Inhaled colistin monotherapy for respiratory tract infections in adults without cystic fibrosis: a systematic review and meta-analysis

Highlights

• Clinical and microbiological outcomes of patients receiving inhaled colistin therapy as monotherapy are encouraging.

• Inhaled monotherapy may deserve further consideration as a mode for colistin administration for MDR respiratory tract infections.

• Studies are needed to further evaluate the effectiveness/safety of inhaled colistin monotherapy for pulmonary infections.

Abstract

Background

Inhaled colistin is becoming increasingly popular against respiratory tract infections caused by multidrug resistant (MDR) Gram-negative bacteria because it may overcome the problems associated with intravenous (IV) administration.

Objective

To investigate the effectiveness and safety of inhaled colistin as monotherapy (without concomitant IV administration of colistin) in the treatment of respiratory tract infections caused by MDR or colistin–only susceptible Gram–negative bacteria.

Methods

PubMed and Scopus databases were searched. A systematic review and meta-analysis were conducted.

Results

Twelve studies (373 patients receiving inhaled colistin for respiratory tract infection) were included. Ten studies evaluated patients with pneumonia (including 8 studies with ventilator-associated pneumonia) and 2 studies evaluated patients with ventilator-associated tracheobronchitis. Patients with infections due to MDR Acinetobacter baumannii and Pseudomonas aeruginosa were mainly studied. Daily dose of inhaled colistin and treatment duration varied in the individual studies. The pooled all-cause mortality was 33.8% (95% CI 24.6% – 43.6%), clinical success was 70.4% (58.5% – 81.1%) and eradication of Gram-negative bacteria was shown in 71.3% (57.6% – 83.2%) of cases.

Conclusions

Inhaled colistin monotherapy may deserve further consideration as a mode for colistin administration for the treatment of respiratory tract infections caused by MDR A. baumannii and P. aeruginosa.

Introduction

Respiratory tract infections caused by multidrug–resistant (MDR) and extensively drug–resistant (XDR) Gram-negative bacteria, particularly those of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa, have been associated with high morbidity and mortality, mainly among critically ill patients under mechanical ventilation [1], [2], [3]. The lack of effective antimicrobial therapy, mainly attributed to the emergence of resistance, was among the factors associated with mortality [4], [5]. Colistin, a formerly ‘abandoned’ antibiotic, remains one of the few active antimicrobial agents against MDR and XDR Gram-negative bacteria [4], and is currently considered one of the last therapeutic options. However, the safety of intravenous (IV) colistin in critically ill patients has been debated because it has been associated with variable nephrotoxicity and neurotoxicity [6]. Moreover, the physicochemical characteristics of colistin predispose for low lung tissue penetration after IV administration, which may hamper its effectiveness in this group of patients [7], [8].

The use of inhaled colistin is becoming increasingly popular because it may overcome the aforementioned problems associated with IV administration [9]. Several studies compared the effectiveness and safety of inhaled colistin in combination with IV colistin with that of IV colistin alone for the treatment of pneumonia, particularly ventilator-associated pneumonia (VAP) [10], [11], [12], [13]. Recent systematic reviews showed that patient outcomes improved when inhaled colistin was added to the IV colistin–containing regimens [14], [15]. In accordance, the latest guidelines by the Infectious Diseases Society of America and the American Thoracic Society suggested the adjunctive administration of inhaled colistin in patients with hospital–acquired pneumonia (HAP)/VAP caused by colistin-only susceptible pathogen in addition to IV polymyxin (colistin or polymyxin B) [16]. However, possible disadvantages of IV plus inhaled administration may include potential for higher nephrotoxicity, emergence of resistance, particularly in the respiratory tract, and elevated expenditures [16].

It has been suggested that inhaled colistin as monotherapy may result in lower systemic toxicity while achieving a higher drug concentration in the lung tissue early in the course of infection compared with IV colistin [17], [18]. Thus, the aim of the present evaluation of published evidence was to investigate the effectiveness and safety of inhaled colistin as monotherapy (without concomitant IV administration of colistin) in the treatment of respiratory tract infections caused by MDR, XDR or colistin–only susceptible (COS) Gram-negative bacteria.