Adverse drug events (ADEs) occur when patients transition between the hospital and other care settings. Medication reconciliation, a process by which a provider obtains and documents a thorough medication history with specific attention to comparing current and previous medication use, can prevent transition‐related errors and harm in a variety of care locations.13 Nevertheless, poor intersite communication,4 flawed reconciliation of drug regimens,2 unreliable patient history‐taking, and poor provider decision‐making5 continue to contribute to transition‐related ADEs.

The Joint Commission introduced medication reconciliation as a hospital National Patient Safety Goal in 2006. However, because organizations have had difficulty implementing the process, it stopped citing medication reconciliation deficiencies in its accreditation surveys.6 Although regional and national initiatives have attempted to improve implementation of medication reconciliationusing provider education, workflow, and process reorganization, and organizational change7a recent field review by the Joint Commission suggests that healthcare organizations remain unable to ensure effective medication reconciliation, citing factors beyond the organizations' control, especially unreliable patient histories.8 Still, the process is slated to return as an accreditation requirement of the Joint Commission on July 1, 2011.8

The objective of this study was to determine factors that influenced physicians' and pharmacists' performance of medication reconciliation in a hospital setting with a computerized medical record and medication reconciliation tool, with the goal of informing an organization's approach to implementation. We conducted individual cognitive task analysis (CTA) interviews and focus group interviews to ascertain physicians' and pharmacists' opinions on the purpose and effectiveness of medication reconciliation, their approach to completing the task, and task facilitators and barriers.

METHODS

Setting and Medication Reconciliation Process

The study setting was an urban, academic, tertiary‐care Veterans Affairs (VA) medical center. A computerized medication reconciliation tool and process were developed in 2005 to comply with the Joint Commission's National Patient Safety Goal.6 The tool was embedded in the VA's Computerized Patient Record System (CPRS) and consisted of a dialogue with which a provider (physician, pharmacist, or other provider) could: 1) view the patient's outpatient medication use, for the last 90 days, from VA computerized pharmacy data; 2) view current VA inpatient orders; 3) record discrepancies between patient‐reported medications, and outpatient and inpatient medications in the VA computerized database; 4) record diagnostic indications for, and responses to, these discrepancies; and 5) produce a medication reconciliation document, which was a separate progress note (Figure 1). The tool did not directly facilitate ordering; however, in CPRS, outpatient orders could easily be copied to inpatient orders and vice versa.

Figure 1

Two versions of the medication reconciliation process were implemented upon hospital admission: one in which the physician initiated and completed a reconciliation that was then reviewed by a pharmacist (Figure 2A)the process primarily used on the medical and surgical services; and one in which, after the physician wrote admission orders, the pharmacist initiated and completed the reconciliation and communicated his or her findings with the physician (Figure 2B)the process primarily used on the psychiatric service. At discharge, after the physician wrote discharge orders, the pharmacist completed a reconciliation of preadmission, inpatient, and discharge orders using a tool similar to the admission one (Figure 1). The pharmacist then communicated the reconciliation findings to the physician, similar to the admission medication reconciliation process shown in Figure 2B. These processes and tools were in place for 18 months at the time of the cognitive task analysis, which took place in June 2007, and 32 months at the time of the focus groups, which took place in August 2008.

Figure 2

RESULTS

DISCUSSION

In this study of hospital physicians' and pharmacists' perspectives on medication reconciliation, we found that although respondents agreed about its main purposeto improve prescribing safetya near majority believed that it was of uncertain benefit to patients and limited use to providers. This might, in part, be because of a tool that was not adequately integrated into workflow, making it extraneous to patient care. As a consequence, many respondents' indicated that when they had competing tasks, especially other acute care responsibilities, medication reconciliation was displaced in priority. Respondents indicated that unreliability of patient medication histories was also a major barrier, which is consistent with a recent Joint Commission field review in which organizations cited this as a task hindrance beyond their control.8 Lastly, respondents revealed limited perception of it being a team‐oriented task.

Our study also probed providers' perceptions of the effect of computerization on completing medication reconciliation. Although study respondents indicated that the computerized tool reduced the time required to complete the task, they also expressed concern that because medication reconciliation was automated in part at the VA, they spent less time with patients on the process. This finding is important because, according to 1 study, many medications are not captured by the VA's Computerized Patient Record System,15 and a patient's lack of medication adherence may not be evident in the CPRS. This finding is also consistent with our prior work that has not demonstrated an inherent advantage to electronic communication of medication information over paper.16

Our study suggests that, for medication reconciliation to be improved, provider self‐efficacy and engagement with the process must be increased. This might involve addressing negative provider attitudes, changing workflow, and improving provider confidence by improving information reliability. With regard to changing attitudes, team members should be briefed on research evidence that shows that medication reconciliation is effective in preventing ADEs13 and is cost‐effective17 to help to increase the value that providers place on medication reconciliation. With regard to workflow, the tool has to be optimized to facilitate information gathering, processing, and medication ordering. Our findings also suggest that medication reconciliation would benefit from widening the time window in which it should be completed (eg, to the first or second business day after admission), since this increases the time available to access multiple data sources, and for providers to update the preadmission medication history and to act on new medication information. Finally, regional electronic health information exchange would improve information reliability and provider confidence in the information.

Our findings also suggest that assignment of productive teamsconsisting of physicians, physician‐extenders, nurses, pharmacists, and/or administrative support staffrather than individuals to the task might improve task completion. Efficacy and perceived capability might be improved by dividing the task into parts more easily manageable by individual team members. One example would be to assign 1 team member to record all of the sources of medication information available for each patient (the patient's home, pharmacies, doctors, hospitals, etc), and assign 1 or more other team members to access these sources as needed. Another example would be to assign the pharmacist to take and document the preadmission medication history (if not for all patients, then perhaps for the highest‐risk patients), and assign the physician to verify the history, specify the planned action on admission for each medication, and complete the admission orders. These suggestions are consistent with a study that suggested that physician engagement and an effective team are strongly correlated with successful implementation of medication reconciliation.7

A strength of our study was its use of multiple methods (focus groups and cognitive task analysis) to collect data from key users individually while they interfaced with the system and in groups. Nevertheless, a limitation of the study is that it took place in a single hospital. Though it had a limited number of physician and pharmacist participants, the study sample represented a large fraction of the inpatient staff in those disciplines. We also did not include nurses, hospitalist attending physicians, or other disciplines that might be involved in medication reconciliation in other facilities or settings. However, our study explored the relationship between two disciplines (physicians and pharmacists), yielding findings that could apply to optimizing the function of other interdisciplinary teams.

Our findings can be used to inform improvement efforts in hospitals that have struggled to implement medication reconciliation. Given that the process is slated to return as an accreditation requirement of the Joint Commission,8 hospitals will need to find ways to strengthen the process. Our findings suggest that increasing providers' perceived capability, and confidence in the process and its outcomes, would improve their engagement in the process. This could be accomplished by improved information gathering, including better computer information systems and regional electronic health information exchange, a flexible timeframe for the process, provider training and feedback, and teamwork. In addition, hospitals can make sure their process is working by ascertaining a gold standard medication history on a subset of patients, and comparing the gold standard to the team's history, and admission and discharge orders. Because it is a central component of safe medication prescribing, medication reconciliation will continue to be a focus of state,18 national,19 and international safety efforts20 in the near future.

Adverse drug events (ADEs) occur when patients transition between the hospital and other care settings. Medication reconciliation, a process by which a provider obtains and documents a thorough medication history with specific attention to comparing current and previous medication use, can prevent transition‐related errors and harm in a variety of care locations.13 Nevertheless, poor intersite communication,4 flawed reconciliation of drug regimens,2 unreliable patient history‐taking, and poor provider decision‐making5 continue to contribute to transition‐related ADEs.

The Joint Commission introduced medication reconciliation as a hospital National Patient Safety Goal in 2006. However, because organizations have had difficulty implementing the process, it stopped citing medication reconciliation deficiencies in its accreditation surveys.6 Although regional and national initiatives have attempted to improve implementation of medication reconciliationusing provider education, workflow, and process reorganization, and organizational change7a recent field review by the Joint Commission suggests that healthcare organizations remain unable to ensure effective medication reconciliation, citing factors beyond the organizations' control, especially unreliable patient histories.8 Still, the process is slated to return as an accreditation requirement of the Joint Commission on July 1, 2011.8

The objective of this study was to determine factors that influenced physicians' and pharmacists' performance of medication reconciliation in a hospital setting with a computerized medical record and medication reconciliation tool, with the goal of informing an organization's approach to implementation. We conducted individual cognitive task analysis (CTA) interviews and focus group interviews to ascertain physicians' and pharmacists' opinions on the purpose and effectiveness of medication reconciliation, their approach to completing the task, and task facilitators and barriers.

METHODS

Setting and Medication Reconciliation Process

The study setting was an urban, academic, tertiary‐care Veterans Affairs (VA) medical center. A computerized medication reconciliation tool and process were developed in 2005 to comply with the Joint Commission's National Patient Safety Goal.6 The tool was embedded in the VA's Computerized Patient Record System (CPRS) and consisted of a dialogue with which a provider (physician, pharmacist, or other provider) could: 1) view the patient's outpatient medication use, for the last 90 days, from VA computerized pharmacy data; 2) view current VA inpatient orders; 3) record discrepancies between patient‐reported medications, and outpatient and inpatient medications in the VA computerized database; 4) record diagnostic indications for, and responses to, these discrepancies; and 5) produce a medication reconciliation document, which was a separate progress note (Figure 1). The tool did not directly facilitate ordering; however, in CPRS, outpatient orders could easily be copied to inpatient orders and vice versa.

Figure 1

Two versions of the medication reconciliation process were implemented upon hospital admission: one in which the physician initiated and completed a reconciliation that was then reviewed by a pharmacist (Figure 2A)the process primarily used on the medical and surgical services; and one in which, after the physician wrote admission orders, the pharmacist initiated and completed the reconciliation and communicated his or her findings with the physician (Figure 2B)the process primarily used on the psychiatric service. At discharge, after the physician wrote discharge orders, the pharmacist completed a reconciliation of preadmission, inpatient, and discharge orders using a tool similar to the admission one (Figure 1). The pharmacist then communicated the reconciliation findings to the physician, similar to the admission medication reconciliation process shown in Figure 2B. These processes and tools were in place for 18 months at the time of the cognitive task analysis, which took place in June 2007, and 32 months at the time of the focus groups, which took place in August 2008.

Figure 2

RESULTS

DISCUSSION

In this study of hospital physicians' and pharmacists' perspectives on medication reconciliation, we found that although respondents agreed about its main purposeto improve prescribing safetya near majority believed that it was of uncertain benefit to patients and limited use to providers. This might, in part, be because of a tool that was not adequately integrated into workflow, making it extraneous to patient care. As a consequence, many respondents' indicated that when they had competing tasks, especially other acute care responsibilities, medication reconciliation was displaced in priority. Respondents indicated that unreliability of patient medication histories was also a major barrier, which is consistent with a recent Joint Commission field review in which organizations cited this as a task hindrance beyond their control.8 Lastly, respondents revealed limited perception of it being a team‐oriented task.

