M. Alexander Otto

DENVER – A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug’s maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The "trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events," in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the annual meeting of the American Society of Nephrology.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m2.

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group. That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, Dr. Baigent noted.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. "With full compliance, we would be likely to reduce the risk of vascular events by about a quarter," he predicted.

However, lowering patients’ LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that "it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death," and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent. As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

The study largely "confirms what we already know" – that statins benefit kidney patients, said nephrologist Dr. Pablo Pergola, clinical associate professor of medicine at the University of Texas Health Science Center, San Antonio.

Dr. Pergola was curious, however, about what role, if any, ezetimibe may have played in the outcomes.

Following his presentation of the study results, Dr. Baigent noted the study wasn’t powered to answer that question.

The trial included a simvastatin-alone arm for the first year as a control to assess the safety of the ezetimibe/simvastatin combination.

However, "we didn’t continue it long-term, because to do so would have required a massive sample size – 30,000-40,000 patients – and we struggled to recruit 9,000," Dr. Baigent said.

In addition, "we didn’t think that was the key question," he explained. "The key question was, Does a large reduction in LDL cholesterol benefit kidney patients? This trial shows very clearly that it does.

"My guess is it’s not something special ezetimibe is doing," Dr. Baigent added. "It’s lowering LDL cholesterol in the same way statins do."

Dr. Baigent and Dr. Pergola said they have no conflicts of interest. Dr. Baigent added that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

DENVER – A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug’s maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The "trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events," in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the annual meeting of the American Society of Nephrology.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m2.

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group. That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, Dr. Baigent noted.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. "With full compliance, we would be likely to reduce the risk of vascular events by about a quarter," he predicted.

However, lowering patients’ LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that "it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death," and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent. As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

The study largely "confirms what we already know" – that statins benefit kidney patients, said nephrologist Dr. Pablo Pergola, clinical associate professor of medicine at the University of Texas Health Science Center, San Antonio.

Dr. Pergola was curious, however, about what role, if any, ezetimibe may have played in the outcomes.

Following his presentation of the study results, Dr. Baigent noted the study wasn’t powered to answer that question.

The trial included a simvastatin-alone arm for the first year as a control to assess the safety of the ezetimibe/simvastatin combination.

However, "we didn’t continue it long-term, because to do so would have required a massive sample size – 30,000-40,000 patients – and we struggled to recruit 9,000," Dr. Baigent said.

In addition, "we didn’t think that was the key question," he explained. "The key question was, Does a large reduction in LDL cholesterol benefit kidney patients? This trial shows very clearly that it does.

"My guess is it’s not something special ezetimibe is doing," Dr. Baigent added. "It’s lowering LDL cholesterol in the same way statins do."

Dr. Baigent and Dr. Pergola said they have no conflicts of interest. Dr. Baigent added that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

DENVER – A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug’s maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The "trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events," in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the annual meeting of the American Society of Nephrology.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m2.

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group. That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, Dr. Baigent noted.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. "With full compliance, we would be likely to reduce the risk of vascular events by about a quarter," he predicted.

However, lowering patients’ LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that "it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death," and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent. As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

The study largely "confirms what we already know" – that statins benefit kidney patients, said nephrologist Dr. Pablo Pergola, clinical associate professor of medicine at the University of Texas Health Science Center, San Antonio.

Dr. Pergola was curious, however, about what role, if any, ezetimibe may have played in the outcomes.

Following his presentation of the study results, Dr. Baigent noted the study wasn’t powered to answer that question.

The trial included a simvastatin-alone arm for the first year as a control to assess the safety of the ezetimibe/simvastatin combination.

However, "we didn’t continue it long-term, because to do so would have required a massive sample size – 30,000-40,000 patients – and we struggled to recruit 9,000," Dr. Baigent said.

In addition, "we didn’t think that was the key question," he explained. "The key question was, Does a large reduction in LDL cholesterol benefit kidney patients? This trial shows very clearly that it does.

"My guess is it’s not something special ezetimibe is doing," Dr. Baigent added. "It’s lowering LDL cholesterol in the same way statins do."

Dr. Baigent and Dr. Pergola said they have no conflicts of interest. Dr. Baigent added that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

DENVER – A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug’s maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The "trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events," in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the annual meeting of the American Society of Nephrology.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m2.

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group. That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, Dr. Baigent noted.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. "With full compliance, we would be likely to reduce the risk of vascular events by about a quarter," he predicted.

However, lowering patients’ LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that "it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death," and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent. As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

The study largely "confirms what we already know" – that statins benefit kidney patients, said nephrologist Dr. Pablo Pergola, clinical associate professor of medicine at the University of Texas Health Science Center, San Antonio.

Dr. Pergola was curious, however, about what role, if any, ezetimibe may have played in the outcomes.

Following his presentation of the study results, Dr. Baigent noted the study wasn’t powered to answer that question.

The trial included a simvastatin-alone arm for the first year as a control to assess the safety of the ezetimibe/simvastatin combination.

However, "we didn’t continue it long-term, because to do so would have required a massive sample size – 30,000-40,000 patients – and we struggled to recruit 9,000," Dr. Baigent said.

In addition, "we didn’t think that was the key question," he explained. "The key question was, Does a large reduction in LDL cholesterol benefit kidney patients? This trial shows very clearly that it does.

"My guess is it’s not something special ezetimibe is doing," Dr. Baigent added. "It’s lowering LDL cholesterol in the same way statins do."

Dr. Baigent and Dr. Pergola said they have no conflicts of interest. Dr. Baigent added that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

DENVER – A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug’s maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The "trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events," in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the annual meeting of the American Society of Nephrology.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m2.

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group. That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, Dr. Baigent noted.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. "With full compliance, we would be likely to reduce the risk of vascular events by about a quarter," he predicted.

However, lowering patients’ LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that "it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death," and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent. As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

The study largely "confirms what we already know" – that statins benefit kidney patients, said nephrologist Dr. Pablo Pergola, clinical associate professor of medicine at the University of Texas Health Science Center, San Antonio.

Dr. Pergola was curious, however, about what role, if any, ezetimibe may have played in the outcomes.

Following his presentation of the study results, Dr. Baigent noted the study wasn’t powered to answer that question.

The trial included a simvastatin-alone arm for the first year as a control to assess the safety of the ezetimibe/simvastatin combination.

However, "we didn’t continue it long-term, because to do so would have required a massive sample size – 30,000-40,000 patients – and we struggled to recruit 9,000," Dr. Baigent said.

In addition, "we didn’t think that was the key question," he explained. "The key question was, Does a large reduction in LDL cholesterol benefit kidney patients? This trial shows very clearly that it does.

