ReviewIntravenous plus inhaled versus intravenous colistin monotherapy for lower respiratory tract infections: A systematic review and meta-analysis
Introduction
Multi-drug (MDR) and extensively-drug resistant (XDR) Gram-negative bacterial lung infections have become increasingly common.1 Colistin is among the last-line treatment options.2 Because colistin disposition in the lungs after intravenous administration is debated and high colistin dose has been associated with nephrotoxicity and neurotoxicity, alternative administration modes have been proposed.3 Thus, colistin has been commonly administered via inhalation in cases of hospital-acquired (HAP) and especially ventilator-associated pneumonia (VAP). In fact, the latest guidelines from the Infectious Diseases Society of America suggested its use in cases of colistin only susceptible bacteria and for patients who are not responding to intravenous antibiotics alone.4 On the contrary, a recent position statement from the European Society of Clinical Microbiology and Infectious Diseases suggested that inhaled antibiotics should be avoided.5
Individual studies did not find any mortality benefit when inhaled colistin was added to intravenous colistin in patients with VAP/HAP.6, 7 Likewise, meta-analyses reported that combination of aerosolized and parenteral colistin can improve clinical effectiveness but not mortality.4, 8 In addition, these analyses did not take into account potential differences between the reviewed studies. The purpose of this systematic review and meta-analysis was to summarize mortality data of patients with MDR/XDR Gram negative lower respiratory tract infections after treatment with colistin according to the mode of administration [intravenous plus inhaled combination (IV/INHCC) versus intravenous monotherapy (IVCM)] and identify factors that could affect mortality in the individual studies.
Section snippets
Literature search and data extraction
The meta-analysis protocol was not registered to any database. Literature search was performed using PubMed and Scopus search engines until November 2016. Two authors (ADM and MG) searched both databases independently. The terms used for the PubMed search were the following: “colistin OR colistimethate” [MeSH Terms] AND “mortality” [MeSH Terms]. In Scopus database, search was limited to “MEDICINE subject” and the study type to “Articles” using the same terms. Conference abstracts were not
Results
Out of the 1062 articles in PubMed and Scopus databases, 13 studies were finally included in the meta-analysis (Fig. 1).6, 7, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 Table 1 summarizes their characteristics. RCTs were not available. The MINORS scores for the above studies ranged from 7 to 16 (median 13). Eleven of the 13 studies that were included in this analysis were designed to study the comparative mortality of patients treated with inhaled combined with IV colistin and IV colistin
Discussion
In this analysis no difference in mortality was observed between IV/INHCC and IVCM. In general, heterogeneity was not observed. Despite the small number of available studies the funnel plot did not show evidence for reporting bias. Analyses of adjusted data could not be performed. IV/INHCC was associated with lower mortality only in the studies evaluating low dose IV colistin. If this finding is not due to confounders, selection or other forms of bias and since all studies in this analysis had
Conflict of interest
None.
Funding
None.
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