Miriam E. Tucker

NATIONAL HARBOR, MD. — Weight loss, verbally abusive behavior, and moderate pain were all significant predictors of a new diagnosis of depression among established nursing home residents in a longitudinal analysis.

Studies have shown that depression affects 20%-55% of nursing home residents, but the condition frequently goes unrecognized. Developing a set of observable indicators of depression may facilitate earlier diagnosis and treatment by nursing home staffs, said Dr. Lorraine J. Phillips and her associates in a poster at the annual meeting of the Gerontological Society of America.

The data were taken from 13,588 nursing home residents who were among the 127,587 in the Missouri Minimum Data Set (MDS) from Jan. 1, 2003, to March 31, 2005. Among the inclusion criteria were two sequential assessments 90 days apart (excluding admission and discharge), age 65 years and older, no prior diagnosis of depression or use of antidepressants, and no severe cognitive impairment.

Mean age of the study population was 85 years, 74% were female, and 88% were white. More than 66% were widowed, 19.5% married, and 12% had never married. About 49% had less than a high school education, 37% had finished high school, and 14% had a college education.

Documentation of weight loss at the study's first assessment was associated with a significantly increased chance of being diagnosed with depression between the first and second assessments (odds ratio 1.68). Verbally abusive behaviors, such as threatening, screaming, or cursing at others, also predicted a depression diagnosis between the assessments (OR 1.44). Moderate pain was a third significant predictor (OR 1.43), reported Dr. Phillips of the Sinclair School of Nursing at the University of Missouri-Columbia, and her associates.

Conversely, frequent urinary incontinence was significantly associated with a lower incidence of depression (OR 0.70). Post hoc analysis showed a correlation between incontinence and cognitive impairment, suggesting that the lower incidence of depression being diagnosed in nursing home residents can be explained by cognitive impairment impeding the recognition of depression, the investigators said.

Never being married also predicted a lower incidence of depression (OR 0.66), as did age 95 and above (OR 0.70).

The University of Missouri MDS and Quality Research Team funded the research. The team began work in 1993, and members have received funding since 1994 through the Missouri Division of Aging, the Health Care Financing Administration, the National Institute for Nursing Research, the Agency for Health Care Policy and Research, and other groups.

NATIONAL HARBOR, MD. — Weight loss, verbally abusive behavior, and moderate pain were all significant predictors of a new diagnosis of depression among established nursing home residents in a longitudinal analysis.

Studies have shown that depression affects 20%-55% of nursing home residents, but the condition frequently goes unrecognized. Developing a set of observable indicators of depression may facilitate earlier diagnosis and treatment by nursing home staffs, said Dr. Lorraine J. Phillips and her associates in a poster at the annual meeting of the Gerontological Society of America.

The data were taken from 13,588 nursing home residents who were among the 127,587 in the Missouri Minimum Data Set (MDS) from Jan. 1, 2003, to March 31, 2005. Among the inclusion criteria were two sequential assessments 90 days apart (excluding admission and discharge), age 65 years and older, no prior diagnosis of depression or use of antidepressants, and no severe cognitive impairment.

Mean age of the study population was 85 years, 74% were female, and 88% were white. More than 66% were widowed, 19.5% married, and 12% had never married. About 49% had less than a high school education, 37% had finished high school, and 14% had a college education.

Documentation of weight loss at the study's first assessment was associated with a significantly increased chance of being diagnosed with depression between the first and second assessments (odds ratio 1.68). Verbally abusive behaviors, such as threatening, screaming, or cursing at others, also predicted a depression diagnosis between the assessments (OR 1.44). Moderate pain was a third significant predictor (OR 1.43), reported Dr. Phillips of the Sinclair School of Nursing at the University of Missouri-Columbia, and her associates.

Conversely, frequent urinary incontinence was significantly associated with a lower incidence of depression (OR 0.70). Post hoc analysis showed a correlation between incontinence and cognitive impairment, suggesting that the lower incidence of depression being diagnosed in nursing home residents can be explained by cognitive impairment impeding the recognition of depression, the investigators said.

Never being married also predicted a lower incidence of depression (OR 0.66), as did age 95 and above (OR 0.70).

The University of Missouri MDS and Quality Research Team funded the research. The team began work in 1993, and members have received funding since 1994 through the Missouri Division of Aging, the Health Care Financing Administration, the National Institute for Nursing Research, the Agency for Health Care Policy and Research, and other groups.

NATIONAL HARBOR, MD. — Weight loss, verbally abusive behavior, and moderate pain were all significant predictors of a new diagnosis of depression among established nursing home residents in a longitudinal analysis.

Studies have shown that depression affects 20%-55% of nursing home residents, but the condition frequently goes unrecognized. Developing a set of observable indicators of depression may facilitate earlier diagnosis and treatment by nursing home staffs, said Dr. Lorraine J. Phillips and her associates in a poster at the annual meeting of the Gerontological Society of America.

The data were taken from 13,588 nursing home residents who were among the 127,587 in the Missouri Minimum Data Set (MDS) from Jan. 1, 2003, to March 31, 2005. Among the inclusion criteria were two sequential assessments 90 days apart (excluding admission and discharge), age 65 years and older, no prior diagnosis of depression or use of antidepressants, and no severe cognitive impairment.

Mean age of the study population was 85 years, 74% were female, and 88% were white. More than 66% were widowed, 19.5% married, and 12% had never married. About 49% had less than a high school education, 37% had finished high school, and 14% had a college education.

Documentation of weight loss at the study's first assessment was associated with a significantly increased chance of being diagnosed with depression between the first and second assessments (odds ratio 1.68). Verbally abusive behaviors, such as threatening, screaming, or cursing at others, also predicted a depression diagnosis between the assessments (OR 1.44). Moderate pain was a third significant predictor (OR 1.43), reported Dr. Phillips of the Sinclair School of Nursing at the University of Missouri-Columbia, and her associates.

Conversely, frequent urinary incontinence was significantly associated with a lower incidence of depression (OR 0.70). Post hoc analysis showed a correlation between incontinence and cognitive impairment, suggesting that the lower incidence of depression being diagnosed in nursing home residents can be explained by cognitive impairment impeding the recognition of depression, the investigators said.

Never being married also predicted a lower incidence of depression (OR 0.66), as did age 95 and above (OR 0.70).

The University of Missouri MDS and Quality Research Team funded the research. The team began work in 1993, and members have received funding since 1994 through the Missouri Division of Aging, the Health Care Financing Administration, the National Institute for Nursing Research, the Agency for Health Care Policy and Research, and other groups.

WASHINGTON — Acute care hospitals were the most common source of health care-associated legionnaires disease reported to the Centers for Disease Control and Prevention during 2005–2007.

In that period, 94 cases of clinically compatible illness with laboratory evidence of legionellosis infection occurring within 10 days of inpatient health care exposure were reported to the CDC's supplemental legionnaires disease surveillance system (www.cdc.gov/legionella

Acute care hospitals accounted for 88% of the reports, while long-term care and rehabilitation facilities contributed to 12%. Six of the total 41 facilities had clusters, ranging from two to four cases, indicating a “missed opportunity for prevention,” Dr. Lauri A. Hicks and her associates reported in a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and annual meeting of the Infectious Diseases Society of America.

Mean age of the patients was 61 years (range, 1–87), two-thirds were male, and most were white. The case fatality rate was high: 28 of 82 patients (34%) for whom the information was reported died of the infection.

Urine antigen was used to diagnose 71 (76%) of the cases, followed by culture in 11 (12%), direct fluorescent antibody in 3 (3%), and multiple methods in 9 (10%). It's important to obtain a respiratory specimen for Legionella in all potential cases in addition to the urine sample, because urine antigen testing is specific to L. pneumophila serogroup 1 and will not detect legionnaires disease caused by other Legionella species or serogroups, said Dr. Hicks and her associates of the CDC's National Center for Immunization and Respiratory Diseases.

Culture should also be used in addition to the urine antigen test because it allows for matching of clinical and environmental isolates so that the source can be identified and remediated. “A diagnosis of [legionnaires disease] should be considered in cases of health care-associated pneumonia. … Health care facility plans to systematically identify and reduce the environmental conditions that are conducive to Legionella growth may improve prevention,” the investigators said.

Dr. Hicks had no financial disclosures.

WASHINGTON — Acute care hospitals were the most common source of health care-associated legionnaires disease reported to the Centers for Disease Control and Prevention during 2005–2007.

In that period, 94 cases of clinically compatible illness with laboratory evidence of legionellosis infection occurring within 10 days of inpatient health care exposure were reported to the CDC's supplemental legionnaires disease surveillance system (www.cdc.gov/legionella

Acute care hospitals accounted for 88% of the reports, while long-term care and rehabilitation facilities contributed to 12%. Six of the total 41 facilities had clusters, ranging from two to four cases, indicating a “missed opportunity for prevention,” Dr. Lauri A. Hicks and her associates reported in a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and annual meeting of the Infectious Diseases Society of America.

Mean age of the patients was 61 years (range, 1–87), two-thirds were male, and most were white. The case fatality rate was high: 28 of 82 patients (34%) for whom the information was reported died of the infection.

Urine antigen was used to diagnose 71 (76%) of the cases, followed by culture in 11 (12%), direct fluorescent antibody in 3 (3%), and multiple methods in 9 (10%). It's important to obtain a respiratory specimen for Legionella in all potential cases in addition to the urine sample, because urine antigen testing is specific to L. pneumophila serogroup 1 and will not detect legionnaires disease caused by other Legionella species or serogroups, said Dr. Hicks and her associates of the CDC's National Center for Immunization and Respiratory Diseases.

Culture should also be used in addition to the urine antigen test because it allows for matching of clinical and environmental isolates so that the source can be identified and remediated. “A diagnosis of [legionnaires disease] should be considered in cases of health care-associated pneumonia. … Health care facility plans to systematically identify and reduce the environmental conditions that are conducive to Legionella growth may improve prevention,” the investigators said.

Dr. Hicks had no financial disclosures.

WASHINGTON — Acute care hospitals were the most common source of health care-associated legionnaires disease reported to the Centers for Disease Control and Prevention during 2005–2007.

In that period, 94 cases of clinically compatible illness with laboratory evidence of legionellosis infection occurring within 10 days of inpatient health care exposure were reported to the CDC's supplemental legionnaires disease surveillance system (www.cdc.gov/legionella

Acute care hospitals accounted for 88% of the reports, while long-term care and rehabilitation facilities contributed to 12%. Six of the total 41 facilities had clusters, ranging from two to four cases, indicating a “missed opportunity for prevention,” Dr. Lauri A. Hicks and her associates reported in a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and annual meeting of the Infectious Diseases Society of America.

Mean age of the patients was 61 years (range, 1–87), two-thirds were male, and most were white. The case fatality rate was high: 28 of 82 patients (34%) for whom the information was reported died of the infection.

Urine antigen was used to diagnose 71 (76%) of the cases, followed by culture in 11 (12%), direct fluorescent antibody in 3 (3%), and multiple methods in 9 (10%). It's important to obtain a respiratory specimen for Legionella in all potential cases in addition to the urine sample, because urine antigen testing is specific to L. pneumophila serogroup 1 and will not detect legionnaires disease caused by other Legionella species or serogroups, said Dr. Hicks and her associates of the CDC's National Center for Immunization and Respiratory Diseases.

Culture should also be used in addition to the urine antigen test because it allows for matching of clinical and environmental isolates so that the source can be identified and remediated. “A diagnosis of [legionnaires disease] should be considered in cases of health care-associated pneumonia. … Health care facility plans to systematically identify and reduce the environmental conditions that are conducive to Legionella growth may improve prevention,” the investigators said.

Dr. Hicks had no financial disclosures.

WASHINGTON — The risk of a nosocomial Clostridium difficile infection was doubled in one intensive care unit when patients occupied rooms that were previously occupied by an infected patient.

The finding was seen in a retrospective cohort study. Records were reviewed from 1,844 patients admitted over an 18-month period to a 20-bed intensive care unit at a large tertiary care hospital in Michigan. The increased risk was noted even though the unit observed cleaning protocols, and it persisted after correcting for other risk factors associated with C. difficile infection (CDI), according to Dr. Megan Shaughnessy of the University of Michigan, Ann Arbor.