"My guess is it’s not something special ezetimibe is doing," Dr. Baigent added. "It’s lowering LDL cholesterol in the same way statins do."

Dr. Baigent and Dr. Pergola said they have no conflicts of interest. Dr. Baigent added that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

DENVER – A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug’s maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The "trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events," in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the annual meeting of the American Society of Nephrology.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m2.

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group. That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, Dr. Baigent noted.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. "With full compliance, we would be likely to reduce the risk of vascular events by about a quarter," he predicted.

However, lowering patients’ LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that "it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death," and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent. As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

The study largely "confirms what we already know" – that statins benefit kidney patients, said nephrologist Dr. Pablo Pergola, clinical associate professor of medicine at the University of Texas Health Science Center, San Antonio.

Dr. Pergola was curious, however, about what role, if any, ezetimibe may have played in the outcomes.

Following his presentation of the study results, Dr. Baigent noted the study wasn’t powered to answer that question.

The trial included a simvastatin-alone arm for the first year as a control to assess the safety of the ezetimibe/simvastatin combination.

However, "we didn’t continue it long-term, because to do so would have required a massive sample size – 30,000-40,000 patients – and we struggled to recruit 9,000," Dr. Baigent said.

In addition, "we didn’t think that was the key question," he explained. "The key question was, Does a large reduction in LDL cholesterol benefit kidney patients? This trial shows very clearly that it does.

"My guess is it’s not something special ezetimibe is doing," Dr. Baigent added. "It’s lowering LDL cholesterol in the same way statins do."

Dr. Baigent and Dr. Pergola said they have no conflicts of interest. Dr. Baigent added that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type II diabetes, according to a randomized phase IIb study funded by the drug’s sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m2 leads to better patient outcomes, according to nephrologist Dr. Pablo Pergola of the University of Texas Health Science Center, San Antonio, who presented the findings.

"You want to make sure this drug will be associated with a clinical outcome," said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type II diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/min per 1.73m2.

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m2, with gains noted in each group ranging from 8.3 to 11.5 mL/minute per 1.73 m2. There was a 0.1 mL/minute per 1.73 m2 eGFR gain in the placebo group. The treatment effect of bardoxolone relative to placebo was significant.

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

"The maximal effect seems to be at 75 mg," Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But "the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage."

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type II diabetes, according to a randomized phase IIb study funded by the drug’s sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m2 leads to better patient outcomes, according to nephrologist Dr. Pablo Pergola of the University of Texas Health Science Center, San Antonio, who presented the findings.

"You want to make sure this drug will be associated with a clinical outcome," said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type II diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/min per 1.73m2.

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m2, with gains noted in each group ranging from 8.3 to 11.5 mL/minute per 1.73 m2. There was a 0.1 mL/minute per 1.73 m2 eGFR gain in the placebo group. The treatment effect of bardoxolone relative to placebo was significant.

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

"The maximal effect seems to be at 75 mg," Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But "the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage."

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type II diabetes, according to a randomized phase IIb study funded by the drug’s sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m2 leads to better patient outcomes, according to nephrologist Dr. Pablo Pergola of the University of Texas Health Science Center, San Antonio, who presented the findings.

"You want to make sure this drug will be associated with a clinical outcome," said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type II diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/min per 1.73m2.

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m2, with gains noted in each group ranging from 8.3 to 11.5 mL/minute per 1.73 m2. There was a 0.1 mL/minute per 1.73 m2 eGFR gain in the placebo group. The treatment effect of bardoxolone relative to placebo was significant.

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

"The maximal effect seems to be at 75 mg," Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But "the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage."

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type II diabetes, according to a randomized phase IIb study funded by the drug’s sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m2 leads to better patient outcomes, according to nephrologist Dr. Pablo Pergola of the University of Texas Health Science Center, San Antonio, who presented the findings.

"You want to make sure this drug will be associated with a clinical outcome," said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type II diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/min per 1.73m2.

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m2, with gains noted in each group ranging from 8.3 to 11.5 mL/minute per 1.73 m2. There was a 0.1 mL/minute per 1.73 m2 eGFR gain in the placebo group. The treatment effect of bardoxolone relative to placebo was significant.

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

"The maximal effect seems to be at 75 mg," Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But "the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage."

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type II diabetes, according to a randomized phase IIb study funded by the drug’s sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m2 leads to better patient outcomes, according to nephrologist Dr. Pablo Pergola of the University of Texas Health Science Center, San Antonio, who presented the findings.

"You want to make sure this drug will be associated with a clinical outcome," said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type II diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/min per 1.73m2.

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m2, with gains noted in each group ranging from 8.3 to 11.5 mL/minute per 1.73 m2. There was a 0.1 mL/minute per 1.73 m2 eGFR gain in the placebo group. The treatment effect of bardoxolone relative to placebo was significant.

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

"The maximal effect seems to be at 75 mg," Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But "the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage."

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type II diabetes, according to a randomized phase IIb study funded by the drug’s sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m2 leads to better patient outcomes, according to nephrologist Dr. Pablo Pergola of the University of Texas Health Science Center, San Antonio, who presented the findings.

"You want to make sure this drug will be associated with a clinical outcome," said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type II diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/min per 1.73m2.

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m2, with gains noted in each group ranging from 8.3 to 11.5 mL/minute per 1.73 m2. There was a 0.1 mL/minute per 1.73 m2 eGFR gain in the placebo group. The treatment effect of bardoxolone relative to placebo was significant.

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

"The maximal effect seems to be at 75 mg," Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But "the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage."

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

VANCOUVER, B.C. – A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient’s resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

"Why do it? Because it works," Dr. Johan Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., said at the annual meeting of the Infectious Diseases Society of America.

"It’s a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It’s safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours," he said.

Among the severely ill, he said, "I have not encountered any patients who have not welcomed it."

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation’s merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

"This is 2010, not 1910. We can do better than fecal transplantation," Dr. Gerding said.

Even so, there is "no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials," he said.

"The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff," Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It’s less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

About 25-30 g of stool are collected from the donor as close to the time of instillation as possible (within 24 hours). The stool is then blended into a slurry with saline or milk.

"You need to dedicate a blender" for the procedure, Dr. Bakken noted.

Next, the stool slurry is passed through a coffee filter or gauze to remove particulate matter.

Nasogastric tube tip placement in the proximal duodenum is confirmed by x-ray; then about 25 mL of the slurry are delivered via syringe.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis.

Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients.

"Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse," Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. – A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient’s resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

"Why do it? Because it works," Dr. Johan Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., said at the annual meeting of the Infectious Diseases Society of America.

"It’s a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It’s safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours," he said.

Among the severely ill, he said, "I have not encountered any patients who have not welcomed it."

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation’s merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

"This is 2010, not 1910. We can do better than fecal transplantation," Dr. Gerding said.

