic on CoPAT.

Figure 6

Conclusions

Attention to antimicrobial stewardship and patient care should not end once the patient is discharged from the hospital or other institutional setting. Patients expect and should receive value‐based health care across the full cycle of their medical condition, and it is the responsibility of those caring for them to prepare for and provide such care during as well as after hospital discharge. The CoPAT program at the Cleveland Clinic provides a model for the extension of antimicrobial stewardship into the outpatient setting. The effectiveness of the program depends on a patient‐centric approach involving coordination and use of the expertise of multiple members of a team dedicated to patient value and facilitated by hospital‐based EHRs specialized for optimizing the transition of care into the outpatient setting for all patients scheduled to receive CoPAT. The quality of medical care provided by the Cleveland Clinic or other hospitals can be accessed through measurements of the structure, processes, and outcomes of care provided by the respective institutions. The data obtained can then be used to further refine care to optimize outcomes and provide high value for the patients treated at the institution. Achieving and then maintaining high‐quality medical care that provides value to patients is an ongoing process that should never be taken for granted.

Collaboration between members of a multidisciplinary team is a key component of an effective institutional antimicrobial stewardship program, which itself is a key component of optimizing the care of hospitalized patients being treated with antimicrobial agents for proven or suspected infectious diseases. However, patient care does not and should not end once the patient is discharged from the hospital. In fact, high‐quality, value‐based health care across the full range of a medical condition depends on planning for optimization of care within the hospital as well as transitions of care to the outpatient setting. This extended care plan includes collaboration with multiple members of the health care community, both inside and outside the institution. The current review examines 3 aspects of patient care across the full cycle of an infectious disease condition: (1) value‐based health care, (2) stewardship of antimicrobials, and (3) community‐based parenteral anti‐infective therapy (CoPAT) as a model for antimicrobial stewardship outside the institutional setting.

Value‐Based Health Care

Patients first want to know that the health care professionals treating them actually care about them as individuals, and only then are patients concerned about how much the medical team knows. Patient‐centered care is a critical component of value‐based health care, a term that was bandied about quite a bit during the recent and ongoing health care debate in the United States. But what exactly does it mean? First, value in health care is defined by health care outcomes as a function of or divided by the cost of delivery of care. As Dr. Michael Porter and Dr. Elizabeth Olmsted Teisberg delineated in their 2007 article in the Journal of the American Medical Association,2 as well as in the 2006 book Redefining Health Care,3 The purpose of the healthcare system is not to minimize costs but to deliver value to patients, that is, better health per dollar spent. As they discuss value, it is a patient‐centric measure, and is focused on individual patient (not just diagnosis‐related group) outcomes and the cost of care across the full cycle. In this way of looking at things, an episode of care goes beyond the treatment provided during the acute admission to also include the transition of care to the outpatient or posthospital setting.

The reforms proposed by Porter and Teisberg are best achieved when the participating health care institutions have developed an information technology platform able to integrate and fully measure care across the full cycle of a medical condition. Furthermore, there is strong evidence that patient value increases with physician and team experience and volume for a particular condition.2 High volumes tend to correlate with the development of better information technology, as well as the formation of dedicated teams with tailored facilities, and with a greater capacity for constructive feedback to improve patient outcomes. The more experience a physician and team have with the management of a particular medical condition, the greater is the opportunity to learn and refine practices to provide greater value to the patient.

The Institute of Medicine has recommended that all healthcare professionals should be educated to deliver patient‐centered care as members of an interdisciplinary team emphasizing evidence‐based practice, quality improvement, and informatics.4 As has been demonstrated for patients with congestive heart failure59 and other conditions,10, 11 outcomes improve when components of care are integrated (often by nurse‐directed teams), preparing for the transition of care from the hospital to the home.12 This concept is the basis for the community‐based parenteral anti‐infective therapy program (CoPAT) at the Cleveland Clinic as a model for antimicrobial stewardship for patients requiring parenteral antimicrobial therapy at the time of discharge from the inpatient setting.

Community‐Based Parenteral Anti‐Infective Therapy as a Systems‐Based Approach to Antimicrobial Stewardship

A systems‐based approach for antimicrobial stewardship, CoPAT has been in operation at the Cleveland Clinic, a 1200‐bed hospital in downtown Cleveland, Ohio, since November 1979. The experiences of the authors and their colleagues demonstrate it to be a value‐based proposition for the patient that uses an antimicrobial stewardship platform. Also known as outpatient parenteral antimicrobial therapy (OPAT), CoPAT refers to the practice of administering antimicrobial therapy in the home or other outpatient settings, first introduced by Rucker and Harrison in 1974 in the context of outpatient management of cystic fibrosis.16 In the United States, CoPAT is a common practice today, and the IDSA has created practice guidelines for it.17

In 1983, Rehm and Weinstein coauthored an article describing their experiences at the Cleveland Clinic, in which selected patients were trained for home‐based antimicrobial therapy.12 Figure 1 illustrates the astronomical growth that has occurred over the years at the Cleveland Clinic in the number of patients discharged from the acute care center undergoing CoPAT (Gordon, unpublished data). It is anticipated that this growth will continue and in large part reflects the complexity of patients being seen and the desire to reduce length of stay. Evaluating the quality of any medical care is difficult, but there are 3 general approaches to assessing or measuring the quality of medical care: assessing the structure of care, assessing processes of care, and assessing outcomes.18 The quality of the CoPAT program at the Cleveland Clinic can be examined in the context of these 3 areas of assessment.

Figure 1

Settings or the Structure of Care

In a 1966 publication on quality of medical care evaluations, Donabedian described assessment of the structure of care as one of the primary approaches to measuring the quality of care.18 By structure, Donabedian meant the settings in which medical care takes place, including the adequacy of facilities and equipment, qualifications or expertise of medical staff and their organization, the administrative structure of the institution or institutional program of interest, and other administrative and related processes supporting and directing the delivery of care. Although the structure of care has the advantage of being concrete and relatively easy to assess, to be most meaningful, it ultimately needs to be related to the processes and outcomes of care.

With respect to the CoPAT program at the Cleveland Clinic main hospital, infectious diseases consultation is required for every patient being considered for discharge with parenteral antibiotics, whether the patient is going home or to another facility, including the clinic's own skilled nursing facility (SNF). Arrangements are then made for the delivery of antibiotics at home or in SNFs or long‐term acute care (LTAC) centers. The Cleveland Clinic CoPAT program does not use an outpatient infusion center.

The Cleveland Clinic uses a mandatory infectious diseases consultation for CoPAT because there are a number of important issues that need to be addressed before the patient is discharged, and for our system this is best accomplished by an infectious diseases specialist.12 For example, is antimicrobial therapy actually required in the first place? If it is, what is the optimal type, route, and duration of therapy? Are there other medical issues that need to be addressed? Decisions also need to be made about optimal vascular access and antimicrobial selection and administration, as well as arrangements being made for monitoring clinical and laboratory aspects. It is important that there is a smooth transition of care and prescheduled follow‐up in the outpatient clinic. The identification and use of an infectious diseases clinician directing the process leads to accountability. Notably, mandatory infectious disease consultation for outpatient parenteral antibiotic therapy has been used at Baystate Medical Center with improvement in reducing costs.19

The Process of Care

Assessments of the process of care involve examination of the particulars of medical care delivery, or whether what is recognized or accepted as good medical care has been applied. As discussed by Donabedian, process of care deals with issues such as the appropriateness and completeness of information obtained through clinical history, physical examination, and diagnostic tests; justification of diagnosis and therapy; technical competence in the performance of diagnostic and therapeutic procedures; and coordination and continuity of care.18

The CoPAT initiation process at the Cleveland Clinic is illustrated in Figure 2. It is a bundled process. As already mentioned, an infectious diseases consultation and evaluation is scheduled for all patients considered for CoPAT, after which a CoPAT form is completed and a follow‐up appointment made before the patient is discharged. In addition, the vascular access team is consulted and an appropriate vascular access device is placed in the patient prior to discharge. Likewise, a case manager is enlisted to identify a health care agency or SNF for patient placement or to determine whether the patient will receive home treatment. Once the appropriate setting is identified, the case manager transmits a completed CoPAT form to the health care agency or SNF, while forwarding a copy to the CoPAT nurse coordinator in the infectious disease department.

Figure 2

An electronic health record system is used at the Cleveland Clinic to provide real‐time information relevant for patient management. In 2007, a structured data form for CoPAT start‐of‐care was created within the Cleveland Clinic hospital electronic health record (EHR). This form contains a number of elements relevant for setting up patients for transition to CoPAT. In particular, the electronic CoPAT form contains information about the infection(s) and microorganism(s) being treated, intravenous antibiotic(s) prescribed (including treatment stop date), concurrent oral antibiotics, premedication recommendations (if appropriate), and recommended monitoring of laboratory tests. In addition, the form contains the telephone and fax numbers of the CoPAT coordinator and the name of the responsible physician, including a scheduled appointment for follow‐up (Fig. 3). The staff physician is responsible for completing the electronic CoPAT form or prescription. This CoPAT prescription then becomes part of the patient's electronic record and is transmissible and viewable by anyone with access to the EHR. This is important in terms of follow‐up and care accountability: an infectious disease staff clinician is identified as the contact person for clinical issues when a patient is on CoPAT.

Figure 3

After the patient is discharged, the CoPAT coordinator in the infectious disease department becomes responsible, together with the clinic's outpatient pharmacy, for reviewing laboratory results and notifying clinicians of potential problems that need to be addressed. These issues can pertain to laboratory findings, vascular access, or new symptoms or signs observed by the home nurse or patient. All this information is communicated via electronic health record messaging and/or through direct calls to the physician, when needed.

The CoPAT program has been widely accepted by internal customers of the Cleveland Clinic, which include hospitalists. This is probably because there is autonomy and accountability with the infectious diseases staff, the program or team is available 7 days per week, and the EHR facilitates communication. In addition, the use of infectious disease‐specific subspecialty groups (eg, bone marrow and solid‐organ transplant, bone and joint, and infective endocarditis groups) increases clinical credibility, as well as value received by patients of the clinic. Furthermore, the electronic CoPAT script facilitates discharge planning. CoPATs constitute approximately 25% of all ID consultation requests at the Cleveland Clinic and help to justify the 20 clinical ID clinical FTEs.