In the study, 47 patients had CDI prior to or at the time of ICU admission and were excluded from the analysis. Another 91 patients were not infected and were placed in rooms previously occupied by patients with CDI; 10 (11%) developed CDI. Of the other 1,679 patients, 77 (4.6%) developed CDI.

The difference was statistically significant, with a P value of .002. Difference in risk remained significant, with a hazard ratio of 2.35 and P value of .01, even after researchers controlled for other risk factors associated with CDI, including patient age, Acute Physiology and Chronic Health Evaluation (APACHE) III score, proton pump inhibitor use, and antibiotic use.

“These findings have implications for room placement and isolation, room-cleaning practices, and hospital design,” Dr. Shaughnessy said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and annual meeting of the Infectious Diseases Society of America.

Protocols for the intensive care unit dictated that bathrooms in patient rooms were cleaned daily with bleach, and that the rooms themselves were cleaned with bleach upon patient discharge. Further, infection risk didn't appear to vary depending on where in the room a patient was placed, according to Dr. Shaughnessy.

Dr. Shaughnessy stated that she had no disclosures.

WASHINGTON — The risk of a nosocomial Clostridium difficile infection was doubled in one intensive care unit when patients occupied rooms that were previously occupied by an infected patient.

The finding was seen in a retrospective cohort study. Records were reviewed from 1,844 patients admitted over an 18-month period to a 20-bed intensive care unit at a large tertiary care hospital in Michigan. The increased risk was noted even though the unit observed cleaning protocols, and it persisted after correcting for other risk factors associated with C. difficile infection (CDI), according to Dr. Megan Shaughnessy of the University of Michigan, Ann Arbor.

In the study, 47 patients had CDI prior to or at the time of ICU admission and were excluded from the analysis. Another 91 patients were not infected and were placed in rooms previously occupied by patients with CDI; 10 (11%) developed CDI. Of the other 1,679 patients, 77 (4.6%) developed CDI.

The difference was statistically significant, with a P value of .002. Difference in risk remained significant, with a hazard ratio of 2.35 and P value of .01, even after researchers controlled for other risk factors associated with CDI, including patient age, Acute Physiology and Chronic Health Evaluation (APACHE) III score, proton pump inhibitor use, and antibiotic use.

“These findings have implications for room placement and isolation, room-cleaning practices, and hospital design,” Dr. Shaughnessy said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and annual meeting of the Infectious Diseases Society of America.

Protocols for the intensive care unit dictated that bathrooms in patient rooms were cleaned daily with bleach, and that the rooms themselves were cleaned with bleach upon patient discharge. Further, infection risk didn't appear to vary depending on where in the room a patient was placed, according to Dr. Shaughnessy.

Dr. Shaughnessy stated that she had no disclosures.

WASHINGTON — The risk of a nosocomial Clostridium difficile infection was doubled in one intensive care unit when patients occupied rooms that were previously occupied by an infected patient.

The finding was seen in a retrospective cohort study. Records were reviewed from 1,844 patients admitted over an 18-month period to a 20-bed intensive care unit at a large tertiary care hospital in Michigan. The increased risk was noted even though the unit observed cleaning protocols, and it persisted after correcting for other risk factors associated with C. difficile infection (CDI), according to Dr. Megan Shaughnessy of the University of Michigan, Ann Arbor.

In the study, 47 patients had CDI prior to or at the time of ICU admission and were excluded from the analysis. Another 91 patients were not infected and were placed in rooms previously occupied by patients with CDI; 10 (11%) developed CDI. Of the other 1,679 patients, 77 (4.6%) developed CDI.

The difference was statistically significant, with a P value of .002. Difference in risk remained significant, with a hazard ratio of 2.35 and P value of .01, even after researchers controlled for other risk factors associated with CDI, including patient age, Acute Physiology and Chronic Health Evaluation (APACHE) III score, proton pump inhibitor use, and antibiotic use.

“These findings have implications for room placement and isolation, room-cleaning practices, and hospital design,” Dr. Shaughnessy said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and annual meeting of the Infectious Diseases Society of America.

Protocols for the intensive care unit dictated that bathrooms in patient rooms were cleaned daily with bleach, and that the rooms themselves were cleaned with bleach upon patient discharge. Further, infection risk didn't appear to vary depending on where in the room a patient was placed, according to Dr. Shaughnessy.

Dr. Shaughnessy stated that she had no disclosures.

WASHINGTON — At long last, new treatments for Clostridium difficile appear to be on the horizon.

For the last 30 years, the treatment of a first episode of C. difficile infection (CDI) has involved stopping the offending antibiotics if possible—effective in 25% of patients—and treating with either oral metronidazole or oral vancomycin. “I could have given this talk in 1983,” Dr. Dale N. Gerding quipped during a symposium on CDI at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Recently, vancomycin has appeared somewhat more effective than metronidazole, particularly in patients with severe disease. In one prospective, randomized, blinded trial of 150 patients with diarrhea due to CDI, response rates were similar for the 81 with mild disease (98% with vancomycin vs. 90% with metronidazole), but the difference was significant—97% with vancomycin vs. 76% for metronidazole—among the 69 patients with severe disease (Clin. Infect. Dis. 2007;45:302–7).

In a recent observational study of 52 patients, however, most patients responded clinically to either drug, but microbiologic response appeared to be slower and less consistent with metronidazole than with vancomycin (Clin. Infect. Dis. 2008;47:56–62).

The lack of a standard definition for disease severity is a problem, and no prospective scoring system for CDI severity has been validated. Candidate scoring elements such as peripheral leukocytosis, increased serum creatinine, or low albumin aren't specific enough, while stool frequency is difficult to measure. “Who's counting after 15–20 bowel movements?” remarked Dr. Gerding, professor of medicine at Loyola University Chicago, Maywood.

Other elements, such as documented pseudomembranous colitis or abdominal CT findings, may be useful but haven't been validated. “We really need validated data for a scoring system available on the day of diagnosis, so we can look at the parameters and make a judgment or a change in initial therapy. … We'd like something simple, maybe two or three elements, to hang our hats on,” he said.

But new treatment options now offer the possibility that the severity of CDI may be reduced—or the infection cleared entirely. “We're currently seeing a marked resurgence in interest in the disease and seeing a lot more research being done and new drugs under development,” Dr. Gerding said.

Among those are narrow-spectrum antimicrobials that spare the normal flora. One, called OPT-80, is a poorly absorbed macrolide that is selectively active against gram-positive anaerobes. (In this case, poor absorption is desirable because it remains in the colon longer.) Phase IIa open label data in 45 patients with mild to moderate CDI showed an overall diarrhea response of 91% (41 of 45 patients) and recurrence rate of 4.9% (2 of 41). There were no treatment failures at the highest dose of 200 mg given every 12 hours.

The agent, which is made by Optimer Inc., has now completed its first phase III trial, in which the response rate was equivalent to vancomycin. The recurrence rate was reduced from 24% with vancomycin to 13.3% with OPT-80, Dr. Gerding said in an interview after the meeting.

Another poorly absorbed narrow-spectrum antimicrobial, rifaximin, already is approved on the U.S. market (Xifaxan, Salix Pharmaceuticals Inc.) for traveler's diarrhea but not for CDI. It is highly active against C. difficile in vitro, and data suggest it may be particularly effective as a “chaser” following vancomycin therapy for multiple relapses (Clin. Infect. Dis. 2007;44:846–8). However, resistance has become an increasing concern, Dr. Gerding noted.

Nitazoxanide (Alinia, Romark Laboratories L.C.) has broad-spectrum activity against helminthic and protozoan intestinal parasites, as well as anaerobic bacterial enteric pathogens, including C. difficile. It is currently approved for the treatment of diarrhea caused by Giardia and Cryptosporidium but not for CDI. In a randomized double-blind study of 110 patients with CDI, 500 mg nitazoxanide given twice daily for 7 days produced a response in 89.5% of 76 patients, compared with 82.4% of 34 who received 250 mg metronidazole four times daily for 7 days, suggesting that it was “at least as effective” as metronidazole (Clin. Infect. Dis. 2006;43:421–7).

In a small, prospective, randomized double-blind trial of 27 patients who received vancomycin 125 mg four times daily vs. 22 patients given nitazoxanide twice daily for 10 days, response rates were 77% for nitazoxanide vs. 74% for vancomycin, and recurrence rates were 5% vs. 7%, respectively. In that study, presented at the Digestive Disease Week conference in 2008, there was no stratification for severity but about 50% of the patients had leukocytosis, Dr. Gerding said.

Potential “out of the box” therapies for CDI include toxin binders, monoclonal antibodies (Mabs), vaccines, and administration of nontoxigenic C. difficile.

Tolevamer (Genzyme Corp.) is a high-molecular-weight polymer that binds the C. difficile toxins A and B, thus representing a potential nonantibiotic therapy. It failed to meet criteria for noninferiority to vancomycin in its first phase III study, presented at the 2007 ICAAC meeting. Still, the recurrence rate for tolevamer (3.4%) was significantly lower than for vancomycin (23.4%) or metronidazole (27.1%), suggesting that this agent could prevent relapse in patients who are able to stay off antibiotics, Dr. Gerding said.

Phase II data on the neutralizing monoclonal antibody to C. difficile toxin A, developed by Massachusetts Biologic Lab and Medarex Inc., were presented in a poster at the 2008 ICAAC/IDSA meeting. There were no differences in recurrence among 29 patients who received the agent, compared with 17 receiving placebo (17% vs. 18%), but recurrence of disease was associated with significantly lower concentrations of antitoxin B antibody, suggesting that both toxins need to be targeted.

The companies are now conducting phase II trials of antitoxin A and B human Mabs as an adjunctive treatment and for the prevention of recurrence. In one such phase II study of 200 patients treated with vancomycin or metronidazole and randomized to Mabs against toxin A and toxin B versus placebo, there was a 70% reduction in recurrence with the Mabs, Dr. Gerding said in the interview.

Also targeting the two toxins is a toxin A/B toxoid vaccine made by Acambis PLC, which has completed phase I immunogenicity and safety trials and is undergoing phase II trials for patients with recurrent CDI in the United Kingdom.

Finally, Dr. Gerding outlined his own work on toxigenic C. difficile, a product he is working on in collaboration with ViroPharma Inc. The idea is based on work initially done 2 decades ago, in which prior colonization of clindamycin-treated hamsters with nontoxigenic strains of C. difficile protected them from subsequent colonization with a toxigenic pathogenic strain (J. Med. Microbiol. 1985;19:339–50). More recent work again showed that colonization with nontoxigenic CD strains is highly effective in preventing CDI in hamsters challenged with toxigenic CD strains (J. Infect. Dis. 2002;186:1781–9).

Similarly, Dr. Gerding's work has shown that, in hamsters that have been treated for CDI with vancomycin, giving a nontoxigenic CD strain followed by a toxigenic strain protected 9 out of 10 hamsters from relapse, compared with 0 of 5 that had not been pretreated. Human trials are set to begin in early 2009. “To the extent that hamsters are like humans, we may have something going here,” he said.

Dr. Gerding holds patents for the treatment and prevention of CDI licensed to ViroPharma and is a consultant for and/or holds research grants from Genzyme, Massachusetts Biological Laboratories, GOJO Industries Inc., Optimer, Salix, Merck & Co., Cepheid, Schering-Plough Corp., and ViroPharma.

WASHINGTON — At long last, new treatments for Clostridium difficile appear to be on the horizon.

For the last 30 years, the treatment of a first episode of C. difficile infection (CDI) has involved stopping the offending antibiotics if possible—effective in 25% of patients—and treating with either oral metronidazole or oral vancomycin. “I could have given this talk in 1983,” Dr. Dale N. Gerding quipped during a symposium on CDI at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Recently, vancomycin has appeared somewhat more effective than metronidazole, particularly in patients with severe disease. In one prospective, randomized, blinded trial of 150 patients with diarrhea due to CDI, response rates were similar for the 81 with mild disease (98% with vancomycin vs. 90% with metronidazole), but the difference was significant—97% with vancomycin vs. 76% for metronidazole—among the 69 patients with severe disease (Clin. Infect. Dis. 2007;45:302–7).

