Jim Kling

September 24, 2013

DENVER — High-dose oral vancomycin is no more effective than a low-dose regimen for the treatment of Clostridium difficile infections, a new study has shown.

A recent antimicrobial stewardship program implemented at the Montefiore Medical Center in the Bronx, New York, began to encourage the prescription of lower doses. The rationale for the switch was that fecal vancomycin concentrations at lower doses were far higher than the C difficile minimal inhibitory concentration, explained study author Philip Chung, PharmD, clinical pharmacy manager of infectious diseases at Montefiore.

"We wanted to see if there was a change in outcome after this practice change," he told Medscape Medical News.

Dr. Chung presented the study results here at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

The stewardship program encouraged prescribers to use a regimen of oral vancomycin 125 mg 4 times a day. Before that, higher doses were common.

 
The lower dose is cost-saving, decreases side effects, and has less chance of adverse outcomes.
 

Dr. Chung's team performed a retrospective analysis of medical records. Patients were at least 18 years of age, had polymerase chain reaction results that were positive for C difficile or C difficile toxin, had symptoms of C difficile infection, and received oral vancomycin for at least 72 hours.

The primary study end point was clinical improvement at 72 hours.

In the study cohort, 197 patients received high-dose therapy (>500 mg/day) and 103 received low-dose therapy (<500 mg/day).

Risk factors for C difficile infection and the severity of the infection were similar in the 2 groups, as was antibiotic use before and after the C difficile diagnosis.

Overall, low-dose regimens were as effective as high-dose regimens.

Table. Outcomes With Oral Vancomycin

Therapy and Outcomes Low-Dose Regimen, % (n = 103) High-Dose Regimen, % (n = 197) P Value
Oral vancomycin use      
—As initial therapy 48 57  
—As final therapy >97 >97  
Concurrent metronidazole use 34 50 <.01
Clinical improvement      
—At 72 hours 85 86 <.05
—At end of therapy/hospital discharge 93 96  
In-hospital mortality 15 23  
Retreatment rate 4 6  
All-cause 30-day readmission 34 24  
Readmission for C difficile 12 5  

 

"The lower dose is cost-saving, decreases side effects, and has less chance of adverse outcomes," said Dr. Chung. "Studies have shown that oral vancomycin use increases the chance of vancomycin-resistant Enterococci populations in the GI tract. It is hoped that a lower dose will make that chance of colonization less," he explained.

The only reason to use a high-dose regimen is in cases of obstruction or when there is some other reason to believe that oral vancomycin might be impeded from reaching the lower gastrointestinal tract, he added.

The lower-dose regimen has been recommended in a number of current guidelines, and other studies have shown similar effectiveness. "These data validate the recommendations," said Dr. Chung.

This study is encouraging, although the sample sizes were smaller than the researchers had hoped, according to session moderator Clifford McDonald, MD, a medical epidemiologist at the Centers for Disease Control and Prevention in Atlanta.

"One might assume that the lower dose of oral vancomycin will damage the microbiome less, but still be more than adequate for treatment," Dr. McDonald told Medscape Medical News. "I think the results are comforting because — as one might expect from pharmacokinetic data alone — there appears to be no difference in short-term C difficile outcomes between the 2 doses."

Dr. Chung and Dr. McDonald have disclosed no relevant financial relationships.

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract K-335. Presented September 10, 2013.

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