Our study also probed providers' perceptions of the effect of computerization on completing medication reconciliation. Although study respondents indicated that the computerized tool reduced the time required to complete the task, they also expressed concern that because medication reconciliation was automated in part at the VA, they spent less time with patients on the process. This finding is important because, according to 1 study, many medications are not captured by the VA's Computerized Patient Record System,15 and a patient's lack of medication adherence may not be evident in the CPRS. This finding is also consistent with our prior work that has not demonstrated an inherent advantage to electronic communication of medication information over paper.16

Our study suggests that, for medication reconciliation to be improved, provider self‐efficacy and engagement with the process must be increased. This might involve addressing negative provider attitudes, changing workflow, and improving provider confidence by improving information reliability. With regard to changing attitudes, team members should be briefed on research evidence that shows that medication reconciliation is effective in preventing ADEs13 and is cost‐effective17 to help to increase the value that providers place on medication reconciliation. With regard to workflow, the tool has to be optimized to facilitate information gathering, processing, and medication ordering. Our findings also suggest that medication reconciliation would benefit from widening the time window in which it should be completed (eg, to the first or second business day after admission), since this increases the time available to access multiple data sources, and for providers to update the preadmission medication history and to act on new medication information. Finally, regional electronic health information exchange would improve information reliability and provider confidence in the information.

Our findings also suggest that assignment of productive teamsconsisting of physicians, physician‐extenders, nurses, pharmacists, and/or administrative support staffrather than individuals to the task might improve task completion. Efficacy and perceived capability might be improved by dividing the task into parts more easily manageable by individual team members. One example would be to assign 1 team member to record all of the sources of medication information available for each patient (the patient's home, pharmacies, doctors, hospitals, etc), and assign 1 or more other team members to access these sources as needed. Another example would be to assign the pharmacist to take and document the preadmission medication history (if not for all patients, then perhaps for the highest‐risk patients), and assign the physician to verify the history, specify the planned action on admission for each medication, and complete the admission orders. These suggestions are consistent with a study that suggested that physician engagement and an effective team are strongly correlated with successful implementation of medication reconciliation.7

A strength of our study was its use of multiple methods (focus groups and cognitive task analysis) to collect data from key users individually while they interfaced with the system and in groups. Nevertheless, a limitation of the study is that it took place in a single hospital. Though it had a limited number of physician and pharmacist participants, the study sample represented a large fraction of the inpatient staff in those disciplines. We also did not include nurses, hospitalist attending physicians, or other disciplines that might be involved in medication reconciliation in other facilities or settings. However, our study explored the relationship between two disciplines (physicians and pharmacists), yielding findings that could apply to optimizing the function of other interdisciplinary teams.

Our findings can be used to inform improvement efforts in hospitals that have struggled to implement medication reconciliation. Given that the process is slated to return as an accreditation requirement of the Joint Commission,8 hospitals will need to find ways to strengthen the process. Our findings suggest that increasing providers' perceived capability, and confidence in the process and its outcomes, would improve their engagement in the process. This could be accomplished by improved information gathering, including better computer information systems and regional electronic health information exchange, a flexible timeframe for the process, provider training and feedback, and teamwork. In addition, hospitals can make sure their process is working by ascertaining a gold standard medication history on a subset of patients, and comparing the gold standard to the team's history, and admission and discharge orders. Because it is a central component of safe medication prescribing, medication reconciliation will continue to be a focus of state,18 national,19 and international safety efforts20 in the near future.

Adverse drug events (ADEs) occur when patients transition between the hospital and other care settings. Medication reconciliation, a process by which a provider obtains and documents a thorough medication history with specific attention to comparing current and previous medication use, can prevent transition‐related errors and harm in a variety of care locations.13 Nevertheless, poor intersite communication,4 flawed reconciliation of drug regimens,2 unreliable patient history‐taking, and poor provider decision‐making5 continue to contribute to transition‐related ADEs.

The Joint Commission introduced medication reconciliation as a hospital National Patient Safety Goal in 2006. However, because organizations have had difficulty implementing the process, it stopped citing medication reconciliation deficiencies in its accreditation surveys.6 Although regional and national initiatives have attempted to improve implementation of medication reconciliationusing provider education, workflow, and process reorganization, and organizational change7a recent field review by the Joint Commission suggests that healthcare organizations remain unable to ensure effective medication reconciliation, citing factors beyond the organizations' control, especially unreliable patient histories.8 Still, the process is slated to return as an accreditation requirement of the Joint Commission on July 1, 2011.8

The objective of this study was to determine factors that influenced physicians' and pharmacists' performance of medication reconciliation in a hospital setting with a computerized medical record and medication reconciliation tool, with the goal of informing an organization's approach to implementation. We conducted individual cognitive task analysis (CTA) interviews and focus group interviews to ascertain physicians' and pharmacists' opinions on the purpose and effectiveness of medication reconciliation, their approach to completing the task, and task facilitators and barriers.

METHODS

Setting and Medication Reconciliation Process

The study setting was an urban, academic, tertiary‐care Veterans Affairs (VA) medical center. A computerized medication reconciliation tool and process were developed in 2005 to comply with the Joint Commission's National Patient Safety Goal.6 The tool was embedded in the VA's Computerized Patient Record System (CPRS) and consisted of a dialogue with which a provider (physician, pharmacist, or other provider) could: 1) view the patient's outpatient medication use, for the last 90 days, from VA computerized pharmacy data; 2) view current VA inpatient orders; 3) record discrepancies between patient‐reported medications, and outpatient and inpatient medications in the VA computerized database; 4) record diagnostic indications for, and responses to, these discrepancies; and 5) produce a medication reconciliation document, which was a separate progress note (Figure 1). The tool did not directly facilitate ordering; however, in CPRS, outpatient orders could easily be copied to inpatient orders and vice versa.

Figure 1

Two versions of the medication reconciliation process were implemented upon hospital admission: one in which the physician initiated and completed a reconciliation that was then reviewed by a pharmacist (Figure 2A)the process primarily used on the medical and surgical services; and one in which, after the physician wrote admission orders, the pharmacist initiated and completed the reconciliation and communicated his or her findings with the physician (Figure 2B)the process primarily used on the psychiatric service. At discharge, after the physician wrote discharge orders, the pharmacist completed a reconciliation of preadmission, inpatient, and discharge orders using a tool similar to the admission one (Figure 1). The pharmacist then communicated the reconciliation findings to the physician, similar to the admission medication reconciliation process shown in Figure 2B. These processes and tools were in place for 18 months at the time of the cognitive task analysis, which took place in June 2007, and 32 months at the time of the focus groups, which took place in August 2008.

Figure 2

RESULTS

DISCUSSION

In this study of hospital physicians' and pharmacists' perspectives on medication reconciliation, we found that although respondents agreed about its main purposeto improve prescribing safetya near majority believed that it was of uncertain benefit to patients and limited use to providers. This might, in part, be because of a tool that was not adequately integrated into workflow, making it extraneous to patient care. As a consequence, many respondents' indicated that when they had competing tasks, especially other acute care responsibilities, medication reconciliation was displaced in priority. Respondents indicated that unreliability of patient medication histories was also a major barrier, which is consistent with a recent Joint Commission field review in which organizations cited this as a task hindrance beyond their control.8 Lastly, respondents revealed limited perception of it being a team‐oriented task.

Our study also probed providers' perceptions of the effect of computerization on completing medication reconciliation. Although study respondents indicated that the computerized tool reduced the time required to complete the task, they also expressed concern that because medication reconciliation was automated in part at the VA, they spent less time with patients on the process. This finding is important because, according to 1 study, many medications are not captured by the VA's Computerized Patient Record System,15 and a patient's lack of medication adherence may not be evident in the CPRS. This finding is also consistent with our prior work that has not demonstrated an inherent advantage to electronic communication of medication information over paper.16

Our study suggests that, for medication reconciliation to be improved, provider self‐efficacy and engagement with the process must be increased. This might involve addressing negative provider attitudes, changing workflow, and improving provider confidence by improving information reliability. With regard to changing attitudes, team members should be briefed on research evidence that shows that medication reconciliation is effective in preventing ADEs13 and is cost‐effective17 to help to increase the value that providers place on medication reconciliation. With regard to workflow, the tool has to be optimized to facilitate information gathering, processing, and medication ordering. Our findings also suggest that medication reconciliation would benefit from widening the time window in which it should be completed (eg, to the first or second business day after admission), since this increases the time available to access multiple data sources, and for providers to update the preadmission medication history and to act on new medication information. Finally, regional electronic health information exchange would improve information reliability and provider confidence in the information.

Our findings also suggest that assignment of productive teamsconsisting of physicians, physician‐extenders, nurses, pharmacists, and/or administrative support staffrather than individuals to the task might improve task completion. Efficacy and perceived capability might be improved by dividing the task into parts more easily manageable by individual team members. One example would be to assign 1 team member to record all of the sources of medication information available for each patient (the patient's home, pharmacies, doctors, hospitals, etc), and assign 1 or more other team members to access these sources as needed. Another example would be to assign the pharmacist to take and document the preadmission medication history (if not for all patients, then perhaps for the highest‐risk patients), and assign the physician to verify the history, specify the planned action on admission for each medication, and complete the admission orders. These suggestions are consistent with a study that suggested that physician engagement and an effective team are strongly correlated with successful implementation of medication reconciliation.7

A strength of our study was its use of multiple methods (focus groups and cognitive task analysis) to collect data from key users individually while they interfaced with the system and in groups. Nevertheless, a limitation of the study is that it took place in a single hospital. Though it had a limited number of physician and pharmacist participants, the study sample represented a large fraction of the inpatient staff in those disciplines. We also did not include nurses, hospitalist attending physicians, or other disciplines that might be involved in medication reconciliation in other facilities or settings. However, our study explored the relationship between two disciplines (physicians and pharmacists), yielding findings that could apply to optimizing the function of other interdisciplinary teams.

Our findings can be used to inform improvement efforts in hospitals that have struggled to implement medication reconciliation. Given that the process is slated to return as an accreditation requirement of the Joint Commission,8 hospitals will need to find ways to strengthen the process. Our findings suggest that increasing providers' perceived capability, and confidence in the process and its outcomes, would improve their engagement in the process. This could be accomplished by improved information gathering, including better computer information systems and regional electronic health information exchange, a flexible timeframe for the process, provider training and feedback, and teamwork. In addition, hospitals can make sure their process is working by ascertaining a gold standard medication history on a subset of patients, and comparing the gold standard to the team's history, and admission and discharge orders. Because it is a central component of safe medication prescribing, medication reconciliation will continue to be a focus of state,18 national,19 and international safety efforts20 in the near future.

