Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B.

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.

Clinical features and mortality of patients on renal replacement therapy receiving polymyxin B.

There are no clinical data for polymyxin B (PMB) in patients on renal replacement therapy (RRT). The aim of this study was to evaluate the characteristics of patients on RRT receiving PMB and to identify predictors of 30-day mortality, with special focus on dosage. A multicentre prospective cohort study including patients aged ≥18 years treated with PMB for ≥48h while on any type of RRT was performed. In total, 88 patients were evaluated, including 34 (38.6%) on continuous venovenous haemodialysis (CVVH) and 54 (61.4%) on intermittent haemodialysis. Most patients (81.8%) received recommended doses between 1.5mg/kg/day and 3.0mg/kg/day. The 30-day mortality was 51.1% (45/88 patients). There was no significant association of dose (in mg/kg) with mortality. A PMB average daily dose ≥200mg was predictive of decreased 30-day mortality in the multivariate model (hazard ratio=0.35, 95% confidence interval 0.14-0.90; P=0.03), whilst CVVH (P=0.04), higher Charlson co-morbidity index (P=0.02) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (P=0.04), and Pseudomonas aeruginosa infection (P=0.001) were independent risk factors for mortality. The results were not changed by the inclusion of patient weight or dose (in mg/kg) in the model, although the latter was significantly correlated with total daily dose. This is the first clinical study to show that higher doses of PMB are associated with lower mortality in patients on RRT.

Polymyxin B in Combination with Antimicrobials Lacking In Vitro Activity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections.

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 ß-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 drug-resistant A. baumannii or P. aeruginosa infections.

Risk factors for acute kidney injury (AKI) in patients treated with polymyxin B and influence of AKI on mortality: a multicentre prospective cohort study.

OBJECTIVES: The objectives of this study were to assess risk factors for acute kidney injury (AKI) in patients treated with polymyxin B, a last resort antibiotic against Gram-negative bacteria, with a focus on dose, and to determine the impact of AKI on mortality of these patients. METHODS: A multicentre prospective cohort study was performed including patients ≥18 years treated with intravenous polymyxin B for ≥48 h. The primary outcome was AKI defined by RIFLE criteria. Secondary outcomes were 30 day mortality and failure stage of AKI. Multivariate analysis with a Cox regression model was performed. The probability of developing AKI was determined in a logistic regression model. RESULTS: Four-hundred-and-ten patients were included. AKI occurred in 189 (46.1%) patients. Polymyxin B dose ≥150 mg/day was a risk factor for AKI: adjusted HR = 1.95, 95% CI = 1.31-2.89, P = 0.01. Higher weight and age were also independently associated with AKI. The probability of developing AKI significantly increased with doses between 150 and 199 mg/day, regardless of patient weight, with no significant increase with higher doses. Higher weight also increased the risk in patients receiving the same daily doses. AKI was barely associated with increased risk for 30 day mortality (adjusted HR = 1.35, 95% CI = 0.99-1.85, P = 0.06), while ≥150 mg/day did not increase this risk despite its association with AKI. CONCLUSIONS: 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.