Chest
Volume 144, Issue 6, December 2013, Pages 1768-1775
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Original Research
Critical Care
Effect of Aerosolized Colistin as Adjunctive Treatment on the Outcomes of Microbiologically Documented Ventilator-Associated Pneumonia Caused by Colistin-Only Susceptible Gram-Negative Bacteria

https://doi.org/10.1378/chest.13-1018Get rights and content

Background

The increasing frequency of ventilator-associated pneumonia (VAP) caused by colistin-only susceptible (COS) gram-negative bacteria (GNB) is of great concern. Adjunctive aerosolized (AS) colistin can reportedly increase alveolar levels of the drug without increasing systemic toxicity. Good clinical results have been obtained in patients with cystic fibrosis, but conflicting data have been reported in patients with VAP.

Methods

We conducted a retrospective, 1:1 matched case-control study to evaluate the efficacy and safety of AS plus IV colistin vs IV colistin alone in 208 patients in the ICU with VAP caused by COS Acinetobacter baumannii, Pseudomonas aeruginosa, or Klebsiella pneumoniae.

Results

Compared with the IV colistin cohort, the AS-IV colistin cohort had a higher clinical cure rate (69.2% vs 54.8%, P = .03) and required fewer days of mechanical ventilation after VAP onset (8 days vs 12 days, P = .001). In the 166 patients with posttreatment cultures, eradication of the causative organism was also more common in the AS-IV colistin group (63.4% vs 50%, P = .08). No between-cohort differences were observed in all-cause ICU mortality, length of ICU stay after VAP onset, or rates of acute kidney injury (AKI) during colistin therapy. Independent predictors of clinical cure were trauma-related ICU admission (P = .01) and combined AS-IV colistin therapy (P = .009). Higher mean Simplified Acute Physiology Score II (P = .002) and Sequential Organ Failure Assessment (P = .05) scores, septic shock (P < .001), and AKI onset during colistin treatment (P = .04) were independently associated with clinical failure.

Conclusions

Our results suggest that AS colistin might be a beneficial adjunct to IV colistin in the management of VAP caused by COS GNB.

Section snippets

Setting, Study Design, and Data Sources

A retrospective matched-cohort analysis was conducted in the 18-bed general ICU of a 1,400-bed teaching hospital in Rome, Italy. The protocol was approved by the Catholic University's Ethics Committee (approval number: P/237/CE/2012). Informed patient consent was not required given the study's retrospective, observational nature. Data were collected via manual review of hospital charts and computerized interrogation of the ICU and Microbiology Laboratory databases.

Population

Eligibility criteria were as

Population Characteristics and VAP Incidence

During the 8-year study period, 5,812 adults were admitted to the ICU, and > 95% received MV. Two hundred eighty-eight of the patients receiving MV (5%) developed monomicrobial VAP caused by COS GNB and were treated with IV colistin. Forty-two percent (n = 121) of these also received AS colistin, and 104 met all the criteria for enrollment in the AS-IV colistin cohort. Their characteristics and those of the age-, SAPS II-, and SOFA score-matched cohort treated with IV colistin alone are shown

Discussion

This large, retrospective, matched-cohort study of patients with VAP caused by COS GNB showed that AS-IV colistin therapy can significantly shorten the duration of MV after pneumonia onset and increase clinical cure rates, as compared with IV colistin monotherapy alone. Indeed, adjunctive AS colistin was an independent predictor of clinical cure. However, the significance of its favorable impact on microbiologic cure rates was only borderline, and it had no appreciable effects on all-cause ICU

Conclusions

To our knowledge, this is the second matched-cohort study involving direct comparison of AS-IV colistin and IV colistin regimens for treating VAP caused by COS GNB. Our findings tend to conflict with those of two earlier studies,23, 38 both conducted in populations substantially smaller than (and in one case microbiologically different from) our own. Our data indicate that in critically ill patients with VAP caused by COS GNB, AS-IV colistin (as compared with IV colistin alone) can

Acknowledgments

Author contributions: Dr Tumbarello takes responsibility for the content of the manuscript, including the data and analysis.

Dr Tumbarello: contributed to conception and design, acquisition of data, or analysis and interpretation of data; drafted the submitted article or revised it critically for important intellectual content; and provided final approval of the version to be published.

Dr De Pascale: contributed to conception and design, acquisition of data, or analysis and interpretation of

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    Funding/Support: This study was partially supported by a grant from the Università Cattolica del Sacro Cuore, Linea D1 2012.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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