In a recent observational study of 52 patients, however, most patients responded clinically to either drug, but microbiologic response appeared to be slower and less consistent with metronidazole than with vancomycin (Clin. Infect. Dis. 2008;47:56–62).

The lack of a standard definition for disease severity is a problem, and no prospective scoring system for CDI severity has been validated. Candidate scoring elements such as peripheral leukocytosis, increased serum creatinine, or low albumin aren't specific enough, while stool frequency is difficult to measure. “Who's counting after 15–20 bowel movements?” remarked Dr. Gerding, professor of medicine at Loyola University Chicago, Maywood.

Other elements, such as documented pseudomembranous colitis or abdominal CT findings, may be useful but haven't been validated. “We really need validated data for a scoring system available on the day of diagnosis, so we can look at the parameters and make a judgment or a change in initial therapy. … We'd like something simple, maybe two or three elements, to hang our hats on,” he said.

But new treatment options now offer the possibility that the severity of CDI may be reduced—or the infection cleared entirely. “We're currently seeing a marked resurgence in interest in the disease and seeing a lot more research being done and new drugs under development,” Dr. Gerding said.

Among those are narrow-spectrum antimicrobials that spare the normal flora. One, called OPT-80, is a poorly absorbed macrolide that is selectively active against gram-positive anaerobes. (In this case, poor absorption is desirable because it remains in the colon longer.) Phase IIa open label data in 45 patients with mild to moderate CDI showed an overall diarrhea response of 91% (41 of 45 patients) and recurrence rate of 4.9% (2 of 41). There were no treatment failures at the highest dose of 200 mg given every 12 hours.

The agent, which is made by Optimer Inc., has now completed its first phase III trial, in which the response rate was equivalent to vancomycin. The recurrence rate was reduced from 24% with vancomycin to 13.3% with OPT-80, Dr. Gerding said in an interview after the meeting.

Another poorly absorbed narrow-spectrum antimicrobial, rifaximin, already is approved on the U.S. market (Xifaxan, Salix Pharmaceuticals Inc.) for traveler's diarrhea but not for CDI. It is highly active against C. difficile in vitro, and data suggest it may be particularly effective as a “chaser” following vancomycin therapy for multiple relapses (Clin. Infect. Dis. 2007;44:846–8). However, resistance has become an increasing concern, Dr. Gerding noted.

Nitazoxanide (Alinia, Romark Laboratories L.C.) has broad-spectrum activity against helminthic and protozoan intestinal parasites, as well as anaerobic bacterial enteric pathogens, including C. difficile. It is currently approved for the treatment of diarrhea caused by Giardia and Cryptosporidium but not for CDI. In a randomized double-blind study of 110 patients with CDI, 500 mg nitazoxanide given twice daily for 7 days produced a response in 89.5% of 76 patients, compared with 82.4% of 34 who received 250 mg metronidazole four times daily for 7 days, suggesting that it was “at least as effective” as metronidazole (Clin. Infect. Dis. 2006;43:421–7).

In a small, prospective, randomized double-blind trial of 27 patients who received vancomycin 125 mg four times daily vs. 22 patients given nitazoxanide twice daily for 10 days, response rates were 77% for nitazoxanide vs. 74% for vancomycin, and recurrence rates were 5% vs. 7%, respectively. In that study, presented at the Digestive Disease Week conference in 2008, there was no stratification for severity but about 50% of the patients had leukocytosis, Dr. Gerding said.

Potential “out of the box” therapies for CDI include toxin binders, monoclonal antibodies (Mabs), vaccines, and administration of nontoxigenic C. difficile.

Tolevamer (Genzyme Corp.) is a high-molecular-weight polymer that binds the C. difficile toxins A and B, thus representing a potential nonantibiotic therapy. It failed to meet criteria for noninferiority to vancomycin in its first phase III study, presented at the 2007 ICAAC meeting. Still, the recurrence rate for tolevamer (3.4%) was significantly lower than for vancomycin (23.4%) or metronidazole (27.1%), suggesting that this agent could prevent relapse in patients who are able to stay off antibiotics, Dr. Gerding said.

Phase II data on the neutralizing monoclonal antibody to C. difficile toxin A, developed by Massachusetts Biologic Lab and Medarex Inc., were presented in a poster at the 2008 ICAAC/IDSA meeting. There were no differences in recurrence among 29 patients who received the agent, compared with 17 receiving placebo (17% vs. 18%), but recurrence of disease was associated with significantly lower concentrations of antitoxin B antibody, suggesting that both toxins need to be targeted.

The companies are now conducting phase II trials of antitoxin A and B human Mabs as an adjunctive treatment and for the prevention of recurrence. In one such phase II study of 200 patients treated with vancomycin or metronidazole and randomized to Mabs against toxin A and toxin B versus placebo, there was a 70% reduction in recurrence with the Mabs, Dr. Gerding said in the interview.

Also targeting the two toxins is a toxin A/B toxoid vaccine made by Acambis PLC, which has completed phase I immunogenicity and safety trials and is undergoing phase II trials for patients with recurrent CDI in the United Kingdom.

Finally, Dr. Gerding outlined his own work on toxigenic C. difficile, a product he is working on in collaboration with ViroPharma Inc. The idea is based on work initially done 2 decades ago, in which prior colonization of clindamycin-treated hamsters with nontoxigenic strains of C. difficile protected them from subsequent colonization with a toxigenic pathogenic strain (J. Med. Microbiol. 1985;19:339–50). More recent work again showed that colonization with nontoxigenic CD strains is highly effective in preventing CDI in hamsters challenged with toxigenic CD strains (J. Infect. Dis. 2002;186:1781–9).

Similarly, Dr. Gerding's work has shown that, in hamsters that have been treated for CDI with vancomycin, giving a nontoxigenic CD strain followed by a toxigenic strain protected 9 out of 10 hamsters from relapse, compared with 0 of 5 that had not been pretreated. Human trials are set to begin in early 2009. “To the extent that hamsters are like humans, we may have something going here,” he said.

Dr. Gerding holds patents for the treatment and prevention of CDI licensed to ViroPharma and is a consultant for and/or holds research grants from Genzyme, Massachusetts Biological Laboratories, GOJO Industries Inc., Optimer, Salix, Merck & Co., Cepheid, Schering-Plough Corp., and ViroPharma.

WASHINGTON — At long last, new treatments for Clostridium difficile appear to be on the horizon.

For the last 30 years, the treatment of a first episode of C. difficile infection (CDI) has involved stopping the offending antibiotics if possible—effective in 25% of patients—and treating with either oral metronidazole or oral vancomycin. “I could have given this talk in 1983,” Dr. Dale N. Gerding quipped during a symposium on CDI at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Recently, vancomycin has appeared somewhat more effective than metronidazole, particularly in patients with severe disease. In one prospective, randomized, blinded trial of 150 patients with diarrhea due to CDI, response rates were similar for the 81 with mild disease (98% with vancomycin vs. 90% with metronidazole), but the difference was significant—97% with vancomycin vs. 76% for metronidazole—among the 69 patients with severe disease (Clin. Infect. Dis. 2007;45:302–7).

In a recent observational study of 52 patients, however, most patients responded clinically to either drug, but microbiologic response appeared to be slower and less consistent with metronidazole than with vancomycin (Clin. Infect. Dis. 2008;47:56–62).

The lack of a standard definition for disease severity is a problem, and no prospective scoring system for CDI severity has been validated. Candidate scoring elements such as peripheral leukocytosis, increased serum creatinine, or low albumin aren't specific enough, while stool frequency is difficult to measure. “Who's counting after 15–20 bowel movements?” remarked Dr. Gerding, professor of medicine at Loyola University Chicago, Maywood.

Other elements, such as documented pseudomembranous colitis or abdominal CT findings, may be useful but haven't been validated. “We really need validated data for a scoring system available on the day of diagnosis, so we can look at the parameters and make a judgment or a change in initial therapy. … We'd like something simple, maybe two or three elements, to hang our hats on,” he said.

But new treatment options now offer the possibility that the severity of CDI may be reduced—or the infection cleared entirely. “We're currently seeing a marked resurgence in interest in the disease and seeing a lot more research being done and new drugs under development,” Dr. Gerding said.

Among those are narrow-spectrum antimicrobials that spare the normal flora. One, called OPT-80, is a poorly absorbed macrolide that is selectively active against gram-positive anaerobes. (In this case, poor absorption is desirable because it remains in the colon longer.) Phase IIa open label data in 45 patients with mild to moderate CDI showed an overall diarrhea response of 91% (41 of 45 patients) and recurrence rate of 4.9% (2 of 41). There were no treatment failures at the highest dose of 200 mg given every 12 hours.

The agent, which is made by Optimer Inc., has now completed its first phase III trial, in which the response rate was equivalent to vancomycin. The recurrence rate was reduced from 24% with vancomycin to 13.3% with OPT-80, Dr. Gerding said in an interview after the meeting.

Another poorly absorbed narrow-spectrum antimicrobial, rifaximin, already is approved on the U.S. market (Xifaxan, Salix Pharmaceuticals Inc.) for traveler's diarrhea but not for CDI. It is highly active against C. difficile in vitro, and data suggest it may be particularly effective as a “chaser” following vancomycin therapy for multiple relapses (Clin. Infect. Dis. 2007;44:846–8). However, resistance has become an increasing concern, Dr. Gerding noted.

Nitazoxanide (Alinia, Romark Laboratories L.C.) has broad-spectrum activity against helminthic and protozoan intestinal parasites, as well as anaerobic bacterial enteric pathogens, including C. difficile. It is currently approved for the treatment of diarrhea caused by Giardia and Cryptosporidium but not for CDI. In a randomized double-blind study of 110 patients with CDI, 500 mg nitazoxanide given twice daily for 7 days produced a response in 89.5% of 76 patients, compared with 82.4% of 34 who received 250 mg metronidazole four times daily for 7 days, suggesting that it was “at least as effective” as metronidazole (Clin. Infect. Dis. 2006;43:421–7).

In a small, prospective, randomized double-blind trial of 27 patients who received vancomycin 125 mg four times daily vs. 22 patients given nitazoxanide twice daily for 10 days, response rates were 77% for nitazoxanide vs. 74% for vancomycin, and recurrence rates were 5% vs. 7%, respectively. In that study, presented at the Digestive Disease Week conference in 2008, there was no stratification for severity but about 50% of the patients had leukocytosis, Dr. Gerding said.

Potential “out of the box” therapies for CDI include toxin binders, monoclonal antibodies (Mabs), vaccines, and administration of nontoxigenic C. difficile.

Tolevamer (Genzyme Corp.) is a high-molecular-weight polymer that binds the C. difficile toxins A and B, thus representing a potential nonantibiotic therapy. It failed to meet criteria for noninferiority to vancomycin in its first phase III study, presented at the 2007 ICAAC meeting. Still, the recurrence rate for tolevamer (3.4%) was significantly lower than for vancomycin (23.4%) or metronidazole (27.1%), suggesting that this agent could prevent relapse in patients who are able to stay off antibiotics, Dr. Gerding said.

Phase II data on the neutralizing monoclonal antibody to C. difficile toxin A, developed by Massachusetts Biologic Lab and Medarex Inc., were presented in a poster at the 2008 ICAAC/IDSA meeting. There were no differences in recurrence among 29 patients who received the agent, compared with 17 receiving placebo (17% vs. 18%), but recurrence of disease was associated with significantly lower concentrations of antitoxin B antibody, suggesting that both toxins need to be targeted.

The companies are now conducting phase II trials of antitoxin A and B human Mabs as an adjunctive treatment and for the prevention of recurrence. In one such phase II study of 200 patients treated with vancomycin or metronidazole and randomized to Mabs against toxin A and toxin B versus placebo, there was a 70% reduction in recurrence with the Mabs, Dr. Gerding said in the interview.

Also targeting the two toxins is a toxin A/B toxoid vaccine made by Acambis PLC, which has completed phase I immunogenicity and safety trials and is undergoing phase II trials for patients with recurrent CDI in the United Kingdom.

