Daptomycin dosing in obese patients: analysis of the use of adjusted body weight versus actual body weight.

BACKGROUND: Food and Drug Administration-approved daptomycin dosing uses actual body weight, despite limited dosing information for obese patients. Studies report alterations in daptomycin pharmacokinetics and creatine phosphokinase elevations associated with higher weight-based doses required for obese patients. Limited information regarding clinical outcomes with alternative daptomycin dosing strategies in obesity exists. OBJECTIVE: This study evaluates equivalency of clinical and safety outcomes in obese patients with daptomycin dosed on adjusted body weight versus a historical cohort using actual body weight. METHODS: This retrospective, single center study compared equivalency of outcomes with two one-sided tests in patients with body mass index ⩾30 kg/m2 who received daptomycin dosed on actual body weight versus adjusted body weight. The primary outcome was clinical failure. Secondary outcomes included 90-day readmission and 90-day mortality. A combined safety endpoint included creatine phosphokinase elevation, patient-reported myopathy, and rhabdomyolysis. RESULTS: A total of 667 patients were screened for inclusion; 101 patients were analyzed with 50 in the actual body weight cohort and 51 in the adjusted body weight cohort. The two regimens were statistically equivalent for clinical failure (2% actual body weight versus 4% adjusted body weight; p < 0.001 for equivalency). The two regimens were also statistically equivalent for 90-day mortality (6% actual body weight versus 4% adjusted body weight; p = 0.0014 for equivalency). Limitations include single center, retrospective design, and sample size. Daptomycin dosing intensified throughout the study period. CONCLUSION: The two daptomycin dosing cohorts were statistically equivalent for both clinical failure and 90-day mortality. More data are needed to assess outcomes with higher (⩾8 mg/kg/day) daptomycin doses in this patient population.

Clostridium difficile treatment in neutropenic patients: Clinical outcomes of metronidazole, vancomycin, combinations, and switch therapy.

BACKGROUND: Clostridium difficile infection treatment guidelines exist for immunocompetent patients; however, there is a paucity of data evaluating clinical outcomes and time to C. difficile-associated diarrhea resolution in neutropenic patients. OBJECTIVE: To assess clinical outcomes in neutropenic patients treated with metronidazole, oral vancomycin, the combination of metronidazole plus oral vancomycin, and switch of metronidazole to oral vancomycin. METHODS: This retrospective, observational cohort study assessed adult neutropenic inpatients with C. difficile-associated diarrhea treated with metronidazole, oral vancomycin, combination (metronidazole and oral vancomycin), or switch therapy (metronidazole to oral vancomycin). The primary outcome was time to diarrhea resolution based on treatment regimen. Secondary outcomes included C. difficile-associated diarrhea resolution of diarrhea by day 14, recurrence, and occurrence of major complications. RESULTS: Overall, 44 patients met full inclusion criteria (52.2% metronidazole monotherapy, 22.7% combination, and 25.0% switch therapy). Two patients on oral vancomycin monotherapy were excluded due to insufficient sample size. Overall time to C. difficile-associated diarrhea resolution was 9.1 ± 10.7 days. The Cox regression results suggested both switch and combination therapy were associated with 65.5% (p = 0.002) and 65.9% (p = 0.046) longer time to C. difficile-associated diarrhea resolution compared to metronidazole monotherapy, respectively. An increasing absolute neutrophil count was associated with an increase in C. difficile-associated diarrhea resolution (p = 0.007). CONCLUSION: Switch or combination therapy was associated with a prolonged time to C. difficile-associated diarrhea resolution. The decision to use switch or combination therapy may represent a surrogate marker for more severe disease and need for therapy escalation. It is unknown if initial therapy with oral vancomycin would provide better outcomes as this could not be assessed.

Zidovudine as modern day salvage therapy for HIV infection.

Resistance to the first-line NRTIs, tenofovir and emtricitabine, does not generally confer resistance to zidovudine. The objective of this study was to describe the efficacy of zidovudine as modern day salvage antiretroviral therapy. This was a single-center, retrospective, observational, cohort study. Adult HIV-positive patients prescribed a zidovudine-containing regimen between 2005 and 2010 were identified from a computer database. All patients had failed at least one prior antiretroviral regimen before zidovudine. The primary outcome measure was virologic success at 24 weeks. Other efficacy and safety outcomes were determined, including virologic success at 48 and 96 weeks, CD4 count change from baseline, and incidence of adverse effects. Sixty-nine subjects were enrolled. The mean age was 43 years, 70% were male, and 85.5% were black. Most patients were highly antiretroviral experienced. At 24 weeks, 63.8% and 72.5% of patients achieved HIV RNA less than 50 and 400 c/mL, respectively. The median change in CD4 count from baseline to week 24 was +70 cells/mm(3). The percent of patients who discontinued zidovudine due to adverse effects was 10%. In this highly treatment-experienced population, zidovudine as part of a salvage regimen appeared effective. Gastrointestinal adverse effects were reported, but zidovudine-associated metabolic effects were uncommon, suggesting zidovudine was generally well tolerated.