Treatment outcome and adverse effects of colistin in adult patients with carbapenem-resistant gram-negative bacteremia from Pakistan

Abstract

BackgroundPolymyxins (colistin) have emerged for the treatment of carbapenem resistant (CR) gram-negative infections. There is a paucity of data on treatment outcomes and adverse effects of high-dose colistin treatment in Pakistan. The aim of this study was to determine the efficacy and toxicity of colistin in CR bacteremia, including patients with renal failure and on hemodialysis, and to determine patient outcomes. MethodsThis prospective cohort study was performed from May to December 2017 at Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Patients aged >18 years with documented gram-negative bacteremia were included. Data were compared between those who received colistin and those who did not, including risk factors for CR bacteremia, bacterial clearance, adverse effects, and all-cause mortality up to 14 days of follow-up. ResultsThe study included 137 patients, 73 (53.3%) in the colistin group and 64 (46.7%) in the non-colistin group. Patients in the colistin group were 1.47 times more likely to have died by day 14 of follow-up as compared to those in the non-colistin group (19.2% vs 7.8%; relative risk 1.47, p= 0.05). Patients in both groups achieved more than 80% bacteriological clearance. The colistin group patients were less likely to have received appropriate empirical antibiotics as compared to the non-colistin group patients (4.1% vs 62.5%; relative risk 0.09, p< 0.001). Factors significantly associated with mortality were inappropriate empirical antibiotics and acute renal failure. Of the 73 patients in the colistin group, 27 (37.0%) developed reversible neurological adverse effects. Patients with renal insufficiency, not on hemodialysis, were evaluated for colistin nephrotoxicity. Creatinine decreased from 8.08 mg/dl at baseline to 4.85 mg/dl on day 7 in the colistin group, and from 6.5 mg/dl to 3.9 mg/dl in the non-colistin group. Patients with normal renal function had no significant rise in serum creatinine. ConclusionsColistin is efficacious in clearing bacteremia even in patients with impaired renal function. The adverse effects were found to be minimal and reversible. We recommend the use of colistin in combination with carbapenems for CR gram-negative bacteria in renal failure. Most importantly, however, this study highlights the role of empirical colistin treatment in patients with risk factors for CR bacteremia.