Finally, Dr. Gerding outlined his own work on toxigenic C. difficile, a product he is working on in collaboration with ViroPharma Inc. The idea is based on work initially done 2 decades ago, in which prior colonization of clindamycin-treated hamsters with nontoxigenic strains of C. difficile protected them from subsequent colonization with a toxigenic pathogenic strain (J. Med. Microbiol. 1985;19:339–50). More recent work again showed that colonization with nontoxigenic CD strains is highly effective in preventing CDI in hamsters challenged with toxigenic CD strains (J. Infect. Dis. 2002;186:1781–9).

Similarly, Dr. Gerding's work has shown that, in hamsters that have been treated for CDI with vancomycin, giving a nontoxigenic CD strain followed by a toxigenic strain protected 9 out of 10 hamsters from relapse, compared with 0 of 5 that had not been pretreated. Human trials are set to begin in early 2009. “To the extent that hamsters are like humans, we may have something going here,” he said.

Dr. Gerding holds patents for the treatment and prevention of CDI licensed to ViroPharma and is a consultant for and/or holds research grants from Genzyme, Massachusetts Biological Laboratories, GOJO Industries Inc., Optimer, Salix, Merck & Co., Cepheid, Schering-Plough Corp., and ViroPharma.

This year's Adult Immunization Schedule includes the 2008 recommendation to use the pneumococcal polysaccharide vaccine in cigarette smokers and patients with asthma.

No new vaccines have been added to the schedule, but there are several changes to the chart's format, as well as updated footnotes for certain vaccines, said Dr. Gina Mootrey of the CDC's Immunization Services Administration, and her associates.

The schedule, published in January, was approved by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) and endorsed by the American Academy of Family Physicians, the American College of Physicians, and the American College of Obstetricians and Gynecologists (MMWR 2009;57:Q1-Q4).

ACIP voted to recommend pneumococcal polysaccharide vaccine to adults with asthma in June 2008, based on data suggesting that adults with asthma were at more than double the risk (adjusted odds ratio 2.4) for invasive pneumococcal disease. The ACIP decision on smokers was made in October 2008, based on data that smoking is the strongest independent risk factor for pneumococcal disease in nonelderly immunocompetent adults, with an adjusted odds ratio of 4.1.

In an editorial, Dr. Gregory A. Poland and Dr. William Schaffner noted that most asthmatic adults who develop invasive pneumococcal disease already have another condition for which the vaccine is indicated, but they don't receive it (Ann. Intern. Med. 2009;150:53–6).

“Making asthma an indication for pneumococcal vaccination will resolve previous ambiguity, be consistent with the influenza vaccine recommendations, and challenge us to identify and vaccinate these patients,” said Dr. Poland of the Mayo Clinic, Rochester, Minn., and Dr. Schaffner of Vanderbilt University, Nashville, Tenn.

It is now recommended that all children from 5 years through 18 years of age (in addition to children aged 6 months to 5 years, per the previous recommendation), receive the influenza vaccine, as well as individuals who live with or care for people at increased risk for influenza-related complications, including all health care workers. As the target population for influenza vaccination continues to rise, it will become necessary to extend the “vaccination season” into December and January, “and even beyond,” Dr. Poland and Dr. Schaffner said.

Additional changes to the childhood schedule involve dosing schedule provisions to accommodate the availability of a second oral rotavirus vaccine licensed by the FDA. The first dose of either vaccine should be administered at 6 weeks through 14 weeks 6 days of age. Immunization should not be initiated for infants 15 weeks 0 days of age or older. The final dose should be administered by 8 months 0 days of age.

Other changes and clarifications in the footnotes of the 2009 adult schedule include:

▸ A note was added to say that health care personnel are not at increased risk for human papillomavirus through occupational exposure, and that they should receive the vaccine consistent with age-based recommendations.

▸ A second dose of varicella vaccine should be given to adults who previously received only one dose.

▸ Information was added about an alternative four-dose schedule for the combined hepatitis A/B vaccine.

▸ The 5-year revaccination interval for the meningococcal vaccine was clarified.

Last fall, the American College of Physicians and the Infectious Diseases Society of America issued a joint statement on the importance of adult immunization, which was subsequently endorsed by 17 other medical societies. The statement advises that all physicians conduct an immunization review with their adult patients, that they provide recommended immunizations or refer patients to someone who will, and that all physicians and their staffs should be vaccinated according to the CDC, with particular attention to annual influenza immunization.

“We hope that publication of the annual Adult Immunization Schedule in this issue will prompt clinicians to redouble their efforts to improve their practices' immunization rates. Doing so will prevent needless morbidity, mortality, and expense,” Dr. Poland and Dr. Schaffner concluded. Both doctors disclosed financial ties to several vaccine manufacturers.

ACIP members follow strict conflict of interest guidelines.

The Adult Immunization Schedule is available at www.cdc.gov/vaccines/recs/schedules/adult-schedule.htm

This year's Adult Immunization Schedule includes the 2008 recommendation to use the pneumococcal polysaccharide vaccine in cigarette smokers and patients with asthma.

No new vaccines have been added to the schedule, but there are several changes to the chart's format, as well as updated footnotes for certain vaccines, said Dr. Gina Mootrey of the CDC's Immunization Services Administration, and her associates.

The schedule, published in January, was approved by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) and endorsed by the American Academy of Family Physicians, the American College of Physicians, and the American College of Obstetricians and Gynecologists (MMWR 2009;57:Q1-Q4).

ACIP voted to recommend pneumococcal polysaccharide vaccine to adults with asthma in June 2008, based on data suggesting that adults with asthma were at more than double the risk (adjusted odds ratio 2.4) for invasive pneumococcal disease. The ACIP decision on smokers was made in October 2008, based on data that smoking is the strongest independent risk factor for pneumococcal disease in nonelderly immunocompetent adults, with an adjusted odds ratio of 4.1.

In an editorial, Dr. Gregory A. Poland and Dr. William Schaffner noted that most asthmatic adults who develop invasive pneumococcal disease already have another condition for which the vaccine is indicated, but they don't receive it (Ann. Intern. Med. 2009;150:53–6).

“Making asthma an indication for pneumococcal vaccination will resolve previous ambiguity, be consistent with the influenza vaccine recommendations, and challenge us to identify and vaccinate these patients,” said Dr. Poland of the Mayo Clinic, Rochester, Minn., and Dr. Schaffner of Vanderbilt University, Nashville, Tenn.

It is now recommended that all children from 5 years through 18 years of age (in addition to children aged 6 months to 5 years, per the previous recommendation), receive the influenza vaccine, as well as individuals who live with or care for people at increased risk for influenza-related complications, including all health care workers. As the target population for influenza vaccination continues to rise, it will become necessary to extend the “vaccination season” into December and January, “and even beyond,” Dr. Poland and Dr. Schaffner said.

Additional changes to the childhood schedule involve dosing schedule provisions to accommodate the availability of a second oral rotavirus vaccine licensed by the FDA. The first dose of either vaccine should be administered at 6 weeks through 14 weeks 6 days of age. Immunization should not be initiated for infants 15 weeks 0 days of age or older. The final dose should be administered by 8 months 0 days of age.

Other changes and clarifications in the footnotes of the 2009 adult schedule include:

▸ A note was added to say that health care personnel are not at increased risk for human papillomavirus through occupational exposure, and that they should receive the vaccine consistent with age-based recommendations.

▸ A second dose of varicella vaccine should be given to adults who previously received only one dose.

▸ Information was added about an alternative four-dose schedule for the combined hepatitis A/B vaccine.

▸ The 5-year revaccination interval for the meningococcal vaccine was clarified.

Last fall, the American College of Physicians and the Infectious Diseases Society of America issued a joint statement on the importance of adult immunization, which was subsequently endorsed by 17 other medical societies. The statement advises that all physicians conduct an immunization review with their adult patients, that they provide recommended immunizations or refer patients to someone who will, and that all physicians and their staffs should be vaccinated according to the CDC, with particular attention to annual influenza immunization.

“We hope that publication of the annual Adult Immunization Schedule in this issue will prompt clinicians to redouble their efforts to improve their practices' immunization rates. Doing so will prevent needless morbidity, mortality, and expense,” Dr. Poland and Dr. Schaffner concluded. Both doctors disclosed financial ties to several vaccine manufacturers.

ACIP members follow strict conflict of interest guidelines.

The Adult Immunization Schedule is available at www.cdc.gov/vaccines/recs/schedules/adult-schedule.htm

This year's Adult Immunization Schedule includes the 2008 recommendation to use the pneumococcal polysaccharide vaccine in cigarette smokers and patients with asthma.

No new vaccines have been added to the schedule, but there are several changes to the chart's format, as well as updated footnotes for certain vaccines, said Dr. Gina Mootrey of the CDC's Immunization Services Administration, and her associates.

The schedule, published in January, was approved by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) and endorsed by the American Academy of Family Physicians, the American College of Physicians, and the American College of Obstetricians and Gynecologists (MMWR 2009;57:Q1-Q4).

ACIP voted to recommend pneumococcal polysaccharide vaccine to adults with asthma in June 2008, based on data suggesting that adults with asthma were at more than double the risk (adjusted odds ratio 2.4) for invasive pneumococcal disease. The ACIP decision on smokers was made in October 2008, based on data that smoking is the strongest independent risk factor for pneumococcal disease in nonelderly immunocompetent adults, with an adjusted odds ratio of 4.1.

In an editorial, Dr. Gregory A. Poland and Dr. William Schaffner noted that most asthmatic adults who develop invasive pneumococcal disease already have another condition for which the vaccine is indicated, but they don't receive it (Ann. Intern. Med. 2009;150:53–6).

“Making asthma an indication for pneumococcal vaccination will resolve previous ambiguity, be consistent with the influenza vaccine recommendations, and challenge us to identify and vaccinate these patients,” said Dr. Poland of the Mayo Clinic, Rochester, Minn., and Dr. Schaffner of Vanderbilt University, Nashville, Tenn.

It is now recommended that all children from 5 years through 18 years of age (in addition to children aged 6 months to 5 years, per the previous recommendation), receive the influenza vaccine, as well as individuals who live with or care for people at increased risk for influenza-related complications, including all health care workers. As the target population for influenza vaccination continues to rise, it will become necessary to extend the “vaccination season” into December and January, “and even beyond,” Dr. Poland and Dr. Schaffner said.

Additional changes to the childhood schedule involve dosing schedule provisions to accommodate the availability of a second oral rotavirus vaccine licensed by the FDA. The first dose of either vaccine should be administered at 6 weeks through 14 weeks 6 days of age. Immunization should not be initiated for infants 15 weeks 0 days of age or older. The final dose should be administered by 8 months 0 days of age.

Other changes and clarifications in the footnotes of the 2009 adult schedule include:

▸ A note was added to say that health care personnel are not at increased risk for human papillomavirus through occupational exposure, and that they should receive the vaccine consistent with age-based recommendations.

▸ A second dose of varicella vaccine should be given to adults who previously received only one dose.

▸ Information was added about an alternative four-dose schedule for the combined hepatitis A/B vaccine.

▸ The 5-year revaccination interval for the meningococcal vaccine was clarified.

Last fall, the American College of Physicians and the Infectious Diseases Society of America issued a joint statement on the importance of adult immunization, which was subsequently endorsed by 17 other medical societies. The statement advises that all physicians conduct an immunization review with their adult patients, that they provide recommended immunizations or refer patients to someone who will, and that all physicians and their staffs should be vaccinated according to the CDC, with particular attention to annual influenza immunization.

“We hope that publication of the annual Adult Immunization Schedule in this issue will prompt clinicians to redouble their efforts to improve their practices' immunization rates. Doing so will prevent needless morbidity, mortality, and expense,” Dr. Poland and Dr. Schaffner concluded. Both doctors disclosed financial ties to several vaccine manufacturers.

ACIP members follow strict conflict of interest guidelines.