Outcomes of Medical Care

Assessment of medical care outcomes is another frequently used approach for measuring the quality of medical care.18 Medical care outcomes that have been examined as measures of quality of care include survival, number of hospital readmissions, time between discharge and readmissions, length of initial hospital stay and subsequent readmissions, quality of life, and health care costs. As has often been said, If you cannot measure it, you cannot manage it. The CoPAT program using the EHR has facilitated retrieval of structured reports in a format that provides clinicians with real‐time data enabling assessment of outcomes. By examining this data, the CoPAT team is in a better position to contemplate potential interventions for improving outpatient care and the value patients receive.

A 36‐month review of Cleveland Clinic CoPAT patient demographics from July 2007 to June 2010 demonstrated 6287 patients (56% male) had been prescribed 9471 courses of CoPAT (Gordon, unpublished data). Seventy‐nine percent of the patients were white, 16% African American, and 5% of other races. Most patients received 1 antibiotic per CoPAT course (79.1%), whereas 18.2%, 2.5%, and 0.2% received 2, 3, and 4 antibiotics per CoPAT course, respectively. Figure 4 highlights CoPAT distribution by source for anatomic site of infection. Bone and joint infections were the most common diagnoses associated with CoPAT at the Cleveland Clinic, followed by abdominal, cardiovascular, primary disseminated disease (eg, catheter‐associated bloodstream infections), and skin and soft‐tissue infection.

Figure 4

Figure 5 highlights the top‐10 pathogenic microorganisms in patients being discharged from the Cleveland Clinic with CoPAT, and the top‐10 antimicrobials prescribed for these patients. As can be seen, Staphylococcus aureus (methicillin susceptible and methicillin resistant) was the number one pathogen identified for patients undergoing CoPAT, followed by coagulase‐negative Staphylococcus and Enterococcus species. The most commonly identified gram‐negative bacteria among discharged patients was Pseudomonas aeruginosa. Only 2 of the top 10 pathogens were nonbacterial: Candida species and cytomegalovirus (CMV), the latter being the result of the high volume of transplantations performed at the clinic. With respect to the intravenous antimicrobials prescribed for patients undergoing CoPAT, the most commonly prescribed agent was vancomycin, followed by piperacillin/tazobactam. Of the 10 agents, only micafungin and ganciclovir were not antibacterial agents, indicating that the vast majority of patients discharged from the Cleveland Clinic with CoPAT had had bacterial, rather than fungal or viral, infections.

Figure 5

Of particular note, data collected from July 2007 through December 2008 demonstrated that more than 80% of patients discharged from the hospital with CoPAT did so with a prescheduled follow‐up visit. This patient‐centric measure is important because patients may not follow through with establishing appointments for follow‐up visits once discharge has already occurred. The Cleveland Clinic prides itself on making sure that a follow‐up appointment is actually made before the time of discharge for the vast majority of patients. The process also facilitates continuity of care with a specific infectious disease physician.

The various outcomes data collected by the Cleveland Clinic CoPAT Registry puts it in the position of being able to use the data to identify areas for improvement. Some of the projects made possible by the CoPAT Registry include analysis of: (1) outcomes of CoPAT in patients with bone and joint infections, (2) intensity of care in patients with cardiac and cardiac device infections while undergoing CoPAT, (3) C. difficile infections in patients undergoing CoPAT, and (4) emergency department (ED) visits or unanticipated readmissions in patients undergoing CoPAT. With respect to the last point, a 2009 article by Jencks and colleagues reported that 19.6% of the approximately 12 million Medicare beneficiaries who had been discharged from a hospital were rehospitalized within 30 days.20 Moreover, more than a third (34%) were rehospitalized within 90 days of discharge. It was estimated that no more than 10% of these readmissions were scheduled. More than 50% of patients with a medical condition who were rehospitalized within 30 days of discharge had not been billed for a physician visit between the time of discharge and hospitalization.20 This suggests that scheduling a follow‐up visit at the time of discharge might have reduced the need for many of these rehospitalizations. Unplanned rehospitalizations among the Medicare patients examined were not only relatively common but were also costly, resulting in an estimated $17.4 billion in additional Medicare costs.20 A New York Times editorial accompanying publication of the Jencks article noted that rehospitalizations and accompanying costs might be reduced by better discharge planning and closer cooperation between hospitals and physicians to ensure follow‐up care.21

At the Cleveland Clinic, data have recently been collected on the reasons for ED visits or hospital readmissions for patients receiving CoPAT at home through the Cleveland Clinic home care program. As illustrated in Figure 6, 24% of ED visits22 and 41% of hospital readmissions (Gordon, unpublished data) were for the infection being treated. Vascular access complications accounted for 23% of ED visits but only 2% of hospital readmissions. Nearly 50% of ED visits and 60% of hospital readmissions were for a reason unrelated to the infection being treated or CoPAT. It is hoped that closer examination of the data and perhaps additional analyses will suggest interventions to further reduce preventable readmissions or ED visits among patients discharged from the Cleveland Clinic on CoPAT.

Figure 6

Conclusions

Attention to antimicrobial stewardship and patient care should not end once the patient is discharged from the hospital or other institutional setting. Patients expect and should receive value‐based health care across the full cycle of their medical condition, and it is the responsibility of those caring for them to prepare for and provide such care during as well as after hospital discharge. The CoPAT program at the Cleveland Clinic provides a model for the extension of antimicrobial stewardship into the outpatient setting. The effectiveness of the program depends on a patient‐centric approach involving coordination and use of the expertise of multiple members of a team dedicated to patient value and facilitated by hospital‐based EHRs specialized for optimizing the transition of care into the outpatient setting for all patients scheduled to receive CoPAT. The quality of medical care provided by the Cleveland Clinic or other hospitals can be accessed through measurements of the structure, processes, and outcomes of care provided by the respective institutions. The data obtained can then be used to further refine care to optimize outcomes and provide high value for the patients treated at the institution. Achieving and then maintaining high‐quality medical care that provides value to patients is an ongoing process that should never be taken for granted.

Collaboration between members of a multidisciplinary team is a key component of an effective institutional antimicrobial stewardship program, which itself is a key component of optimizing the care of hospitalized patients being treated with antimicrobial agents for proven or suspected infectious diseases. However, patient care does not and should not end once the patient is discharged from the hospital. In fact, high‐quality, value‐based health care across the full range of a medical condition depends on planning for optimization of care within the hospital as well as transitions of care to the outpatient setting. This extended care plan includes collaboration with multiple members of the health care community, both inside and outside the institution. The current review examines 3 aspects of patient care across the full cycle of an infectious disease condition: (1) value‐based health care, (2) stewardship of antimicrobials, and (3) community‐based parenteral anti‐infective therapy (CoPAT) as a model for antimicrobial stewardship outside the institutional setting.

Value‐Based Health Care

Patients first want to know that the health care professionals treating them actually care about them as individuals, and only then are patients concerned about how much the medical team knows. Patient‐centered care is a critical component of value‐based health care, a term that was bandied about quite a bit during the recent and ongoing health care debate in the United States. But what exactly does it mean? First, value in health care is defined by health care outcomes as a function of or divided by the cost of delivery of care. As Dr. Michael Porter and Dr. Elizabeth Olmsted Teisberg delineated in their 2007 article in the Journal of the American Medical Association,2 as well as in the 2006 book Redefining Health Care,3 The purpose of the healthcare system is not to minimize costs but to deliver value to patients, that is, better health per dollar spent. As they discuss value, it is a patient‐centric measure, and is focused on individual patient (not just diagnosis‐related group) outcomes and the cost of care across the full cycle. In this way of looking at things, an episode of care goes beyond the treatment provided during the acute admission to also include the transition of care to the outpatient or posthospital setting.

The reforms proposed by Porter and Teisberg are best achieved when the participating health care institutions have developed an information technology platform able to integrate and fully measure care across the full cycle of a medical condition. Furthermore, there is strong evidence that patient value increases with physician and team experience and volume for a particular condition.2 High volumes tend to correlate with the development of better information technology, as well as the formation of dedicated teams with tailored facilities, and with a greater capacity for constructive feedback to improve patient outcomes. The more experience a physician and team have with the management of a particular medical condition, the greater is the opportunity to learn and refine practices to provide greater value to the patient.

The Institute of Medicine has recommended that all healthcare professionals should be educated to deliver patient‐centered care as members of an interdisciplinary team emphasizing evidence‐based practice, quality improvement, and informatics.4 As has been demonstrated for patients with congestive heart failure59 and other conditions,10, 11 outcomes improve when components of care are integrated (often by nurse‐directed teams), preparing for the transition of care from the hospital to the home.12 This concept is the basis for the community‐based parenteral anti‐infective therapy program (CoPAT) at the Cleveland Clinic as a model for antimicrobial stewardship for patients requiring parenteral antimicrobial therapy at the time of discharge from the inpatient setting.

Community‐Based Parenteral Anti‐Infective Therapy as a Systems‐Based Approach to Antimicrobial Stewardship

A systems‐based approach for antimicrobial stewardship, CoPAT has been in operation at the Cleveland Clinic, a 1200‐bed hospital in downtown Cleveland, Ohio, since November 1979. The experiences of the authors and their colleagues demonstrate it to be a value‐based proposition for the patient that uses an antimicrobial stewardship platform. Also known as outpatient parenteral antimicrobial therapy (OPAT), CoPAT refers to the practice of administering antimicrobial therapy in the home or other outpatient settings, first introduced by Rucker and Harrison in 1974 in the context of outpatient management of cystic fibrosis.16 In the United States, CoPAT is a common practice today, and the IDSA has created practice guidelines for it.17

In 1983, Rehm and Weinstein coauthored an article describing their experiences at the Cleveland Clinic, in which selected patients were trained for home‐based antimicrobial therapy.12 Figure 1 illustrates the astronomical growth that has occurred over the years at the Cleveland Clinic in the number of patients discharged from the acute care center undergoing CoPAT (Gordon, unpublished data). It is anticipated that this growth will continue and in large part reflects the complexity of patients being seen and the desire to reduce length of stay. Evaluating the quality of any medical care is difficult, but there are 3 general approaches to assessing or measuring the quality of medical care: assessing the structure of care, assessing processes of care, and assessing outcomes.18 The quality of the CoPAT program at the Cleveland Clinic can be examined in the context of these 3 areas of assessment.