Even so, there is "no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials," he said.

"The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff," Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It’s less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

About 25-30 g of stool are collected from the donor as close to the time of instillation as possible (within 24 hours). The stool is then blended into a slurry with saline or milk.

"You need to dedicate a blender" for the procedure, Dr. Bakken noted.

Next, the stool slurry is passed through a coffee filter or gauze to remove particulate matter.

Nasogastric tube tip placement in the proximal duodenum is confirmed by x-ray; then about 25 mL of the slurry are delivered via syringe.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis.

Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients.

"Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse," Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. – A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient’s resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

"Why do it? Because it works," Dr. Johan Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., said at the annual meeting of the Infectious Diseases Society of America.

"It’s a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It’s safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours," he said.

Among the severely ill, he said, "I have not encountered any patients who have not welcomed it."

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation’s merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

"This is 2010, not 1910. We can do better than fecal transplantation," Dr. Gerding said.

Even so, there is "no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials," he said.

"The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff," Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It’s less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

About 25-30 g of stool are collected from the donor as close to the time of instillation as possible (within 24 hours). The stool is then blended into a slurry with saline or milk.

"You need to dedicate a blender" for the procedure, Dr. Bakken noted.

Next, the stool slurry is passed through a coffee filter or gauze to remove particulate matter.

Nasogastric tube tip placement in the proximal duodenum is confirmed by x-ray; then about 25 mL of the slurry are delivered via syringe.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis.

Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients.

"Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse," Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. – A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient’s resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

"Why do it? Because it works," Dr. Johan Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., said at the annual meeting of the Infectious Diseases Society of America.

"It’s a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It’s safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours," he said.

Among the severely ill, he said, "I have not encountered any patients who have not welcomed it."

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation’s merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

"This is 2010, not 1910. We can do better than fecal transplantation," Dr. Gerding said.

Even so, there is "no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials," he said.

"The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff," Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It’s less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

About 25-30 g of stool are collected from the donor as close to the time of instillation as possible (within 24 hours). The stool is then blended into a slurry with saline or milk.

"You need to dedicate a blender" for the procedure, Dr. Bakken noted.

Next, the stool slurry is passed through a coffee filter or gauze to remove particulate matter.

Nasogastric tube tip placement in the proximal duodenum is confirmed by x-ray; then about 25 mL of the slurry are delivered via syringe.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis.

Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients.

"Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse," Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. – A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient’s resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

"Why do it? Because it works," Dr. Johan Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., said at the annual meeting of the Infectious Diseases Society of America.

"It’s a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It’s safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours," he said.

Among the severely ill, he said, "I have not encountered any patients who have not welcomed it."

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation’s merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

"This is 2010, not 1910. We can do better than fecal transplantation," Dr. Gerding said.

Even so, there is "no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials," he said.

"The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff," Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It’s less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

About 25-30 g of stool are collected from the donor as close to the time of instillation as possible (within 24 hours). The stool is then blended into a slurry with saline or milk.

"You need to dedicate a blender" for the procedure, Dr. Bakken noted.

Next, the stool slurry is passed through a coffee filter or gauze to remove particulate matter.

Nasogastric tube tip placement in the proximal duodenum is confirmed by x-ray; then about 25 mL of the slurry are delivered via syringe.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis.

Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients.

"Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse," Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. – A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient’s resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

"Why do it? Because it works," Dr. Johan Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., said at the annual meeting of the Infectious Diseases Society of America.

"It’s a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It’s safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours," he said.

Among the severely ill, he said, "I have not encountered any patients who have not welcomed it."

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation’s merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

"This is 2010, not 1910. We can do better than fecal transplantation," Dr. Gerding said.

Even so, there is "no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials," he said.

"The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff," Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It’s less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

About 25-30 g of stool are collected from the donor as close to the time of instillation as possible (within 24 hours). The stool is then blended into a slurry with saline or milk.

"You need to dedicate a blender" for the procedure, Dr. Bakken noted.

Next, the stool slurry is passed through a coffee filter or gauze to remove particulate matter.

Nasogastric tube tip placement in the proximal duodenum is confirmed by x-ray; then about 25 mL of the slurry are delivered via syringe.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis.

Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients.

"Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse," Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. – An adenovirus outbreak in a Chicago neonatal intensive care unit led to an important realization about infection control.

"Soaking ophthalmology equipment in 70% isopropyl alcohol – which is commonly done in NICUs for retinopathy of prematurity equipment – is probably not sufficient to eradicate adenovirus contamination," said Dr. Emily Mawdsley, an instructor of medicine at the University of Chicago.

Seven infants in the NICU developed adenovirus keratoconjunctivitis in March 2009; four more with the condition, soon identified, had recently been discharged.

"Our initial call was to the pediatric ophthalmologist. He told us that he was at home sick with conjunctivitis," said Dr. Mawdsley, who works in the university medical center’s infectious diseases and global health section.

"After a discussion with him, he recalled that a pediatric ophthalmology resident had [recently] worked with symptomatic conjunctivitis. He’d been sent home, but not until after he had seen a few patients in the NICU," she said.

All the infants had recently been examined for retinopathy of prematurity. Virus typing by the Centers for Disease Control and Prevention revealed that the infants had the same virus strain as did the resident.

"So we took a look at the ophthalmology equipment," said Dr. Mawdsley, to see if that was the transmission vector.

Scleral specula and ocular depressors, which were reused on the unit after being soaked for 10-30 minutes in 70% isopropyl alcohol, were positive for adenovirus on polymerase chain reaction assay. They had been set aside in a sterile bowl several days earlier, after the unit suspended eye exams pending investigation results.

The ophthalmology cart handles, miscellaneous supply bags, a lens case, a headlight and battery pack, the contents of an eye spray irrigation bottle, and the alcohol bottle used for disinfection were also positive for adenovirus. Three samples grew live virus.

Previous studies have found 70% isopropyl alcohol – and 3% hydrogen peroxide – insufficient to kill adenovirus. The authors of one study recommended disinfecting ophthalmologic equipment with 70% ethyl alcohol or 5,000 ppm chlorine. They also recommended cleaning environmental surfaces with 1,900 ppm chlorine, 65% ethanol/0.63% quaternary ammonium, or 79% ethanol/0.1% quaternary ammonium (Antimicrob. Agents Chemother. 2006;50:1419-24).

To keep the virus in check, NICU staff started to clean equipment and surfaces with bleach or quaternary ammonium wipes and nurses wore gloves and gowns during their shifts. Sick children were segregated from well children and contact precautions were used, among other measures. Two NICU workers, two family members, and an additional infant developed conjunctivitis.