The Adult Immunization Schedule is available at www.cdc.gov/vaccines/recs/schedules/adult-schedule.htm

The Adult Immunization Schedule is available at www.cdc.gov/vaccines/recs/schedules/adult-schedule.htmwww.cdc.gov/vaccines/pubs/acip-list.comwww.vaers.hhs.gov

This year's Adult Immunization Schedule includes the 2008 recommendation to use the pneumococcal polysaccharide vaccine in cigarette smokers and patients with asthma.

No new vaccines have been added to the schedule, but there are several changes to the chart's format, as well as updated footnotes for certain vaccines, said Dr. Gina Mootrey of the CDC's Immunization Services Administration, and her associates.

The schedule, published in January, was approved by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) and endorsed by the American College of Physicians, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists (MMWR 2009;57:Q1–4).

ACIP voted to recommend pneumococcal polysaccharide vaccine to adults with asthma in June 2008, based on data suggesting that adults with asthma were at more than double the risk (adjusted odds ratio 2.4) for invasive pneumococcal disease (INTERNAL MEDICINE NEWS, July 15, 2008, p. 1). The ACIP decision on smokers was made in October 2008, based on data that smoking is the strongest independent risk factor for pneumococcal disease in nonelderly immunocompetent adults, with an adjusted odds ratio of 4.1 (INTERNAL MEDICINE NEWS, Nov. 15, 2008, p. 1).

In an editorial, Dr. Gregory A. Poland and Dr. William Schaffner noted that most asthmatic adults who develop invasive pneumococcal disease already have another condition for which the vaccine is indicated, but they don't receive it (Ann. Intern. Med. 2009;150:53–6).

“Making asthma an indication for pneumococcal vaccination will resolve previous ambiguity, be consistent with the influenza vaccine recommendations, and challenge us to identify and vaccinate these patients,” said Dr. Poland of the Mayo Clinic, Rochester, Minn., and Dr. Schaffner of Vanderbilt University, Nashville, Tenn.

It is now recommended that all children from 5 years through 18 years of age (in addition to children aged 6 months to 5 years, as previously recommended), receive the influenza vaccine, as well as individuals who live with or care for people at increased risk for influenza-related complications, including all health care workers.

Other changes and clarifications in the footnotes of the 2009 schedule include the following:

▸ A note was added to say that health care personnel are not at increased risk for human papillomavirus through occupational exposure, and that they should receive the vaccine consistent with age-based recommendations.

▸ A second dose of varicella vaccine should be given to adults who previously received only one dose.

▸ Information was added about an alternative four-dose schedule for the combined hepatitis A/B vaccine.

▸ The 5-year revaccination interval for the meningococcal vaccine was clarified.

Dr. Poland and Dr. Schaffner both disclosed financial ties to several vaccine manufacturers. Members of ACIP who disclosed relationships with vaccine manufacturers were not allowed to vote on issues pertaining to those companies' products.

The Adult Immunization Schedule is available at www.cdc.gov/vaccines/recs/schedules/adult-schedule.htmwww.cdc.gov/vaccines/pubs/acip-list.comwww.vaers.hhs.gov

This year's Adult Immunization Schedule includes the 2008 recommendation to use the pneumococcal polysaccharide vaccine in cigarette smokers and patients with asthma.

No new vaccines have been added to the schedule, but there are several changes to the chart's format, as well as updated footnotes for certain vaccines, said Dr. Gina Mootrey of the CDC's Immunization Services Administration, and her associates.

The schedule, published in January, was approved by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) and endorsed by the American College of Physicians, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists (MMWR 2009;57:Q1–4).

ACIP voted to recommend pneumococcal polysaccharide vaccine to adults with asthma in June 2008, based on data suggesting that adults with asthma were at more than double the risk (adjusted odds ratio 2.4) for invasive pneumococcal disease (INTERNAL MEDICINE NEWS, July 15, 2008, p. 1). The ACIP decision on smokers was made in October 2008, based on data that smoking is the strongest independent risk factor for pneumococcal disease in nonelderly immunocompetent adults, with an adjusted odds ratio of 4.1 (INTERNAL MEDICINE NEWS, Nov. 15, 2008, p. 1).

In an editorial, Dr. Gregory A. Poland and Dr. William Schaffner noted that most asthmatic adults who develop invasive pneumococcal disease already have another condition for which the vaccine is indicated, but they don't receive it (Ann. Intern. Med. 2009;150:53–6).

“Making asthma an indication for pneumococcal vaccination will resolve previous ambiguity, be consistent with the influenza vaccine recommendations, and challenge us to identify and vaccinate these patients,” said Dr. Poland of the Mayo Clinic, Rochester, Minn., and Dr. Schaffner of Vanderbilt University, Nashville, Tenn.

It is now recommended that all children from 5 years through 18 years of age (in addition to children aged 6 months to 5 years, as previously recommended), receive the influenza vaccine, as well as individuals who live with or care for people at increased risk for influenza-related complications, including all health care workers.

Other changes and clarifications in the footnotes of the 2009 schedule include the following:

▸ A note was added to say that health care personnel are not at increased risk for human papillomavirus through occupational exposure, and that they should receive the vaccine consistent with age-based recommendations.

▸ A second dose of varicella vaccine should be given to adults who previously received only one dose.

▸ Information was added about an alternative four-dose schedule for the combined hepatitis A/B vaccine.

▸ The 5-year revaccination interval for the meningococcal vaccine was clarified.

Dr. Poland and Dr. Schaffner both disclosed financial ties to several vaccine manufacturers. Members of ACIP who disclosed relationships with vaccine manufacturers were not allowed to vote on issues pertaining to those companies' products.

The Adult Immunization Schedule is available at www.cdc.gov/vaccines/recs/schedules/adult-schedule.htmwww.cdc.gov/vaccines/pubs/acip-list.comwww.vaers.hhs.gov

This year's Adult Immunization Schedule includes the 2008 recommendation to use the pneumococcal polysaccharide vaccine in cigarette smokers and patients with asthma.

No new vaccines have been added to the schedule, but there are several changes to the chart's format, as well as updated footnotes for certain vaccines, said Dr. Gina Mootrey of the CDC's Immunization Services Administration, and her associates.

The schedule, published in January, was approved by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) and endorsed by the American College of Physicians, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists (MMWR 2009;57:Q1–4).

ACIP voted to recommend pneumococcal polysaccharide vaccine to adults with asthma in June 2008, based on data suggesting that adults with asthma were at more than double the risk (adjusted odds ratio 2.4) for invasive pneumococcal disease (INTERNAL MEDICINE NEWS, July 15, 2008, p. 1). The ACIP decision on smokers was made in October 2008, based on data that smoking is the strongest independent risk factor for pneumococcal disease in nonelderly immunocompetent adults, with an adjusted odds ratio of 4.1 (INTERNAL MEDICINE NEWS, Nov. 15, 2008, p. 1).

In an editorial, Dr. Gregory A. Poland and Dr. William Schaffner noted that most asthmatic adults who develop invasive pneumococcal disease already have another condition for which the vaccine is indicated, but they don't receive it (Ann. Intern. Med. 2009;150:53–6).

“Making asthma an indication for pneumococcal vaccination will resolve previous ambiguity, be consistent with the influenza vaccine recommendations, and challenge us to identify and vaccinate these patients,” said Dr. Poland of the Mayo Clinic, Rochester, Minn., and Dr. Schaffner of Vanderbilt University, Nashville, Tenn.

It is now recommended that all children from 5 years through 18 years of age (in addition to children aged 6 months to 5 years, as previously recommended), receive the influenza vaccine, as well as individuals who live with or care for people at increased risk for influenza-related complications, including all health care workers.

Other changes and clarifications in the footnotes of the 2009 schedule include the following:

▸ A note was added to say that health care personnel are not at increased risk for human papillomavirus through occupational exposure, and that they should receive the vaccine consistent with age-based recommendations.

▸ A second dose of varicella vaccine should be given to adults who previously received only one dose.

▸ Information was added about an alternative four-dose schedule for the combined hepatitis A/B vaccine.

▸ The 5-year revaccination interval for the meningococcal vaccine was clarified.

Dr. Poland and Dr. Schaffner both disclosed financial ties to several vaccine manufacturers. Members of ACIP who disclosed relationships with vaccine manufacturers were not allowed to vote on issues pertaining to those companies' products.

WASHINGTON — A novel topical antiviral nanoemulsion reduced the time to healing of cold sores by more than 1 day in a phase IIB study of patients with recurrent herpes labialis.

The lotion, called NB-001, is an oil-in-water emulsion containing nanometer-size droplets that permeate the skin and fuse with the herpes virus, thereby disrupting its outer surface and lysing it, without irritating normal skin. The physical mechanism of action makes drug resistance unlikely, Dr. Mary R. Flack said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

The 1-day benefit seen with NB-001 is similar to that seen with oral antiviral drugs such as famciclovir and valacyclovir, available only by prescription because the Food and Drug Administration is concerned about drug resistance. Prescription and over-the-counter topical antivirals, such as docosanol, acyclovir, and penciclovir, speed healing by about half a day.

“We need a topical product that is as effective as the orals. Nanoemulsion could provide such a product,” said Dr. Flack, vice president of clinical affairs at NanoBio Corp., Ann Arbor, Mich.

In a 28-center, double-blind, vehicle-controlled trial conducted by the company, 991 patients with a history of at least three cold sores per year were randomized to receive either vehicle alone or NB-001 in concentrations of 0.1%, 0.3%, or 0.5%. At symptom onset, patients began treatment five times daily until the lesion healed, or a maximum of 4 days. Of 484 patients who had an outbreak during the 6-month study, 482 received at least one dose of study medication. Of those, 92% started treatment within 4 hours of symptom onset at the prodrome or erythema stage.

The 482 patients in the intent-to-treat population had a mean age of 44 years, 71% were women, and 94% were white. Both median and mean times to healing for the group that received 0.3% NB-001 were a day or more improved, vs. vehicle alone. The group receiving 0.1% NB-001 healed about half a day faster, which was not statistically significant but was similar to the benefit seen with current topical antivirals.

The 0.5% concentration, in contrast, did not significantly reduce time to healing. At concentrations greater than 0.3%, there was precipitation of one ingredient that formed crystals, preventing permeation of the drug. This is a common phenomenon with topical agents, Dr. Flack said.

None of the subjects had drug-related skin irritation. Only negligible levels of plasma cetylpyridinium chloride (a marker for nanodroplet delivery) were seen in both treated and vehicle subjects, indicating no systemic exposure, she said.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A novel topical antiviral nanoemulsion reduced the time to healing of cold sores by more than 1 day in a phase IIB study of patients with recurrent herpes labialis.

The lotion, called NB-001, is an oil-in-water emulsion containing nanometer-size droplets that permeate the skin and fuse with the herpes virus, thereby disrupting its outer surface and lysing it, without irritating normal skin. The physical mechanism of action makes drug resistance unlikely, Dr. Mary R. Flack said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

The 1-day benefit seen with NB-001 is similar to that seen with oral antiviral drugs such as famciclovir and valacyclovir, available only by prescription because the Food and Drug Administration is concerned about drug resistance. Prescription and over-the-counter topical antivirals, such as docosanol, acyclovir, and penciclovir, speed healing by about half a day.

“We need a topical product that is as effective as the orals. Nanoemulsion could provide such a product,” said Dr. Flack, vice president of clinical affairs at NanoBio Corp., Ann Arbor, Mich.

In a 28-center, double-blind, vehicle-controlled trial conducted by the company, 991 patients with a history of at least three cold sores per year were randomized to receive either vehicle alone or NB-001 in concentrations of 0.1%, 0.3%, or 0.5%. At symptom onset, patients began treatment five times daily until the lesion healed, or a maximum of 4 days. Of 484 patients who had an outbreak during the 6-month study, 482 received at least one dose of study medication. Of those, 92% started treatment within 4 hours of symptom onset at the prodrome or erythema stage.

The 482 patients in the intent-to-treat population had a mean age of 44 years, 71% were women, and 94% were white. Both median and mean times to healing for the group that received 0.3% NB-001 were a day or more improved, vs. vehicle alone. The group receiving 0.1% NB-001 healed about half a day faster, which was not statistically significant but was similar to the benefit seen with current topical antivirals.

