Polymyxin Resistance Among XDR ST1 Carbapenem-Resistant Acinetobacter baumannii Clone Expanding in a Teaching Hospital

Abstract

Acinetobacter baumannii is an opportunistic pathogen primarily associated with multidrug-resistant nosocomial infections, for which polymyxins are the last-resort antibiotics. This study investigated carbapenem-resistant A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, including four isolates considered locally pan drug-resistant (LPDR), isolated from inpatients during an outbreak at a teaching hospital in Brazil. ApaI DNA macrorestriction followed by PFGE clustered the strains in three pulsotypes, named A to C, among carbapenem-resistant A. baumannii strains. Pulsotypes A and B clustered six polymyxin-resistant A. baumannii strains. MLST analysis of representative strains of pulsotypes A, B, and C showed that they belong, respectively, to sequence types ST1 (clonal complex, CC1), ST79 (CC79), and ST903. Genomic analysis of international clones ST1 and ST79 representative strains predicted a wide resistome for β-lactams, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, with blaOXA–23 and blaOXA–72 genes encoding carbapenem resistance. Amino acid substitutions in PmrB (Thr232Ile or Pro170Leu) and PmrC (Arg125His) were responsible for polymyxin resistance. Although colistin MICs were all high (MIC ≥ 128 mg/L), polymyxin B MICs varied; strains with Pro170Leu substitution in PmrB had MICs > 128 mg/L, while those with Thr232Ile had lower MICs (16–64 mg/L), irrespective of the clone. Although the first identified polymyxin-resistant A. baumannii strain belonged to ST79, the ST1 strains were endemic and caused the outbreak most likely due to polymyxin B use. The genome comparison of two ST1 strains from the same patient, but one susceptible and the other resistant to polymyxin, revealed mutations in 28 ORFs in addition to pmrBC. The ORF codifying an acyl-CoA dehydrogenase has gained attention due to its fatty acid breakdown and membrane fluidity involvement. However, the role of these mutations in the polymyxin resistance mechanism remains unknown. To prevent the dissemination of XDR bacteria, the hospital infection control committee implemented the patient bathing practice with a 2% chlorhexidine solution, a higher concentration than all A. baumannii chlorhexidine MICs. In conclusion, we showed the emergence of polymyxin resistance due to mutations in the chromosome of the carbapenem-resistant A. baumannii ST1, a high-risk global clone spreading in this hospital.

Dissemination and Genetic Relatedness of Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Isolates from a Burn Hospital in Iraq

“…The emergence of MDR/XDR pathogens over the last decade is dramatically increasing. Many studies have been conducted to magnify the impact of MDR, XDR, and PDR (pan-drug resistance) on strategies and protocols of treatment, especially nosocomial infections caused by A. baumannii [ 27 - 29 ]. Recent developments in the field of antimicrobial drugs are devoted to the use of natural antimicrobial and nanoparticle delivery agents [ 30 ].…”

Synergistic Inhibitory Effect of Polymyxin B in Combination with Ceftazidime against Robust Biofilm Formed by Acinetobacter baumannii with Genetic Deficiency in AbaI/AbaR Quorum Sensing

“…Since the return of polymyxins as effective drugs for the treatment of multidrug-resistant bacterial infections, especially carbapenem-resistant Gram-negative bacterial infections, the emergence of PB-resistant A. baumannii has increased in recent years ( 51 , 52 ). In this study, the antimicrobial effect of PB in combination with antibiotics on the growth of planktonic cells varied on the strains and genotypes.…”

Molecular characterisation of Acinetobacter baumannii isolates from bloodstream infections in a tertiary-level hospital in South Africa

“…All six colistin-resistant isolates were resistant to carbapenems and exhibited an XDR phenotype. Recently, colistin-resistant A. baumannii ST1 and ST2 isolates were reported in Brazil and South Africa; the authors also showed that the collected isolates were resistant to carbapenems and exhibited XDR phenotypes (Snyman et al, 2020;Carrasco et al, 2021;Nogbou et al, 2022). The most frequent β-lactamase genes detected in this study were bla OXA−23 , bla NDM−1 , and bla PER−7 .…”