Abstract
Extended Spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are of major concern as they are implicated in multidrug resistant nosocomial infections. They are listed on a recently published global priority list of antibiotic-resistant bacteria by the World Health Organization which raises concern in both healthcare and community settings. This study aimed at determining the frequency of ESBL genes in multidrug resistant human clinical Enterobacteriaceae isolates from Edo state Nigeria and to characterize the resistance mechanisms using whole genome sequencing. A total of 217 consecutive clinical isolates of Enterobacteriaceae, selection based on inclusion criteria, were collected from March-May 2015 from three medical microbiology laboratories of hospitals in Edo state Nigeria. All isolates were analyzed using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Antibiotic susceptibility testing was performed by Kirby-Bauer method and minimum inhibitory concentration (MIC) determination by E-test method. Double disc synergy test was used to screen for the production of ESBL. Whole genome sequencing (WGS) was performed for isolate characterization and identification of resistance determinants. Out of 217 consecutive clinical Enterobacteriaceae isolates, 148 (68.2%) were multi-drug resistant. Of these multi-drug resistant isolates, 60 (40.5%) were positive for the ESBL phenotypic test and carried ESBL genes. CTX-M-15 was the predominant ESBL found, among 93.3% (n = 56/60). Thirty-two plasmid incompatibility groups and 28 known and two new sequence types were identified among the ESBL isolates. The high occurrence of CTX-M-15 with associated resistant determinants in multidrug resistant Enterobacteriaceae harboring different plasmid incompatibility groups and sequence types calls for the need of continuous monitoring of this resistance threat to reduce its public health impact. To our knowledge, this study presents the first genomic characterization of ESBL production mediated by blaCTX-M-15 in human clinical isolates of Enterobacter hormaechei, Citrobacter werkmanii and Atlantibacter hermannii from Nigeria.
Highlights
Enterobacteriaceae can cause various infections and can be found as commensals in the gastrointestinal tract
Out of 217 consecutive clinical Enterobacteriaceae isolates, 148 (68.2%) were multi-drug resistant and were further investigated by whole genome sequence (WGS) analysis (Table 1)
Whole genome sequencing of extended-spectrum β-lactamase genes antibiotics by health professionals, unskilled practitioners, self-medication, unhygienic conditions accounting for the spread of resistant bacteria and inadequate surveillance programs [54, 55]
Summary
Enterobacteriaceae can cause various infections and can be found as commensals in the gastrointestinal tract. Beta lactam antibiotics are widely used for treatment of infections caused by Enterobacteriaceae. Increased use of these antibiotics, of third generation cephalosporins, is associated with the emergence of bacterial resistance caused by extended-spectrum beta-lactamases. Extended spectrum β-lactamases are enzymes capable of hydrolyzing a wide range of extended-spectrum β-lactams, including oxyiminocephalosporins and aztreonam, but are less active against cephamycins and carbapenems [1]. Gram-negative bacteria producing ESBLs often acquire associated resistance to fluoroquinolones, aminoglycosides, tetracycline and chloramphenicol [2]. ESBL genes and quinolone resistance (PMQR) genes can be co-located either on the same plasmid or on different plasmids within the same isolate [3, 4]
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