The outbreak was contained within a few weeks. Previously ill infants returned negative viral cultures, and the unit reopened to transfers. Retinopathy of prematurity exams were also resumed, but this time with disposable depressors and specula.

The virus didn’t cause infants respiratory compromise, Dr. Mawdsley said.

During the investigation, families were told that an exam had given their children conjunctivitis.

But "we didn’t have a lot of backlash from this. They could see that we were doing a lot to try to control spread. That contributed a lot to helping families feel better about what happened," she said.

According to Dr. Janet Englund, a pediatric infectious diseases professor at the University of Washington, Seattle, “There’s a great take-home message here.” 

Dr. Mawdsley said she has no disclosures. Dr. Englund also reported no disclosures.

VANCOUVER, B.C. – An adenovirus outbreak in a Chicago neonatal intensive care unit led to an important realization about infection control.

"Soaking ophthalmology equipment in 70% isopropyl alcohol – which is commonly done in NICUs for retinopathy of prematurity equipment – is probably not sufficient to eradicate adenovirus contamination," said Dr. Emily Mawdsley, an instructor of medicine at the University of Chicago.

Seven infants in the NICU developed adenovirus keratoconjunctivitis in March 2009; four more with the condition, soon identified, had recently been discharged.

"Our initial call was to the pediatric ophthalmologist. He told us that he was at home sick with conjunctivitis," said Dr. Mawdsley, who works in the university medical center’s infectious diseases and global health section.

"After a discussion with him, he recalled that a pediatric ophthalmology resident had [recently] worked with symptomatic conjunctivitis. He’d been sent home, but not until after he had seen a few patients in the NICU," she said.

All the infants had recently been examined for retinopathy of prematurity. Virus typing by the Centers for Disease Control and Prevention revealed that the infants had the same virus strain as did the resident.

"So we took a look at the ophthalmology equipment," said Dr. Mawdsley, to see if that was the transmission vector.

Scleral specula and ocular depressors, which were reused on the unit after being soaked for 10-30 minutes in 70% isopropyl alcohol, were positive for adenovirus on polymerase chain reaction assay. They had been set aside in a sterile bowl several days earlier, after the unit suspended eye exams pending investigation results.

The ophthalmology cart handles, miscellaneous supply bags, a lens case, a headlight and battery pack, the contents of an eye spray irrigation bottle, and the alcohol bottle used for disinfection were also positive for adenovirus. Three samples grew live virus.

Previous studies have found 70% isopropyl alcohol – and 3% hydrogen peroxide – insufficient to kill adenovirus. The authors of one study recommended disinfecting ophthalmologic equipment with 70% ethyl alcohol or 5,000 ppm chlorine. They also recommended cleaning environmental surfaces with 1,900 ppm chlorine, 65% ethanol/0.63% quaternary ammonium, or 79% ethanol/0.1% quaternary ammonium (Antimicrob. Agents Chemother. 2006;50:1419-24).

To keep the virus in check, NICU staff started to clean equipment and surfaces with bleach or quaternary ammonium wipes and nurses wore gloves and gowns during their shifts. Sick children were segregated from well children and contact precautions were used, among other measures. Two NICU workers, two family members, and an additional infant developed conjunctivitis.

The outbreak was contained within a few weeks. Previously ill infants returned negative viral cultures, and the unit reopened to transfers. Retinopathy of prematurity exams were also resumed, but this time with disposable depressors and specula.

The virus didn’t cause infants respiratory compromise, Dr. Mawdsley said.

During the investigation, families were told that an exam had given their children conjunctivitis.

But "we didn’t have a lot of backlash from this. They could see that we were doing a lot to try to control spread. That contributed a lot to helping families feel better about what happened," she said.

According to Dr. Janet Englund, a pediatric infectious diseases professor at the University of Washington, Seattle, “There’s a great take-home message here.” 

Dr. Mawdsley said she has no disclosures. Dr. Englund also reported no disclosures.

VANCOUVER, B.C. – An adenovirus outbreak in a Chicago neonatal intensive care unit led to an important realization about infection control.

"Soaking ophthalmology equipment in 70% isopropyl alcohol – which is commonly done in NICUs for retinopathy of prematurity equipment – is probably not sufficient to eradicate adenovirus contamination," said Dr. Emily Mawdsley, an instructor of medicine at the University of Chicago.

Seven infants in the NICU developed adenovirus keratoconjunctivitis in March 2009; four more with the condition, soon identified, had recently been discharged.

"Our initial call was to the pediatric ophthalmologist. He told us that he was at home sick with conjunctivitis," said Dr. Mawdsley, who works in the university medical center’s infectious diseases and global health section.

"After a discussion with him, he recalled that a pediatric ophthalmology resident had [recently] worked with symptomatic conjunctivitis. He’d been sent home, but not until after he had seen a few patients in the NICU," she said.

All the infants had recently been examined for retinopathy of prematurity. Virus typing by the Centers for Disease Control and Prevention revealed that the infants had the same virus strain as did the resident.

"So we took a look at the ophthalmology equipment," said Dr. Mawdsley, to see if that was the transmission vector.

Scleral specula and ocular depressors, which were reused on the unit after being soaked for 10-30 minutes in 70% isopropyl alcohol, were positive for adenovirus on polymerase chain reaction assay. They had been set aside in a sterile bowl several days earlier, after the unit suspended eye exams pending investigation results.

The ophthalmology cart handles, miscellaneous supply bags, a lens case, a headlight and battery pack, the contents of an eye spray irrigation bottle, and the alcohol bottle used for disinfection were also positive for adenovirus. Three samples grew live virus.

Previous studies have found 70% isopropyl alcohol – and 3% hydrogen peroxide – insufficient to kill adenovirus. The authors of one study recommended disinfecting ophthalmologic equipment with 70% ethyl alcohol or 5,000 ppm chlorine. They also recommended cleaning environmental surfaces with 1,900 ppm chlorine, 65% ethanol/0.63% quaternary ammonium, or 79% ethanol/0.1% quaternary ammonium (Antimicrob. Agents Chemother. 2006;50:1419-24).

To keep the virus in check, NICU staff started to clean equipment and surfaces with bleach or quaternary ammonium wipes and nurses wore gloves and gowns during their shifts. Sick children were segregated from well children and contact precautions were used, among other measures. Two NICU workers, two family members, and an additional infant developed conjunctivitis.

The outbreak was contained within a few weeks. Previously ill infants returned negative viral cultures, and the unit reopened to transfers. Retinopathy of prematurity exams were also resumed, but this time with disposable depressors and specula.

The virus didn’t cause infants respiratory compromise, Dr. Mawdsley said.

During the investigation, families were told that an exam had given their children conjunctivitis.

But "we didn’t have a lot of backlash from this. They could see that we were doing a lot to try to control spread. That contributed a lot to helping families feel better about what happened," she said.

