Elsevier

Journal of Infection

Volume 76, Issue 4, April 2018, Pages 321-327
Journal of Infection

Review
Intravenous plus inhaled versus intravenous colistin monotherapy for lower respiratory tract infections: A systematic review and meta-analysis

https://doi.org/10.1016/j.jinf.2018.02.002Get rights and content

Abstract

Objective

To evaluate whether intravenous plus inhaled combination (IV/INHCC) compared to intravenous monotherapy (IVCM) was associated with patient outcomes and identify factors influencing study outcomes.

Methods

PubMed and Scopus were searched till November 2016. Studies were included if they evaluated adult patients with lower respiratory tract infections due to MDR/XDR Gram-negative bacteria and reported comparative mortality data (adjusted and unadjusted) for patients receiving IV/INHCC versus IVCM. Random effects meta-analyses were performed.

Results

Thirteen studies (11 retrospective, 2 prospective) were included. The overall quality of data was low to very low and characterized by the lack of adjusted data. The majority of the studies were designed to evaluate the outcome of the meta-analysis. Both IV and inhaled colistin were administered at variable doses. There was no difference in mortality between IV/INHCC and IVCM when all studies were combined (13 studies, 1115 patients, risk ratio 0.94, 95% confidence interval 0.81–1.08). Only the analysis that included studies with low-dose IV colistin showed significant difference in favor of IV/INHCC versus IVCM (0.65, 0.45–0.94).

Conclusions

Overall, low quality data suggest that IV/INHCC did not lower mortality in patients with MDR Gram negative infections unless low IV colistin dose was administered.

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.

References (28)

  • K.Z. Vardakas et al.

    Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: the study, the patient, the bug or the drug?

    J Infect

    (2013)
  • M.E. Falagas et al.

    Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections

    Clin Infect Dis

    (2005)
  • T. Kelesidis et al.

    The safety of polymyxin antibiotics

    Expert Opin Drug Saf

    (2015)
  • A.C. Kalil et al.

    Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society

    Clin Infect Dis

    (2016)
  • Cited by (21)

    • Successful treatment of pneumonia caused by multidrug-resistant Pseudomonas aeruginosa after allogeneic hematopoietic stem cell transplantation with colistin and amikacin inhalation therapy

      2022, Journal of Infection and Chemotherapy
      Citation Excerpt :

      Colistin and amikacin are often used for the treatment of MDRP infections, but it is known to be poorly absorbed into the lung. It has been reported that intravenous colistin combined with inhalation therapy improves the therapeutic outcome of MDRP pneumonia [4]. On the other hand, inhalation of amikacin has been reported to be effective against respiratory infections caused by gram-negative rods, including P. aeruginosa [5,6].

    View all citing articles on Scopus
    View full text