Role of nebulized colistin as a substitutive strategy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective cohort study

Role of nebulized colistin as a substitutive strategy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective cohort study

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Introduction

Nosocomial pneumonia caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) is a growing concern worldwide due to limited treatment options and poor prognosis. VAP-prevention strategies have recently been grouped together into care bundles. These strategies, including hand hygiene, daily sedation interruption, protocolized weaning evaluation, and semirecumbent positioning, have been shown to effectively reduce rates of VAP in ICU. Colistin is effective against many GNBs and poses a high sensitivity rate against CR-Acinetobacter baumannii complex (CRAB), CR-enterobacteriaceae (CRE), and CR-Pseudomonas aeroginosa (CRPA). Colistin exerts its bactericidal effects by disrupting the integrity of the outer membrane, resulting in leakage of the cytoplasmic content, and neutralization of GNB endotoxins. Adverse reactions, especially nephrotoxicity, are great concerns of intravenous colistin treatment.

Also, the low penetration of colistin in lung tissue may lead to inadequate antibacterial activity of intravenous colistin. Nebulization has been shown to increase colistin concentration in lung tissue effectively. The role of adjunctive nebulized colistin remains controversial in most recent HAP/VAP guidelines and CR-GNB treatment guidance due to limited evidences from randomized clinical trials. Nebulized colistin in substitutive strategy, which means nebulized colistin without intravenous colistin, has also been used occasionally, especially in patients with impaired renal function and concerns of nephrotoxicity related to intravenous colistin. However, clinical evidences regarding the effectiveness of substitutive nebulized colistin are more scarce. This retrospective study included critically ill patients with nosocomial pneumonia caused by CR-GNB.

Methods

This retrospective study enrolled patients with nosocomial pneumonia caused by colistin-susceptible CRGNB in the intensive care unit (ICU) without intravenous colistin treatment. Patients were categorized based on whether substitutive nebulized colistin was used alongside other intravenous antibiotics. Clinical responses and mortality rates were compared between the two groups in the original and propensity score (PS)-matched cohorts. This study aimed to investigate the clinical effectiveness of substitutive nebulized colistin in treatment outcomes of nosocomial pneumonia caused by CR-GNB. The impact of dosing strategy of nebulized colistin was also explored.

Results

A total of 825 ICU-admitted patients with nosocomial pneumonia caused by CR-GNB were eligible for enrollment. A flow diagram showing the numbers of cases and reasons for exclusion is shown in Fig. 1. In total, 343 and 214 patients with and without substitutive nebulized colistin, respectively, were enrolled for analysis. In the PS-matched cohort, clinical failure rates on day 7 (22.6 vs. 42.6%, p = 0.001), day 14 (27.0 vs. 42.6%, p = 0.013), and day 28 (27.8 vs. 41.7%, p = 0.027) were significantly lower in patients with nebulized colistin. In multivariate analysis, nebulized colistin was an independent factor associated with lower day 14 clinical failure (Original cohort: adjusted odds ratio (aOR) 0.45, 95% confidence interval (CI) 0.30–0.67; PS-matched cohort: aOR 0.48, 95% CI 0.27–0.87). There were no differences in clinical failure rate and mortality rate between patients receiving high (> 6 MIU/day) and low (≤ 6 MIU/day) dose nebulized colistin in the PS-matched cohort.

Conclusions

In comparison to patients treated with non-colistin regimens, patients treated with substitute nebulized colistin had a decreased rate of clinical failure and a similar mortality rate. According to a sub-group analysis, individuals who are older, smokers, have chronic lung diseases, and are more severely ill may benefit more from high-dose nebulization. Our findings only apply to environments where CR-GNB, primarily CRAB, is the primary cause of endemic HAP/VAP. The therapeutic advantages of substitutive nebulized colistin, particularly the use of high dose nebulized colistin in a particular population, need further prospective study.

Source:  Feng, JY., Huang, JR., Lee, CC. et al. Role of nebulized colistin as a substitutive strategy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective cohort study. Ann. Intensive Care 13, 1 (2023). https://doi.org/10.1186/s13613-022-01088-4.