Figure 1

Settings or the Structure of Care

In a 1966 publication on quality of medical care evaluations, Donabedian described assessment of the structure of care as one of the primary approaches to measuring the quality of care.18 By structure, Donabedian meant the settings in which medical care takes place, including the adequacy of facilities and equipment, qualifications or expertise of medical staff and their organization, the administrative structure of the institution or institutional program of interest, and other administrative and related processes supporting and directing the delivery of care. Although the structure of care has the advantage of being concrete and relatively easy to assess, to be most meaningful, it ultimately needs to be related to the processes and outcomes of care.

With respect to the CoPAT program at the Cleveland Clinic main hospital, infectious diseases consultation is required for every patient being considered for discharge with parenteral antibiotics, whether the patient is going home or to another facility, including the clinic's own skilled nursing facility (SNF). Arrangements are then made for the delivery of antibiotics at home or in SNFs or long‐term acute care (LTAC) centers. The Cleveland Clinic CoPAT program does not use an outpatient infusion center.

The Cleveland Clinic uses a mandatory infectious diseases consultation for CoPAT because there are a number of important issues that need to be addressed before the patient is discharged, and for our system this is best accomplished by an infectious diseases specialist.12 For example, is antimicrobial therapy actually required in the first place? If it is, what is the optimal type, route, and duration of therapy? Are there other medical issues that need to be addressed? Decisions also need to be made about optimal vascular access and antimicrobial selection and administration, as well as arrangements being made for monitoring clinical and laboratory aspects. It is important that there is a smooth transition of care and prescheduled follow‐up in the outpatient clinic. The identification and use of an infectious diseases clinician directing the process leads to accountability. Notably, mandatory infectious disease consultation for outpatient parenteral antibiotic therapy has been used at Baystate Medical Center with improvement in reducing costs.19

The Process of Care

Assessments of the process of care involve examination of the particulars of medical care delivery, or whether what is recognized or accepted as good medical care has been applied. As discussed by Donabedian, process of care deals with issues such as the appropriateness and completeness of information obtained through clinical history, physical examination, and diagnostic tests; justification of diagnosis and therapy; technical competence in the performance of diagnostic and therapeutic procedures; and coordination and continuity of care.18

The CoPAT initiation process at the Cleveland Clinic is illustrated in Figure 2. It is a bundled process. As already mentioned, an infectious diseases consultation and evaluation is scheduled for all patients considered for CoPAT, after which a CoPAT form is completed and a follow‐up appointment made before the patient is discharged. In addition, the vascular access team is consulted and an appropriate vascular access device is placed in the patient prior to discharge. Likewise, a case manager is enlisted to identify a health care agency or SNF for patient placement or to determine whether the patient will receive home treatment. Once the appropriate setting is identified, the case manager transmits a completed CoPAT form to the health care agency or SNF, while forwarding a copy to the CoPAT nurse coordinator in the infectious disease department.

Figure 2

An electronic health record system is used at the Cleveland Clinic to provide real‐time information relevant for patient management. In 2007, a structured data form for CoPAT start‐of‐care was created within the Cleveland Clinic hospital electronic health record (EHR). This form contains a number of elements relevant for setting up patients for transition to CoPAT. In particular, the electronic CoPAT form contains information about the infection(s) and microorganism(s) being treated, intravenous antibiotic(s) prescribed (including treatment stop date), concurrent oral antibiotics, premedication recommendations (if appropriate), and recommended monitoring of laboratory tests. In addition, the form contains the telephone and fax numbers of the CoPAT coordinator and the name of the responsible physician, including a scheduled appointment for follow‐up (Fig. 3). The staff physician is responsible for completing the electronic CoPAT form or prescription. This CoPAT prescription then becomes part of the patient's electronic record and is transmissible and viewable by anyone with access to the EHR. This is important in terms of follow‐up and care accountability: an infectious disease staff clinician is identified as the contact person for clinical issues when a patient is on CoPAT.

Figure 3

After the patient is discharged, the CoPAT coordinator in the infectious disease department becomes responsible, together with the clinic's outpatient pharmacy, for reviewing laboratory results and notifying clinicians of potential problems that need to be addressed. These issues can pertain to laboratory findings, vascular access, or new symptoms or signs observed by the home nurse or patient. All this information is communicated via electronic health record messaging and/or through direct calls to the physician, when needed.

The CoPAT program has been widely accepted by internal customers of the Cleveland Clinic, which include hospitalists. This is probably because there is autonomy and accountability with the infectious diseases staff, the program or team is available 7 days per week, and the EHR facilitates communication. In addition, the use of infectious disease‐specific subspecialty groups (eg, bone marrow and solid‐organ transplant, bone and joint, and infective endocarditis groups) increases clinical credibility, as well as value received by patients of the clinic. Furthermore, the electronic CoPAT script facilitates discharge planning. CoPATs constitute approximately 25% of all ID consultation requests at the Cleveland Clinic and help to justify the 20 clinical ID clinical FTEs.

Outcomes of Medical Care

Assessment of medical care outcomes is another frequently used approach for measuring the quality of medical care.18 Medical care outcomes that have been examined as measures of quality of care include survival, number of hospital readmissions, time between discharge and readmissions, length of initial hospital stay and subsequent readmissions, quality of life, and health care costs. As has often been said, If you cannot measure it, you cannot manage it. The CoPAT program using the EHR has facilitated retrieval of structured reports in a format that provides clinicians with real‐time data enabling assessment of outcomes. By examining this data, the CoPAT team is in a better position to contemplate potential interventions for improving outpatient care and the value patients receive.

A 36‐month review of Cleveland Clinic CoPAT patient demographics from July 2007 to June 2010 demonstrated 6287 patients (56% male) had been prescribed 9471 courses of CoPAT (Gordon, unpublished data). Seventy‐nine percent of the patients were white, 16% African American, and 5% of other races. Most patients received 1 antibiotic per CoPAT course (79.1%), whereas 18.2%, 2.5%, and 0.2% received 2, 3, and 4 antibiotics per CoPAT course, respectively. Figure 4 highlights CoPAT distribution by source for anatomic site of infection. Bone and joint infections were the most common diagnoses associated with CoPAT at the Cleveland Clinic, followed by abdominal, cardiovascular, primary disseminated disease (eg, catheter‐associated bloodstream infections), and skin and soft‐tissue infection.

Figure 4

Figure 5 highlights the top‐10 pathogenic microorganisms in patients being discharged from the Cleveland Clinic with CoPAT, and the top‐10 antimicrobials prescribed for these patients. As can be seen, Staphylococcus aureus (methicillin susceptible and methicillin resistant) was the number one pathogen identified for patients undergoing CoPAT, followed by coagulase‐negative Staphylococcus and Enterococcus species. The most commonly identified gram‐negative bacteria among discharged patients was Pseudomonas aeruginosa. Only 2 of the top 10 pathogens were nonbacterial: Candida species and cytomegalovirus (CMV), the latter being the result of the high volume of transplantations performed at the clinic. With respect to the intravenous antimicrobials prescribed for patients undergoing CoPAT, the most commonly prescribed agent was vancomycin, followed by piperacillin/tazobactam. Of the 10 agents, only micafungin and ganciclovir were not antibacterial agents, indicating that the vast majority of patients discharged from the Cleveland Clinic with CoPAT had had bacterial, rather than fungal or viral, infections.

Figure 5

Of particular note, data collected from July 2007 through December 2008 demonstrated that more than 80% of patients discharged from the hospital with CoPAT did so with a prescheduled follow‐up visit. This patient‐centric measure is important because patients may not follow through with establishing appointments for follow‐up visits once discharge has already occurred. The Cleveland Clinic prides itself on making sure that a follow‐up appointment is actually made before the time of discharge for the vast majority of patients. The process also facilitates continuity of care with a specific infectious disease physician.

The various outcomes data collected by the Cleveland Clinic CoPAT Registry puts it in the position of being able to use the data to identify areas for improvement. Some of the projects made possible by the CoPAT Registry include analysis of: (1) outcomes of CoPAT in patients with bone and joint infections, (2) intensity of care in patients with cardiac and cardiac device infections while undergoing CoPAT, (3) C. difficile infections in patients undergoing CoPAT, and (4) emergency department (ED) visits or unanticipated readmissions in patients undergoing CoPAT. With respect to the last point, a 2009 article by Jencks and colleagues reported that 19.6% of the approximately 12 million Medicare beneficiaries who had been discharged from a hospital were rehospitalized within 30 days.20 Moreover, more than a third (34%) were rehospitalized within 90 days of discharge. It was estimated that no more than 10% of these readmissions were scheduled. More than 50% of patients with a medical condition who were rehospitalized within 30 days of discharge had not been billed for a physician visit between the time of discharge and hospitalization.20 This suggests that scheduling a follow‐up visit at the time of discharge might have reduced the need for many of these rehospitalizations. Unplanned rehospitalizations among the Medicare patients examined were not only relatively common but were also costly, resulting in an estimated $17.4 billion in additional Medicare costs.20 A New York Times editorial accompanying publication of the Jencks article noted that rehospitalizations and accompanying costs might be reduced by better discharge planning and closer cooperation between hospitals and physicians to ensure follow‐up care.21

At the Cleveland Clinic, data have recently been collected on the reasons for ED visits or hospital readmissions for patients receiving CoPAT at home through the Cleveland Clinic home care program. As illustrated in Figure 6, 24% of ED visits22 and 41% of hospital readmissions (Gordon, unpublished data) were for the infection being treated. Vascular access complications accounted for 23% of ED visits but only 2% of hospital readmissions. Nearly 50% of ED visits and 60% of hospital readmissions were for a reason unrelated to the infection being treated or CoPAT. It is hoped that closer examination of the data and perhaps additional analyses will suggest interventions to further reduce preventable readmissions or ED visits among patients discharged from the Cleveland Clinic on CoPAT.