Recent studies of the growth of the hospitalist movement have confirmed that hospitalists are taking care of an increasing percentage of hospitalized older adults.1, 2 Unfortunately, few hospitalist groups have specific programs or protocols to address the special needs of older patients.3, 4 We were inspired by a top 10 article written by nephrologists for primary care physicians to compile 10 evidence‐based pearls that may be helpful to hospitalists caring for older persons.5

1. Many Health Conditions in Older Patients are Multifactorial and Require a Multifactorial Approach to Care

A geriatric syndrome is a multifactorial condition occurring primarily in frail elderly which is usually due to multiple contributing factors and results from an interaction between patient‐specific impairments and situation‐specific stressors.68 Geriatric syndromes cannot be treated easily with a single intervention; the approach must target each modifiable risk factor. Table 1 illustrates for an example of how this approach differs from the traditional medical approach in the case of falls, a common geriatric syndrome. Hospitalists commonly encounter the geriatric syndromes that either lead to hospitalization, such as falls or dementia, or that can complicate a hospitalization for another condition, such as delirium, falls, or urinary incontinence. Two geriatric syndromes in particular, delirium and falls, are associated with increased length of stay, increased healthcare costs, and substantial morbidity.9, 10 Multifactorial interventions such as the Hospital Elder Life Project (HELP) have been shown to prevent delirium and falls.1114 Studies of the HELP intervention demonstrated benefits on outcomes that are important to hospitalists, including shortened length of stay.10, 15 While implementing these interventions is not possible at every institution, it may be possible to implement some aspects in a targeted fashion (for example, early physical therapy and mobilization to decrease risk of delirium and falls) or to work with hospital administration to implement the larger interventions.

2. Screening Elderly Patients for the Presence of Common Geriatric Syndromes can Improve Care

Comprehensive geriatric assessment, a process of multifactorial health evaluation of the older patient, is an important part of geriatric medicine and has been shown to reduce functional decline.16 While comprehensive geriatric assessment may not be practical in the acute care setting, some basic principles and tools of geriatric assessment, namely screening for geriatric syndromes, can be helpful. Here is one efficient, evidence‐based approach to screening hospitalized elderly patients for cognitive impairment and falls, and then using the results of screening to improve care:

3. Elderly Patients are at Risk for Functional Decline During Hospitalization and Measures Can Be Taken to Prevent This

A cascade to dependency has been described in which the effects of usual aging (eg, fragile skin) and hospitalization (eg, immobilization) interact with each other, often producing complications (eg, pressure ulcers) that can lead to the loss of the ability to live independently.30 Functional decline during hospitalization is common and is associated with poor prognosis. In one study of elderly patients with new Activities of Daily Living (ADL) disability at discharge, over 40% were dead by 12 months after discharge, and only 30% had returned to baseline function.31, 32 Functional status may affect discharge planning, especially if the patient is not able to return safely to his or her previous living environment. Elderly patients are very vulnerable to new ADL dependency and loss of ambulatory ability as a result of a hospitalization.33, 34 The initial evaluation of an elderly patient should always include an inquiry into the patient's functional abilities, including whether the patient requires assistance to perform self‐care (ADL) activities or instrumental activities of daily living (IADLs), and who is available to help at home. We remember ADLs as those activities we learn as a young child (bathing, dressing, feeding, toileting, transfers) and IADLs as activities we learn when we leave our parents' home to live independently (shopping, cooking, laundry, housekeeping, managing money, using public transportation). Patients in assisted living facilities and adult family homes receive varying degrees of help with ADLs and IADLs, and no particular level of assistance can be assumed; assisted living residents may be at higher risk of functional decline during hospitalization than community‐dwelling persons.35

Acute Care of Elderly (ACE) units have been shown to reduce functional disability and discharge to long‐term care settings, with length of stay and hospital charges similar to that of usual care.36 Most hospitals do not have ACE units, but implementing some components of the intervention, such as early physical and occupational therapy, early discharge planning, early mobility, and adequate nutrition may reduce functional disability. A Cochrane review found a small decrease in length of stay of about a day among elderly patients who participated in a structured exercise program, which could be extrapolated to support the usefulness of increased mobility and early physical therapy.37

4. Delirium is a Common but Serious Condition Among Hospitalized Elderly Patients and in Some Cases Can Be Prevented

The incidence of delirium appears to be as high as 60% in hospitalized elderly patients with multiple risk factors for this condition.38, 39 Delirium predicts longer hospital stay, increases likelihood of discharge to a skilled nursing facility, and is a marker for significant morbidity and mortality.4042 Cognitive screening, as discussed above, can help determine who is at risk for delirium, and the Confusion Assessment Method (CAM) is becoming more widely used as a bedside screening tool for detecting delirium.43 Other important risk factors for delirium in addition to preexisting cognitive impairment include age over 65, prior delirium, polypharmacy, functional dependence, and sensory impairment.44 A landmark randomized controlled trial by Sharon Inouye et al. showed that delirium can often be prevented in high‐risk patients by ensuring frequent reorientation, maintenance of the patient's usual sleep‐wake cycle, early mobilization, adequate nutrition and hydration, and regular use of sensory aids such as glasses and hearing aids.11

When delirium does occur despite preventive efforts, it should trigger a thorough investigation for an underlying cause. Common contributing factors to delirium in hospitalized patients include infections such as urinary tract infections or hospital‐acquired pneumonia, pain, electrolyte abnormalities, cardiac ischemia, medication side effects, and urinary retention or constipation. Any psychoactive or anticholinergic medication can contribute to, or exacerbate, delirium; common culprits include diphenhydramine, benzodiazepines, and muscle relaxants.44 Although one or more treatable underlying causes should always be sought, many cases of delirium in the hospital are multifactorial.

If pharmacologic treatment for delirium is necessary, low‐dose haloperidol is the first‐line agent, starting with 0.25 mg intravenously or 0.5 mg by mouth, nightly to twice a day. A recent systematic review supported the use of haloperidol as a first‐line agent in the acute setting; second‐generation antipsychotics are an alternative, but studies have shown no benefits of these agents over haloperidol in terms of safety or efficacy.45 Physical restraints should be avoided in delirious patients, as they may actually worsen delirium and have not been proven to reduce falls or secondary injury.46

5. Treating Nondementia Illnesses in Hospitalized Elders With Dementia Requires Consideration of the Patient's Limited Life Expectancy and Cognitive Deficits

Elderly patients with dementia are frequently hospitalized for medical illness and pose special challenges to the hospitalist. Patients with dementia may not be able to accurately report symptoms and side effects of therapy, and may lack decisional capacity. The clinician should also carefully consider the benefits and burdens of a proposed therapy or diagnostic test, taking into account the patient's cognitive deficits and limited life expectancy.47 The median postdiagnosis life expectancy of a patient with Alzheimer disease is about 4 years for men and about 6 years for women, with a range from about 2 to 9 years, according to population‐based studies of incident Alzheimer dementia.48, 49 In a patient with early or mild dementia, the hospitalist may first need to establish whether the patient does indeed have dementia. It is also important to question family about how the patient is managing at home so that appropriate discharge plans can be made.

Any intervention such as surgery or intubation in a patient with dementia should be considered carefully in the context of the patient's dementia, keeping in mind the remaining life expectancy, increased risk for delirium after surgery, and potential difficulty with adherence to postoperative precautions or participation in rehabilitation. Invasive procedures such as mechanical ventilation or central line placement may not be indicated in patients with advanced dementia. In one prospective cohort study, patients with advanced dementia admitted to the hospital for hip fractures or pneumonia had much higher mortality than those without dementia, despite having equal rates of procedures such as mechanical ventilation and central line placement.50

A common scenario in a patient with advanced dementia is the patient presenting with decreased intake and dysphagia; family and/or caregivers inquire about enteral tube feeding and/or long‐term intravenous hydration. This situation requires a thoughtfully presented, informative discussion with the family about artificial feeding in advanced dementia. There is no evidence that artificial feeding improves outcomes, and a recent Cochrane systematic review found insufficient evidence to suggest that enteral tube feeding is beneficial in patients with dementia.5153 Instead, dementia patients at the end of their lives benefit from a palliative approach, which would include hand‐feeding for comfort if the patient indicates hunger.54

6. Frail Elderly Patients are at High Risk for Iatrogenic Complications During Hospitalization

Frail elders are at increased risk for iatrogenic complications, including surgical‐ and procedure‐related events, adverse drug events, nosocomial infections, pressure ulcers, and falls.5557 In the Harvard Medical Practice Study, a retrospective study of adverse events in 30,000 patients, those age 65 and over accounted for 27% of the hospitalized population but 43% of the adverse events. In this study, four types of adverse events occurred at least twice as often in older patients: fractures, falls, nontechnical postoperative complications, and adverse events related to noninvasive treatments.58 The risk of hospital‐acquired infection also rises dramatically with age; risk is ten times higher in patients over 70 than those aged 49 and under, with urinary tract infections and surgical site infections the most common.59 The oldest, most seriously ill and most functionally impaired elderly patients are at particularly high risk of cascade iatrogenesis, where one medical intervention triggers a series of adverse events.60 Frail elderly patients are at greater risk for adverse events during hospitalization, and careful consideration of the need for all diagnostic tests and procedures may reduce risks. Table 3 lists the iatrogenic complications that disproportionately affect the elderly.

7. Pain Should Be Aggressively Identified and Appropriately Treated

Adequate treatment of pain in the elderly can improve functional status, mobility, and mood. Clinicians are understandably wary of prescribing opioids in the elderly, but undertreatment of pain is also common and in hospitalized patients can lead to delirium, delays in rehabilitation, and higher healthcare costs.44, 61 Acetaminophen is generally safe and is recommended as first‐line therapy in most cases of pain. Nonsteroidal antiinflammatory drugs (NSAIDS) should be used with caution, as the risk of gastrointestinal toxicity increases with age; long‐acting agents such as toradol should be avoided.62 A study of adverse drug reactions causing hospitalization in elderly individuals implicated NSAIDs in 23.5% of cases.63 If a patient has severe pain that limits functional capacity but does not respond to acetaminophen, it is reasonable to consider low‐dose opioids. The 2009 American Geriatrics Society guidelines recommend that opioids be used for severe pain, especially when it limits functional capacity. Opioids should be given orally when possible and started at low doses (for example, 2.5 to 5 milligrams of oxycodone offered every 4 hours as needed). Either oxycodone or morphine can be used as a first‐line, short‐acting opioid, but morphine should be used cautiously in patients with renal insufficiency, as toxic metabolites are renally cleared. Methadone should be used very cautiously and ideally by clinicians experienced in its use because of its long and variable half‐life. Serotonin‐norepinephrine reuptake inhibitors such as duloxetine, and anticonvulsants such as gabapentin, can be helpful adjuncts for neuropathic pain; tricyclics should generally be avoided, because the elderly are particularly sensitive to the anticholinergic side effects (ie, sedation, orthostatic hypotension, urinary retention, constipation) of these agents.61 Nortriptyline, which has the least anticholinergic properties of this medication class, may be the best option if a tricyclic is desired.

