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.

Abstract. Mycobacterium senegalense infection is rare. We present the third documented case of M. senegalense infection and the first to involve the musculoskeletal system. A 55-year old immunocompetent male developed chronic osteomyelitis of the ankle and required antibiotic spacers, an Ilizarov external fixator and multiple antibiotic regimens to eradicate the infection.

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.

Background Fluconazole is the drug of choice for candiduria requiring treatment; however, it may not be optimal in some cases because of resistance, drug interactions, or adverse effects. Case reports and retrospective analyses suggest that echinocandins may be effective in treating candiduria and Candida urinary tract infections, despite low urinary concentrations. The purpose of this investigation was to evaluate the effectiveness of echinocandins for the treatment of Candida urinary tract infections in hospitalized patients. Methods This was a 5-year, retrospective evaluation of patients treated with micafungin for Candida urinary tract infections (symptomatic) or asymptomatic candiduria with qualifying conditions (pregnancy, neutropenia, recent urologic procedure). The primary outcome was clinical success, defined as symptom resolution (symptomatic patients) or urine sterilization (asymptomatic patients) by the end of treatment. Secondary outcomes included urine sterilization in all patients and time to symptom resolution. Results A total of 302 patients with candiduria received micafungin during the study period. Of these, 97 met the inclusion criteria; however, 83 were excluded. Fourteen patients were included in the case series. Twelve patients (85.7%) were symptomatic, and 2 (14.3%) were asymptomatic with neutropenia. Ten patients (71.4%) achieved the primary outcome of symptom resolution or urine sterilization by the end of treatment. Six patients (42.9%) had urine sterilization by the end of therapy; however, a follow-up urine culture was not performed in the remaining 8 patients. Median time to symptom resolution was 4 days. Conclusions In some clinical settings, micafungin may be an effective therapy for Candida urinary tract infections in hospitalized patients.

Ceftazidime-avibactam is a novel combination antimicrobial agent consisting of a broad-spectrum cephalosporin, ceftazidime, and a non–β-lactam β-lactamase inhibitor, avibactam. This agent has demonstrated activity against resistant gram-negative bacteria, including Klebsiella pneumoniae carbapenemase–producing organisms; however, it is US Food and Drug Administration approved for use in urinary tract and intra-abdominal infections only. We present a case of successful treatment of K. pneumoniae carbapenemase–producing K. pneumoniae bacteremia with a combination of meropenem and colistin followed by ceftazidime-avibactam and colistin.