Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) are emerging worldwide. In South America, clinical isolates presenting such a phenotype usually do not belong to the globally distributed international clone 2 (IC2). The majority of these isolates are also resistant to multiple other antimicrobials and are often designated extremely drug-resistant (XDR). The aim of this study was to characterize the resistance mechanisms presented by 18 carbapenem-resistant A. baumannii isolates from five different Brazilian hospitals. Species identification was determined by rpoB sequencing, and antimicrobial susceptibility was determined by broth microdilution. Isolates were submitted to whole genome sequencing using Illumina platform and genetic similarity was determined by PFGE, MLST, and cgMLST. Genome analysis was used to identify intrinsic and acquired resistance determinants, including mutations in the AdeRSABC efflux system and in outer membrane proteins (OMPs). All isolates were identified as A. baumannii and grouped into 4 pulsotypes by PFGE, which belonged to clonal complexes (CC) 15Pas/103Ox (n = 4) and 79Pas/113Ox (n = 14), corresponding to IC4 and IC5, respectively. High MIC values to carbapenems, broad-spectrum cephalosporins, amikacin, and ciprofloxacin were observed in all isolates, while MICs of ampicillin/sulbactam, gentamicin, and tigecycline varied among the isolates. Minocycline was the most active antimicrobial agent tested. Moreover, 12 isolates (66.7%) were considered resistant to polymyxins. Besides intrinsic OXA-51 and ADC variants, all isolates harbored an acquired carbapenem-hydrolyzing class D β-lactamase (CHDL) encoding gene, either blaOXA–23 or blaOXA–72. A diversity of aminoglycoside modifying enzymes and resistance determinants to other antimicrobial classes were found, as well as mutations in gyrA and parC. Non-synonymous mutations have also been identified in the AdeRSABC efflux system and in most OMPs, but they were considered natural polymorphisms. Moreover, resistance to polymyxins among isolates belonging to IC5 were associated to non-synonymous mutations in pmrB, but no known polymyxin resistance mechanism was identified in isolates belonging to IC4. In conclusion, A. baumannii clinical isolates belonging to South America’s major clones present a myriad of antimicrobial resistance determinants. Special attention should be paid to natural polymorphisms observed in each clonal lineage, especially regarding non-synonymous mutations in constitutive genes associated with distinct resistance phenotypes.
Highlights
Acinetobacter baumannii is a major nosocomial pathogen causing serious infections (Antunes et al, 2014)
According to pulsed-field gel electrophoresis (PFGE), they were grouped into four distinct pulsotypes, which were included in different sequence types (STs) belonging to Institute Pasteur scheme (Pas) CC79 and CC15, and corresponded to the Oxford scheme (Ox) CC113 and CC103, respectively (Table 1 and Supplementary Figure 1)
The ST distribution following the Oxford scheme presented a better correlation to the results observed with PFGE, since ST227, ST233, ST236, and the novel ST2141 were strongly associated with PFGE clusters 1, 2, 4, and 3, respectively (Supplementary Figure 1)
Summary
Acinetobacter baumannii is a major nosocomial pathogen causing serious infections (Antunes et al, 2014). In Brazil, it is the fourth most frequent pathogen recovered from central catheterassociated bloodstream infections (BSI) in adult intensive care units (ICU), with carbapenem resistance rates as high as 79% (Agência Nacional de Vigilância Sanitária [ANVISA], 2020). Carbapenem resistance in A. baumannii is mainly caused by horizontal transfer of carbapenem-hydrolyzing class D βlactamases (CHDL) encoding genes, in worldwide epidemic clones (Higgins et al, 2010). Carbapenem-resistant A. baumannii (CRAB) isolates usually belong to the worldwide disseminated international clone 2 (IC2) (Hamidian and Nigro, 2019) and carbapenem-resistance rates vary between 40 and 80% (Kuo et al, 2012; Chmielarczyk et al, 2016). In Latin America, the frequency of XDR A. baumannii has increased from 17 to 86.6% between 1997 and 2016 (Gales et al, 2019)
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