8. Hospitalization Can Be an Opportunity for a Thorough Review and Reduction of Outpatient Medications in Collaboration With the Patient's Primary Care Provider

Adverse drug reactions (ADRs) are potentially life‐threatening for all patients, but elderly individuals are disproportionately affected. It is estimated that 30% of hospital admissions of older patients are due to drug‐related toxicity.64 The Beers criteria provide expert consensus on drugs that should either be avoided or used cautiously in the elderly; we have highlighted some of the drugs on the Beers list that are relevant to the hospitalist in Table 4. Notable inclusions on the most recent Beers list include nitrofurantoin, ferrous sulfate at dosages greater than 325 mg per day, doxazosin, and fluoxetine.65 Anticholinergics (such as oxybutynin) and cholinesterase inhibitors (such as donepezil) should not be used together, because the interaction makes them ineffective.

Many ADRs are caused by medications that are not on the Beers list but have narrow therapeutic windows, especially warfarin and insulin; digoxin, which is on the Beers list, is another common culprit in ADRs leading to emergency room visits.66 Medications that are clearly causing ADRs should be discontinued, with the knowledge and input of the primary care provider, and with written documentation on the discharge summary and clear instructions to the patient. Even when a hospital admission is not a result of an ADR, it may provide an opportunity to review the patient's medication list, clarify that the patient is taking medications as directed by their primary care provider, and determine if the list contains medications where risks now outweigh benefits, in which case those medications should be discontinued. Studies have shown that elimination of medications that are associated with falls reduces the risk of future falls.67 Adjustments to patient's medications should be made in close collaboration with the primary care provider and with a clinical pharmacist, if available.

9. Discharge Planning for an Elderly Patient Should Start Early, Be Comprehensive, and Involve the Patient and Caregivers

A successful discharge plan for an elderly patient must start early, take functional status into account, and perhaps most importantly, the planning process should involve the patient and family, if appropriate. One study of patients over 70 discharged from an urban, academic public hospital found that only 10% recalled receiving written discharge instructions, and only 53% who were prescribed a new medication actually had that medication at home.68 Growing evidence suggests that older patients have poorer functional health literacy regarding medications.69 Care transitions are an active area of research, and multiple studies have shown lower rates of rehospitalization with comprehensive transitional care programs involving transition coaches or advance practice nurses providing home visits and follow‐up telephone calls.70, 71 More research is needed in this area to develop simple, cost‐effective care transitions programs. In the meantime, hospitalists can actively involve a multidisciplinary team (pharmacists and social workers, for example) early in the hospitalization, provide more patient‐friendly discharge materials such as those available as part of the Society of Hospital Medicine's BOOST, and place targeted follow‐up phone calls after discharge.52, 7274 Ensuring that a frail elderly patient's primary care provider is aware of the hospitalization may be particularly important in avoiding postdischarge problems.75

10. Elderly Patients are Often Very Clear About Their Preferences for Treatment. Discussing This on Admission Can Help Clarify the Goals of the Hospitalization

The risks and benefits of any intervention being considered should be presented and discussed with the patient in the context of the likelihood of the intervention restoring an acceptable quality of life to the patient. Many common chronic conditions in the elderly such as Parkinson disease, congestive heart failure, and dementia are progressive and life‐limiting. Qualitative studies confirm that elderly patients want to know the likelihood that a proposed intervention will help them return to their previous level of functioning or a level that is acceptable to them.76, 77 In one prospective cohort study, older age was found to correlate with a higher rate of withholding ventilatory support, dialysis, and surgery.78 However, a more recent study has suggested that patient preferences are more dynamic, and that older patients will make decisions based on current health status rather than core values.76 While families should be involved in the process of clarification of goals of care, the patients' own values should be elicited whenever possible, with bedside assessment of decision‐making capacity to ensure that patients are allowed to speak for themselves if they possess decisional capacity for the decision at hand.79

Hospitalists should have a special approach to the elderly patient which takes into account the elder's increased vulnerability to iatrogenic complications and acute functional decline, the presence of geriatric syndromes, and individual preferences. Early assessment of an elderly patient's cognitive and physical functioning, level of pain, fall risk, and preferences for care are necessary for optimal inpatient care and may result in preserved function and a decrease in adverse events.

Recent studies of the growth of the hospitalist movement have confirmed that hospitalists are taking care of an increasing percentage of hospitalized older adults.1, 2 Unfortunately, few hospitalist groups have specific programs or protocols to address the special needs of older patients.3, 4 We were inspired by a top 10 article written by nephrologists for primary care physicians to compile 10 evidence‐based pearls that may be helpful to hospitalists caring for older persons.5

1. Many Health Conditions in Older Patients are Multifactorial and Require a Multifactorial Approach to Care

A geriatric syndrome is a multifactorial condition occurring primarily in frail elderly which is usually due to multiple contributing factors and results from an interaction between patient‐specific impairments and situation‐specific stressors.68 Geriatric syndromes cannot be treated easily with a single intervention; the approach must target each modifiable risk factor. Table 1 illustrates for an example of how this approach differs from the traditional medical approach in the case of falls, a common geriatric syndrome. Hospitalists commonly encounter the geriatric syndromes that either lead to hospitalization, such as falls or dementia, or that can complicate a hospitalization for another condition, such as delirium, falls, or urinary incontinence. Two geriatric syndromes in particular, delirium and falls, are associated with increased length of stay, increased healthcare costs, and substantial morbidity.9, 10 Multifactorial interventions such as the Hospital Elder Life Project (HELP) have been shown to prevent delirium and falls.1114 Studies of the HELP intervention demonstrated benefits on outcomes that are important to hospitalists, including shortened length of stay.10, 15 While implementing these interventions is not possible at every institution, it may be possible to implement some aspects in a targeted fashion (for example, early physical therapy and mobilization to decrease risk of delirium and falls) or to work with hospital administration to implement the larger interventions.

2. Screening Elderly Patients for the Presence of Common Geriatric Syndromes can Improve Care

Comprehensive geriatric assessment, a process of multifactorial health evaluation of the older patient, is an important part of geriatric medicine and has been shown to reduce functional decline.16 While comprehensive geriatric assessment may not be practical in the acute care setting, some basic principles and tools of geriatric assessment, namely screening for geriatric syndromes, can be helpful. Here is one efficient, evidence‐based approach to screening hospitalized elderly patients for cognitive impairment and falls, and then using the results of screening to improve care:

3. Elderly Patients are at Risk for Functional Decline During Hospitalization and Measures Can Be Taken to Prevent This

A cascade to dependency has been described in which the effects of usual aging (eg, fragile skin) and hospitalization (eg, immobilization) interact with each other, often producing complications (eg, pressure ulcers) that can lead to the loss of the ability to live independently.30 Functional decline during hospitalization is common and is associated with poor prognosis. In one study of elderly patients with new Activities of Daily Living (ADL) disability at discharge, over 40% were dead by 12 months after discharge, and only 30% had returned to baseline function.31, 32 Functional status may affect discharge planning, especially if the patient is not able to return safely to his or her previous living environment. Elderly patients are very vulnerable to new ADL dependency and loss of ambulatory ability as a result of a hospitalization.33, 34 The initial evaluation of an elderly patient should always include an inquiry into the patient's functional abilities, including whether the patient requires assistance to perform self‐care (ADL) activities or instrumental activities of daily living (IADLs), and who is available to help at home. We remember ADLs as those activities we learn as a young child (bathing, dressing, feeding, toileting, transfers) and IADLs as activities we learn when we leave our parents' home to live independently (shopping, cooking, laundry, housekeeping, managing money, using public transportation). Patients in assisted living facilities and adult family homes receive varying degrees of help with ADLs and IADLs, and no particular level of assistance can be assumed; assisted living residents may be at higher risk of functional decline during hospitalization than community‐dwelling persons.35

Acute Care of Elderly (ACE) units have been shown to reduce functional disability and discharge to long‐term care settings, with length of stay and hospital charges similar to that of usual care.36 Most hospitals do not have ACE units, but implementing some components of the intervention, such as early physical and occupational therapy, early discharge planning, early mobility, and adequate nutrition may reduce functional disability. A Cochrane review found a small decrease in length of stay of about a day among elderly patients who participated in a structured exercise program, which could be extrapolated to support the usefulness of increased mobility and early physical therapy.37

4. Delirium is a Common but Serious Condition Among Hospitalized Elderly Patients and in Some Cases Can Be Prevented

The incidence of delirium appears to be as high as 60% in hospitalized elderly patients with multiple risk factors for this condition.38, 39 Delirium predicts longer hospital stay, increases likelihood of discharge to a skilled nursing facility, and is a marker for significant morbidity and mortality.4042 Cognitive screening, as discussed above, can help determine who is at risk for delirium, and the Confusion Assessment Method (CAM) is becoming more widely used as a bedside screening tool for detecting delirium.43 Other important risk factors for delirium in addition to preexisting cognitive impairment include age over 65, prior delirium, polypharmacy, functional dependence, and sensory impairment.44 A landmark randomized controlled trial by Sharon Inouye et al. showed that delirium can often be prevented in high‐risk patients by ensuring frequent reorientation, maintenance of the patient's usual sleep‐wake cycle, early mobilization, adequate nutrition and hydration, and regular use of sensory aids such as glasses and hearing aids.11

When delirium does occur despite preventive efforts, it should trigger a thorough investigation for an underlying cause. Common contributing factors to delirium in hospitalized patients include infections such as urinary tract infections or hospital‐acquired pneumonia, pain, electrolyte abnormalities, cardiac ischemia, medication side effects, and urinary retention or constipation. Any psychoactive or anticholinergic medication can contribute to, or exacerbate, delirium; common culprits include diphenhydramine, benzodiazepines, and muscle relaxants.44 Although one or more treatable underlying causes should always be sought, many cases of delirium in the hospital are multifactorial.

If pharmacologic treatment for delirium is necessary, low‐dose haloperidol is the first‐line agent, starting with 0.25 mg intravenously or 0.5 mg by mouth, nightly to twice a day. A recent systematic review supported the use of haloperidol as a first‐line agent in the acute setting; second‐generation antipsychotics are an alternative, but studies have shown no benefits of these agents over haloperidol in terms of safety or efficacy.45 Physical restraints should be avoided in delirious patients, as they may actually worsen delirium and have not been proven to reduce falls or secondary injury.46

5. Treating Nondementia Illnesses in Hospitalized Elders With Dementia Requires Consideration of the Patient's Limited Life Expectancy and Cognitive Deficits

Elderly patients with dementia are frequently hospitalized for medical illness and pose special challenges to the hospitalist. Patients with dementia may not be able to accurately report symptoms and side effects of therapy, and may lack decisional capacity. The clinician should also carefully consider the benefits and burdens of a proposed therapy or diagnostic test, taking into account the patient's cognitive deficits and limited life expectancy.47 The median postdiagnosis life expectancy of a patient with Alzheimer disease is about 4 years for men and about 6 years for women, with a range from about 2 to 9 years, according to population‐based studies of incident Alzheimer dementia.48, 49 In a patient with early or mild dementia, the hospitalist may first need to establish whether the patient does indeed have dementia. It is also important to question family about how the patient is managing at home so that appropriate discharge plans can be made.