The 0.5% concentration, in contrast, did not significantly reduce time to healing. At concentrations greater than 0.3%, there was precipitation of one ingredient that formed crystals, preventing permeation of the drug. This is a common phenomenon with topical agents, Dr. Flack said.

None of the subjects had drug-related skin irritation. Only negligible levels of plasma cetylpyridinium chloride (a marker for nanodroplet delivery) were seen in both treated and vehicle subjects, indicating no systemic exposure, she said.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A novel topical antiviral nanoemulsion reduced the time to healing of cold sores by more than 1 day in a phase IIB study of patients with recurrent herpes labialis.

The lotion, called NB-001, is an oil-in-water emulsion containing nanometer-size droplets that permeate the skin and fuse with the herpes virus, thereby disrupting its outer surface and lysing it, without irritating normal skin. The physical mechanism of action makes drug resistance unlikely, Dr. Mary R. Flack said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

The 1-day benefit seen with NB-001 is similar to that seen with oral antiviral drugs such as famciclovir and valacyclovir, available only by prescription because the Food and Drug Administration is concerned about drug resistance. Prescription and over-the-counter topical antivirals, such as docosanol, acyclovir, and penciclovir, speed healing by about half a day.

“We need a topical product that is as effective as the orals. Nanoemulsion could provide such a product,” said Dr. Flack, vice president of clinical affairs at NanoBio Corp., Ann Arbor, Mich.

In a 28-center, double-blind, vehicle-controlled trial conducted by the company, 991 patients with a history of at least three cold sores per year were randomized to receive either vehicle alone or NB-001 in concentrations of 0.1%, 0.3%, or 0.5%. At symptom onset, patients began treatment five times daily until the lesion healed, or a maximum of 4 days. Of 484 patients who had an outbreak during the 6-month study, 482 received at least one dose of study medication. Of those, 92% started treatment within 4 hours of symptom onset at the prodrome or erythema stage.

The 482 patients in the intent-to-treat population had a mean age of 44 years, 71% were women, and 94% were white. Both median and mean times to healing for the group that received 0.3% NB-001 were a day or more improved, vs. vehicle alone. The group receiving 0.1% NB-001 healed about half a day faster, which was not statistically significant but was similar to the benefit seen with current topical antivirals.

The 0.5% concentration, in contrast, did not significantly reduce time to healing. At concentrations greater than 0.3%, there was precipitation of one ingredient that formed crystals, preventing permeation of the drug. This is a common phenomenon with topical agents, Dr. Flack said.

None of the subjects had drug-related skin irritation. Only negligible levels of plasma cetylpyridinium chloride (a marker for nanodroplet delivery) were seen in both treated and vehicle subjects, indicating no systemic exposure, she said.

ELSEVIER GLOBAL MEDICAL NEWS

The Food and Drug Administration has added a boxed warning to the prescription oral sodium phosphate bowel preparation products Visicol and OsmoPrep concerning the risk of acute phosphate nephropathy.

The agency is also recommending consumers not use over-the-counter oral sodium phosphate product (OSPs) for bowel cleansing. Although available data do not show a risk of acute kidney injury when the OTC products are taken at the lower doses for laxative use, when used at higher doses for bowel cleansing they are associated with the same risks as the prescription OSP products. Boxed warnings are not used for OTC products, but the agency plans to issue an amended label for OTC OSP products by May of 2009, Dr. Charles Ganley, director of the FDA's Office of Nonprescription Products, said in a telephone press briefing.

The FDA has also directed Salix Pharmaceuticals, maker of both products, to develop a risk evaluation and mitigation strategy, distribute a Medication Guide to alert patients to the risk of acute kidney injury associated with the use of OSP products and conduct a postmarketing clinical trial to further assess the risk of acute kidney injury associated with these products, Dr. Joyce Korvick, deputy director of the FDA's Division of Gastroenterology Products said at the briefing.

In 2006, the FDA issued a Science Paper and a Healthcare Professional sheet on the risks associated with the use of OSP products for bowel cleansing. Since then, the agency has received reports of acute phosphate nephropathy with both prescription and products available in the OTC setting, including 20 unique cases of kidney injury associated with the use of OsmoPrep. Of the reported cases, three were biopsy-proven acute phosphate nephropathy. The onset of kidney injury in these cases varied, occurring in some cases within several hours of OSP use and in other cases up to 21 days after use.

Health care providers are advised to consider the following when prescribing OSPs for bowel preparation:

▸ Provide easy-to-understand instructions to the patient about preparing for the procedure. Tell them what symptoms to be aware of so they can recognize and possibly mitigate the risk of acute kidney injury.

▸ Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing. An electrolyte or carbohydrate-electrolyte replacement solution may help decrease the electrolyte abnormalities and hypovolemia associated with OSP bowel cleansing.

▸ Avoid exceeding the maximum recommended OSP doses.

▸ Avoid concomitant use of laxatives containing sodium phosphate.

▸ Avoid use in patients under age 18.

▸ Use with caution in patients over age 55.

▸ Use OSPs with caution in patients with dehydration, kidney disease, delayed bowel emptying, or acute colitis.

▸ Use OSPs with caution in patients taking medicines that affect kidney function or perfusion, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and possibly nonsteroidal anti-inflammatory drugs.

▸ Obtain baseline and postprocedure labs (electrolytes, calcium, phosphate, BUN, and creatinine) in patients who may be at increased risk for acute phosphate nephropathy, including those with vomiting and/or signs of dehydration. For smaller, frail individuals, also monitor glomerular filtration rate.

▸ Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or have no assistance at home.

Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment in patients recently exposed to OSP. Renal biopsy typically reveals acute and/or chronic renal tubular injury (depending on time to diagnosis), calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histologic injury.

Serious adverse events or product quality problems associated with these products can be reported www.fda.gov/MedWatch/

The Food and Drug Administration has added a boxed warning to the prescription oral sodium phosphate bowel preparation products Visicol and OsmoPrep concerning the risk of acute phosphate nephropathy.

The agency is also recommending consumers not use over-the-counter oral sodium phosphate product (OSPs) for bowel cleansing. Although available data do not show a risk of acute kidney injury when the OTC products are taken at the lower doses for laxative use, when used at higher doses for bowel cleansing they are associated with the same risks as the prescription OSP products. Boxed warnings are not used for OTC products, but the agency plans to issue an amended label for OTC OSP products by May of 2009, Dr. Charles Ganley, director of the FDA's Office of Nonprescription Products, said in a telephone press briefing.

The FDA has also directed Salix Pharmaceuticals, maker of both products, to develop a risk evaluation and mitigation strategy, distribute a Medication Guide to alert patients to the risk of acute kidney injury associated with the use of OSP products and conduct a postmarketing clinical trial to further assess the risk of acute kidney injury associated with these products, Dr. Joyce Korvick, deputy director of the FDA's Division of Gastroenterology Products said at the briefing.

In 2006, the FDA issued a Science Paper and a Healthcare Professional sheet on the risks associated with the use of OSP products for bowel cleansing. Since then, the agency has received reports of acute phosphate nephropathy with both prescription and products available in the OTC setting, including 20 unique cases of kidney injury associated with the use of OsmoPrep. Of the reported cases, three were biopsy-proven acute phosphate nephropathy. The onset of kidney injury in these cases varied, occurring in some cases within several hours of OSP use and in other cases up to 21 days after use.

Health care providers are advised to consider the following when prescribing OSPs for bowel preparation:

▸ Provide easy-to-understand instructions to the patient about preparing for the procedure. Tell them what symptoms to be aware of so they can recognize and possibly mitigate the risk of acute kidney injury.

▸ Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing. An electrolyte or carbohydrate-electrolyte replacement solution may help decrease the electrolyte abnormalities and hypovolemia associated with OSP bowel cleansing.

▸ Avoid exceeding the maximum recommended OSP doses.

▸ Avoid concomitant use of laxatives containing sodium phosphate.

▸ Avoid use in patients under age 18.

▸ Use with caution in patients over age 55.

▸ Use OSPs with caution in patients with dehydration, kidney disease, delayed bowel emptying, or acute colitis.

▸ Use OSPs with caution in patients taking medicines that affect kidney function or perfusion, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and possibly nonsteroidal anti-inflammatory drugs.

▸ Obtain baseline and postprocedure labs (electrolytes, calcium, phosphate, BUN, and creatinine) in patients who may be at increased risk for acute phosphate nephropathy, including those with vomiting and/or signs of dehydration. For smaller, frail individuals, also monitor glomerular filtration rate.

▸ Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or have no assistance at home.

Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment in patients recently exposed to OSP. Renal biopsy typically reveals acute and/or chronic renal tubular injury (depending on time to diagnosis), calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histologic injury.

Serious adverse events or product quality problems associated with these products can be reported www.fda.gov/MedWatch/

The Food and Drug Administration has added a boxed warning to the prescription oral sodium phosphate bowel preparation products Visicol and OsmoPrep concerning the risk of acute phosphate nephropathy.

The agency is also recommending consumers not use over-the-counter oral sodium phosphate product (OSPs) for bowel cleansing. Although available data do not show a risk of acute kidney injury when the OTC products are taken at the lower doses for laxative use, when used at higher doses for bowel cleansing they are associated with the same risks as the prescription OSP products. Boxed warnings are not used for OTC products, but the agency plans to issue an amended label for OTC OSP products by May of 2009, Dr. Charles Ganley, director of the FDA's Office of Nonprescription Products, said in a telephone press briefing.

The FDA has also directed Salix Pharmaceuticals, maker of both products, to develop a risk evaluation and mitigation strategy, distribute a Medication Guide to alert patients to the risk of acute kidney injury associated with the use of OSP products and conduct a postmarketing clinical trial to further assess the risk of acute kidney injury associated with these products, Dr. Joyce Korvick, deputy director of the FDA's Division of Gastroenterology Products said at the briefing.

In 2006, the FDA issued a Science Paper and a Healthcare Professional sheet on the risks associated with the use of OSP products for bowel cleansing. Since then, the agency has received reports of acute phosphate nephropathy with both prescription and products available in the OTC setting, including 20 unique cases of kidney injury associated with the use of OsmoPrep. Of the reported cases, three were biopsy-proven acute phosphate nephropathy. The onset of kidney injury in these cases varied, occurring in some cases within several hours of OSP use and in other cases up to 21 days after use.

Health care providers are advised to consider the following when prescribing OSPs for bowel preparation:

▸ Provide easy-to-understand instructions to the patient about preparing for the procedure. Tell them what symptoms to be aware of so they can recognize and possibly mitigate the risk of acute kidney injury.

▸ Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing. An electrolyte or carbohydrate-electrolyte replacement solution may help decrease the electrolyte abnormalities and hypovolemia associated with OSP bowel cleansing.

▸ Avoid exceeding the maximum recommended OSP doses.

▸ Avoid concomitant use of laxatives containing sodium phosphate.

▸ Avoid use in patients under age 18.

▸ Use with caution in patients over age 55.

▸ Use OSPs with caution in patients with dehydration, kidney disease, delayed bowel emptying, or acute colitis.

▸ Use OSPs with caution in patients taking medicines that affect kidney function or perfusion, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and possibly nonsteroidal anti-inflammatory drugs.

▸ Obtain baseline and postprocedure labs (electrolytes, calcium, phosphate, BUN, and creatinine) in patients who may be at increased risk for acute phosphate nephropathy, including those with vomiting and/or signs of dehydration. For smaller, frail individuals, also monitor glomerular filtration rate.

▸ Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or have no assistance at home.

Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment in patients recently exposed to OSP. Renal biopsy typically reveals acute and/or chronic renal tubular injury (depending on time to diagnosis), calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histologic injury.

Serious adverse events or product quality problems associated with these products can be reported www.fda.gov/MedWatch/

WASHINGTON — High rates of both overall and subclinical viral shedding continue even beyond 10 years among people with genital herpes simplex virus type 2 infection, suggesting that there is a continued risk of transmission to sexual partners long after initial infection.

