Causative Agents of Ventilator-Associated Pneumonia and Resistance to Antibiotics in COVID-19 Patients: A Systematic Review

Abstract

Patients with coronavirus disease 2019 (COVID-19) have an increased risk of ventilator-associated pneumonia (VAP). This systematic review updates information on the causative agents of VAP and resistance to antibiotics in COVID-19 patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, and LILACS databases from December 2019 to December 2021. Studies that described the frequency of causative pathogens associated with VAP and their antibiotic resistance patterns in critically ill COVID-19 adult patients were included. The Newcastle-Ottawa Quality Assessment Scale was used for critical appraisal. The data are presented according to the number or proportions reported in the studies. A total of 25 articles were included, involving 2766 VAP cases in COVID-19 patients (range 5-550 VAP cases). Most of the studies included were carried out in France (32%), Italy (20%), Spain (12%) and the United States (8%). Gram-negative bacteria were the most frequent causative pathogens of VAP (range of incidences in studies: P. aeruginosa 7.5-72.5%, K. pneumoniae 6.9-43.7%, E. cloacae 1.6-20% and A. baumannii 1.2-20%). S. aureus was the most frequent Gram-positive pathogen, with a range of incidence of 3.3-57.9%. The median incidence of Aspergillus spp. was 6.4%. Few studies have recorded susceptibility patterns among Gram-negative causative pathogens and have mainly reported extended-spectrum beta-lactamase (ESBL), AmpC, and carbapenem resistance. The median frequency of methicillin resistance among S. aureus isolates was 44.4%. Our study provides the first comprehensive description of the causative agents and antibiotic resistance in COVID-19 patients with VAP. Gram-negative bacteria were the most common pathogens causing VAP. Data on antibiotic resistance patterns in the published medical literature are limited, as well as information about VAP from low- and middle-income countries.