Figure 6

Conclusions

Attention to antimicrobial stewardship and patient care should not end once the patient is discharged from the hospital or other institutional setting. Patients expect and should receive value‐based health care across the full cycle of their medical condition, and it is the responsibility of those caring for them to prepare for and provide such care during as well as after hospital discharge. The CoPAT program at the Cleveland Clinic provides a model for the extension of antimicrobial stewardship into the outpatient setting. The effectiveness of the program depends on a patient‐centric approach involving coordination and use of the expertise of multiple members of a team dedicated to patient value and facilitated by hospital‐based EHRs specialized for optimizing the transition of care into the outpatient setting for all patients scheduled to receive CoPAT. The quality of medical care provided by the Cleveland Clinic or other hospitals can be accessed through measurements of the structure, processes, and outcomes of care provided by the respective institutions. The data obtained can then be used to further refine care to optimize outcomes and provide high value for the patients treated at the institution. Achieving and then maintaining high‐quality medical care that provides value to patients is an ongoing process that should never be taken for granted.

Background

Influenza viruses are among the most common respiratory viral infections in humans. There are two major types of human influenza viruses, A and B, with influenza A strains responsible for seasonal or pandemic influenza. Influenza illness is characterized by fever, lower respiratory and often upper respiratory symptoms, myalgia, and malaise and occurs seasonally in temperate climates between late fall and early spring. The average flu season in the United States is marked by 30,000‐40,000 deaths, primarily in elderly patients with significant comorbidity and in the very young. Many of these deaths are caused by secondary bacterial pneumonias. Long interpandemic periods, including the current one of almost 40 years, involve minor mutations of the predominant influenza strain from year to year. Typically, adequate time exists to predict the prevailing strain with reasonable accuracy and to tailor a vaccine accordingly. Periodically an influenza pandemic involving a novel influenza strain emerges, attended by greater‐than‐expected morbidity and mortality.

All influenza viruses are subtyped on the basis of two surface glycoproteins. One of these, hemagglutinin (H), is responsible for viral cell entry; whereas the other, neuraminidase (N), facilitates release of the virus from infected cells, thus allowing perpetuation and amplification of infection. Antigenic drift is the ongoing process of genetic mutations that lead to new strains demonstrating variable change in antigenicity and is the basis for the annual updating of vaccine strains. Antigenic shift is the emergence of a novel influenza A subtype among humans, usually as the result of a recombination event. This radical change is necessary but not sufficient to initiate pandemic influenza, with efficient transmission from person to person also a critical feature. Pandemic influenza strains arise in 1 of 2 fashions. Genetic reassortment may occur when a mammalian host (human or porcine) is infected with both an avian and a human influenza virus, with subsequent dramatic movement into human populations, the source of the 1957 and 1968 pandemics. Alternatively, a novel virus may, after sufficient mutation, move directly from the avian population to humans, as appears to have occurred in 1918.

The 1918‐19 Pandemic

Abruptly in 1918, an influenza pandemic of seemingly unprecedented severity swept the world. Although disagreement remains regarding the source of the outbreak (China, the front lines of World War I, and even the United States have all been suggested), within 6‐9 months essentially the entire globe had been affected. Unlike more typical influenza seasons, the virus preferentially infected previously healthy young individuals, with those aged 15‐40 bearing the brunt of the illness. US military training installations, overcrowded with troops staging for service on the European front, played a particularly ill‐fated role in the pandemic as it swept through the United States.

Estimates of the pandemic's worldwide impact on mortality are sketchy at best, but many authorities believe that at least 50 million deaths resulted, with some suggesting a figure as high as 100 million. In the United States the virus was responsible for an estimated 700,000 deaths, with an untold burden of morbidity. Economic and social disruption was the norm in many areas, with widespread closure of businesses and schools and suspension of public gatherings of any kind. Many communities were simply overwhelmed by the sheer numbers of dying individuals. In Philadelphia, steam shovels were used to dig mass graves for influenza victims.1 The pandemic's effect on the health care system was likewise profound. Most hospitals counted their own physicians and nurses among those who died during the pandemic, and many of the health care workers who succumbed were infected in the course of caring for influenza patients. Overall, an estimated 2%‐3% of those infected with the virus died, a far higher percentage than is seen during interpandemic seasons. Strikingly, the vast majority of deaths do not appear to have resulted from secondary bacterial pneumonias, but rather to have been directly virally mediated through ARDS, a necrotizing viral pneumonia, or both.

The mystery of the 1918 pandemic has recently been partially unlocked, with the successful sequencing of the entire RNA genome of strains recovered from pathology tissue of two soldiers, as well as from lung tissue of a victim frozen in Alaskan permafrost since 1918.2, 3 The data suggest that the 1918 virus was derived from an avian source. Notably, some of the same changes in the polymerase proteins have been found in the highly pathogenic H5N1 viruses.

Avian Influenza Viruses

Influenza viruses that primarily infect birds are characterized as avian influenza viruses. These are always type A and are classified as either of low or high pathogenicity on the basis of the severity of the illness they cause in birds. The currently circulating H5N1 avian viruses are highly pathogenic.

Avian influenza viruses do not usually infect humans; however, several instances of human infections have been reported since 1997. The 1997 Hong Kong outbreak of avian (H5N1) influenza in 18 humans resulted in 6 deaths and was a seminal event that provided evidence that avian influenza viruses can infect people. It also provided the epidemiologic link between avian influenza infection in poultry with disease in humans and was proclaimed as a pandemic warning. These sentinel human infections led to the culling of the entire Hong Kong poultry population, with no subsequent human infection reported at that time. In 2003, more than 80 cases of avian influenza A (H7N7) illness occurred in the Netherlands among persons who handled infected poultry. Sustained human‐to‐human transmission did not occur in this or other outbreaks of avian influenza to date.

Since 2003, sporadic human cases of H5N1 have occurred, most recently reported from Turkey and Iraq. Human cases have also occurred in Vietnam, China, Cambodia, Thailand, and Indonesia, with a total of 173 reported cases and a case fatality rate exceeding 50% as of this writing.4 This mortality rate may be artificially inflated, as less severe cases have certainly gone unreported. All countries reporting human avian influenza diseases since 2003 have had concurrent epizoonotics in birds (both poultry and migratory birds).

Human cases of H5N1 influenza illness have been characterized by high fever and symptoms in the lower respiratory tract, as would be expected. Less predictable has been the presence of watery diarrhea in many patients and of abdominal and pleuritic pain and bleeding from the nose and gums in some. Sputum production has been variably present, and hemoptysis has been seen in some individuals. Most patients have had clinical and radiological evidence of pneumonia at the time they sought medical care, and progression to ARDS and multiorgan failure has been common. The majority of patients to date have required the initiation of mechanical ventilation early in their hospital course. Laboratory studies have typically shown lymphopenia, thrombocytopenia, and, in many cases, modestly elevated transaminase levels.5 Notably, the currently predominant strain of H5N1 (Z strain) is resistant to the M2 ion channel inhibitors amantadine and rimantadine but is susceptible to the newer class of neuraminidase inhibitors, zanamivir (Relenza) and oseltamivir (Tamiflu). Neuraminidase inhibitors and corticosteroids have been used to treat patients, although their efficacy in this setting is unclear. To date, virtually all cases appear to have been transmitted directly from poultry, although person‐to‐person transmission appears likely to have occurred in at least one family in Thailand.6 A recent study of the 14 clusters of avian influenza among humans emphasized the lack of sustained person‐to‐person transmission of H5N1 to date.7

Three factors are necessary for the emergence of a pandemic influenza strain: the ability to infect humans, a novel genetic makeup, and the ability for sustained transmission between people. A virus that in addition proves highly virulent, as did the 1918‐19 H1N1 strain, essentially creates the perfect storm. H5N1 influenza has currently fulfilled 2 of these 3 criteria. The virus is highly pathogenic, although how much of this fitness would be sacrificed with mutation to a more transmissible strain is uncertain. As many have observed, whether there will be another influenza pandemic does not seem in doubt; rather, it is when such a pandemic will occur and whether the pandemic will be caused by H5N1 or another influenza virus, that are the questions.

Potential Effects of the Next Pandemic

The global and national effects of an influenza pandemic will vary in direct proportion to the virulence of the circulating viral strain, but if such a virus is highly virulent, significant and perhaps severe economic and social disruption are likely.

The global economic impact has been estimated to be $800 billion with anticipated quarantines and interruption in global trade. On a national level, it has been estimated that in the United States a pandemic virus whose severity is comparable to that of the 1968 Hong Kong influenza pandemic would lead to approximately 200,000 deaths and 700,000 hospitalizations, of which roughly 100,000 would require treatment in intensive care unit settings. A more virulent strain, similar to that of the 1918‐19 pandemic, might easily result in 1 million deaths; with the number of patients hospitalized approaching 10 million, well over 1 million of which would require ICU‐level care. As an estimated 75% of the 105,000 ventilators in this country are in use at any given time under normal circumstances, the potential for demand to greatly outstrip supply is evident.8 Depending on the severity of a pandemic, suspension or curtailment of international trade and travel could be reasonably likely. Although the World Health Organization has recommended against closing borders or quarantining countries even in the throes of a pandemic, the prospect of this occurring does not seem implausible. In a worst‐case scenario, even the type of national and international chaos envisioned in the Dark Winter smallpox planning exercise might occur.9

Fortress America Versus Containment Strategies

Although the pandemic influenza plan calls for stockpiling antiviral drugs and increasing vaccine production capabilities, the most effective plan for pandemic preparedness may involve a surveillance and containment strategy. No country has enough medicines or vaccines to control a widespread outbreak of pandemic avian influenza. The best solution to prevention of a pandemic is stopping any virus from spreading in the first place. Increased surveillance for avian influenza among poultry and migratory birds in key Asian countries, along with provision of funds to compensate farmers for culling of potentially infected flocks, would align incentives for early detection and eradication. Containing an initial outbreak wherever it occurs is the best defense against a pandemic. Notably, China is thought to be a potential hot zone for emergence of pandemic avian influenza. China is not only the most populous nation in the world but has one quarter of the world's chickens, two thirds of the world's domesticated ducks, and 90% of the world's domesticated geese.