According to Dr. Janet Englund, a pediatric infectious diseases professor at the University of Washington, Seattle, “There’s a great take-home message here.” 

Dr. Mawdsley said she has no disclosures. Dr. Englund also reported no disclosures.

VANCOUVER, B.C. – An adenovirus outbreak in a Chicago neonatal intensive care unit led to an important realization about infection control.

"Soaking ophthalmology equipment in 70% isopropyl alcohol – which is commonly done in NICUs for retinopathy of prematurity equipment – is probably not sufficient to eradicate adenovirus contamination," said Dr. Emily Mawdsley, an instructor of medicine at the University of Chicago.

Seven infants in the NICU developed adenovirus keratoconjunctivitis in March 2009; four more with the condition, soon identified, had recently been discharged.

"Our initial call was to the pediatric ophthalmologist. He told us that he was at home sick with conjunctivitis," said Dr. Mawdsley, who works in the university medical center’s infectious diseases and global health section.

"After a discussion with him, he recalled that a pediatric ophthalmology resident had [recently] worked with symptomatic conjunctivitis. He’d been sent home, but not until after he had seen a few patients in the NICU," she said.

All the infants had recently been examined for retinopathy of prematurity. Virus typing by the Centers for Disease Control and Prevention revealed that the infants had the same virus strain as did the resident.

"So we took a look at the ophthalmology equipment," said Dr. Mawdsley, to see if that was the transmission vector.

Scleral specula and ocular depressors, which were reused on the unit after being soaked for 10-30 minutes in 70% isopropyl alcohol, were positive for adenovirus on polymerase chain reaction assay. They had been set aside in a sterile bowl several days earlier, after the unit suspended eye exams pending investigation results.

The ophthalmology cart handles, miscellaneous supply bags, a lens case, a headlight and battery pack, the contents of an eye spray irrigation bottle, and the alcohol bottle used for disinfection were also positive for adenovirus. Three samples grew live virus.

Previous studies have found 70% isopropyl alcohol – and 3% hydrogen peroxide – insufficient to kill adenovirus. The authors of one study recommended disinfecting ophthalmologic equipment with 70% ethyl alcohol or 5,000 ppm chlorine. They also recommended cleaning environmental surfaces with 1,900 ppm chlorine, 65% ethanol/0.63% quaternary ammonium, or 79% ethanol/0.1% quaternary ammonium (Antimicrob. Agents Chemother. 2006;50:1419-24).

To keep the virus in check, NICU staff started to clean equipment and surfaces with bleach or quaternary ammonium wipes and nurses wore gloves and gowns during their shifts. Sick children were segregated from well children and contact precautions were used, among other measures. Two NICU workers, two family members, and an additional infant developed conjunctivitis.

The outbreak was contained within a few weeks. Previously ill infants returned negative viral cultures, and the unit reopened to transfers. Retinopathy of prematurity exams were also resumed, but this time with disposable depressors and specula.

The virus didn’t cause infants respiratory compromise, Dr. Mawdsley said.

During the investigation, families were told that an exam had given their children conjunctivitis.

But "we didn’t have a lot of backlash from this. They could see that we were doing a lot to try to control spread. That contributed a lot to helping families feel better about what happened," she said.

According to Dr. Janet Englund, a pediatric infectious diseases professor at the University of Washington, Seattle, “There’s a great take-home message here.” 

Dr. Mawdsley said she has no disclosures. Dr. Englund also reported no disclosures.

VANCOUVER, B.C. – An adenovirus outbreak in a Chicago neonatal intensive care unit led to an important realization about infection control.

"Soaking ophthalmology equipment in 70% isopropyl alcohol – which is commonly done in NICUs for retinopathy of prematurity equipment – is probably not sufficient to eradicate adenovirus contamination," said Dr. Emily Mawdsley, an instructor of medicine at the University of Chicago.

Seven infants in the NICU developed adenovirus keratoconjunctivitis in March 2009; four more with the condition, soon identified, had recently been discharged.

"Our initial call was to the pediatric ophthalmologist. He told us that he was at home sick with conjunctivitis," said Dr. Mawdsley, who works in the university medical center’s infectious diseases and global health section.

"After a discussion with him, he recalled that a pediatric ophthalmology resident had [recently] worked with symptomatic conjunctivitis. He’d been sent home, but not until after he had seen a few patients in the NICU," she said.

All the infants had recently been examined for retinopathy of prematurity. Virus typing by the Centers for Disease Control and Prevention revealed that the infants had the same virus strain as did the resident.

"So we took a look at the ophthalmology equipment," said Dr. Mawdsley, to see if that was the transmission vector.

Scleral specula and ocular depressors, which were reused on the unit after being soaked for 10-30 minutes in 70% isopropyl alcohol, were positive for adenovirus on polymerase chain reaction assay. They had been set aside in a sterile bowl several days earlier, after the unit suspended eye exams pending investigation results.

The ophthalmology cart handles, miscellaneous supply bags, a lens case, a headlight and battery pack, the contents of an eye spray irrigation bottle, and the alcohol bottle used for disinfection were also positive for adenovirus. Three samples grew live virus.

Previous studies have found 70% isopropyl alcohol – and 3% hydrogen peroxide – insufficient to kill adenovirus. The authors of one study recommended disinfecting ophthalmologic equipment with 70% ethyl alcohol or 5,000 ppm chlorine. They also recommended cleaning environmental surfaces with 1,900 ppm chlorine, 65% ethanol/0.63% quaternary ammonium, or 79% ethanol/0.1% quaternary ammonium (Antimicrob. Agents Chemother. 2006;50:1419-24).

To keep the virus in check, NICU staff started to clean equipment and surfaces with bleach or quaternary ammonium wipes and nurses wore gloves and gowns during their shifts. Sick children were segregated from well children and contact precautions were used, among other measures. Two NICU workers, two family members, and an additional infant developed conjunctivitis.

The outbreak was contained within a few weeks. Previously ill infants returned negative viral cultures, and the unit reopened to transfers. Retinopathy of prematurity exams were also resumed, but this time with disposable depressors and specula.

The virus didn’t cause infants respiratory compromise, Dr. Mawdsley said.

During the investigation, families were told that an exam had given their children conjunctivitis.

But "we didn’t have a lot of backlash from this. They could see that we were doing a lot to try to control spread. That contributed a lot to helping families feel better about what happened," she said.

According to Dr. Janet Englund, a pediatric infectious diseases professor at the University of Washington, Seattle, “There’s a great take-home message here.” 

Dr. Mawdsley said she has no disclosures. Dr. Englund also reported no disclosures.

VANCOUVER, B.C. – An adenovirus outbreak in a Chicago neonatal intensive care unit led to an important realization about infection control.

