Our study showed that doses of intravenous polymyxin B are best scaled by total body weight. Importantly, dosage selection of this drug should not be based on renal function.

Polymyxin B total dose is highly related to the risk of AKI, regardless of patient weight. Thirty-day mortality tended to be higher in patients who developed AKI. The relationship between dose, AKI and mortality must be further investigated in studies specifically designed to evaluate this latter outcome.

Our findings indicate that the recommended polymyxin B doses should not be reduced for patients on CVVHD.

There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa isolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for >48 h for severe A. baumannii or P. aeruginosa infections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lacking in vitro activity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P ‫؍‬ 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P ‫؍‬ 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64; P ‫؍‬ 0.001). Creatinine clearance of >60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with ␤-lactam or carbapenem was considered and in both subgroups of patients: those with A. baumannii infection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drugresistant A. baumannii or P. aeruginosa infections.T he emergence of carbapenem-resistant Gram-negative bacteria (GNB) in the last decade, mostly driven by carbapenemase-producing strains, importantly changed the epidemiology of hospital-acquired infections (1). Carbapenem-resistant GNB frequently present an extensively drug-resistant (XDR) profile (2), and these isolates have been an increasing public health concern worldwide (1, 2). Among XDR bacteria, Acinetobacter baumannii and Pseudomonas aeruginosa are pathogens of major clinical and epidemiological importance, notably in intensive care unit (ICU) patients (3, 4).Since the discovery of new anti-GNB agents has dried up, polymyxins, both B and E (colistin), have reemerged in clinical practice as agents of last resort against XDR A. baumannii and P. aeruginosa (5, 6). However, despite the in vitro activity of polymyxins, some factors, such as a possible limited clinical efficacy and the potential for the emergence of resistance during treatment, along with some support from preclinical studies, have led many physicians to prescribe combination therapy, mostly a polymyxin combined with a second agent, for patients infec...

High-dose cefepime therapy was associated with lower mortality rates in patients with GNB BSIs, even for GNB with low cefepime MICs.