The challenges of biosecurity (protecting humans against animal‐borne diseases such as bird flu) in developing countries include the reality that populations living in close proximity to poultry are also the most illiterate and impoverished, with the most limited access to health care. The recent introduction of H5N1 into Europe has heightened surveillance efforts in the United States. The introduction of H5N1 into the United States may occur through movement of migratory birds and/or importation of exotic birds. The surveillance system has been expanded to include sampling for the influenza virus not only in poultry but also in bodies of water, as the virus is shed in bird feces.

Pandemic Planning

In the setting of a severe pandemic, hospitals will face an enormous burden of patients, with a huge influx of individuals requiring both intensive care unit as well as regular nursing floor care. At the local height of such a pandemic, the ability to successfully discharge every patient whose condition will permit this to the community or elsewhere will be critical, and almost certainly hospitals will need to expand to accept more patients than they are normally configured to hold. Hospitals staffs, particularly nurses and physicians, will be required to handle very large patient censuses. Among medical staffs, emergency physicians, hospitalists, critical care specialists, and infectious disease specialists will certainly be called on to play leading roles, much as they were during and in the aftermath of Hurricane Katrina recently. Despite all of the above, the ability of existing hospitals to accommodate all gravely ill patients may be outstripped, and auxiliary hospitals in schools and other public edifices may need to be established. Hospitalists are likely to be called on to play a major role in such temporary hospitals. The frustration and anguish of not being able to provide a standard level of care to patients (for example, being forced to triage which patients are most deserving of mechanical ventilation) should not be underestimated.

Although characterized by a relatively limited number of patients, the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, Canada, presented some of the same challenges that will be encountered in a virulent influenza pandemic. These include the need to quickly and drastically modify the usual emergency department and inpatient procedures, as hospitals initially serve to amplify the epidemic, as well as the additional stressor of health care workers becoming ill as a result of work‐related exposure. That fewer than 400 cases of SARS pushed the medical system of one of North America's largest cities nearly to its breaking point is both sobering and instructive.10, 11 Interested readers are directed to an excellent summary of lessons learned from the SARS outbreak, most of which are widely applicable to preparations for future infectious epidemics.12

Infection Control

Although the CDC and other Web sites currently recommend airborne isolation (respiratory personal protection) for avian influenza in humans, there is not strong epidemiologic evidence of transmission other than via droplets (the transmission mode of human influenza). The emergence of a limited number of cases of avian influenza in the United States would allow employment of airborne isolation measures; but in the event of a larger outbreak, the use of surgical masks and the practice of good hand hygiene would be sufficient by health care workers caring for persons with suspected or proven disease.

The CDC recently released proposed changes to help prevent disease outbreaks from contacts of those exposed to ill persons on airplanes. Proposed guidelines would require airlines to maintain computerized lists of passengers taken at point of departure in order to facilitate tracking of contacts and implementation of quarantine if necessary. These measures are part of pandemic planning and result from problems in tracking passengers on planes with SARS cases. By executive order, imposition of quarantine is limited to 9 diseases: cholera, diphtheria, smallpox, yellow fever, viral hemorrhagic fevers (eg, Ebola), plague, infectious tuberculosis, SARS and influenza caused by new strains with pandemic potential.

What Can Be Done?

Although valuable time has elapsed to prepare for the possibility of an H5N1 influenza pandemic, the US and global communities are presently taking the threat seriously and are engaging in a variety of activities to prepare for such an eventuality. Although currently available influenza vaccines do not provide any appreciable protection against H5N1, significant work is under way to develop an effective vaccine; with Chiron and sanofi pasteur preparing vaccine trials in association with the National Institute of Allergy and Infectious Diseases. Current influenza vaccine production is hampered by use of obsolete egg‐based manufacturing processes requiring 6 months, along with a limited capacity to manufacture adequate vaccine supplies even in many usual influenza seasons. The herculean task of providing hundreds of millions of doses of vaccine as soon as possible after the emergence of a pandemic strain, as daunting as it is, is further complicated by the fact that a successful H5N1 vaccine would not necessarily be effective against a strain that mutated sufficiently to move efficiently from person to person. Nonetheless, even partially solving these problems will pay dividends, whether or not H5N1 proves to be responsible for the next pandemic.

Given these difficulties with vaccine development and production, the backbone of any successful early response to a pandemic in the near future will be development of an adequate stockpile of antiviral medication, accompanied by a successful plan to distribute the drug when and where disease erupts. Despite uncertainties regarding their effectiveness as well as questions regarding optimal dose and duration in the setting of avian influenza, the neuraminidase inhibitors are the current drugs of choice. Of the 2 currently available agents, oseltamivir is the preferred drug for pandemic use, given its oral administration,. Unfortunately, the ability to manufacture the drug in sufficient quantities to stockpile has thus far proved problematic. Roche, the manufacturer of Tamiflu, has recently opened a new manufacturing plant and has stated that it can increase its current production of 55 million doses per year to 300 million doses by 2007. We do not recommend a role for personal stockpiling of neuraminidase inhibitors. Concerns include a shortage of the drug for seasonal influenza, absence of a pandemic at present, ignorance regarding the efficacy and optimal dose for H5N1, inappropriate use by individuals, and inequitable distribution. Recent case reports of oseltamivir resistance emerging during prophylaxis13 and treatment14 are of potential concern but do not alter current recommendations.

What can be done locally and specifically, and what can hospitalists do to prepare? First, although we are not sure that Dr Michael Osterholm's goal that planning for a pandemic must be on the agenda of every public health agency, school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor8 is entirely realistic, every hospital clearly needs to include pandemic influenza as a significant part of its disaster preparedness plan. Such planning will have broad overlap with planning for other potential disasters, including bioterrorist attacks, SARS outbreaks, and others. Hospitals must develop a plan for surge capacity, and such a plan should include not only coordination with other local hospitals, but also planning with local communities to identify sites where temporary flu hospitals can be established. Within hospital medicine groups, emergency staffing plans should be established before pandemic influenza (or another disaster) strikes. Such staffing plans need to include the ability to care for a much higher than normal number of patients for an extended period. Conceivably, a large number of patients will need to be manually ventilated for prolonged periods, which of course will tax the resources of any institution. Prompt discharge of all patients stable enough to leave the hospital will be critical, and given the investment of most hospital medicine groups in hospital throughput issues under normal conditions, much of the responsibility for helping to create beds during a crisis will inevitably fall on the shoulders of hospitalists.

Experiences during and shortly after Hurricane Katrina served to underscore that issues such as physical and mental fatigue, concern for the safety of family members, lack of supplies, communication difficulties, and absenteeism all add additional layers of complexity to the task of providing hospital care under extraordinary conditions such as during a natural disaster. These lessons can and should be extended to a major epidemic. This disaster also showed the importance of military involvement in the response to disasters that exceed local and state capabilities. The primary objective of the federal government in responding to disaster is to maintain security and essential services while preventing chaos. A pandemic of virulent influenza will raise the stakes still further, as physicians and nurses become casualties themselves. Despite these challenges, we are confident that the vast majority of hospitalists and other health care workers will rise to the occasion, and just as during the peri‐Katrina period, stories of selflessness and heroism will be de rigueur. Appropriate advance planning on all levels will serve to reduce the morbidity and mortality associated with the next pandemic and will help to ensure that health care workers do not sacrifice needlessly.0

Background

Influenza viruses are among the most common respiratory viral infections in humans. There are two major types of human influenza viruses, A and B, with influenza A strains responsible for seasonal or pandemic influenza. Influenza illness is characterized by fever, lower respiratory and often upper respiratory symptoms, myalgia, and malaise and occurs seasonally in temperate climates between late fall and early spring. The average flu season in the United States is marked by 30,000‐40,000 deaths, primarily in elderly patients with significant comorbidity and in the very young. Many of these deaths are caused by secondary bacterial pneumonias. Long interpandemic periods, including the current one of almost 40 years, involve minor mutations of the predominant influenza strain from year to year. Typically, adequate time exists to predict the prevailing strain with reasonable accuracy and to tailor a vaccine accordingly. Periodically an influenza pandemic involving a novel influenza strain emerges, attended by greater‐than‐expected morbidity and mortality.

All influenza viruses are subtyped on the basis of two surface glycoproteins. One of these, hemagglutinin (H), is responsible for viral cell entry; whereas the other, neuraminidase (N), facilitates release of the virus from infected cells, thus allowing perpetuation and amplification of infection. Antigenic drift is the ongoing process of genetic mutations that lead to new strains demonstrating variable change in antigenicity and is the basis for the annual updating of vaccine strains. Antigenic shift is the emergence of a novel influenza A subtype among humans, usually as the result of a recombination event. This radical change is necessary but not sufficient to initiate pandemic influenza, with efficient transmission from person to person also a critical feature. Pandemic influenza strains arise in 1 of 2 fashions. Genetic reassortment may occur when a mammalian host (human or porcine) is infected with both an avian and a human influenza virus, with subsequent dramatic movement into human populations, the source of the 1957 and 1968 pandemics. Alternatively, a novel virus may, after sufficient mutation, move directly from the avian population to humans, as appears to have occurred in 1918.

The 1918‐19 Pandemic

Abruptly in 1918, an influenza pandemic of seemingly unprecedented severity swept the world. Although disagreement remains regarding the source of the outbreak (China, the front lines of World War I, and even the United States have all been suggested), within 6‐9 months essentially the entire globe had been affected. Unlike more typical influenza seasons, the virus preferentially infected previously healthy young individuals, with those aged 15‐40 bearing the brunt of the illness. US military training installations, overcrowded with troops staging for service on the European front, played a particularly ill‐fated role in the pandemic as it swept through the United States.