The findings, from a study of 377 healthy adults with a history of symptomatic herpes simplex virus type 2 (HSV-2) infection, “have implications for long-term management of transmission and treatment of clinical recurrences, including long-term use of antiviral medications for clinical suppression and condom use to reduce transmission to partners,” Dr. Warren Phipps said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Previous studies suggest that rates of HSV-2 shedding during the first year of infection range from 9% to 40% of days sampled using polymerase chain reaction (PCR), and that clinical recurrences are common, with a median of about four outbreaks per year. Subclinical shedding (that is, shedding without lesions) during the first year is estimated to represent about 50% of days of reactivation. Much less is known about the natural history of genital herpes beyond the first year, noted Dr. Phipps of the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle.

The study population included participants in several prospective observational studies, some of them funded by GlaxoSmithKline, conducted at two clinics from 1992 to 2008. Subjects collected swabs on at least 30 consecutive days from perianal, vulvar, cervical, penile, and/or urethral sites. They also kept symptom diaries. The swabs were tested for HSV-2 using PCR.

The 377 subjects had a mean age of 39 years (range 20–76 years); 62% were female and 89% were white. The entire group collected swabs on a total of 28,252 days. Participants were grouped as having had “less than 1 year,” “1–9 years,” and “10 or more years” since their initial episode.

Time since initial genital herpes episode was associated with reductions in both total and subclinical HSV-2 shedding, from 26% of sampled days within 1 year, to 16% at 1–9 years, to 14% at 10 years and beyond for total shedding, and from 19% to 8% to 4% of sampled days, respectively, for subclinical shedding. The appearance of clinical lesions dropped insignificantly with time, from 11% to 10% to 7% of sampled days for the three groups, respectively. “Although shedding was reduced, it is important to note that rates still remained high even beyond 10 years or more from the initial clinical episode,” Dr. Phipps commented.

Nonwhites had much higher reactivation rates than whites within the first year (65% vs. 26%), but rates were much lower at 1–9 years (7% vs. 18%) and at 10 or more years (4% vs. 16%). Rates of subclinical shedding also decreased to a greater degree with time in blacks vs. whites. There were no associations with rates of shedding by gender, sexual orientation, HSV antibody status, age at first sexual contact, or age at first herpes lesion.

Small but significant decreases were seen in HSV-2 DNA copy numbers, from 4.8 to 4.6 log10 copies/mL between the less than 1 year and 10 years or greater groups. “Although there is no known 'infectivity threshold,' it is generally thought that virus is infectious at greater than 3 log10 copies/mL, so these titers remain in presumed infectious range remote from initial infection,” Dr. Phipps said.

Duration of any reactivation and subclinical reactivation episodes did not change over time, but the duration of clinical episodes did decrease significantly over time, from a median of 8.5 days within 1 year, to 5.8 days at 1–9 years, to 5.0 days at 10 years and beyond. These data support the notion that a virologic set point may be established in genital herpes infections, with lower rates and copy numbers after the first year of infection, but with ultimately persistent reactivation, he commented.

Dr. Phipps said that he had no financial disclosures.

WASHINGTON — High rates of both overall and subclinical viral shedding continue even beyond 10 years among people with genital herpes simplex virus type 2 infection, suggesting that there is a continued risk of transmission to sexual partners long after initial infection.

The findings, from a study of 377 healthy adults with a history of symptomatic herpes simplex virus type 2 (HSV-2) infection, “have implications for long-term management of transmission and treatment of clinical recurrences, including long-term use of antiviral medications for clinical suppression and condom use to reduce transmission to partners,” Dr. Warren Phipps said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Previous studies suggest that rates of HSV-2 shedding during the first year of infection range from 9% to 40% of days sampled using polymerase chain reaction (PCR), and that clinical recurrences are common, with a median of about four outbreaks per year. Subclinical shedding (that is, shedding without lesions) during the first year is estimated to represent about 50% of days of reactivation. Much less is known about the natural history of genital herpes beyond the first year, noted Dr. Phipps of the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle.

The study population included participants in several prospective observational studies, some of them funded by GlaxoSmithKline, conducted at two clinics from 1992 to 2008. Subjects collected swabs on at least 30 consecutive days from perianal, vulvar, cervical, penile, and/or urethral sites. They also kept symptom diaries. The swabs were tested for HSV-2 using PCR.

The 377 subjects had a mean age of 39 years (range 20–76 years); 62% were female and 89% were white. The entire group collected swabs on a total of 28,252 days. Participants were grouped as having had “less than 1 year,” “1–9 years,” and “10 or more years” since their initial episode.

Time since initial genital herpes episode was associated with reductions in both total and subclinical HSV-2 shedding, from 26% of sampled days within 1 year, to 16% at 1–9 years, to 14% at 10 years and beyond for total shedding, and from 19% to 8% to 4% of sampled days, respectively, for subclinical shedding. The appearance of clinical lesions dropped insignificantly with time, from 11% to 10% to 7% of sampled days for the three groups, respectively. “Although shedding was reduced, it is important to note that rates still remained high even beyond 10 years or more from the initial clinical episode,” Dr. Phipps commented.

Nonwhites had much higher reactivation rates than whites within the first year (65% vs. 26%), but rates were much lower at 1–9 years (7% vs. 18%) and at 10 or more years (4% vs. 16%). Rates of subclinical shedding also decreased to a greater degree with time in blacks vs. whites. There were no associations with rates of shedding by gender, sexual orientation, HSV antibody status, age at first sexual contact, or age at first herpes lesion.

Small but significant decreases were seen in HSV-2 DNA copy numbers, from 4.8 to 4.6 log10 copies/mL between the less than 1 year and 10 years or greater groups. “Although there is no known 'infectivity threshold,' it is generally thought that virus is infectious at greater than 3 log10 copies/mL, so these titers remain in presumed infectious range remote from initial infection,” Dr. Phipps said.

Duration of any reactivation and subclinical reactivation episodes did not change over time, but the duration of clinical episodes did decrease significantly over time, from a median of 8.5 days within 1 year, to 5.8 days at 1–9 years, to 5.0 days at 10 years and beyond. These data support the notion that a virologic set point may be established in genital herpes infections, with lower rates and copy numbers after the first year of infection, but with ultimately persistent reactivation, he commented.

Dr. Phipps said that he had no financial disclosures.

WASHINGTON — High rates of both overall and subclinical viral shedding continue even beyond 10 years among people with genital herpes simplex virus type 2 infection, suggesting that there is a continued risk of transmission to sexual partners long after initial infection.

The findings, from a study of 377 healthy adults with a history of symptomatic herpes simplex virus type 2 (HSV-2) infection, “have implications for long-term management of transmission and treatment of clinical recurrences, including long-term use of antiviral medications for clinical suppression and condom use to reduce transmission to partners,” Dr. Warren Phipps said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Previous studies suggest that rates of HSV-2 shedding during the first year of infection range from 9% to 40% of days sampled using polymerase chain reaction (PCR), and that clinical recurrences are common, with a median of about four outbreaks per year. Subclinical shedding (that is, shedding without lesions) during the first year is estimated to represent about 50% of days of reactivation. Much less is known about the natural history of genital herpes beyond the first year, noted Dr. Phipps of the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle.

The study population included participants in several prospective observational studies, some of them funded by GlaxoSmithKline, conducted at two clinics from 1992 to 2008. Subjects collected swabs on at least 30 consecutive days from perianal, vulvar, cervical, penile, and/or urethral sites. They also kept symptom diaries. The swabs were tested for HSV-2 using PCR.

The 377 subjects had a mean age of 39 years (range 20–76 years); 62% were female and 89% were white. The entire group collected swabs on a total of 28,252 days. Participants were grouped as having had “less than 1 year,” “1–9 years,” and “10 or more years” since their initial episode.

Time since initial genital herpes episode was associated with reductions in both total and subclinical HSV-2 shedding, from 26% of sampled days within 1 year, to 16% at 1–9 years, to 14% at 10 years and beyond for total shedding, and from 19% to 8% to 4% of sampled days, respectively, for subclinical shedding. The appearance of clinical lesions dropped insignificantly with time, from 11% to 10% to 7% of sampled days for the three groups, respectively. “Although shedding was reduced, it is important to note that rates still remained high even beyond 10 years or more from the initial clinical episode,” Dr. Phipps commented.

Nonwhites had much higher reactivation rates than whites within the first year (65% vs. 26%), but rates were much lower at 1–9 years (7% vs. 18%) and at 10 or more years (4% vs. 16%). Rates of subclinical shedding also decreased to a greater degree with time in blacks vs. whites. There were no associations with rates of shedding by gender, sexual orientation, HSV antibody status, age at first sexual contact, or age at first herpes lesion.

Small but significant decreases were seen in HSV-2 DNA copy numbers, from 4.8 to 4.6 log10 copies/mL between the less than 1 year and 10 years or greater groups. “Although there is no known 'infectivity threshold,' it is generally thought that virus is infectious at greater than 3 log10 copies/mL, so these titers remain in presumed infectious range remote from initial infection,” Dr. Phipps said.

Duration of any reactivation and subclinical reactivation episodes did not change over time, but the duration of clinical episodes did decrease significantly over time, from a median of 8.5 days within 1 year, to 5.8 days at 1–9 years, to 5.0 days at 10 years and beyond. These data support the notion that a virologic set point may be established in genital herpes infections, with lower rates and copy numbers after the first year of infection, but with ultimately persistent reactivation, he commented.

Dr. Phipps said that he had no financial disclosures.

WASHINGTON — A preparation of fecal bacteria from healthy donors successfully resolved chronic relapsing Clostridium difficile-associated diarrhea in 46 of 48 patients, of whom all but one underwent the procedure in their homes.

Few conventional therapeutic options are available for patients with multiply recurrent C. difficile diarrhea. Such patients often become trapped in “vancomycin dependence” as antimicrobial suppression of the intestinal microbiome maintains vulnerability to recurrence, with a likelihood of relapse exceeding 65% after the third episode. Treatments that have been tried—including vancomycin tapering or pulse dosing, and probiotic therapy using Lactobacillus GG or Saccharomyces boulardii—have not been shown effective in arresting recurrences of C. difficile, Dr. Thomas J. Louie said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“Normal” stool microbes, most of which cannot be cultivated, constitute the “ultimate probiotic” and have been shown to be highly effective in arresting recurrences of C. difficile infection. Delivery of the microflora by jejunal tube or during colonic endoscopy would typically require clinic or hospital facilities.

Dr. Louie, professor of medicine, microbiology, and infectious disease at the University of Calgary (Canada), has developed a home-based method for colonic fecal transfer that incurs no hospital or clinic costs and allows the patient to remain in bed to promote inoculum retention.

Over an 11-year period, 35 women and 13 men received a total of 59 fecal transfers. All of the patients had been referred by a gastroenterologist or an infectious disease specialist for recalcitrant recurrent disease involving at least four episodes over a period of 6 months or longer; the episodes would respond to vancomycin but would recur despite the use of vancomycin tapering or pulse dosing and probiotics. All but 1 of the 48 patients were ambulatory. They had a mean age of 62 years (range 30–91 years), with a mean relapse duration of 10 months (range 6–24 months).

Prior to the procedure, patients were treated with vancomycin to control the symptoms and signs of C. difficile infection completely, generally for 14 days or more, followed by either a 4-day washout period or oral Fleet enema 12 hours before the procedure, in order to reduce vancomycin concentrations in the stool.

Donors had to be healthy, with no antibiotic exposure in the previous 6 months. All were screened for pathogens using the same guidelines used for blood donors. All but 10 donors were genetic relatives of the patient (siblings, parents, or offspring). This was preferred because some data suggest a “relatedness” of stool is beneficial, Dr. Louie noted.

Donors collected sequential stools for 3 days in plastic-lidded pails, stored at 4–8° C, with the final sample collected on the morning of the procedure. The stools were mixed with phosphate-buffered saline with added cysteine and then sieved through a wire mesh to remove particulates.

Following a normal bowel movement or clearing enema and diazepam sedation, the fecal preparation was inserted via a balloon catheter, with the patient lying in a lateral position. This usually was done on the patient's own bed, atop a plastic sheet and layers of absorptive pads to prevent soiling the mattress.

