Plasmid-Mediated OqxAB Is an Important Mechanism for Nitrofurantoin Resistance in Escherichia coli

Abstract

Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study investigated the molecular epidemiology of the multidrugresistant efflux gene oqxAB and its contribution to nitrofurantoin resistance by using Escherichia coli isolates originating from patients with UTI (n ‫؍‬ 205; collected in 2004 to 2013) and food-producing animals (n ‫؍‬ 136; collected in 2012 to 2013) in Hong Kong. The oqxAB gene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the oqxAB gene was associated with IS26 and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of oqxAB-positive E. coli were diverse. The combination of oqxAB and nfsA mutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 g/ml to 34.3 g/ml. In the plasmid-cured variants, 20% (1/5) of isolates with nfsA mutations were NIT-S, while 80% (12/15) of isolates without nfsA mutations were NIT-S (P ‫؍‬ 0.015). The presence of plasmid-based oqxAB increased the mutation prevention concentration of NIT from 128 g/ml to 256 g/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid-mediated oqxAB is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump.

Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical Escherichia coli Isolates

“…2a ). Ciprofloxacin resistance was also associated with possession of IncFIA (tau = 0.27, P < 0.05) and IncFIC (tau = 0.46, P < 0.001), consistent with past observations of quinolone resistance and extended-spectrum β-lactamases being associated with F plasmids ( 30 , 31 ). Because the same resistance gene is not always associated with the same plasmid or replicon, some correlations across isolates can be explained by shared resistance genes but not shared plasmid profiles.…”

Complete Sequence of a F33:A-:B- Conjugative Plasmid Carrying the oqxAB, fosA3, and blaCTX-M-55 Elements from a Foodborne Escherichia coli Strain

“…The PMQR gene oqxAB has been demonstrated to be associated with reduced fluoroquinolone susceptibility in E. coli and Salmonella spp., and was also found to be linked to nitrofurantoin resistance (Ho et al, 2016). While oqxAB is commonly carried by IncHI2 and IncFII plasmids (Liu et al, 2013; Li et al, 2014), bla CTX-M-1 group elements and fosA3 , as well as the aminoglycoside resistance gene rmtB , have been frequently detected on IncFII plasmids carried by E. coli isolates of various origins (Pan et al, 2014; Alrowais et al, 2015).…”

Resistance Patterns of Escherichia coli and Klebsiella pneumoniae Bacteria Against Amikacin, Ceftazidime, Meropenem, Nitrofurantoin Antibiotics in Elderly Patients with UTI in RSUD Dr. Soetomo

“…The resistance mechanism of carbapenem antibiotics is caused by carbapenemase production and also due to deletion or loss of outer protein membranes 18 . Amikacin can actively fight against Escherichia coli by transporting through the cytoplasmic membrane which in the process depends on the available oxygen.…”