Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial.

OBJECTIVES: To evaluate the effect of melatonin versus placebo on the incidence of acute kidney injury (AKI) in patients treated with polymyxin B. METHODS: We performed a single-centre, double-blind, randomized clinical trial (NCT03725267) of 30-mg oral melatonin versus placebo for patients treated with intravenous polymyxin B. Patients aged ≥18 years receiving polymyxin B for ≤48 hours were eligible. Melatonin or placebo pills were administered until the end of polymyxin B treatment or for a maximum of 14 days. The main outcome was any level of AKI. RESULTS: Eighty-eight patients were randomized: 44 in the melatonin group and 44 in the placebo group. The study ended prematurely because of polymyxin B shortage during the COVID-19 pandemic. The patients' mean age was 63.6 ± 17.3 years, and 60.2% of the patients were men. Forty-six (52.3%, 23 in each group) patients developed AKI during the follow-up period. The incidence rate of AKI was 81.9/1000 and 77.4/1000 patients per day in melatonin and placebo groups, respectively (hazard ratio, 1.09; 95% CI, 0.61-1.94; p 0.78). Renal failure and 30-day mortality were similar between the groups. Moreover, the incidence of AKI was not different in pre-specified sub-groups. DISCUSSION: Melatonin initiated in the first 48 hours of therapy did not reduce the incidence of AKI in patients treated with polymyxin B.

Polymyxin B versus other antimicrobials for the treatment of pseudomonas aeruginosa bacteraemia.

OBJECTIVES: to compare the efficacy of intravenous polymyxin B with other antimicrobials in the treatment of nosocomial Pseudomonas aeruginosa bacteraemia, assessing many potential confounding factors, including optimal dosage regimens of drugs. METHODS: a retrospective cohort study was performed. Patients ≥ 18 years of age and who received appropriate therapy for ≥ 48 h for P. aeruginosa bacteraemia were analysed. Clinical covariates were assessed and compared between patients treated with polymyxin B and other drugs (comparators). Data were retrieved from medical records. Renal toxicity was also assessed. A Cox regression model was performed including variables with a P  ≤  0.20 in the comparison between both groups. RESULTS: a total of 133 patients were included: 45 (33.8%) treated with polymyxin B and 88 (66.2%) with comparators. Most comparators (83.0%) were ß-lactams. The overall in-hospital mortality was 41.4% (55/133): 66.7% (30/45) and 28.4% (25/88) in polymyxin B and comparator groups, respectively (P  ≤  0.001). The final multivariate model showed that treatment with polymyxin B was independently associated with in-hospital mortality (adjusted hazard ratio 1.91, 95% confidence interval 1.05-3.45), after adjustment for Pitt bacteraemia score, and the presence of mechanical ventilation and primary bloodstream infection. Patients treated with polymyxin B presented a higher rate of ≥ 100% increase in creatinine level from baseline than comparators [11/45 (24.4%) versus 4/88 (4.5%); P = 0.002], although this was not subjected to multivariate analysis. CONCLUSIONS: intravenous polymyxin B therapy was inferior to other drugs in the treatment of P. aeruginosa bacteraemia, as indicated by the higher rate of in-hospital mortality.