The procedures were carried out over 10–45 minutes, depending on the presence or absence of colonic contractions. During the transfer of 800–1,400 mL of bacterial preparation, the patients were positioned so that the fluid could reach the right side of the colon. They were instructed to eat a very light breakfast and consume only liquids the rest of the day, to avoid triggering a “mass movement.” They were also told to rest for 4–6 hours to promote retention of the inoculum.

The C. difficile infection was completely resolved with just one fecal transfer in most of the patients, with three required in one patient and two required in four patients. Of the two patients in whom the infection did not resolve, one had a recurrence with initiation of proton pump inhibitor treatment for gastroesophageal reflux, and the other did not respond to a single procedure and was expected to undergo a repeat procedure.

All 10 of the patients whose donors were spouses resolved, but 4 of them had irritable bowel-like symptoms (intestinal cramping and gas) for 3–6 months after the procedure; such symptoms were not noted in those who received stool from genetic relatives. It's not clear if the genetic makeup of the microbiome is the reason, Dr. Louie commented.

Performing this procedure in patients' homes—or even doing them at all—was something that Dr. Louie “got into by accident.” He performed the first one in 1996, when a patient presented with multiply recurrent C. difficile for which other treatments had failed. Dr. Louie requested permission from Calgary General Hospital to do the procedure there, but the nurses objected, citing the lack of a precedent and aesthetic issues. “Hence, the idea of a hospital involvement was shelved,” he recounted in an interview.

Weeks later, that patient asked Dr. Louie if the procedure could be done at home. Such an ambulatory, nonhospital approach was supported by previous U.S. literature dating back to the 1950s, and by more recent reports from Australia, Scandinavia, and the United States.

It became clear that the home-based approach had many advantages. “Patient privacy was difficult to achieve in hospital, especially with shared toilet facilities. Also, because of difficulty admitting patients to a hospital for a procedure when they are otherwise well, it became immensely more practical to do the procedure as a home-based approach,” Dr. Louie said in the interview.

He has received research grants from companies that make or are developing products to treat C. difficile infection.

A home ceiling fan can be an innovative substitute for an IV pole.

The fecal preparation is inserted via a balloon catheter over 10–45 minutes while the patient lies in their own bed. Photos courtesy Dr. Thomas J. Louie

WASHINGTON — A preparation of fecal bacteria from healthy donors successfully resolved chronic relapsing Clostridium difficile-associated diarrhea in 46 of 48 patients, of whom all but one underwent the procedure in their homes.

Few conventional therapeutic options are available for patients with multiply recurrent C. difficile diarrhea. Such patients often become trapped in “vancomycin dependence” as antimicrobial suppression of the intestinal microbiome maintains vulnerability to recurrence, with a likelihood of relapse exceeding 65% after the third episode. Treatments that have been tried—including vancomycin tapering or pulse dosing, and probiotic therapy using Lactobacillus GG or Saccharomyces boulardii—have not been shown effective in arresting recurrences of C. difficile, Dr. Thomas J. Louie said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“Normal” stool microbes, most of which cannot be cultivated, constitute the “ultimate probiotic” and have been shown to be highly effective in arresting recurrences of C. difficile infection. Delivery of the microflora by jejunal tube or during colonic endoscopy would typically require clinic or hospital facilities.

Dr. Louie, professor of medicine, microbiology, and infectious disease at the University of Calgary (Canada), has developed a home-based method for colonic fecal transfer that incurs no hospital or clinic costs and allows the patient to remain in bed to promote inoculum retention.

Over an 11-year period, 35 women and 13 men received a total of 59 fecal transfers. All of the patients had been referred by a gastroenterologist or an infectious disease specialist for recalcitrant recurrent disease involving at least four episodes over a period of 6 months or longer; the episodes would respond to vancomycin but would recur despite the use of vancomycin tapering or pulse dosing and probiotics. All but 1 of the 48 patients were ambulatory. They had a mean age of 62 years (range 30–91 years), with a mean relapse duration of 10 months (range 6–24 months).

Prior to the procedure, patients were treated with vancomycin to control the symptoms and signs of C. difficile infection completely, generally for 14 days or more, followed by either a 4-day washout period or oral Fleet enema 12 hours before the procedure, in order to reduce vancomycin concentrations in the stool.

Donors had to be healthy, with no antibiotic exposure in the previous 6 months. All were screened for pathogens using the same guidelines used for blood donors. All but 10 donors were genetic relatives of the patient (siblings, parents, or offspring). This was preferred because some data suggest a “relatedness” of stool is beneficial, Dr. Louie noted.

Donors collected sequential stools for 3 days in plastic-lidded pails, stored at 4–8° C, with the final sample collected on the morning of the procedure. The stools were mixed with phosphate-buffered saline with added cysteine and then sieved through a wire mesh to remove particulates.

Following a normal bowel movement or clearing enema and diazepam sedation, the fecal preparation was inserted via a balloon catheter, with the patient lying in a lateral position. This usually was done on the patient's own bed, atop a plastic sheet and layers of absorptive pads to prevent soiling the mattress.

The procedures were carried out over 10–45 minutes, depending on the presence or absence of colonic contractions. During the transfer of 800–1,400 mL of bacterial preparation, the patients were positioned so that the fluid could reach the right side of the colon. They were instructed to eat a very light breakfast and consume only liquids the rest of the day, to avoid triggering a “mass movement.” They were also told to rest for 4–6 hours to promote retention of the inoculum.

The C. difficile infection was completely resolved with just one fecal transfer in most of the patients, with three required in one patient and two required in four patients. Of the two patients in whom the infection did not resolve, one had a recurrence with initiation of proton pump inhibitor treatment for gastroesophageal reflux, and the other did not respond to a single procedure and was expected to undergo a repeat procedure.

All 10 of the patients whose donors were spouses resolved, but 4 of them had irritable bowel-like symptoms (intestinal cramping and gas) for 3–6 months after the procedure; such symptoms were not noted in those who received stool from genetic relatives. It's not clear if the genetic makeup of the microbiome is the reason, Dr. Louie commented.

Performing this procedure in patients' homes—or even doing them at all—was something that Dr. Louie “got into by accident.” He performed the first one in 1996, when a patient presented with multiply recurrent C. difficile for which other treatments had failed. Dr. Louie requested permission from Calgary General Hospital to do the procedure there, but the nurses objected, citing the lack of a precedent and aesthetic issues. “Hence, the idea of a hospital involvement was shelved,” he recounted in an interview.

Weeks later, that patient asked Dr. Louie if the procedure could be done at home. Such an ambulatory, nonhospital approach was supported by previous U.S. literature dating back to the 1950s, and by more recent reports from Australia, Scandinavia, and the United States.

It became clear that the home-based approach had many advantages. “Patient privacy was difficult to achieve in hospital, especially with shared toilet facilities. Also, because of difficulty admitting patients to a hospital for a procedure when they are otherwise well, it became immensely more practical to do the procedure as a home-based approach,” Dr. Louie said in the interview.

He has received research grants from companies that make or are developing products to treat C. difficile infection.

A home ceiling fan can be an innovative substitute for an IV pole.

The fecal preparation is inserted via a balloon catheter over 10–45 minutes while the patient lies in their own bed. Photos courtesy Dr. Thomas J. Louie

WASHINGTON — A preparation of fecal bacteria from healthy donors successfully resolved chronic relapsing Clostridium difficile-associated diarrhea in 46 of 48 patients, of whom all but one underwent the procedure in their homes.

Few conventional therapeutic options are available for patients with multiply recurrent C. difficile diarrhea. Such patients often become trapped in “vancomycin dependence” as antimicrobial suppression of the intestinal microbiome maintains vulnerability to recurrence, with a likelihood of relapse exceeding 65% after the third episode. Treatments that have been tried—including vancomycin tapering or pulse dosing, and probiotic therapy using Lactobacillus GG or Saccharomyces boulardii—have not been shown effective in arresting recurrences of C. difficile, Dr. Thomas J. Louie said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“Normal” stool microbes, most of which cannot be cultivated, constitute the “ultimate probiotic” and have been shown to be highly effective in arresting recurrences of C. difficile infection. Delivery of the microflora by jejunal tube or during colonic endoscopy would typically require clinic or hospital facilities.

Dr. Louie, professor of medicine, microbiology, and infectious disease at the University of Calgary (Canada), has developed a home-based method for colonic fecal transfer that incurs no hospital or clinic costs and allows the patient to remain in bed to promote inoculum retention.

Over an 11-year period, 35 women and 13 men received a total of 59 fecal transfers. All of the patients had been referred by a gastroenterologist or an infectious disease specialist for recalcitrant recurrent disease involving at least four episodes over a period of 6 months or longer; the episodes would respond to vancomycin but would recur despite the use of vancomycin tapering or pulse dosing and probiotics. All but 1 of the 48 patients were ambulatory. They had a mean age of 62 years (range 30–91 years), with a mean relapse duration of 10 months (range 6–24 months).

Prior to the procedure, patients were treated with vancomycin to control the symptoms and signs of C. difficile infection completely, generally for 14 days or more, followed by either a 4-day washout period or oral Fleet enema 12 hours before the procedure, in order to reduce vancomycin concentrations in the stool.

Donors had to be healthy, with no antibiotic exposure in the previous 6 months. All were screened for pathogens using the same guidelines used for blood donors. All but 10 donors were genetic relatives of the patient (siblings, parents, or offspring). This was preferred because some data suggest a “relatedness” of stool is beneficial, Dr. Louie noted.

Donors collected sequential stools for 3 days in plastic-lidded pails, stored at 4–8° C, with the final sample collected on the morning of the procedure. The stools were mixed with phosphate-buffered saline with added cysteine and then sieved through a wire mesh to remove particulates.

Following a normal bowel movement or clearing enema and diazepam sedation, the fecal preparation was inserted via a balloon catheter, with the patient lying in a lateral position. This usually was done on the patient's own bed, atop a plastic sheet and layers of absorptive pads to prevent soiling the mattress.

The procedures were carried out over 10–45 minutes, depending on the presence or absence of colonic contractions. During the transfer of 800–1,400 mL of bacterial preparation, the patients were positioned so that the fluid could reach the right side of the colon. They were instructed to eat a very light breakfast and consume only liquids the rest of the day, to avoid triggering a “mass movement.” They were also told to rest for 4–6 hours to promote retention of the inoculum.

The C. difficile infection was completely resolved with just one fecal transfer in most of the patients, with three required in one patient and two required in four patients. Of the two patients in whom the infection did not resolve, one had a recurrence with initiation of proton pump inhibitor treatment for gastroesophageal reflux, and the other did not respond to a single procedure and was expected to undergo a repeat procedure.

All 10 of the patients whose donors were spouses resolved, but 4 of them had irritable bowel-like symptoms (intestinal cramping and gas) for 3–6 months after the procedure; such symptoms were not noted in those who received stool from genetic relatives. It's not clear if the genetic makeup of the microbiome is the reason, Dr. Louie commented.

Performing this procedure in patients' homes—or even doing them at all—was something that Dr. Louie “got into by accident.” He performed the first one in 1996, when a patient presented with multiply recurrent C. difficile for which other treatments had failed. Dr. Louie requested permission from Calgary General Hospital to do the procedure there, but the nurses objected, citing the lack of a precedent and aesthetic issues. “Hence, the idea of a hospital involvement was shelved,” he recounted in an interview.

Weeks later, that patient asked Dr. Louie if the procedure could be done at home. Such an ambulatory, nonhospital approach was supported by previous U.S. literature dating back to the 1950s, and by more recent reports from Australia, Scandinavia, and the United States.

It became clear that the home-based approach had many advantages. “Patient privacy was difficult to achieve in hospital, especially with shared toilet facilities. Also, because of difficulty admitting patients to a hospital for a procedure when they are otherwise well, it became immensely more practical to do the procedure as a home-based approach,” Dr. Louie said in the interview.

He has received research grants from companies that make or are developing products to treat C. difficile infection.

A home ceiling fan can be an innovative substitute for an IV pole.

The fecal preparation is inserted via a balloon catheter over 10–45 minutes while the patient lies in their own bed. Photos courtesy Dr. Thomas J. Louie