"Soaking ophthalmology equipment in 70% isopropyl alcohol – which is commonly done in NICUs for retinopathy of prematurity equipment – is probably not sufficient to eradicate adenovirus contamination," said Dr. Emily Mawdsley, an instructor of medicine at the University of Chicago.

Seven infants in the NICU developed adenovirus keratoconjunctivitis in March 2009; four more with the condition, soon identified, had recently been discharged.

"Our initial call was to the pediatric ophthalmologist. He told us that he was at home sick with conjunctivitis," said Dr. Mawdsley, who works in the university medical center’s infectious diseases and global health section.

"After a discussion with him, he recalled that a pediatric ophthalmology resident had [recently] worked with symptomatic conjunctivitis. He’d been sent home, but not until after he had seen a few patients in the NICU," she said.

All the infants had recently been examined for retinopathy of prematurity. Virus typing by the Centers for Disease Control and Prevention revealed that the infants had the same virus strain as did the resident.

"So we took a look at the ophthalmology equipment," said Dr. Mawdsley, to see if that was the transmission vector.

Scleral specula and ocular depressors, which were reused on the unit after being soaked for 10-30 minutes in 70% isopropyl alcohol, were positive for adenovirus on polymerase chain reaction assay. They had been set aside in a sterile bowl several days earlier, after the unit suspended eye exams pending investigation results.

The ophthalmology cart handles, miscellaneous supply bags, a lens case, a headlight and battery pack, the contents of an eye spray irrigation bottle, and the alcohol bottle used for disinfection were also positive for adenovirus. Three samples grew live virus.

Previous studies have found 70% isopropyl alcohol – and 3% hydrogen peroxide – insufficient to kill adenovirus. The authors of one study recommended disinfecting ophthalmologic equipment with 70% ethyl alcohol or 5,000 ppm chlorine. They also recommended cleaning environmental surfaces with 1,900 ppm chlorine, 65% ethanol/0.63% quaternary ammonium, or 79% ethanol/0.1% quaternary ammonium (Antimicrob. Agents Chemother. 2006;50:1419-24).

To keep the virus in check, NICU staff started to clean equipment and surfaces with bleach or quaternary ammonium wipes and nurses wore gloves and gowns during their shifts. Sick children were segregated from well children and contact precautions were used, among other measures. Two NICU workers, two family members, and an additional infant developed conjunctivitis.

The outbreak was contained within a few weeks. Previously ill infants returned negative viral cultures, and the unit reopened to transfers. Retinopathy of prematurity exams were also resumed, but this time with disposable depressors and specula.

The virus didn’t cause infants respiratory compromise, Dr. Mawdsley said.

During the investigation, families were told that an exam had given their children conjunctivitis.

But "we didn’t have a lot of backlash from this. They could see that we were doing a lot to try to control spread. That contributed a lot to helping families feel better about what happened," she said.

According to Dr. Janet Englund, a pediatric infectious diseases professor at the University of Washington, Seattle, “There’s a great take-home message here.” 

Dr. Mawdsley said she has no disclosures. Dr. Englund also reported no disclosures.

VANCOUVER, B.C. - Fluoroquinolone use increased the risk of B1-strain Clostridium difficile infection, a strain that is associated with severe disease and has caused outbreaks in hospitals throughout North America and Europe, according to a study at a Veterans Affairs hospital.

"We were able to demonstrate that patients in our hospital who developed CDI due to the epidemic B1 strain were more likely than patients infected with other strains to have been treated with fluoroquinolones prior to developing CDI," and that the B1 strain is highly resistant to fluoroquinolones, said Dr. Stuart Johnson, an infectious disease specialist at Loyola University, Chicago, and Hines (Ill.) VA Hospital, who presented the study at the annual meeting of the Infectious Diseases Society of America.

"We were using [the fluoroquinolone] ciprofloxacin for many years until we knew that this was a risk for C. difficile; all the fluoroquinolones have this particular risk," he said.

Dr. Johnson said the findings mimic those of the 1990s, when he and his colleagues found that the J strain of the pathogen was highly resistant to clindamycin and was associated with outbreaks in hospitals that used clindamycin heavily (N. Engl. J. Med. 1999;341:1645-51).

"In those instances, restriction of clindamycin was very effective in interrupting outbreaks," he said.

In general, "if you are having an outbreak or increased rates of C. difficile, you may be able to target antibiotic stewardship programs to those antibiotics that are leading to the outbreak," Dr. Johnson said.

In a case-control study funded by the Department of Veterans Affairs, stool samples from newly diagnosed CDI patients at the Hines VA Hospital were cultured and typed by restriction endonuclease analysis. Patients’ antibiotic exposures over the previous 6 weeks were then checked.

Fluoroquinolone use was more frequent in the 67 patients who developed B1-strain CDI, and greatly increased their risk for a B1 infection (odds ratio, 3.6; 95% confidence interval, 1.3-9.8; P = .01).

Clindamycin use was more frequent in the 30 patients who developed non–B1-strain CDI.

B1 isolates demonstrated high-level resistance to azithromycin and moxifloxacin, a newer generation fluoroquinolone. Non-B1 isolates demonstrated high-level clindamycin resistance. All strains were resistant to ceftriaxone, but none were resistant to piperacillin/tazobactam, Dr. Johnson said.

In a separate abstract presented at the meeting by Dr. Dimitri Drekonja, an infectious disease specialist at the Minneapolis VA Medical Center, 51 of 89 patients with CDI received at least one course of antibiotics within 30 days of completing CDI treatment.

"Roughly one-third of all antimicrobial use was judged to be inappropriate" in a preliminary analysis, he said. Pending additional investigation, however, Dr. Drekonja did not provide additional details.

Dr. Drekonja said he has no disclosures. Dr. Johnson said he is a consultant for Optimer Pharmaceuticals Inc., Viropharma Inc., Novartis, Cubist Pharmaceuticals Inc., and Bio-K+ International Inc.

VANCOUVER, B.C. - Fluoroquinolone use increased the risk of B1-strain Clostridium difficile infection, a strain that is associated with severe disease and has caused outbreaks in hospitals throughout North America and Europe, according to a study at a Veterans Affairs hospital.

"We were able to demonstrate that patients in our hospital who developed CDI due to the epidemic B1 strain were more likely than patients infected with other strains to have been treated with fluoroquinolones prior to developing CDI," and that the B1 strain is highly resistant to fluoroquinolones, said Dr. Stuart Johnson, an infectious disease specialist at Loyola University, Chicago, and Hines (Ill.) VA Hospital, who presented the study at the annual meeting of the Infectious Diseases Society of America.

"We were using [the fluoroquinolone] ciprofloxacin for many years until we knew that this was a risk for C. difficile; all the fluoroquinolones have this particular risk," he said.

