Despite concerns of nephrotoxicity, polymyxin antibiotics often remain the only susceptible agents for multidrug-resistant (MDR) Gram-negative bacteria. Colistin has been more commonly used clinically due to a perceived safety benefit. We compared the nephrotoxicity of colistin to polymyxin B. The in vitro cytotoxicity of colistin was compared to polymyxin B in two mammalian renal cell lines. To validate the clinical relevance of the findings, we evaluated adult patients with normal renal function who received a minimum of 72 h of polymyxin therapy in a multicenter study. The primary outcome was the prevalence of nephrotoxicity, as defined by the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. Colistin exhibited an in vitro cytotoxicity profile similar to polymyxin B. A total of 225 patients (121 receiving colistimethate, 104 receiving polymyxin B) were evaluated. Independent risk factors for colistimethate-associated nephrotoxicity included age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00 to 1.07; P ‫؍‬ 0.03), duration of therapy (OR 1.08; 95% CI, 1.02 to 1.15; P ‫؍‬ 0.02), and daily dose by ideal body weight (OR 1.40; 95% CI, 1.05 to 1.88; P ‫؍‬ 0.02). In contrast, cystic fibrosis was found to be a protective factor in patients who received colistimethate (OR, 0.03; 95% CI, 0.001 to 0.79; P ‫؍‬ 0.04). In a matched analysis based on the risk factors identified (n ‫؍‬ 76), the prevalence of nephrotoxicity was higher with colistimethate than with polymyxin B (55.3% versus 21.1%; P ‫؍‬ 0.004). Polymyxin B was not found to be more nephrotoxic than colistin and may be the preferred polymyxin for MDR infections. A prospective study comparing the two polymyxins directly is warranted.

Secretory diarrhea is a leading cause of morbidity and mortality worldwide. Crofelemer is a first-in-class antidiarrheal agent that simultaneously targets two distinct channels, the cystic fibrosis conductance regulator and calcium-activated chloride channel, responsible for chloride and fluid secretion in the GI tract. Crofelemer is a novel compound extracted from the stem bark latex of the Croton lechleri tree found in the western Amazonian region of South America. There is little to no systemic absorption of crofelemer when given orally and studies have shown minimal toxicity beyond mild gastrointestinal effects. In studies in diarrheal illness associated with primarily a secretory component, such as cholera, travelers' diarrhea and acute infectious diarrhea, crofelemer has shown improvements in stool consistency and duration of symptoms. Less clear, but interesting, results have been observed in other diarrheal diseases associated with a mixed pathology, including diarrhea in patients with HIV and diarrhea-predominant irritable bowel syndrome.

Implementation of an antimicrobial stewardship program at a health system helped decrease the inappropriate use of antibiotics, improve patient care and outcomes, further clinical research, and increase training opportunities for future clinical infectious diseases pharmacists.

Due to the increasing number of articles published each year, it is difficult to maintain a current knowledge of significant publications in the field of ID pharmacotherapy. This review of key publications in 2010 may be helpful to the nonspecialist clinician by lessening this burden.