Mapping Phenotypic and Genotypic Antimicrobial Susceptibility Profile of E. coli and K. pneumoniae in Complicated Urinary Tract Infection in the Era of Mounting Drug Resistance

Background: Mapping the local etiology and antimicrobial susceptibility profile of pathogens causing complicated urinary tract infection (cUTI) is important for promoting evidence based antimicrobial prescribing. WGS plays an important role in genomic surveillance of AMR and understanding circulating clades. Methods: Antimicrobial susceptibility profile of patients presenting with cUTI were analysed. ESBLs, AmpC β-lactamases, and CRE were detected by combined disc test (ESBL), D69C AmpC detection set (AmpC) and KPC/IMP/NDM/VIM/OXA-48 Combo test kit (CRE). Whole genome sequencing (WGS) was carried out in eleven E. coli AmpC and twenty-two K. pneumoniae CRE isolates. Bioinformatic analysis was performed using online tools. Results: The susceptibility patterns of E. coli and K. pneumoniae were as follows: nitrofurantoin (96%, 38%), fosfomycin (100%,89%), fluoroquinolones (44%, 47%), aminoglycosides (93%, 82%), piperacillin-tazobactam (95%,72% ) and carbapenems (98%, 83%). The overall prevalence of ESBL among E. coli and K. pneumoniae was 37.2%, while the estimated prevalence of AmpC was 5.4% and the prevalence of CRE was 6.2%. E. coli was the predominant ESBL and AmpC producer, whereas K. pneumoniae was the major CRE producer. Nine E. coli MLST lineages were identified: ST-10, ST-69, ST-77, ST-131, ST-156, ST-167, ST-361, ST-1125 and ST-2520, while in K. pneumoniae 5 MLST lineages were observed: ST-2096, ST-231, ST-147, ST-1770 and ST-111. ST-2096 (12 isolates) and ST-147 (7 isolates) predominated. WGS revealed DHA-1 as the predominant plasmid-mediated AmpC gene, while OXA-232 and NDM-5 as the most common carbapenemase genes. All E. coli DHA-1 positive isolates co-harboured the quinolone resistance gene qnrB4 and the sulfonamide resistance gene sul1 while no aminoglycoside resistance genes were detected. The majority of CRE K. pneumoniae carried other β-lactamase genes such as blaCTX-M-15, blaSHV, blaTEM, and all co-harboured the quinolone resistance gene OqxAB and 77% carried the aminoglycoside resistance gene armA. Conclusions: Fosfomycin is an excellent choice for treating complicated cystitis caused by multi drug resistant pathogens. Nitrofurantoin retains excellent activity against E. coli but not K. pneumoniae. Aminoglycosides and piperacillin tazobactam are alternatives which spare carbapenems. WGS results revealed DHA-1 was the predominant AmpC while OXA-232 and NDM-5 were the circulating carbapenemases. In AmpC producing E.coli no MLST predominated while in CRE Klebsiella pneumoniae ST-2096 and ST-147 predominated.