Dr. Johnson said the findings mimic those of the 1990s, when he and his colleagues found that the J strain of the pathogen was highly resistant to clindamycin and was associated with outbreaks in hospitals that used clindamycin heavily (N. Engl. J. Med. 1999;341:1645-51).

"In those instances, restriction of clindamycin was very effective in interrupting outbreaks," he said.

In general, "if you are having an outbreak or increased rates of C. difficile, you may be able to target antibiotic stewardship programs to those antibiotics that are leading to the outbreak," Dr. Johnson said.

In a case-control study funded by the Department of Veterans Affairs, stool samples from newly diagnosed CDI patients at the Hines VA Hospital were cultured and typed by restriction endonuclease analysis. Patients’ antibiotic exposures over the previous 6 weeks were then checked.

Fluoroquinolone use was more frequent in the 67 patients who developed B1-strain CDI, and greatly increased their risk for a B1 infection (odds ratio, 3.6; 95% confidence interval, 1.3-9.8; P = .01).

Clindamycin use was more frequent in the 30 patients who developed non–B1-strain CDI.

B1 isolates demonstrated high-level resistance to azithromycin and moxifloxacin, a newer generation fluoroquinolone. Non-B1 isolates demonstrated high-level clindamycin resistance. All strains were resistant to ceftriaxone, but none were resistant to piperacillin/tazobactam, Dr. Johnson said.

In a separate abstract presented at the meeting by Dr. Dimitri Drekonja, an infectious disease specialist at the Minneapolis VA Medical Center, 51 of 89 patients with CDI received at least one course of antibiotics within 30 days of completing CDI treatment.

"Roughly one-third of all antimicrobial use was judged to be inappropriate" in a preliminary analysis, he said. Pending additional investigation, however, Dr. Drekonja did not provide additional details.

Dr. Drekonja said he has no disclosures. Dr. Johnson said he is a consultant for Optimer Pharmaceuticals Inc., Viropharma Inc., Novartis, Cubist Pharmaceuticals Inc., and Bio-K+ International Inc.

VANCOUVER, B.C. - Fluoroquinolone use increased the risk of B1-strain Clostridium difficile infection, a strain that is associated with severe disease and has caused outbreaks in hospitals throughout North America and Europe, according to a study at a Veterans Affairs hospital.

"We were able to demonstrate that patients in our hospital who developed CDI due to the epidemic B1 strain were more likely than patients infected with other strains to have been treated with fluoroquinolones prior to developing CDI," and that the B1 strain is highly resistant to fluoroquinolones, said Dr. Stuart Johnson, an infectious disease specialist at Loyola University, Chicago, and Hines (Ill.) VA Hospital, who presented the study at the annual meeting of the Infectious Diseases Society of America.

"We were using [the fluoroquinolone] ciprofloxacin for many years until we knew that this was a risk for C. difficile; all the fluoroquinolones have this particular risk," he said.

Dr. Johnson said the findings mimic those of the 1990s, when he and his colleagues found that the J strain of the pathogen was highly resistant to clindamycin and was associated with outbreaks in hospitals that used clindamycin heavily (N. Engl. J. Med. 1999;341:1645-51).

"In those instances, restriction of clindamycin was very effective in interrupting outbreaks," he said.

In general, "if you are having an outbreak or increased rates of C. difficile, you may be able to target antibiotic stewardship programs to those antibiotics that are leading to the outbreak," Dr. Johnson said.

In a case-control study funded by the Department of Veterans Affairs, stool samples from newly diagnosed CDI patients at the Hines VA Hospital were cultured and typed by restriction endonuclease analysis. Patients’ antibiotic exposures over the previous 6 weeks were then checked.

Fluoroquinolone use was more frequent in the 67 patients who developed B1-strain CDI, and greatly increased their risk for a B1 infection (odds ratio, 3.6; 95% confidence interval, 1.3-9.8; P = .01).

Clindamycin use was more frequent in the 30 patients who developed non–B1-strain CDI.

B1 isolates demonstrated high-level resistance to azithromycin and moxifloxacin, a newer generation fluoroquinolone. Non-B1 isolates demonstrated high-level clindamycin resistance. All strains were resistant to ceftriaxone, but none were resistant to piperacillin/tazobactam, Dr. Johnson said.

In a separate abstract presented at the meeting by Dr. Dimitri Drekonja, an infectious disease specialist at the Minneapolis VA Medical Center, 51 of 89 patients with CDI received at least one course of antibiotics within 30 days of completing CDI treatment.

"Roughly one-third of all antimicrobial use was judged to be inappropriate" in a preliminary analysis, he said. Pending additional investigation, however, Dr. Drekonja did not provide additional details.

Dr. Drekonja said he has no disclosures. Dr. Johnson said he is a consultant for Optimer Pharmaceuticals Inc., Viropharma Inc., Novartis, Cubist Pharmaceuticals Inc., and Bio-K+ International Inc.

VANCOUVER, B.C. – Fluoroquinolone use increased the risk of B1-strain Clostridium difficile infection, a strain that is associated with severe disease and has caused outbreaks in hospitals throughout North America and Europe, according to a study at a Veterans Affairs hospital.

"We were able to demonstrate that patients in our hospital who developed CDI due to the epidemic B1 strain were more likely than patients infected with other strains to have been treated with fluoroquinolones prior to developing CDI," and that the B1 strain is highly resistant to fluoroquinolones, said Dr. Stuart Johnson, an infectious disease specialist at Loyola University, Chicago, and Hines (Ill.) VA Hospital, who presented the study at the annual meeting of the Infectious Diseases Society of America.

"We were using [the fluoroquinolone] ciprofloxacin for many years until we knew that this was a risk for C. difficile; all the fluoroquinolones have this particular risk," he said.

Dr. Johnson said the findings mimic those of the 1990s, when he and his colleagues found that the J strain of the pathogen was highly resistant to clindamycin and was associated with outbreaks in hospitals that used clindamycin heavily (N. Engl. J. Med. 1999;341:1645-51).

"In those instances, restriction of clindamycin was very effective in interrupting outbreaks," he said.

In general, "if you are having an outbreak or increased rates of C. difficile, you may be able to target antibiotic stewardship programs to those antibiotics that are leading to the outbreak," Dr. Johnson said.

In a case-control study funded by the Department of Veterans Affairs, stool samples from newly diagnosed CDI patients at the Hines VA Hospital were cultured and typed by restriction endonuclease analysis. Patients’ antibiotic exposures over the previous 6 weeks were then checked.

Fluoroquinolone use was more frequent in the 67 patients who developed B1-strain CDI, and greatly increased their risk for a B1 infection (odds ratio, 3.6; 95% confidence interval, 1.3-9.8; P = .01).

