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(1) Background: It is not known whether different daily dosing schemes have different effects on colistin nephrotoxicity. We examined the effect of once- versus twice- or thrice-daily doses of colistin on renal function. (2) Methods: We performed a multicenter retrospective cohort study of hospitalized patients with a baseline glomerular filtration rate ≥ 50 mL/min who received intravenously the same colistin dose once (regimen A), twice (regimen B) or thrice daily (regimen C). The primary endpoint was acute kidney injury (AKI), defined as fulfilment of any of the RIFLE (Risk-Injury-Failure-Loss-End stage renal disease) criteria. (3) Results: We included 306 patients; 132 (43.1%) received regimen A, 151 (49.3%) regimen B, and 23 (7.5%) regimen C. Ninety-nine (32.4%) patients developed AKI; there was no difference between regimen A vs. B and C [45 (34.1%) vs. 54 (31.0%), p = 0.57]. In a propensity score−matched cohort, AKI was similar in patients receiving Regimen A, Regimen B, and Regimen C (31.6% vs. 33.3%, p = 0.78). On logistic regression analysis, diabetes was an independent predictor of AKI (OR = 4.59, 95% CI 2.03−10.39, p = 0.001) while eGFR > 80 mL/min (OR = 0.50, 95% CI 0.25−0.99, p = 0.048) was inversely associated with AKI. (4) Conclusions: Colistin once daily is not more nephrotoxic than the standard colistin regimens. The only independent predictor of nephrotoxicity was diabetes mellitus, while eGFR > 80 mL/min had a protective effect.
RESUMO
INTRODUCTION: The aim of this study was to evaluate the clinical outcomes and safety of daptomycin therapy in patients with serious Gram-positive infections. METHODS: Patients were enrolled in the European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a non-interventional, multicenter, observational registry. The real-world data were collected across 18 countries (Europe, Latin America, and Asia) for patients who had received at least one dose of daptomycin between January 2006 and April 2012. Two-year follow-up data were collected until 2014 for patients with endocarditis, intracardiac/intravascular device infection, osteomyelitis, or orthopedic device infection. RESULTS: A total of 6075 patients were enrolled. The most common primary infections were complicated skin and soft tissue infection (31.7%) and bacteremia (20.7%). Staphylococcus aureus was the most frequently reported pathogen (42.9%; methicillin-resistant S. aureus [MRSA], 23.2%), followed by Staphylococcus epidermidis and other coagulase-negative staphylococci (CoNS, 28.5%). The most commonly prescribed dose of daptomycin was 6 mg/kg/day (43.6%), and the median duration of therapy was 11 (range 1-300) days. Overall clinical success rate was 80.5%, and was similar whether daptomycin was used as first-line (82.9%) or second-line (79.2%) therapy. Clinical success rates were high in patients with S. aureus (83.9%; MRSA 83.0%) and CoNS (including S. epidermidis, 82.5%) infections. The majority of patients with endocarditis or intracardiac/intravascular device infection (86.7%) or osteomyelitis/orthopedic device infection (85.9%) had a sustained response during the 2-year follow-up period. There were no new or unexpected safety findings. CONCLUSION: Results from real-world clinical experience showed that daptomycin is a valuable therapeutic option in the management of various difficult-to-treat Gram-positive infections. FUNDING: This study was funded by Novartis Pharma AG.