Combination Therapy with Intravenous Colistin for Management of Infections Due to Multidrug-Resistant Gram-Negative Bacteria in Patients without Cystic Fibrosis

Abstract

Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gramnegative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 ؎ 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.

Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients

“…Only the first episode of MDR Gram-negative bacterial infection M a n u s c r i p t treated with colistin was included in the analysis. An a priori decision was made not to remove from this analysis patients who received care during the period October 2000 to May 2005 for whom a subset of data has been reported previously [5][6][7]. Specifically, some data on 108 patients included in this analysis have been previously reported.…”

“…polymyxins (colistin and polymyxin B), an antibiotic class discovered more that 60 years ago that had been abandoned for nearly 20 years, except for in the distinct population of patients with cystic fibrosis [2]. A number of recently published clinical studies have suggested that colistin may be considered in the treatment of patients with MDR Gram-negative bacterial infections [3][4][5][6][7][8][9].…”

Colistín en infecciones nosocomiales por bacilos gramnegativos pan-resistentes

“…Él y otros autores griegos utilizan habitualmente tres millones de UI cada ocho horas; el triple de la dosis utilizada en nuestros pacientes sin falla renal 6,11 . Las tasas de respuesta en sus trabajos bordean el 70% 6,11,18 . Sin embargo, explorar la importancia de las dosis de colistín o la duración del tratamiento a través de series de casos que difieren en cuanto al tipo de pacientes e infecciones, los agentes involucrados, su gravedad o el uso de terapias combinadas, es una tarea difícil y especulativa.…”

Intravenous polymyxins: Revival with puzzle

“…The cure rates of colistin based regimens are reported to be 53.7-79.1% in GNB infections (16,17). A recently published 10-year case series indicated that CMS use increased, more than half of the patients were discharged alive, and no significant nephrotoxicity was observed in the 5603 patients prescribed CMS (along with other antibiotics) (18).…”

“…In order to obtain synergistic effects, antimicrobials used frequently with colistin include imipenem/ meropenem and sulbactam (16,44). An early retrospective study indicated that the effectiveness of colistin monotherapy did not appear to be inferior to that of colistin-meropenem combination therapy for patients with MDR bacterial infections (27).…”