Any intervention such as surgery or intubation in a patient with dementia should be considered carefully in the context of the patient's dementia, keeping in mind the remaining life expectancy, increased risk for delirium after surgery, and potential difficulty with adherence to postoperative precautions or participation in rehabilitation. Invasive procedures such as mechanical ventilation or central line placement may not be indicated in patients with advanced dementia. In one prospective cohort study, patients with advanced dementia admitted to the hospital for hip fractures or pneumonia had much higher mortality than those without dementia, despite having equal rates of procedures such as mechanical ventilation and central line placement.50

A common scenario in a patient with advanced dementia is the patient presenting with decreased intake and dysphagia; family and/or caregivers inquire about enteral tube feeding and/or long‐term intravenous hydration. This situation requires a thoughtfully presented, informative discussion with the family about artificial feeding in advanced dementia. There is no evidence that artificial feeding improves outcomes, and a recent Cochrane systematic review found insufficient evidence to suggest that enteral tube feeding is beneficial in patients with dementia.5153 Instead, dementia patients at the end of their lives benefit from a palliative approach, which would include hand‐feeding for comfort if the patient indicates hunger.54

6. Frail Elderly Patients are at High Risk for Iatrogenic Complications During Hospitalization

Frail elders are at increased risk for iatrogenic complications, including surgical‐ and procedure‐related events, adverse drug events, nosocomial infections, pressure ulcers, and falls.5557 In the Harvard Medical Practice Study, a retrospective study of adverse events in 30,000 patients, those age 65 and over accounted for 27% of the hospitalized population but 43% of the adverse events. In this study, four types of adverse events occurred at least twice as often in older patients: fractures, falls, nontechnical postoperative complications, and adverse events related to noninvasive treatments.58 The risk of hospital‐acquired infection also rises dramatically with age; risk is ten times higher in patients over 70 than those aged 49 and under, with urinary tract infections and surgical site infections the most common.59 The oldest, most seriously ill and most functionally impaired elderly patients are at particularly high risk of cascade iatrogenesis, where one medical intervention triggers a series of adverse events.60 Frail elderly patients are at greater risk for adverse events during hospitalization, and careful consideration of the need for all diagnostic tests and procedures may reduce risks. Table 3 lists the iatrogenic complications that disproportionately affect the elderly.

7. Pain Should Be Aggressively Identified and Appropriately Treated

Adequate treatment of pain in the elderly can improve functional status, mobility, and mood. Clinicians are understandably wary of prescribing opioids in the elderly, but undertreatment of pain is also common and in hospitalized patients can lead to delirium, delays in rehabilitation, and higher healthcare costs.44, 61 Acetaminophen is generally safe and is recommended as first‐line therapy in most cases of pain. Nonsteroidal antiinflammatory drugs (NSAIDS) should be used with caution, as the risk of gastrointestinal toxicity increases with age; long‐acting agents such as toradol should be avoided.62 A study of adverse drug reactions causing hospitalization in elderly individuals implicated NSAIDs in 23.5% of cases.63 If a patient has severe pain that limits functional capacity but does not respond to acetaminophen, it is reasonable to consider low‐dose opioids. The 2009 American Geriatrics Society guidelines recommend that opioids be used for severe pain, especially when it limits functional capacity. Opioids should be given orally when possible and started at low doses (for example, 2.5 to 5 milligrams of oxycodone offered every 4 hours as needed). Either oxycodone or morphine can be used as a first‐line, short‐acting opioid, but morphine should be used cautiously in patients with renal insufficiency, as toxic metabolites are renally cleared. Methadone should be used very cautiously and ideally by clinicians experienced in its use because of its long and variable half‐life. Serotonin‐norepinephrine reuptake inhibitors such as duloxetine, and anticonvulsants such as gabapentin, can be helpful adjuncts for neuropathic pain; tricyclics should generally be avoided, because the elderly are particularly sensitive to the anticholinergic side effects (ie, sedation, orthostatic hypotension, urinary retention, constipation) of these agents.61 Nortriptyline, which has the least anticholinergic properties of this medication class, may be the best option if a tricyclic is desired.

8. Hospitalization Can Be an Opportunity for a Thorough Review and Reduction of Outpatient Medications in Collaboration With the Patient's Primary Care Provider

Adverse drug reactions (ADRs) are potentially life‐threatening for all patients, but elderly individuals are disproportionately affected. It is estimated that 30% of hospital admissions of older patients are due to drug‐related toxicity.64 The Beers criteria provide expert consensus on drugs that should either be avoided or used cautiously in the elderly; we have highlighted some of the drugs on the Beers list that are relevant to the hospitalist in Table 4. Notable inclusions on the most recent Beers list include nitrofurantoin, ferrous sulfate at dosages greater than 325 mg per day, doxazosin, and fluoxetine.65 Anticholinergics (such as oxybutynin) and cholinesterase inhibitors (such as donepezil) should not be used together, because the interaction makes them ineffective.

Many ADRs are caused by medications that are not on the Beers list but have narrow therapeutic windows, especially warfarin and insulin; digoxin, which is on the Beers list, is another common culprit in ADRs leading to emergency room visits.66 Medications that are clearly causing ADRs should be discontinued, with the knowledge and input of the primary care provider, and with written documentation on the discharge summary and clear instructions to the patient. Even when a hospital admission is not a result of an ADR, it may provide an opportunity to review the patient's medication list, clarify that the patient is taking medications as directed by their primary care provider, and determine if the list contains medications where risks now outweigh benefits, in which case those medications should be discontinued. Studies have shown that elimination of medications that are associated with falls reduces the risk of future falls.67 Adjustments to patient's medications should be made in close collaboration with the primary care provider and with a clinical pharmacist, if available.

9. Discharge Planning for an Elderly Patient Should Start Early, Be Comprehensive, and Involve the Patient and Caregivers

A successful discharge plan for an elderly patient must start early, take functional status into account, and perhaps most importantly, the planning process should involve the patient and family, if appropriate. One study of patients over 70 discharged from an urban, academic public hospital found that only 10% recalled receiving written discharge instructions, and only 53% who were prescribed a new medication actually had that medication at home.68 Growing evidence suggests that older patients have poorer functional health literacy regarding medications.69 Care transitions are an active area of research, and multiple studies have shown lower rates of rehospitalization with comprehensive transitional care programs involving transition coaches or advance practice nurses providing home visits and follow‐up telephone calls.70, 71 More research is needed in this area to develop simple, cost‐effective care transitions programs. In the meantime, hospitalists can actively involve a multidisciplinary team (pharmacists and social workers, for example) early in the hospitalization, provide more patient‐friendly discharge materials such as those available as part of the Society of Hospital Medicine's BOOST, and place targeted follow‐up phone calls after discharge.52, 7274 Ensuring that a frail elderly patient's primary care provider is aware of the hospitalization may be particularly important in avoiding postdischarge problems.75

10. Elderly Patients are Often Very Clear About Their Preferences for Treatment. Discussing This on Admission Can Help Clarify the Goals of the Hospitalization

The risks and benefits of any intervention being considered should be presented and discussed with the patient in the context of the likelihood of the intervention restoring an acceptable quality of life to the patient. Many common chronic conditions in the elderly such as Parkinson disease, congestive heart failure, and dementia are progressive and life‐limiting. Qualitative studies confirm that elderly patients want to know the likelihood that a proposed intervention will help them return to their previous level of functioning or a level that is acceptable to them.76, 77 In one prospective cohort study, older age was found to correlate with a higher rate of withholding ventilatory support, dialysis, and surgery.78 However, a more recent study has suggested that patient preferences are more dynamic, and that older patients will make decisions based on current health status rather than core values.76 While families should be involved in the process of clarification of goals of care, the patients' own values should be elicited whenever possible, with bedside assessment of decision‐making capacity to ensure that patients are allowed to speak for themselves if they possess decisional capacity for the decision at hand.79

Hospitalists should have a special approach to the elderly patient which takes into account the elder's increased vulnerability to iatrogenic complications and acute functional decline, the presence of geriatric syndromes, and individual preferences. Early assessment of an elderly patient's cognitive and physical functioning, level of pain, fall risk, and preferences for care are necessary for optimal inpatient care and may result in preserved function and a decrease in adverse events.

Recent studies of the growth of the hospitalist movement have confirmed that hospitalists are taking care of an increasing percentage of hospitalized older adults.1, 2 Unfortunately, few hospitalist groups have specific programs or protocols to address the special needs of older patients.3, 4 We were inspired by a top 10 article written by nephrologists for primary care physicians to compile 10 evidence‐based pearls that may be helpful to hospitalists caring for older persons.5

1. Many Health Conditions in Older Patients are Multifactorial and Require a Multifactorial Approach to Care

A geriatric syndrome is a multifactorial condition occurring primarily in frail elderly which is usually due to multiple contributing factors and results from an interaction between patient‐specific impairments and situation‐specific stressors.68 Geriatric syndromes cannot be treated easily with a single intervention; the approach must target each modifiable risk factor. Table 1 illustrates for an example of how this approach differs from the traditional medical approach in the case of falls, a common geriatric syndrome. Hospitalists commonly encounter the geriatric syndromes that either lead to hospitalization, such as falls or dementia, or that can complicate a hospitalization for another condition, such as delirium, falls, or urinary incontinence. Two geriatric syndromes in particular, delirium and falls, are associated with increased length of stay, increased healthcare costs, and substantial morbidity.9, 10 Multifactorial interventions such as the Hospital Elder Life Project (HELP) have been shown to prevent delirium and falls.1114 Studies of the HELP intervention demonstrated benefits on outcomes that are important to hospitalists, including shortened length of stay.10, 15 While implementing these interventions is not possible at every institution, it may be possible to implement some aspects in a targeted fashion (for example, early physical therapy and mobilization to decrease risk of delirium and falls) or to work with hospital administration to implement the larger interventions.

