Conference Coverage

Low, high dose vancomycin equally effective in C. difficile



DENVER – Oral vancomycin at a dose of 125 mg four times daily is just as effective as is a dose of 250 mg or higher given at the same frequency in the treatment of diarrhea associated with Clostridium difficile infection, judging from the results from a retrospective study.

Use of the lower dosing regimen has the potential to decrease treatment costs without worsening outcomes, Philip Chung, Pharm.D., said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

According to current recommendations, oral vancomycin 125 mg q.i.d. is the treatment of choice for severe uncomplicated C. difficile infection. To date, no studies have shown the use of oral vancomycin doses higher than 125 mg q.i.d. to be more efficacious than the recommended 125 mg q.i.d. in this setting, said Dr. Chung, clinical pharmacy manager of infectious diseases at Montefiore Medical Center, New York.

Dr. Philip Chung

"Prior to 2008, prescribers at our institution frequently requested vancomycin doses higher than the recommended 125 mg q.i.d. for treatment of [C. difficile infection] despite the absence of data showing added benefits with the higher dosing regimens," he said. "This practice not only increases medication and/or preparation costs, but it may also increase the potential for untoward effects in patients being treated with the higher doses (e.g., increased risks for vancomycin-resistant enterococci colonization or higher likelihood to further alter the GI flora)."

Since the inception of the Antimicrobial Stewardship Program at Montefiore Medical Center in 2008, Dr. Chung and his associates observed a shift in oral vancomycin prescribing practices from a higher dosing regimen to a lower dosing regimen. "Because of this change in practice, we wished to evaluate the efficacy of the different oral vancomycin dosing regimen in order to ensure treatment outcomes remained unchanged at our institution," he said. To do so, the researchers retrospectively reviewed clinical outcomes of 300 adult patients treated with oral vancomycin at the medical center between 2006 and 2010. They looked at clinical parameters, concomitant antibiotics, in-hospital mortality, and 30-day readmission.

The primary endpoint was clinical improvement at 72 hours of oral vancomycin. Secondary endpoints included clinical improvement at end of therapy or discharge, length of stay, in-hospital mortality, and 30-day readmission rate.

Of the 300 patients, 197 were prescribed oral vancomycin 125 mg q.i.d. (low-dose group) and 103 patients were prescribed 250 mg or higher q.i.d. (high-dose group). Dr. Chung and his associates reported that clinical improvement assessed 72 hours after starting oral vancomycin therapy was observed in 85% and 86% of patients in the low- and high-dose groups, respectively (P less than 0.05). Rates of clinical improvement at end of therapy or time of hospital discharge between the two groups were also found to be similar (93% vs. 96%), as were total length of hospital stay (20 days vs. 19 days), in-hospital mortality (15% vs. 23%), and rates of 30-day readmission (34% vs. 24%).

"The finding that oral vancomycin 125 mg q.i.d. works as well as higher doses for severe uncomplicated C. difficile infection for the most part is not a surprise to us, as some evidence already exists in the literature," said Dr. Chung, also of Albert Einstein College of Medicine in New York. "Our finding only confirmed what is already known."

Limitations include the fact that this is a single-center study, and that it is subject to selection bias because of its retrospective design, Dr. Chung said. "However, we took steps to ensure that all patients treated with oral vancomycin who had laboratory-confirmed [C. difficile infection] and symptoms consistent with [C. difficile infection] were included in the study," he said.

Dr. Chung said that he had no relevant financial conflicts to disclose.

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