Clindamycin use was more frequent in the 30 patients who developed non–B1-strain CDI.

B1 isolates demonstrated high-level resistance to azithromycin and moxifloxacin, a newer generation fluoroquinolone. Non-B1 isolates demonstrated high-level clindamycin resistance. All strains were resistant to ceftriaxone, but none were resistant to piperacillin/tazobactam, Dr. Johnson said.

In a separate abstract presented at the meeting by Dr. Dimitri Drekonja, an infectious disease specialist at the Minneapolis VA Medical Center, 51 of 89 patients with CDI received at least one course of antibiotics within 30 days of completing CDI treatment.

"Roughly one-third of all antimicrobial use was judged to be inappropriate" in a preliminary analysis, he said. Pending additional investigation, however, Dr. Drekonja did not provide additional details.

Dr. Drekonja said he has no disclosures. Dr. Johnson said he is a consultant for Optimer Pharmaceuticals Inc., Viropharma Inc., Novartis, Cubist Pharmaceuticals Inc., and Bio-K+ International Inc.

VANCOUVER, B.C. – Fluoroquinolone use increased the risk of B1-strain Clostridium difficile infection, a strain that is associated with severe disease and has caused outbreaks in hospitals throughout North America and Europe, according to a study at a Veterans Affairs hospital.

"We were able to demonstrate that patients in our hospital who developed CDI due to the epidemic B1 strain were more likely than patients infected with other strains to have been treated with fluoroquinolones prior to developing CDI," and that the B1 strain is highly resistant to fluoroquinolones, said Dr. Stuart Johnson, an infectious disease specialist at Loyola University, Chicago, and Hines (Ill.) VA Hospital, who presented the study at the annual meeting of the Infectious Diseases Society of America.

"We were using [the fluoroquinolone] ciprofloxacin for many years until we knew that this was a risk for C. difficile; all the fluoroquinolones have this particular risk," he said.

Dr. Johnson said the findings mimic those of the 1990s, when he and his colleagues found that the J strain of the pathogen was highly resistant to clindamycin and was associated with outbreaks in hospitals that used clindamycin heavily (N. Engl. J. Med. 1999;341:1645-51).

"In those instances, restriction of clindamycin was very effective in interrupting outbreaks," he said.

In general, "if you are having an outbreak or increased rates of C. difficile, you may be able to target antibiotic stewardship programs to those antibiotics that are leading to the outbreak," Dr. Johnson said.

In a case-control study funded by the Department of Veterans Affairs, stool samples from newly diagnosed CDI patients at the Hines VA Hospital were cultured and typed by restriction endonuclease analysis. Patients’ antibiotic exposures over the previous 6 weeks were then checked.

Fluoroquinolone use was more frequent in the 67 patients who developed B1-strain CDI, and greatly increased their risk for a B1 infection (odds ratio, 3.6; 95% confidence interval, 1.3-9.8; P = .01).

Clindamycin use was more frequent in the 30 patients who developed non–B1-strain CDI.

B1 isolates demonstrated high-level resistance to azithromycin and moxifloxacin, a newer generation fluoroquinolone. Non-B1 isolates demonstrated high-level clindamycin resistance. All strains were resistant to ceftriaxone, but none were resistant to piperacillin/tazobactam, Dr. Johnson said.

In a separate abstract presented at the meeting by Dr. Dimitri Drekonja, an infectious disease specialist at the Minneapolis VA Medical Center, 51 of 89 patients with CDI received at least one course of antibiotics within 30 days of completing CDI treatment.

"Roughly one-third of all antimicrobial use was judged to be inappropriate" in a preliminary analysis, he said. Pending additional investigation, however, Dr. Drekonja did not provide additional details.

Dr. Drekonja said he has no disclosures. Dr. Johnson said he is a consultant for Optimer Pharmaceuticals Inc., Viropharma Inc., Novartis, Cubist Pharmaceuticals Inc., and Bio-K+ International Inc.

VANCOUVER, B.C. – Fluoroquinolone use increased the risk of B1-strain Clostridium difficile infection, a strain that is associated with severe disease and has caused outbreaks in hospitals throughout North America and Europe, according to a study at a Veterans Affairs hospital.

"We were able to demonstrate that patients in our hospital who developed CDI due to the epidemic B1 strain were more likely than patients infected with other strains to have been treated with fluoroquinolones prior to developing CDI," and that the B1 strain is highly resistant to fluoroquinolones, said Dr. Stuart Johnson, an infectious disease specialist at Loyola University, Chicago, and Hines (Ill.) VA Hospital, who presented the study at the annual meeting of the Infectious Diseases Society of America.

"We were using [the fluoroquinolone] ciprofloxacin for many years until we knew that this was a risk for C. difficile; all the fluoroquinolones have this particular risk," he said.

Dr. Johnson said the findings mimic those of the 1990s, when he and his colleagues found that the J strain of the pathogen was highly resistant to clindamycin and was associated with outbreaks in hospitals that used clindamycin heavily (N. Engl. J. Med. 1999;341:1645-51).

"In those instances, restriction of clindamycin was very effective in interrupting outbreaks," he said.

In general, "if you are having an outbreak or increased rates of C. difficile, you may be able to target antibiotic stewardship programs to those antibiotics that are leading to the outbreak," Dr. Johnson said.

In a case-control study funded by the Department of Veterans Affairs, stool samples from newly diagnosed CDI patients at the Hines VA Hospital were cultured and typed by restriction endonuclease analysis. Patients’ antibiotic exposures over the previous 6 weeks were then checked.

Fluoroquinolone use was more frequent in the 67 patients who developed B1-strain CDI, and greatly increased their risk for a B1 infection (odds ratio, 3.6; 95% confidence interval, 1.3-9.8; P = .01).

Clindamycin use was more frequent in the 30 patients who developed non–B1-strain CDI.

B1 isolates demonstrated high-level resistance to azithromycin and moxifloxacin, a newer generation fluoroquinolone. Non-B1 isolates demonstrated high-level clindamycin resistance. All strains were resistant to ceftriaxone, but none were resistant to piperacillin/tazobactam, Dr. Johnson said.

In a separate abstract presented at the meeting by Dr. Dimitri Drekonja, an infectious disease specialist at the Minneapolis VA Medical Center, 51 of 89 patients with CDI received at least one course of antibiotics within 30 days of completing CDI treatment.

"Roughly one-third of all antimicrobial use was judged to be inappropriate" in a preliminary analysis, he said. Pending additional investigation, however, Dr. Drekonja did not provide additional details.

Dr. Drekonja said he has no disclosures. Dr. Johnson said he is a consultant for Optimer Pharmaceuticals Inc., Viropharma Inc., Novartis, Cubist Pharmaceuticals Inc., and Bio-K+ International Inc.