Resistance to last resort drugs such as carbapenem and colistin is a serious global health threat. This study investigated carbapenem and colistin resistance in 583 non-duplicate Enterobacteriaceae isolates utilizing phenotypic methods and whole genome sequencing (WGS). Of the 583 isolates recovered from humans, animals and the environment in Nigeria, 18.9% (110/583) were resistant to at least one carbapenem (meropenem, ertapenem, and imipenem) and 9.1% (53/583) exhibited concurrent carbapenem-colistin resistance. The minimum inhibitory concentrations of carbapenem and colistin were 2–32 μg/mL and 8 to >64 μg/mL, respectively. No carbapenem resistant isolates produced carbapenemase nor harbored any known carbapenemase producing genes. WGS supported that concurrent carbapenem-colistin resistance was mediated by novel and previously described alterations in chromosomal efflux regulatory genes, particularly mgrB (M1V) ompC (M1_V24del) ompK37 (I70M, I128M) ramR (M1V), and marR (M1V). In addition, alterations/mutations were detected in the etpA, arnT, ccrB, pmrB in colistin resistant bacteria and ompK36 in carbapenem resistant bacteria. The bacterial isolates were distributed into 37 sequence types and characterized by the presence of internationally recognized high-risk clones. The results indicate that humans and animals in Nigeria may serve as reservoirs and vehicles for the global spread of the isolates. Further studies on antimicrobial resistance in African countries are warranted.

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The emergence of extended-spectrum-β-lactamases (ESBLs)-producing Escherichia coli represents a serious clinical concern in healthcare. β-lactamases produced by these strains of E. coli render ineffective cephalosporins and other β-lactam antibiotics used to treat infections caused by Gram-negative bacteria. We determined the presence of ESBL in 400 clinical isolates of E. coli isolated from various clinical specimens (urine, stool, blood, sputum, throat and wound swabs) from 216 female and 184 male patients with mean age of 28.1 ± 16.8 years (age range: 2 -71 years), who were attending 6 selected health facilities in Makurdi, Benue State Nigeria. Antibiotic susceptibility test was carried out on the isolates using Kirby Bauer diffusion method. Presence of ESBLs was determined by the double disc synergy test (DDST). Specific primers were employed to characterize the ESBL gene using PCR. The isolates showed high level of resistance to all the antibiotics tested except mipenem. Highest resistance was to penicillin 392(98.0%) followed by ceftriaxone 385(96.3%). Out of the 400 isolates, 64 (16.0%) tested positive for ESBLs by DDST method, while PCR technique confirmed 47(11.8%) to harbour bla TEM genes. Isolates from blood specimens harboured highest percentage of ESBL genes 5(26.3%) and also plasmid-mediated bla TEM genes 5(26.3%), followed by wound swabs 9(17.3). The least percentage of plasmid-mediated bla TEM genes was carried by isolates from sputum specimens 1(8.3). Age group 45 to 58 years harboured the highest percentage of bla TEM genes 15(14.6%), while female patients, 27(12.5%) carried more bla TEM resistance genes than the male patients 20(10.9%). A prevalence of 11.8% (n=47) of bla TEM resistance gene has been reported for the present study. In view of multidrug resistant ESBL-producing Escherichia coli bacteria circulating in the study location, prescription of antibiotics, especially cephalosporins should be based on laboratory results of antibiotic susceptibility tests that are carried out along with ESBL detection. Infection prevention and control strategies should be stepped up in the health facilities under study.

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