Importance of control groups when delineating antibiotic use as a risk factor for carbapenem resistance, extreme-drug resistance, and pan-drug resistance in Acinetobacter baumannii and Pseudomonas aeruginosa: A systematic review and meta-analysis

Abstract

Background: Carbapenem-resistant (CR), extremely drug-resistant (XDR), and pan-drug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa pose a huge clinical threat. This study reviews the impact of control groups on the association of antecedent antibiotic use and the acquisition of CR/XDR/PDR A. baumannii and P. aeruginosa. Methods: Studies investigating the role of antibiotics as a risk factor for CR/XDR/PDR A. baumannii and P. aeruginosa acquisition in adult hospitalized patients from 1950 to 2016 were identified in the databases. These were divided into two groups: antibiotic-resistant versus antibiotic-sensitive pathogens (group I); antibiotic-resistant versus no infection (group II). A random-effects model was performed. Results: Eighty-five studies (46 A. baumannii, 38 P. aeruginosa, and one of both) involving 22 396 patients were included. CR was investigated in 60 studies, XDR in 20 studies, and PDR in two studies. Prior antibiotic exposure was associated with significant acquisition of CR/XDR/PDR A. baumannii and P. aeruginosa in both groups I and II (p < 0.05). Antibiotic classes implicated in both groups included aminoglycosides, carbapenems, glycopeptides, and penicillins. Cephalosporin use was not associated with resistance in either group. Fluoroquinolone exposure was only associated with resistance in group I but not group II. Conclusions: Control groups play an important role in determining the magnitudes of risk estimates for risk factor studies, hence careful selection is necessary. Antibiotic exposure increases the acquisition of highly resistant A. baumannii and P. aeruginosa, thus appropriate antibiotic use is imperative. Keywords: Antibiotic, Risk factor, Carbapenem resistance, Extreme drug resistance, Pan-drug resistance, Acinetobacter baumannii, Pseudomonas aeruginosa, Controls