Estimates of the pandemic's worldwide impact on mortality are sketchy at best, but many authorities believe that at least 50 million deaths resulted, with some suggesting a figure as high as 100 million. In the United States the virus was responsible for an estimated 700,000 deaths, with an untold burden of morbidity. Economic and social disruption was the norm in many areas, with widespread closure of businesses and schools and suspension of public gatherings of any kind. Many communities were simply overwhelmed by the sheer numbers of dying individuals. In Philadelphia, steam shovels were used to dig mass graves for influenza victims.1 The pandemic's effect on the health care system was likewise profound. Most hospitals counted their own physicians and nurses among those who died during the pandemic, and many of the health care workers who succumbed were infected in the course of caring for influenza patients. Overall, an estimated 2%‐3% of those infected with the virus died, a far higher percentage than is seen during interpandemic seasons. Strikingly, the vast majority of deaths do not appear to have resulted from secondary bacterial pneumonias, but rather to have been directly virally mediated through ARDS, a necrotizing viral pneumonia, or both.

The mystery of the 1918 pandemic has recently been partially unlocked, with the successful sequencing of the entire RNA genome of strains recovered from pathology tissue of two soldiers, as well as from lung tissue of a victim frozen in Alaskan permafrost since 1918.2, 3 The data suggest that the 1918 virus was derived from an avian source. Notably, some of the same changes in the polymerase proteins have been found in the highly pathogenic H5N1 viruses.

Avian Influenza Viruses

Influenza viruses that primarily infect birds are characterized as avian influenza viruses. These are always type A and are classified as either of low or high pathogenicity on the basis of the severity of the illness they cause in birds. The currently circulating H5N1 avian viruses are highly pathogenic.

Avian influenza viruses do not usually infect humans; however, several instances of human infections have been reported since 1997. The 1997 Hong Kong outbreak of avian (H5N1) influenza in 18 humans resulted in 6 deaths and was a seminal event that provided evidence that avian influenza viruses can infect people. It also provided the epidemiologic link between avian influenza infection in poultry with disease in humans and was proclaimed as a pandemic warning. These sentinel human infections led to the culling of the entire Hong Kong poultry population, with no subsequent human infection reported at that time. In 2003, more than 80 cases of avian influenza A (H7N7) illness occurred in the Netherlands among persons who handled infected poultry. Sustained human‐to‐human transmission did not occur in this or other outbreaks of avian influenza to date.

Since 2003, sporadic human cases of H5N1 have occurred, most recently reported from Turkey and Iraq. Human cases have also occurred in Vietnam, China, Cambodia, Thailand, and Indonesia, with a total of 173 reported cases and a case fatality rate exceeding 50% as of this writing.4 This mortality rate may be artificially inflated, as less severe cases have certainly gone unreported. All countries reporting human avian influenza diseases since 2003 have had concurrent epizoonotics in birds (both poultry and migratory birds).

Human cases of H5N1 influenza illness have been characterized by high fever and symptoms in the lower respiratory tract, as would be expected. Less predictable has been the presence of watery diarrhea in many patients and of abdominal and pleuritic pain and bleeding from the nose and gums in some. Sputum production has been variably present, and hemoptysis has been seen in some individuals. Most patients have had clinical and radiological evidence of pneumonia at the time they sought medical care, and progression to ARDS and multiorgan failure has been common. The majority of patients to date have required the initiation of mechanical ventilation early in their hospital course. Laboratory studies have typically shown lymphopenia, thrombocytopenia, and, in many cases, modestly elevated transaminase levels.5 Notably, the currently predominant strain of H5N1 (Z strain) is resistant to the M2 ion channel inhibitors amantadine and rimantadine but is susceptible to the newer class of neuraminidase inhibitors, zanamivir (Relenza) and oseltamivir (Tamiflu). Neuraminidase inhibitors and corticosteroids have been used to treat patients, although their efficacy in this setting is unclear. To date, virtually all cases appear to have been transmitted directly from poultry, although person‐to‐person transmission appears likely to have occurred in at least one family in Thailand.6 A recent study of the 14 clusters of avian influenza among humans emphasized the lack of sustained person‐to‐person transmission of H5N1 to date.7

Three factors are necessary for the emergence of a pandemic influenza strain: the ability to infect humans, a novel genetic makeup, and the ability for sustained transmission between people. A virus that in addition proves highly virulent, as did the 1918‐19 H1N1 strain, essentially creates the perfect storm. H5N1 influenza has currently fulfilled 2 of these 3 criteria. The virus is highly pathogenic, although how much of this fitness would be sacrificed with mutation to a more transmissible strain is uncertain. As many have observed, whether there will be another influenza pandemic does not seem in doubt; rather, it is when such a pandemic will occur and whether the pandemic will be caused by H5N1 or another influenza virus, that are the questions.

Potential Effects of the Next Pandemic

The global and national effects of an influenza pandemic will vary in direct proportion to the virulence of the circulating viral strain, but if such a virus is highly virulent, significant and perhaps severe economic and social disruption are likely.

The global economic impact has been estimated to be $800 billion with anticipated quarantines and interruption in global trade. On a national level, it has been estimated that in the United States a pandemic virus whose severity is comparable to that of the 1968 Hong Kong influenza pandemic would lead to approximately 200,000 deaths and 700,000 hospitalizations, of which roughly 100,000 would require treatment in intensive care unit settings. A more virulent strain, similar to that of the 1918‐19 pandemic, might easily result in 1 million deaths; with the number of patients hospitalized approaching 10 million, well over 1 million of which would require ICU‐level care. As an estimated 75% of the 105,000 ventilators in this country are in use at any given time under normal circumstances, the potential for demand to greatly outstrip supply is evident.8 Depending on the severity of a pandemic, suspension or curtailment of international trade and travel could be reasonably likely. Although the World Health Organization has recommended against closing borders or quarantining countries even in the throes of a pandemic, the prospect of this occurring does not seem implausible. In a worst‐case scenario, even the type of national and international chaos envisioned in the Dark Winter smallpox planning exercise might occur.9

Fortress America Versus Containment Strategies

Although the pandemic influenza plan calls for stockpiling antiviral drugs and increasing vaccine production capabilities, the most effective plan for pandemic preparedness may involve a surveillance and containment strategy. No country has enough medicines or vaccines to control a widespread outbreak of pandemic avian influenza. The best solution to prevention of a pandemic is stopping any virus from spreading in the first place. Increased surveillance for avian influenza among poultry and migratory birds in key Asian countries, along with provision of funds to compensate farmers for culling of potentially infected flocks, would align incentives for early detection and eradication. Containing an initial outbreak wherever it occurs is the best defense against a pandemic. Notably, China is thought to be a potential hot zone for emergence of pandemic avian influenza. China is not only the most populous nation in the world but has one quarter of the world's chickens, two thirds of the world's domesticated ducks, and 90% of the world's domesticated geese.

The challenges of biosecurity (protecting humans against animal‐borne diseases such as bird flu) in developing countries include the reality that populations living in close proximity to poultry are also the most illiterate and impoverished, with the most limited access to health care. The recent introduction of H5N1 into Europe has heightened surveillance efforts in the United States. The introduction of H5N1 into the United States may occur through movement of migratory birds and/or importation of exotic birds. The surveillance system has been expanded to include sampling for the influenza virus not only in poultry but also in bodies of water, as the virus is shed in bird feces.

Pandemic Planning

In the setting of a severe pandemic, hospitals will face an enormous burden of patients, with a huge influx of individuals requiring both intensive care unit as well as regular nursing floor care. At the local height of such a pandemic, the ability to successfully discharge every patient whose condition will permit this to the community or elsewhere will be critical, and almost certainly hospitals will need to expand to accept more patients than they are normally configured to hold. Hospitals staffs, particularly nurses and physicians, will be required to handle very large patient censuses. Among medical staffs, emergency physicians, hospitalists, critical care specialists, and infectious disease specialists will certainly be called on to play leading roles, much as they were during and in the aftermath of Hurricane Katrina recently. Despite all of the above, the ability of existing hospitals to accommodate all gravely ill patients may be outstripped, and auxiliary hospitals in schools and other public edifices may need to be established. Hospitalists are likely to be called on to play a major role in such temporary hospitals. The frustration and anguish of not being able to provide a standard level of care to patients (for example, being forced to triage which patients are most deserving of mechanical ventilation) should not be underestimated.

Although characterized by a relatively limited number of patients, the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, Canada, presented some of the same challenges that will be encountered in a virulent influenza pandemic. These include the need to quickly and drastically modify the usual emergency department and inpatient procedures, as hospitals initially serve to amplify the epidemic, as well as the additional stressor of health care workers becoming ill as a result of work‐related exposure. That fewer than 400 cases of SARS pushed the medical system of one of North America's largest cities nearly to its breaking point is both sobering and instructive.10, 11 Interested readers are directed to an excellent summary of lessons learned from the SARS outbreak, most of which are widely applicable to preparations for future infectious epidemics.12

Infection Control

Although the CDC and other Web sites currently recommend airborne isolation (respiratory personal protection) for avian influenza in humans, there is not strong epidemiologic evidence of transmission other than via droplets (the transmission mode of human influenza). The emergence of a limited number of cases of avian influenza in the United States would allow employment of airborne isolation measures; but in the event of a larger outbreak, the use of surgical masks and the practice of good hand hygiene would be sufficient by health care workers caring for persons with suspected or proven disease.

The CDC recently released proposed changes to help prevent disease outbreaks from contacts of those exposed to ill persons on airplanes. Proposed guidelines would require airlines to maintain computerized lists of passengers taken at point of departure in order to facilitate tracking of contacts and implementation of quarantine if necessary. These measures are part of pandemic planning and result from problems in tracking passengers on planes with SARS cases. By executive order, imposition of quarantine is limited to 9 diseases: cholera, diphtheria, smallpox, yellow fever, viral hemorrhagic fevers (eg, Ebola), plague, infectious tuberculosis, SARS and influenza caused by new strains with pandemic potential.

What Can Be Done?