2. Screening Elderly Patients for the Presence of Common Geriatric Syndromes can Improve Care

Comprehensive geriatric assessment, a process of multifactorial health evaluation of the older patient, is an important part of geriatric medicine and has been shown to reduce functional decline.16 While comprehensive geriatric assessment may not be practical in the acute care setting, some basic principles and tools of geriatric assessment, namely screening for geriatric syndromes, can be helpful. Here is one efficient, evidence‐based approach to screening hospitalized elderly patients for cognitive impairment and falls, and then using the results of screening to improve care:

3. Elderly Patients are at Risk for Functional Decline During Hospitalization and Measures Can Be Taken to Prevent This

A cascade to dependency has been described in which the effects of usual aging (eg, fragile skin) and hospitalization (eg, immobilization) interact with each other, often producing complications (eg, pressure ulcers) that can lead to the loss of the ability to live independently.30 Functional decline during hospitalization is common and is associated with poor prognosis. In one study of elderly patients with new Activities of Daily Living (ADL) disability at discharge, over 40% were dead by 12 months after discharge, and only 30% had returned to baseline function.31, 32 Functional status may affect discharge planning, especially if the patient is not able to return safely to his or her previous living environment. Elderly patients are very vulnerable to new ADL dependency and loss of ambulatory ability as a result of a hospitalization.33, 34 The initial evaluation of an elderly patient should always include an inquiry into the patient's functional abilities, including whether the patient requires assistance to perform self‐care (ADL) activities or instrumental activities of daily living (IADLs), and who is available to help at home. We remember ADLs as those activities we learn as a young child (bathing, dressing, feeding, toileting, transfers) and IADLs as activities we learn when we leave our parents' home to live independently (shopping, cooking, laundry, housekeeping, managing money, using public transportation). Patients in assisted living facilities and adult family homes receive varying degrees of help with ADLs and IADLs, and no particular level of assistance can be assumed; assisted living residents may be at higher risk of functional decline during hospitalization than community‐dwelling persons.35

Acute Care of Elderly (ACE) units have been shown to reduce functional disability and discharge to long‐term care settings, with length of stay and hospital charges similar to that of usual care.36 Most hospitals do not have ACE units, but implementing some components of the intervention, such as early physical and occupational therapy, early discharge planning, early mobility, and adequate nutrition may reduce functional disability. A Cochrane review found a small decrease in length of stay of about a day among elderly patients who participated in a structured exercise program, which could be extrapolated to support the usefulness of increased mobility and early physical therapy.37

4. Delirium is a Common but Serious Condition Among Hospitalized Elderly Patients and in Some Cases Can Be Prevented

The incidence of delirium appears to be as high as 60% in hospitalized elderly patients with multiple risk factors for this condition.38, 39 Delirium predicts longer hospital stay, increases likelihood of discharge to a skilled nursing facility, and is a marker for significant morbidity and mortality.4042 Cognitive screening, as discussed above, can help determine who is at risk for delirium, and the Confusion Assessment Method (CAM) is becoming more widely used as a bedside screening tool for detecting delirium.43 Other important risk factors for delirium in addition to preexisting cognitive impairment include age over 65, prior delirium, polypharmacy, functional dependence, and sensory impairment.44 A landmark randomized controlled trial by Sharon Inouye et al. showed that delirium can often be prevented in high‐risk patients by ensuring frequent reorientation, maintenance of the patient's usual sleep‐wake cycle, early mobilization, adequate nutrition and hydration, and regular use of sensory aids such as glasses and hearing aids.11

When delirium does occur despite preventive efforts, it should trigger a thorough investigation for an underlying cause. Common contributing factors to delirium in hospitalized patients include infections such as urinary tract infections or hospital‐acquired pneumonia, pain, electrolyte abnormalities, cardiac ischemia, medication side effects, and urinary retention or constipation. Any psychoactive or anticholinergic medication can contribute to, or exacerbate, delirium; common culprits include diphenhydramine, benzodiazepines, and muscle relaxants.44 Although one or more treatable underlying causes should always be sought, many cases of delirium in the hospital are multifactorial.

If pharmacologic treatment for delirium is necessary, low‐dose haloperidol is the first‐line agent, starting with 0.25 mg intravenously or 0.5 mg by mouth, nightly to twice a day. A recent systematic review supported the use of haloperidol as a first‐line agent in the acute setting; second‐generation antipsychotics are an alternative, but studies have shown no benefits of these agents over haloperidol in terms of safety or efficacy.45 Physical restraints should be avoided in delirious patients, as they may actually worsen delirium and have not been proven to reduce falls or secondary injury.46

5. Treating Nondementia Illnesses in Hospitalized Elders With Dementia Requires Consideration of the Patient's Limited Life Expectancy and Cognitive Deficits

Elderly patients with dementia are frequently hospitalized for medical illness and pose special challenges to the hospitalist. Patients with dementia may not be able to accurately report symptoms and side effects of therapy, and may lack decisional capacity. The clinician should also carefully consider the benefits and burdens of a proposed therapy or diagnostic test, taking into account the patient's cognitive deficits and limited life expectancy.47 The median postdiagnosis life expectancy of a patient with Alzheimer disease is about 4 years for men and about 6 years for women, with a range from about 2 to 9 years, according to population‐based studies of incident Alzheimer dementia.48, 49 In a patient with early or mild dementia, the hospitalist may first need to establish whether the patient does indeed have dementia. It is also important to question family about how the patient is managing at home so that appropriate discharge plans can be made.

Any intervention such as surgery or intubation in a patient with dementia should be considered carefully in the context of the patient's dementia, keeping in mind the remaining life expectancy, increased risk for delirium after surgery, and potential difficulty with adherence to postoperative precautions or participation in rehabilitation. Invasive procedures such as mechanical ventilation or central line placement may not be indicated in patients with advanced dementia. In one prospective cohort study, patients with advanced dementia admitted to the hospital for hip fractures or pneumonia had much higher mortality than those without dementia, despite having equal rates of procedures such as mechanical ventilation and central line placement.50

A common scenario in a patient with advanced dementia is the patient presenting with decreased intake and dysphagia; family and/or caregivers inquire about enteral tube feeding and/or long‐term intravenous hydration. This situation requires a thoughtfully presented, informative discussion with the family about artificial feeding in advanced dementia. There is no evidence that artificial feeding improves outcomes, and a recent Cochrane systematic review found insufficient evidence to suggest that enteral tube feeding is beneficial in patients with dementia.5153 Instead, dementia patients at the end of their lives benefit from a palliative approach, which would include hand‐feeding for comfort if the patient indicates hunger.54

6. Frail Elderly Patients are at High Risk for Iatrogenic Complications During Hospitalization

Frail elders are at increased risk for iatrogenic complications, including surgical‐ and procedure‐related events, adverse drug events, nosocomial infections, pressure ulcers, and falls.5557 In the Harvard Medical Practice Study, a retrospective study of adverse events in 30,000 patients, those age 65 and over accounted for 27% of the hospitalized population but 43% of the adverse events. In this study, four types of adverse events occurred at least twice as often in older patients: fractures, falls, nontechnical postoperative complications, and adverse events related to noninvasive treatments.58 The risk of hospital‐acquired infection also rises dramatically with age; risk is ten times higher in patients over 70 than those aged 49 and under, with urinary tract infections and surgical site infections the most common.59 The oldest, most seriously ill and most functionally impaired elderly patients are at particularly high risk of cascade iatrogenesis, where one medical intervention triggers a series of adverse events.60 Frail elderly patients are at greater risk for adverse events during hospitalization, and careful consideration of the need for all diagnostic tests and procedures may reduce risks. Table 3 lists the iatrogenic complications that disproportionately affect the elderly.

7. Pain Should Be Aggressively Identified and Appropriately Treated

Adequate treatment of pain in the elderly can improve functional status, mobility, and mood. Clinicians are understandably wary of prescribing opioids in the elderly, but undertreatment of pain is also common and in hospitalized patients can lead to delirium, delays in rehabilitation, and higher healthcare costs.44, 61 Acetaminophen is generally safe and is recommended as first‐line therapy in most cases of pain. Nonsteroidal antiinflammatory drugs (NSAIDS) should be used with caution, as the risk of gastrointestinal toxicity increases with age; long‐acting agents such as toradol should be avoided.62 A study of adverse drug reactions causing hospitalization in elderly individuals implicated NSAIDs in 23.5% of cases.63 If a patient has severe pain that limits functional capacity but does not respond to acetaminophen, it is reasonable to consider low‐dose opioids. The 2009 American Geriatrics Society guidelines recommend that opioids be used for severe pain, especially when it limits functional capacity. Opioids should be given orally when possible and started at low doses (for example, 2.5 to 5 milligrams of oxycodone offered every 4 hours as needed). Either oxycodone or morphine can be used as a first‐line, short‐acting opioid, but morphine should be used cautiously in patients with renal insufficiency, as toxic metabolites are renally cleared. Methadone should be used very cautiously and ideally by clinicians experienced in its use because of its long and variable half‐life. Serotonin‐norepinephrine reuptake inhibitors such as duloxetine, and anticonvulsants such as gabapentin, can be helpful adjuncts for neuropathic pain; tricyclics should generally be avoided, because the elderly are particularly sensitive to the anticholinergic side effects (ie, sedation, orthostatic hypotension, urinary retention, constipation) of these agents.61 Nortriptyline, which has the least anticholinergic properties of this medication class, may be the best option if a tricyclic is desired.

8. Hospitalization Can Be an Opportunity for a Thorough Review and Reduction of Outpatient Medications in Collaboration With the Patient's Primary Care Provider

Adverse drug reactions (ADRs) are potentially life‐threatening for all patients, but elderly individuals are disproportionately affected. It is estimated that 30% of hospital admissions of older patients are due to drug‐related toxicity.64 The Beers criteria provide expert consensus on drugs that should either be avoided or used cautiously in the elderly; we have highlighted some of the drugs on the Beers list that are relevant to the hospitalist in Table 4. Notable inclusions on the most recent Beers list include nitrofurantoin, ferrous sulfate at dosages greater than 325 mg per day, doxazosin, and fluoxetine.65 Anticholinergics (such as oxybutynin) and cholinesterase inhibitors (such as donepezil) should not be used together, because the interaction makes them ineffective.

Many ADRs are caused by medications that are not on the Beers list but have narrow therapeutic windows, especially warfarin and insulin; digoxin, which is on the Beers list, is another common culprit in ADRs leading to emergency room visits.66 Medications that are clearly causing ADRs should be discontinued, with the knowledge and input of the primary care provider, and with written documentation on the discharge summary and clear instructions to the patient. Even when a hospital admission is not a result of an ADR, it may provide an opportunity to review the patient's medication list, clarify that the patient is taking medications as directed by their primary care provider, and determine if the list contains medications where risks now outweigh benefits, in which case those medications should be discontinued. Studies have shown that elimination of medications that are associated with falls reduces the risk of future falls.67 Adjustments to patient's medications should be made in close collaboration with the primary care provider and with a clinical pharmacist, if available.

