Polymyxin for treatment of ventilator-associated pneumonia in a setting of high carbapenem resistance.

Thalita Bento Talizin,Eduardo Alexandrino Medeiros,Marcos Toshiyuki Tanita,Isabella Patruceli De Azevedo,Késia Paes,Karine Maria Boll,Camila Ribeiro Lopes,Cláudia Maria Dantas De Maio Carrilho,Cintia Magalhães Carvalho Grion,Lucienne Tibery Queiroz Cardoso,Josiane Festti,Leticia Maria Alves Da Silva,Ivanil Aparecida Moro Kauss,Martina Crivellari

doi:10.1371/journal.pone.0237880

Abstract

ObjectivesTo analyse the use of polymyxins for the treatment of ventilator-associated pneumonia (VAP) at a teaching hospital where carbapenem-resistant gram-negative bacteria are endemic.Patients and methodsThis was a historical cohort study of patients receiving polymyxins to treat VAP in ICUs at a public university hospital in southern Brazil between January 1, 2017 and January 31, 2018.ResultsDuring the study period, 179 cases of VAP were treated with polymyxins. Of the 179 patients, 158 (88.3%) were classified as having chronic critical illness. Death occurred in 145 cases (81.0%). Multivariate analysis showed that the factors independently associated with mortality were the presence of comorbidities (P<0.001) and the SOFA score of the day of polymyxin prescription (P<0.001). Being a burn patient was a protective factor for mortality (P<0.001). Analysis of the 14-day survival probability showed that mortality was higher among the patients who had sepsis or septic shock at the time of polymyxin prescription (P = 0.028 and P<0.001, respectively). Acinetobacter baumannii was identified as the etiological agent of VAP in 121 cases (67.6%). In our cohort, polymyxin consumption and the incidence density of VAP were quite high.ConclusionsIn our study, comprised primarily of chronically critically ill patients, there was a high prevalence of VAP caused by multidrug-resistant bacteria, consistent with healthcare-associated infections in low- and middle-income countries. Presence of comorbidities and the SOFA score at the time of polymyxin prescription were predictors of mortality in this cohort. Despite aggressive antimicrobial treatment, mortality was high, stressing the need for antibiotic stewardship.

Highlights

Healthcare-associated infections (HAI) are a public policy concern in low- and middle-income countries, in terms of providing technological support and qualified human resources, as well as improving antimicrobial stewardship programs and reducing the rates of microbial resistance [1]
179 cases of ventilator-associated pneumonia (VAP) were treated with polymyxins
Acinetobacter baumannii was identified as the etiological agent of VAP in 121 cases (67.6%)

Summary

Introduction

Healthcare-associated infections (HAI) are a public policy concern in low- and middle-income countries, in terms of providing technological support and qualified human resources, as well as improving antimicrobial stewardship programs and reducing the rates of microbial resistance [1]. In Brazil, the prevalence of HAIs in hospitals is 10.8% and pneumonia is the most common HAI [2]. In ICUs in Brazil, the prevalence of HAIs is considerably higher (51.2%) and those caused by Enterobacteriaceae or non-fermenting bacteria are quite common [3]. In the ICU, patients undergo mechanical ventilation, which can lead to ventilator-associated pneumonia (VAP). Multidrug-resistant Acinetobacter baumannii is one of the most common etiologic agents of VAP in critically ill patients, which continues to be a major therapeutic challenge [4]. Polymyxins once again have become one of the only effective drug classes for treating infection with multidrug-resistant gram-negative bacteria such as A. baumannii, Pseudomonas aeruginosa and Enterobacteriaceae. There have been only a few studies analysing the profiles of polymyxin users and attempting to determine the best dosage [5,6]

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