Although valuable time has elapsed to prepare for the possibility of an H5N1 influenza pandemic, the US and global communities are presently taking the threat seriously and are engaging in a variety of activities to prepare for such an eventuality. Although currently available influenza vaccines do not provide any appreciable protection against H5N1, significant work is under way to develop an effective vaccine; with Chiron and sanofi pasteur preparing vaccine trials in association with the National Institute of Allergy and Infectious Diseases. Current influenza vaccine production is hampered by use of obsolete egg‐based manufacturing processes requiring 6 months, along with a limited capacity to manufacture adequate vaccine supplies even in many usual influenza seasons. The herculean task of providing hundreds of millions of doses of vaccine as soon as possible after the emergence of a pandemic strain, as daunting as it is, is further complicated by the fact that a successful H5N1 vaccine would not necessarily be effective against a strain that mutated sufficiently to move efficiently from person to person. Nonetheless, even partially solving these problems will pay dividends, whether or not H5N1 proves to be responsible for the next pandemic.

Given these difficulties with vaccine development and production, the backbone of any successful early response to a pandemic in the near future will be development of an adequate stockpile of antiviral medication, accompanied by a successful plan to distribute the drug when and where disease erupts. Despite uncertainties regarding their effectiveness as well as questions regarding optimal dose and duration in the setting of avian influenza, the neuraminidase inhibitors are the current drugs of choice. Of the 2 currently available agents, oseltamivir is the preferred drug for pandemic use, given its oral administration,. Unfortunately, the ability to manufacture the drug in sufficient quantities to stockpile has thus far proved problematic. Roche, the manufacturer of Tamiflu, has recently opened a new manufacturing plant and has stated that it can increase its current production of 55 million doses per year to 300 million doses by 2007. We do not recommend a role for personal stockpiling of neuraminidase inhibitors. Concerns include a shortage of the drug for seasonal influenza, absence of a pandemic at present, ignorance regarding the efficacy and optimal dose for H5N1, inappropriate use by individuals, and inequitable distribution. Recent case reports of oseltamivir resistance emerging during prophylaxis13 and treatment14 are of potential concern but do not alter current recommendations.

What can be done locally and specifically, and what can hospitalists do to prepare? First, although we are not sure that Dr Michael Osterholm's goal that planning for a pandemic must be on the agenda of every public health agency, school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor8 is entirely realistic, every hospital clearly needs to include pandemic influenza as a significant part of its disaster preparedness plan. Such planning will have broad overlap with planning for other potential disasters, including bioterrorist attacks, SARS outbreaks, and others. Hospitals must develop a plan for surge capacity, and such a plan should include not only coordination with other local hospitals, but also planning with local communities to identify sites where temporary flu hospitals can be established. Within hospital medicine groups, emergency staffing plans should be established before pandemic influenza (or another disaster) strikes. Such staffing plans need to include the ability to care for a much higher than normal number of patients for an extended period. Conceivably, a large number of patients will need to be manually ventilated for prolonged periods, which of course will tax the resources of any institution. Prompt discharge of all patients stable enough to leave the hospital will be critical, and given the investment of most hospital medicine groups in hospital throughput issues under normal conditions, much of the responsibility for helping to create beds during a crisis will inevitably fall on the shoulders of hospitalists.

Experiences during and shortly after Hurricane Katrina served to underscore that issues such as physical and mental fatigue, concern for the safety of family members, lack of supplies, communication difficulties, and absenteeism all add additional layers of complexity to the task of providing hospital care under extraordinary conditions such as during a natural disaster. These lessons can and should be extended to a major epidemic. This disaster also showed the importance of military involvement in the response to disasters that exceed local and state capabilities. The primary objective of the federal government in responding to disaster is to maintain security and essential services while preventing chaos. A pandemic of virulent influenza will raise the stakes still further, as physicians and nurses become casualties themselves. Despite these challenges, we are confident that the vast majority of hospitalists and other health care workers will rise to the occasion, and just as during the peri‐Katrina period, stories of selflessness and heroism will be de rigueur. Appropriate advance planning on all levels will serve to reduce the morbidity and mortality associated with the next pandemic and will help to ensure that health care workers do not sacrifice needlessly.0

Background

Influenza viruses are among the most common respiratory viral infections in humans. There are two major types of human influenza viruses, A and B, with influenza A strains responsible for seasonal or pandemic influenza. Influenza illness is characterized by fever, lower respiratory and often upper respiratory symptoms, myalgia, and malaise and occurs seasonally in temperate climates between late fall and early spring. The average flu season in the United States is marked by 30,000‐40,000 deaths, primarily in elderly patients with significant comorbidity and in the very young. Many of these deaths are caused by secondary bacterial pneumonias. Long interpandemic periods, including the current one of almost 40 years, involve minor mutations of the predominant influenza strain from year to year. Typically, adequate time exists to predict the prevailing strain with reasonable accuracy and to tailor a vaccine accordingly. Periodically an influenza pandemic involving a novel influenza strain emerges, attended by greater‐than‐expected morbidity and mortality.

All influenza viruses are subtyped on the basis of two surface glycoproteins. One of these, hemagglutinin (H), is responsible for viral cell entry; whereas the other, neuraminidase (N), facilitates release of the virus from infected cells, thus allowing perpetuation and amplification of infection. Antigenic drift is the ongoing process of genetic mutations that lead to new strains demonstrating variable change in antigenicity and is the basis for the annual updating of vaccine strains. Antigenic shift is the emergence of a novel influenza A subtype among humans, usually as the result of a recombination event. This radical change is necessary but not sufficient to initiate pandemic influenza, with efficient transmission from person to person also a critical feature. Pandemic influenza strains arise in 1 of 2 fashions. Genetic reassortment may occur when a mammalian host (human or porcine) is infected with both an avian and a human influenza virus, with subsequent dramatic movement into human populations, the source of the 1957 and 1968 pandemics. Alternatively, a novel virus may, after sufficient mutation, move directly from the avian population to humans, as appears to have occurred in 1918.

The 1918‐19 Pandemic

Abruptly in 1918, an influenza pandemic of seemingly unprecedented severity swept the world. Although disagreement remains regarding the source of the outbreak (China, the front lines of World War I, and even the United States have all been suggested), within 6‐9 months essentially the entire globe had been affected. Unlike more typical influenza seasons, the virus preferentially infected previously healthy young individuals, with those aged 15‐40 bearing the brunt of the illness. US military training installations, overcrowded with troops staging for service on the European front, played a particularly ill‐fated role in the pandemic as it swept through the United States.

Estimates of the pandemic's worldwide impact on mortality are sketchy at best, but many authorities believe that at least 50 million deaths resulted, with some suggesting a figure as high as 100 million. In the United States the virus was responsible for an estimated 700,000 deaths, with an untold burden of morbidity. Economic and social disruption was the norm in many areas, with widespread closure of businesses and schools and suspension of public gatherings of any kind. Many communities were simply overwhelmed by the sheer numbers of dying individuals. In Philadelphia, steam shovels were used to dig mass graves for influenza victims.1 The pandemic's effect on the health care system was likewise profound. Most hospitals counted their own physicians and nurses among those who died during the pandemic, and many of the health care workers who succumbed were infected in the course of caring for influenza patients. Overall, an estimated 2%‐3% of those infected with the virus died, a far higher percentage than is seen during interpandemic seasons. Strikingly, the vast majority of deaths do not appear to have resulted from secondary bacterial pneumonias, but rather to have been directly virally mediated through ARDS, a necrotizing viral pneumonia, or both.

The mystery of the 1918 pandemic has recently been partially unlocked, with the successful sequencing of the entire RNA genome of strains recovered from pathology tissue of two soldiers, as well as from lung tissue of a victim frozen in Alaskan permafrost since 1918.2, 3 The data suggest that the 1918 virus was derived from an avian source. Notably, some of the same changes in the polymerase proteins have been found in the highly pathogenic H5N1 viruses.

Avian Influenza Viruses

Influenza viruses that primarily infect birds are characterized as avian influenza viruses. These are always type A and are classified as either of low or high pathogenicity on the basis of the severity of the illness they cause in birds. The currently circulating H5N1 avian viruses are highly pathogenic.

Avian influenza viruses do not usually infect humans; however, several instances of human infections have been reported since 1997. The 1997 Hong Kong outbreak of avian (H5N1) influenza in 18 humans resulted in 6 deaths and was a seminal event that provided evidence that avian influenza viruses can infect people. It also provided the epidemiologic link between avian influenza infection in poultry with disease in humans and was proclaimed as a pandemic warning. These sentinel human infections led to the culling of the entire Hong Kong poultry population, with no subsequent human infection reported at that time. In 2003, more than 80 cases of avian influenza A (H7N7) illness occurred in the Netherlands among persons who handled infected poultry. Sustained human‐to‐human transmission did not occur in this or other outbreaks of avian influenza to date.

Since 2003, sporadic human cases of H5N1 have occurred, most recently reported from Turkey and Iraq. Human cases have also occurred in Vietnam, China, Cambodia, Thailand, and Indonesia, with a total of 173 reported cases and a case fatality rate exceeding 50% as of this writing.4 This mortality rate may be artificially inflated, as less severe cases have certainly gone unreported. All countries reporting human avian influenza diseases since 2003 have had concurrent epizoonotics in birds (both poultry and migratory birds).

Human cases of H5N1 influenza illness have been characterized by high fever and symptoms in the lower respiratory tract, as would be expected. Less predictable has been the presence of watery diarrhea in many patients and of abdominal and pleuritic pain and bleeding from the nose and gums in some. Sputum production has been variably present, and hemoptysis has been seen in some individuals. Most patients have had clinical and radiological evidence of pneumonia at the time they sought medical care, and progression to ARDS and multiorgan failure has been common. The majority of patients to date have required the initiation of mechanical ventilation early in their hospital course. Laboratory studies have typically shown lymphopenia, thrombocytopenia, and, in many cases, modestly elevated transaminase levels.5 Notably, the currently predominant strain of H5N1 (Z strain) is resistant to the M2 ion channel inhibitors amantadine and rimantadine but is susceptible to the newer class of neuraminidase inhibitors, zanamivir (Relenza) and oseltamivir (Tamiflu). Neuraminidase inhibitors and corticosteroids have been used to treat patients, although their efficacy in this setting is unclear. To date, virtually all cases appear to have been transmitted directly from poultry, although person‐to‐person transmission appears likely to have occurred in at least one family in Thailand.6 A recent study of the 14 clusters of avian influenza among humans emphasized the lack of sustained person‐to‐person transmission of H5N1 to date.7

Three factors are necessary for the emergence of a pandemic influenza strain: the ability to infect humans, a novel genetic makeup, and the ability for sustained transmission between people. A virus that in addition proves highly virulent, as did the 1918‐19 H1N1 strain, essentially creates the perfect storm. H5N1 influenza has currently fulfilled 2 of these 3 criteria. The virus is highly pathogenic, although how much of this fitness would be sacrificed with mutation to a more transmissible strain is uncertain. As many have observed, whether there will be another influenza pandemic does not seem in doubt; rather, it is when such a pandemic will occur and whether the pandemic will be caused by H5N1 or another influenza virus, that are the questions.