9. Discharge Planning for an Elderly Patient Should Start Early, Be Comprehensive, and Involve the Patient and Caregivers

A successful discharge plan for an elderly patient must start early, take functional status into account, and perhaps most importantly, the planning process should involve the patient and family, if appropriate. One study of patients over 70 discharged from an urban, academic public hospital found that only 10% recalled receiving written discharge instructions, and only 53% who were prescribed a new medication actually had that medication at home.68 Growing evidence suggests that older patients have poorer functional health literacy regarding medications.69 Care transitions are an active area of research, and multiple studies have shown lower rates of rehospitalization with comprehensive transitional care programs involving transition coaches or advance practice nurses providing home visits and follow‐up telephone calls.70, 71 More research is needed in this area to develop simple, cost‐effective care transitions programs. In the meantime, hospitalists can actively involve a multidisciplinary team (pharmacists and social workers, for example) early in the hospitalization, provide more patient‐friendly discharge materials such as those available as part of the Society of Hospital Medicine's BOOST, and place targeted follow‐up phone calls after discharge.52, 7274 Ensuring that a frail elderly patient's primary care provider is aware of the hospitalization may be particularly important in avoiding postdischarge problems.75

10. Elderly Patients are Often Very Clear About Their Preferences for Treatment. Discussing This on Admission Can Help Clarify the Goals of the Hospitalization

The risks and benefits of any intervention being considered should be presented and discussed with the patient in the context of the likelihood of the intervention restoring an acceptable quality of life to the patient. Many common chronic conditions in the elderly such as Parkinson disease, congestive heart failure, and dementia are progressive and life‐limiting. Qualitative studies confirm that elderly patients want to know the likelihood that a proposed intervention will help them return to their previous level of functioning or a level that is acceptable to them.76, 77 In one prospective cohort study, older age was found to correlate with a higher rate of withholding ventilatory support, dialysis, and surgery.78 However, a more recent study has suggested that patient preferences are more dynamic, and that older patients will make decisions based on current health status rather than core values.76 While families should be involved in the process of clarification of goals of care, the patients' own values should be elicited whenever possible, with bedside assessment of decision‐making capacity to ensure that patients are allowed to speak for themselves if they possess decisional capacity for the decision at hand.79

Hospitalists should have a special approach to the elderly patient which takes into account the elder's increased vulnerability to iatrogenic complications and acute functional decline, the presence of geriatric syndromes, and individual preferences. Early assessment of an elderly patient's cognitive and physical functioning, level of pain, fall risk, and preferences for care are necessary for optimal inpatient care and may result in preserved function and a decrease in adverse events.

Among Gram‐negative pathogens, Escherichia coli is one of the most common causes of both community‐acquired and nosocomial bloodstream infections.1, 2 Fluoroquinolone resistance among E coli clinical isolates was first observed in patients with hematologic malignancies3, 4 but is no longer restricted to this population5 and has spread in the community.6 Multiple studies have examined potential risk factors for fluoroquinolone resistance in E coli infections.79 Prior fluoroquinolone use stands out as a repeatedly documented risk factor.10 In E coli bacteremias, data on the impact of fluoroquinolone resistance on mortality are limited.9, 11, 12 Ortega and colleagues performed a landmark analysis of a large dataset stemming from bacteremia surveillance data collected over 17 years.9 They found that mortality was associated with both shock and inappropriate empirical treatment, and that inappropriate empirical treatment in turn was linked to fluoroquinolone resistance. Laupland et al reported results from a population‐based study in Canada, and could elicit age, comorbidities, ciprofloxacin resistance, and a nonurinary focus of infection as risk factors for mortality.11 Lastly, a smaller study by Cheong et al found a high APACHE II score (ie, high severity of illness) but not fluoroquinolone resistance (P = .08) to be associated with poor outcomes.12

The prevalence of fluoroquinolone resistance among E coli isolates in our hospital has surpassed 20%. In this setting, an adjustment of recommendations for empirical treatment may become necessary. This is particularly important since some studies have demonstrated that inappropriate empiric therapy in patients with bloodstream infection results in higher mortality.13 The aim of this case‐control study was to determine the impact of fluoroquinolone resistance on in‐hospital mortality among patients with E coli bacteremia.

METHODS

RESULTS

DISCUSSION

This case‐control study represents one of the larger studies on fluoroquinolone‐resistant E coli bacteremia and adds to the growing body of literature on the impact of fluoroquinolone resistance and other factors predictive of mortality. In multivariate analysis, fluoroquinolone resistance was associated with in‐hospital mortality from E coli bacteremia, as were the comorbid illnesses cirrhosis and cardiac dysfunction.

Among the risk factors for fluoroquinolone‐resistant E coli bacteremia described in the literature are previous fluoroquinolone exposure,9, 10, 12 nosocomial acquisition,9 presence of a urinary catheter,9 urinary source of bacteremia, previous surgery, and comorbid illnesses.10 If the scope of infections was not limited to the bloodstream, other factors like structural changes in the urinary tract,7 recurrent urinary tract infections,14 residence in a long‐term care facility, age, and prior exposure to aminoglycosides8 were also reported. In our study, previous fluoroquinolone exposure, residence in a long‐term care facility, recent hospitalization, nosocomial acquisition of infection, were associated with cases with fluoroquinolone‐resistant isolates. We also found that a larger proportion of the cases received corticosteroids before the episode of bacteremia; to our knowledge, this finding has not been reported before.

In contrast to results on fluoroquinolone resistance in both E coli and Klebsiella pneumoniae infections reported by Lautenbach et al,13 those patients in our study who were infected with the fluoroquinolone‐resistant phenotype were not more likely to receive inappropriate empiric therapy than control patients (52% vs. 55%; P = .8). This finding may be explained by the relatively low level of appropriate treatment even in the patients with fluoroquinolone‐susceptible E coli. For comparison, Lautenbach and colleagues saw a much higher percentage, 90%, of the patients with the susceptible phenotype received appropriate therapy.13 The high proportion of inappropriate empiric therapy in our study may have played a role in the relatively high overall mortality rate (17%) that we observed. This is in contrast to a recent retrospective study on appropriateness of therapy for E coli bacteremia which found that only 16% of bacteremia episodes (106 of 663) were inadequately treated,15 and the overall mortality was as low as 5%. A significant number of patients in our study, however, did not receive any antimicrobial therapy until blood cultures results were reported as positive and these situations therefore did not meet the definition for appropriate empiric therapy. These same patients did not have all the signs and symptoms associated with sepsis syndrome and so were not treated with any antimicrobials until blood cultures were reported to be positive. Eventually, Lautenbach et al stated thatafter adjusting for inadequate treatmentthere was no longer an association between fluoroquinolone resistance and mortality in their population.13 On the other hand, a recently published landmark Spanish study on factors influencing the outcome of 4758 E coli bacteremias reported that inappropriate treatment and shock were the two independent predictors of mortality; however, inappropriate treatment was significantly associated with fluoroquinolone resistance.9 Laupland et al, who performed a population‐based study of E coli bacteremias in Canada, elicited ciprofloxacin resistance as an independent predictor of mortality but the authors did not adjust for appropriateness of treatment.11 In that study, a urinary source of the bacteremia and younger age turned out to be protective. We studied both variables in our study but failed to confirm their findings.

Previous studies have reported that fluoroquinolone‐resistant clinical isolates collected from urine samples contain less virulence factors compared with the fluoroquinolone‐susceptible E coli.1618 Although no data are available specifically for bloodstream isolates, our finding of increased mortality in fluoroquinolone‐resistant isolates is not consistent with these conceptual findings among E coli isolates from the urinary tract. A delay in delivering the appropriate therapy cannot account for this, because the proportion of patients who did not receive appropriate therapy within 48 hours of the blood cultures being drawn was similar among the cases and control patients. Nevertheless, it would be interesting to assess virulence factor profiles in E coli bloodstream isolates that are stratified by their susceptibility to fluoroquinolones. The pathogens in our cohort may possess unidentified virulence mechanisms as well as resistance mechanisms toward fluoroquinolones. Because only patients with bacteremia were included in this study, it is possible that we have selected for a more virulent subpopulation of E coli strains capable of more invasive disease than uropathogenic isolates. In the past, several small studies have indeed demonstrated differences in virulence factor profiles when comparing E coli isolates strictly from urinary tract infections with those urinary tract isolates causing bacteremia.19, 20 Another potential explanation for the observed association between fluoroquinolone‐resistance and increased mortality may be unmeasured severity of illness among the cases. The cases were more likely to have a health‐care associated infection, more likely to come from a long‐term care facility or have been previously admitted, or associated with a longer length of stay. We did account for severity of illness and risk of mortality from comorbidities using both the APACHE II score and the Charlson Index of Co‐Morbidity, but it is still possible these indices may not be adequate to account for the differences between the cases and controls.

We found a higher crude mortality among patients with fluoroquinolone‐resistant E coli bacteremia than in patients with fluoroquinolone‐susceptible E coli (26% vs. 8%; P = .002). This is similar to the crude mortality rate for fluoroquinolone‐resistant E coli bacteremia reported by Cheong et al (30% in patients with fluoroquinolone‐resistant E coli bacteremia vs. 16% in patients with fluoroquinolone‐susceptible E coli; P = .08).12 In the Cheong et al article, only a high APACHE II score remained an independent risk factor for mortality. And although both Laupland et al and Ortega et al used regression analyses to describe factors associated with mortality, the respective crude mortality rates stratified by fluoroquinolone susceptibility were not reported.9, 11 In our study, the univariate analysis yielded both APACHE II score and Charlson comorbidity score as predictors for in‐hospital mortality but not in the multivariate analysis.

Our findings have important implications in the treatment of Gram‐negative infections. E coli is one of most common Gram‐negative bacilli causing hospital‐acquired infections and is the most common pathogen associated with community‐acquired urinary tract infections. The latest Infectious Diseases Society of America (IDSA) guideline for treatment of acute pyelonephritis recommends the use of fluoroquinolones for empiric therapy of acute pyelonephritis.21 Unfortunately, these guidelines were published in 1999, before reports of the rise in fluoroquinolone resistance among E coli isolates were available. The majority of the patients in our cohort (60%) developed a bacteremia following a complicated urinary tract infection and they would have received a fluoroquinolone for empiric therapy. The risk of providing inappropriate empiric therapy to patients with E coli bacteremia is evident, especially since inappropriate treatment was delivered in approximately half of our patients.

Another group of patients who are at high risk for mortality and are also at risk for development of fluoroquinolone‐resistant E coli bacteremia are patients with liver cirrhosis. Gram‐negative bacilli like E coli are common pathogens implicated in spontaneous bacterial peritonitis (SBP) in these patients.22 Since some patients with cirrhosis are exposed to fluoroquinolones for primary or secondary prophylaxis against SBP,23 they are likely to be colonized and eventually can develop infections with fluoroquinolone‐resistant E coli isolates.8 It may be prudent to select an antimicrobial class that is different from fluoroquinolones in treating sepsis syndrome in this patient population.

Our study has a few limitations. One is that this is a retrospective case‐control study and the accuracy of the data is dependent on the availability of complete medical records. All the admitted patients' charts or medical records were available for review in this study, so we were able to minimize any potential bias that may arise from missing data. This study was conducted at an academic medical center and results may not be generalizable to other healthcare institutions. The rate of inappropriate therapy was particularly high in this study, but it is unlikely to have influenced the final results since this was observed in both cases and controls.

On the basis of our finding that fluoroquinolone resistance is an independent predictor for mortality, we recommend that an alternative antimicrobial class rather than fluoroquinolones be initiated as empiric therapy in patients who are suspected to have an invasive E coli infection. The reason for this increased mortality in fluoroquinolone‐resistant E coli is, at least in our study, not related to inappropriate therapy or a higher severity of illness and may be related to more virulent organisms.

