AUTHOR=Carrasco Letícia Dias de Melo , Dabul Andrei Nicoli Gebieluca , Boralli Camila Maria dos Santos , Righetto Gabriela Marinho , Carvalho Iago Silva e , Dornelas Janaína Valerini , Martins da Mata Camila Pacheco Silveira , Araújo César Augusto de , Leite Edna Mariléa Meireles , Lincopan Nilton , Camargo Ilana Lopes Baratella da Cunha 

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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.622704

DOI=10.3389/fmicb.2021.622704

ISSN=1664-302X

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, n=12) or pan drug-resistant (PDR, n=4) phenotype 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 involvement in the fatty acid breakdown and membrane fluidity. However, the role of these mutations in the polymyxin resistance mechanism remains unknown. To prevent the dissemination of XDR and PDR 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 summary, the emergence of polymyxin resistance among carbapenem-resistant A. baumannii isolates belonging to high-risk global clones is a critical issue that emphasizes the importance of surveillance studies.