Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study

Abstract

BackgroundThe incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia.MethodsA retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher’s exact test while the student’s t-test or Mann–Whitney U test were used for continuous variables.ResultsNinety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033).ConclusionsAddition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.

Inhaled Colistin Use for Multi-Drug Resistant Gram-Negative Pneumonia in an Immunocompromised Patient: Case Report

“…Recently, Tumbarello et al also indicated that in 208 critically ill patients with HAP caused by MDR Gram negative organisms, aerosolized colistin as adjunct to intravenous form could significantly improve clinical cure rates and shorten the duration of mechanical ventilation, as compared with intravenous colistin monotherapy alone. 12 These studies were conflicting with earlier studies showing no significant differences with combination therapy; however they were criticized to have small number of patients leading to power limitations. 12,19,26 Efficacy of colistin can be enhanced with the use of another antibiotic, such as rifampicin or carbapenems.…”

“…12 These studies were conflicting with earlier studies showing no significant differences with combination therapy; however they were criticized to have small number of patients leading to power limitations. 12,19,26 Efficacy of colistin can be enhanced with the use of another antibiotic, such as rifampicin or carbapenems. [27][28][29] Pintado et al reported that colistin use is effective in MDR Gram negative bacteraemia, with a response rate of 71.7%, when used in combination with aminoglycosides.…”

“…22 With the emergence of MDR Gram-negative bacteria, it has been reconsidered as salvage therapy. 12,[14][15][16] Since colistin is a cationic detergent damaging bacterial cytoplasmic membrane, it is more active in infections due to MDR bacteria. 23 But its polycationic/hydrophilic structure limits its penetration to lung tissue; therefore aerosolized form has been evaluated for generating high drug concentrations at site of infection without increasing the risks of systemic toxicity and resistance against colistin.…”

“…[15][16][17][18][19] There are few observational, retrospective, uncontrolled small case series, including patients with malignancies, about use of combination of inhaled and intravenous colistin for management of hospital acquired pneumonia (HAP) caused by MDR Pseudomonas aeruginosa. 12,14,19,20 Herein, we present a case with lymphoma developed neutropenia and subsequently HAP caused by MDR Pseudomonas aeruginosa, and treated successfully with combined colistin therapy.…”

Efficacy and Safety of Aerosolized Colistin in the Treatment of Ventilator-Associated Pneumonia: A Systematic Review and Meta-analysis

“…총 9개의 문헌 (randomized controlled trial 1개 27) , cohort 5개 [22][23][24][25][26] , case-control 3개 24,28,30) ) 중 8개 문헌에 대해서는 Newcastle-Ottawa Quality Assessment Scale을 1개의 문헌에 대해서는 Cochrane risk-of-bias tool을 사용하여 quality를 평 가하였고 그 결과는 Table 1에 제시하였다. 각 문헌의 quality assessment 결과 한 연구 참고문헌…”