Clinical Experience of Colistin-Glycopeptide Combination in Critically Ill Patients Infected with Gram-Negative Bacteria

Abstract

A colistin-glycopeptide combination (CGC) has been shown in vitro to be synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB), especially Acinetobacter baumannii, and to prevent further resistance. However, clinical data are lacking. We carried out a retrospective multicenter study of patients hospitalized in intensive care units (ICUs) who received colistin for GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30-day mortality after treatment onset among patients treated with and without CGC for >48 h. Of the 184 patients treated with colistin, GNB infection was documented for 166. The main causative agents were MDR A. baumannii (59.6%), MDR Pseudomonas aeruginosa (18.7%), and carbapenem-resistant Klebsiella pneumoniae (14.5%); in 16.9% of patients, a Gram-positive bacterium (GPB) coinfection was documented. Overall, 68 patients (40.9%) received CGC. Comparison of patients treated with and without CGC showed significant differences for respiratory failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus 71.4%), MDR A. baumannii infection (70.6% versus 52%), and GPB coinfection (41.2% versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and 30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who survived for >5 days after treatment onset showed that the Charlson index (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44; P ‫؍‬ 0.001) and MDR A. baumannii infection (HR, 2.51; 95% CI, 1.23 to 5.12; P ‫؍‬ 0.01) were independent predictors of 30-day mortality, whereas receiving CGC for >5 days was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93; P ‫؍‬ 0.03). We found that CGC was not associated with higher nephrotoxicity and was a protective factor for mortality if administered for >5 days.

In Vitro and In Vivo Activities of Tigecycline-Colistin Combination Therapies against Carbapenem-Resistant Enterobacteriaceae

“…This may improve the activity of a number of antibiotics which would otherwise have little effect (13). This approach is validated by reports of better clinical outcomes with unorthodox therapies for an increasing range of carbapenem-resistant bacteria (14)(15)(16). In this study, we assessed the activity of TGC in combination with COL against a range of CRE both in vitro and in vivo by using standard checkerboard and time-kill assays and a simple invertebrate model (Galleria mellonella) of infection and therapeutics (17-19) (we do acknowledge that currently the G. mellonella model lacks the required validation with regard to comparability with human therapy).…”

Intravenous polymyxins: Revival with puzzle

“…Petrosillo N et al found no difference in 30-day mortality, in the 4 groups as follows: colistin alone, colistin-glycopeptide, colistin plus other anti-GNB drugs, colistin-glycopeptide plus other anti-GNB drugs (28). But it's also indicated in this study that the colistin-glycopeptide combination was a protective factor for mortality if administered for > 5 days.…”

“…No difference was found between IV colistin monotherapy or combination therapy with rifampicin (53), glycopeptides (28), fosfomycin (54), carbapenem or sulbactam (31,47). But the combination of intravenous colistin plus intravenous vancomycin is associated with an increased risk of renal failure (51).…”

“…intravenous polymyxins alone in MDR GNB infections, most of which were pneumonias. It's indicated that the mortality ranged from 0% to 74.3% (4,21,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), clinical response (cure and improvement) rate 7-82.1%, and microbiological eradication 27.3-73.9% (24,(33)(34)(35)(36)(37)(38). In respect to the colistin only susceptible strains, it's reported that the mortality in hospitals of intravenous colistin monotherapy was 50% (16/32) (Figure 2), 11 patients died in Intensive Care Unit (ICU) (39), and clinical cure was obtained in 82.1% of infectious episodes (23/28) and bacteriological clearance was achieved in 73.9% (17/23) of the cured infectious episodes (38).…”

Diseminación de Klebsiella pneumoniae productoras de KPC-3 en hospitales de Bogotá durante un periodo de tres años

“…Otros antibióticos, como la colistina y la tigeciclina, se utilizan para el tratamiento contra microorganismos portadores de carbapenemasas (20,21), y nuestros aislamientos presentaron sensibilidad in vitro frente a estos dos agentes. Sin embargo, actualmente ya hay reportes de aislamientos portadores de KPC resistentes a estos antibióticos en Estados Unidos (22), Europa (23,24) Asia (25) y, más recientemente, en Suramérica (26).…”