Among Gram‐negative pathogens, Escherichia coli is one of the most common causes of both community‐acquired and nosocomial bloodstream infections.1, 2 Fluoroquinolone resistance among E coli clinical isolates was first observed in patients with hematologic malignancies3, 4 but is no longer restricted to this population5 and has spread in the community.6 Multiple studies have examined potential risk factors for fluoroquinolone resistance in E coli infections.79 Prior fluoroquinolone use stands out as a repeatedly documented risk factor.10 In E coli bacteremias, data on the impact of fluoroquinolone resistance on mortality are limited.9, 11, 12 Ortega and colleagues performed a landmark analysis of a large dataset stemming from bacteremia surveillance data collected over 17 years.9 They found that mortality was associated with both shock and inappropriate empirical treatment, and that inappropriate empirical treatment in turn was linked to fluoroquinolone resistance. Laupland et al reported results from a population‐based study in Canada, and could elicit age, comorbidities, ciprofloxacin resistance, and a nonurinary focus of infection as risk factors for mortality.11 Lastly, a smaller study by Cheong et al found a high APACHE II score (ie, high severity of illness) but not fluoroquinolone resistance (P = .08) to be associated with poor outcomes.12

The prevalence of fluoroquinolone resistance among E coli isolates in our hospital has surpassed 20%. In this setting, an adjustment of recommendations for empirical treatment may become necessary. This is particularly important since some studies have demonstrated that inappropriate empiric therapy in patients with bloodstream infection results in higher mortality.13 The aim of this case‐control study was to determine the impact of fluoroquinolone resistance on in‐hospital mortality among patients with E coli bacteremia.

METHODS

RESULTS

DISCUSSION

This case‐control study represents one of the larger studies on fluoroquinolone‐resistant E coli bacteremia and adds to the growing body of literature on the impact of fluoroquinolone resistance and other factors predictive of mortality. In multivariate analysis, fluoroquinolone resistance was associated with in‐hospital mortality from E coli bacteremia, as were the comorbid illnesses cirrhosis and cardiac dysfunction.

Among the risk factors for fluoroquinolone‐resistant E coli bacteremia described in the literature are previous fluoroquinolone exposure,9, 10, 12 nosocomial acquisition,9 presence of a urinary catheter,9 urinary source of bacteremia, previous surgery, and comorbid illnesses.10 If the scope of infections was not limited to the bloodstream, other factors like structural changes in the urinary tract,7 recurrent urinary tract infections,14 residence in a long‐term care facility, age, and prior exposure to aminoglycosides8 were also reported. In our study, previous fluoroquinolone exposure, residence in a long‐term care facility, recent hospitalization, nosocomial acquisition of infection, were associated with cases with fluoroquinolone‐resistant isolates. We also found that a larger proportion of the cases received corticosteroids before the episode of bacteremia; to our knowledge, this finding has not been reported before.

In contrast to results on fluoroquinolone resistance in both E coli and Klebsiella pneumoniae infections reported by Lautenbach et al,13 those patients in our study who were infected with the fluoroquinolone‐resistant phenotype were not more likely to receive inappropriate empiric therapy than control patients (52% vs. 55%; P = .8). This finding may be explained by the relatively low level of appropriate treatment even in the patients with fluoroquinolone‐susceptible E coli. For comparison, Lautenbach and colleagues saw a much higher percentage, 90%, of the patients with the susceptible phenotype received appropriate therapy.13 The high proportion of inappropriate empiric therapy in our study may have played a role in the relatively high overall mortality rate (17%) that we observed. This is in contrast to a recent retrospective study on appropriateness of therapy for E coli bacteremia which found that only 16% of bacteremia episodes (106 of 663) were inadequately treated,15 and the overall mortality was as low as 5%. A significant number of patients in our study, however, did not receive any antimicrobial therapy until blood cultures results were reported as positive and these situations therefore did not meet the definition for appropriate empiric therapy. These same patients did not have all the signs and symptoms associated with sepsis syndrome and so were not treated with any antimicrobials until blood cultures were reported to be positive. Eventually, Lautenbach et al stated thatafter adjusting for inadequate treatmentthere was no longer an association between fluoroquinolone resistance and mortality in their population.13 On the other hand, a recently published landmark Spanish study on factors influencing the outcome of 4758 E coli bacteremias reported that inappropriate treatment and shock were the two independent predictors of mortality; however, inappropriate treatment was significantly associated with fluoroquinolone resistance.9 Laupland et al, who performed a population‐based study of E coli bacteremias in Canada, elicited ciprofloxacin resistance as an independent predictor of mortality but the authors did not adjust for appropriateness of treatment.11 In that study, a urinary source of the bacteremia and younger age turned out to be protective. We studied both variables in our study but failed to confirm their findings.

Previous studies have reported that fluoroquinolone‐resistant clinical isolates collected from urine samples contain less virulence factors compared with the fluoroquinolone‐susceptible E coli.1618 Although no data are available specifically for bloodstream isolates, our finding of increased mortality in fluoroquinolone‐resistant isolates is not consistent with these conceptual findings among E coli isolates from the urinary tract. A delay in delivering the appropriate therapy cannot account for this, because the proportion of patients who did not receive appropriate therapy within 48 hours of the blood cultures being drawn was similar among the cases and control patients. Nevertheless, it would be interesting to assess virulence factor profiles in E coli bloodstream isolates that are stratified by their susceptibility to fluoroquinolones. The pathogens in our cohort may possess unidentified virulence mechanisms as well as resistance mechanisms toward fluoroquinolones. Because only patients with bacteremia were included in this study, it is possible that we have selected for a more virulent subpopulation of E coli strains capable of more invasive disease than uropathogenic isolates. In the past, several small studies have indeed demonstrated differences in virulence factor profiles when comparing E coli isolates strictly from urinary tract infections with those urinary tract isolates causing bacteremia.19, 20 Another potential explanation for the observed association between fluoroquinolone‐resistance and increased mortality may be unmeasured severity of illness among the cases. The cases were more likely to have a health‐care associated infection, more likely to come from a long‐term care facility or have been previously admitted, or associated with a longer length of stay. We did account for severity of illness and risk of mortality from comorbidities using both the APACHE II score and the Charlson Index of Co‐Morbidity, but it is still possible these indices may not be adequate to account for the differences between the cases and controls.

We found a higher crude mortality among patients with fluoroquinolone‐resistant E coli bacteremia than in patients with fluoroquinolone‐susceptible E coli (26% vs. 8%; P = .002). This is similar to the crude mortality rate for fluoroquinolone‐resistant E coli bacteremia reported by Cheong et al (30% in patients with fluoroquinolone‐resistant E coli bacteremia vs. 16% in patients with fluoroquinolone‐susceptible E coli; P = .08).12 In the Cheong et al article, only a high APACHE II score remained an independent risk factor for mortality. And although both Laupland et al and Ortega et al used regression analyses to describe factors associated with mortality, the respective crude mortality rates stratified by fluoroquinolone susceptibility were not reported.9, 11 In our study, the univariate analysis yielded both APACHE II score and Charlson comorbidity score as predictors for in‐hospital mortality but not in the multivariate analysis.

Our findings have important implications in the treatment of Gram‐negative infections. E coli is one of most common Gram‐negative bacilli causing hospital‐acquired infections and is the most common pathogen associated with community‐acquired urinary tract infections. The latest Infectious Diseases Society of America (IDSA) guideline for treatment of acute pyelonephritis recommends the use of fluoroquinolones for empiric therapy of acute pyelonephritis.21 Unfortunately, these guidelines were published in 1999, before reports of the rise in fluoroquinolone resistance among E coli isolates were available. The majority of the patients in our cohort (60%) developed a bacteremia following a complicated urinary tract infection and they would have received a fluoroquinolone for empiric therapy. The risk of providing inappropriate empiric therapy to patients with E coli bacteremia is evident, especially since inappropriate treatment was delivered in approximately half of our patients.

Another group of patients who are at high risk for mortality and are also at risk for development of fluoroquinolone‐resistant E coli bacteremia are patients with liver cirrhosis. Gram‐negative bacilli like E coli are common pathogens implicated in spontaneous bacterial peritonitis (SBP) in these patients.22 Since some patients with cirrhosis are exposed to fluoroquinolones for primary or secondary prophylaxis against SBP,23 they are likely to be colonized and eventually can develop infections with fluoroquinolone‐resistant E coli isolates.8 It may be prudent to select an antimicrobial class that is different from fluoroquinolones in treating sepsis syndrome in this patient population.

Our study has a few limitations. One is that this is a retrospective case‐control study and the accuracy of the data is dependent on the availability of complete medical records. All the admitted patients' charts or medical records were available for review in this study, so we were able to minimize any potential bias that may arise from missing data. This study was conducted at an academic medical center and results may not be generalizable to other healthcare institutions. The rate of inappropriate therapy was particularly high in this study, but it is unlikely to have influenced the final results since this was observed in both cases and controls.

On the basis of our finding that fluoroquinolone resistance is an independent predictor for mortality, we recommend that an alternative antimicrobial class rather than fluoroquinolones be initiated as empiric therapy in patients who are suspected to have an invasive E coli infection. The reason for this increased mortality in fluoroquinolone‐resistant E coli is, at least in our study, not related to inappropriate therapy or a higher severity of illness and may be related to more virulent organisms.

Among Gram‐negative pathogens, Escherichia coli is one of the most common causes of both community‐acquired and nosocomial bloodstream infections.1, 2 Fluoroquinolone resistance among E coli clinical isolates was first observed in patients with hematologic malignancies3, 4 but is no longer restricted to this population5 and has spread in the community.6 Multiple studies have examined potential risk factors for fluoroquinolone resistance in E coli infections.79 Prior fluoroquinolone use stands out as a repeatedly documented risk factor.10 In E coli bacteremias, data on the impact of fluoroquinolone resistance on mortality are limited.9, 11, 12 Ortega and colleagues performed a landmark analysis of a large dataset stemming from bacteremia surveillance data collected over 17 years.9 They found that mortality was associated with both shock and inappropriate empirical treatment, and that inappropriate empirical treatment in turn was linked to fluoroquinolone resistance. Laupland et al reported results from a population‐based study in Canada, and could elicit age, comorbidities, ciprofloxacin resistance, and a nonurinary focus of infection as risk factors for mortality.11 Lastly, a smaller study by Cheong et al found a high APACHE II score (ie, high severity of illness) but not fluoroquinolone resistance (P = .08) to be associated with poor outcomes.12

The prevalence of fluoroquinolone resistance among E coli isolates in our hospital has surpassed 20%. In this setting, an adjustment of recommendations for empirical treatment may become necessary. This is particularly important since some studies have demonstrated that inappropriate empiric therapy in patients with bloodstream infection results in higher mortality.13 The aim of this case‐control study was to determine the impact of fluoroquinolone resistance on in‐hospital mortality among patients with E coli bacteremia.

METHODS

RESULTS