Potential Effects of the Next Pandemic

The global and national effects of an influenza pandemic will vary in direct proportion to the virulence of the circulating viral strain, but if such a virus is highly virulent, significant and perhaps severe economic and social disruption are likely.

The global economic impact has been estimated to be $800 billion with anticipated quarantines and interruption in global trade. On a national level, it has been estimated that in the United States a pandemic virus whose severity is comparable to that of the 1968 Hong Kong influenza pandemic would lead to approximately 200,000 deaths and 700,000 hospitalizations, of which roughly 100,000 would require treatment in intensive care unit settings. A more virulent strain, similar to that of the 1918‐19 pandemic, might easily result in 1 million deaths; with the number of patients hospitalized approaching 10 million, well over 1 million of which would require ICU‐level care. As an estimated 75% of the 105,000 ventilators in this country are in use at any given time under normal circumstances, the potential for demand to greatly outstrip supply is evident.8 Depending on the severity of a pandemic, suspension or curtailment of international trade and travel could be reasonably likely. Although the World Health Organization has recommended against closing borders or quarantining countries even in the throes of a pandemic, the prospect of this occurring does not seem implausible. In a worst‐case scenario, even the type of national and international chaos envisioned in the Dark Winter smallpox planning exercise might occur.9

Fortress America Versus Containment Strategies

Although the pandemic influenza plan calls for stockpiling antiviral drugs and increasing vaccine production capabilities, the most effective plan for pandemic preparedness may involve a surveillance and containment strategy. No country has enough medicines or vaccines to control a widespread outbreak of pandemic avian influenza. The best solution to prevention of a pandemic is stopping any virus from spreading in the first place. Increased surveillance for avian influenza among poultry and migratory birds in key Asian countries, along with provision of funds to compensate farmers for culling of potentially infected flocks, would align incentives for early detection and eradication. Containing an initial outbreak wherever it occurs is the best defense against a pandemic. Notably, China is thought to be a potential hot zone for emergence of pandemic avian influenza. China is not only the most populous nation in the world but has one quarter of the world's chickens, two thirds of the world's domesticated ducks, and 90% of the world's domesticated geese.

The challenges of biosecurity (protecting humans against animal‐borne diseases such as bird flu) in developing countries include the reality that populations living in close proximity to poultry are also the most illiterate and impoverished, with the most limited access to health care. The recent introduction of H5N1 into Europe has heightened surveillance efforts in the United States. The introduction of H5N1 into the United States may occur through movement of migratory birds and/or importation of exotic birds. The surveillance system has been expanded to include sampling for the influenza virus not only in poultry but also in bodies of water, as the virus is shed in bird feces.

Pandemic Planning

In the setting of a severe pandemic, hospitals will face an enormous burden of patients, with a huge influx of individuals requiring both intensive care unit as well as regular nursing floor care. At the local height of such a pandemic, the ability to successfully discharge every patient whose condition will permit this to the community or elsewhere will be critical, and almost certainly hospitals will need to expand to accept more patients than they are normally configured to hold. Hospitals staffs, particularly nurses and physicians, will be required to handle very large patient censuses. Among medical staffs, emergency physicians, hospitalists, critical care specialists, and infectious disease specialists will certainly be called on to play leading roles, much as they were during and in the aftermath of Hurricane Katrina recently. Despite all of the above, the ability of existing hospitals to accommodate all gravely ill patients may be outstripped, and auxiliary hospitals in schools and other public edifices may need to be established. Hospitalists are likely to be called on to play a major role in such temporary hospitals. The frustration and anguish of not being able to provide a standard level of care to patients (for example, being forced to triage which patients are most deserving of mechanical ventilation) should not be underestimated.

Although characterized by a relatively limited number of patients, the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, Canada, presented some of the same challenges that will be encountered in a virulent influenza pandemic. These include the need to quickly and drastically modify the usual emergency department and inpatient procedures, as hospitals initially serve to amplify the epidemic, as well as the additional stressor of health care workers becoming ill as a result of work‐related exposure. That fewer than 400 cases of SARS pushed the medical system of one of North America's largest cities nearly to its breaking point is both sobering and instructive.10, 11 Interested readers are directed to an excellent summary of lessons learned from the SARS outbreak, most of which are widely applicable to preparations for future infectious epidemics.12

Infection Control

Although the CDC and other Web sites currently recommend airborne isolation (respiratory personal protection) for avian influenza in humans, there is not strong epidemiologic evidence of transmission other than via droplets (the transmission mode of human influenza). The emergence of a limited number of cases of avian influenza in the United States would allow employment of airborne isolation measures; but in the event of a larger outbreak, the use of surgical masks and the practice of good hand hygiene would be sufficient by health care workers caring for persons with suspected or proven disease.

The CDC recently released proposed changes to help prevent disease outbreaks from contacts of those exposed to ill persons on airplanes. Proposed guidelines would require airlines to maintain computerized lists of passengers taken at point of departure in order to facilitate tracking of contacts and implementation of quarantine if necessary. These measures are part of pandemic planning and result from problems in tracking passengers on planes with SARS cases. By executive order, imposition of quarantine is limited to 9 diseases: cholera, diphtheria, smallpox, yellow fever, viral hemorrhagic fevers (eg, Ebola), plague, infectious tuberculosis, SARS and influenza caused by new strains with pandemic potential.

What Can Be Done?

Although valuable time has elapsed to prepare for the possibility of an H5N1 influenza pandemic, the US and global communities are presently taking the threat seriously and are engaging in a variety of activities to prepare for such an eventuality. Although currently available influenza vaccines do not provide any appreciable protection against H5N1, significant work is under way to develop an effective vaccine; with Chiron and sanofi pasteur preparing vaccine trials in association with the National Institute of Allergy and Infectious Diseases. Current influenza vaccine production is hampered by use of obsolete egg‐based manufacturing processes requiring 6 months, along with a limited capacity to manufacture adequate vaccine supplies even in many usual influenza seasons. The herculean task of providing hundreds of millions of doses of vaccine as soon as possible after the emergence of a pandemic strain, as daunting as it is, is further complicated by the fact that a successful H5N1 vaccine would not necessarily be effective against a strain that mutated sufficiently to move efficiently from person to person. Nonetheless, even partially solving these problems will pay dividends, whether or not H5N1 proves to be responsible for the next pandemic.

Given these difficulties with vaccine development and production, the backbone of any successful early response to a pandemic in the near future will be development of an adequate stockpile of antiviral medication, accompanied by a successful plan to distribute the drug when and where disease erupts. Despite uncertainties regarding their effectiveness as well as questions regarding optimal dose and duration in the setting of avian influenza, the neuraminidase inhibitors are the current drugs of choice. Of the 2 currently available agents, oseltamivir is the preferred drug for pandemic use, given its oral administration,. Unfortunately, the ability to manufacture the drug in sufficient quantities to stockpile has thus far proved problematic. Roche, the manufacturer of Tamiflu, has recently opened a new manufacturing plant and has stated that it can increase its current production of 55 million doses per year to 300 million doses by 2007. We do not recommend a role for personal stockpiling of neuraminidase inhibitors. Concerns include a shortage of the drug for seasonal influenza, absence of a pandemic at present, ignorance regarding the efficacy and optimal dose for H5N1, inappropriate use by individuals, and inequitable distribution. Recent case reports of oseltamivir resistance emerging during prophylaxis13 and treatment14 are of potential concern but do not alter current recommendations.

What can be done locally and specifically, and what can hospitalists do to prepare? First, although we are not sure that Dr Michael Osterholm's goal that planning for a pandemic must be on the agenda of every public health agency, school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor8 is entirely realistic, every hospital clearly needs to include pandemic influenza as a significant part of its disaster preparedness plan. Such planning will have broad overlap with planning for other potential disasters, including bioterrorist attacks, SARS outbreaks, and others. Hospitals must develop a plan for surge capacity, and such a plan should include not only coordination with other local hospitals, but also planning with local communities to identify sites where temporary flu hospitals can be established. Within hospital medicine groups, emergency staffing plans should be established before pandemic influenza (or another disaster) strikes. Such staffing plans need to include the ability to care for a much higher than normal number of patients for an extended period. Conceivably, a large number of patients will need to be manually ventilated for prolonged periods, which of course will tax the resources of any institution. Prompt discharge of all patients stable enough to leave the hospital will be critical, and given the investment of most hospital medicine groups in hospital throughput issues under normal conditions, much of the responsibility for helping to create beds during a crisis will inevitably fall on the shoulders of hospitalists.

Experiences during and shortly after Hurricane Katrina served to underscore that issues such as physical and mental fatigue, concern for the safety of family members, lack of supplies, communication difficulties, and absenteeism all add additional layers of complexity to the task of providing hospital care under extraordinary conditions such as during a natural disaster. These lessons can and should be extended to a major epidemic. This disaster also showed the importance of military involvement in the response to disasters that exceed local and state capabilities. The primary objective of the federal government in responding to disaster is to maintain security and essential services while preventing chaos. A pandemic of virulent influenza will raise the stakes still further, as physicians and nurses become casualties themselves. Despite these challenges, we are confident that the vast majority of hospitalists and other health care workers will rise to the occasion, and just as during the peri‐Katrina period, stories of selflessness and heroism will be de rigueur. Appropriate advance planning on all levels will serve to reduce the morbidity and mortality associated with the next pandemic and will help to ensure that health care workers do not sacrifice needlessly.0