Exploring the in situ evolution of nitrofurantoin resistance in clinically derived uropathogenic Escherichia coli isolates.
J Antimicrob Chemother
; 78(2): 373-379, 2023 02 01.
Article
en En
| MEDLINE
| ID: mdl-36480295
ABSTRACT
BACKGROUND:
Nitrofurantoin has been re-introduced as a first-choice antibiotic to treat uncomplicated acute urinary tract infections in England and Wales. Highly effective against common uropathogens such as Escherichia coli, its use is accompanied by a low incidence (<10%) of antimicrobial resistance. Resistance to nitrofurantoin is predominantly via the acquisition of loss-of-function, step-wise mutations in the nitroreductase genes nfsA and nfsB.OBJECTIVE:
To explore the in situ evolution of NitR in E. coli isolates from 17 patients participating in AnTIC, a 12-month open label randomized controlled trial assessing the efficacy of antibiotic prophylaxis in reducing urinary tract infections (UTIs) incidence in clean intermittent self-catheterizing patients.METHODS:
The investigation of NitR evolution in E. coli used general microbiology techniques and genetics to model known NitR mutations in NitSE. coli strains.RESULTS:
Growth rate analysis identified a 2%-10% slower doubling time for nitrofurantoin resistant strains NitS 20.8â±â0.7 min compared to NitR 23â±â0.8 min. Statistically, these data indicated no fitness advantage of evolved strains compared to the sensitive predecessor (P-valueâ=â0.13). Genetic manipulation of E. coli to mimic NitR evolution, supported no fitness advantage (P-valueâ=â0.22). In contrast, data argued that a first-step mutant gained a selective advantage, at sub-MIC (4-8 mg/L) nitrofurantoin concentrations.CONCLUSION:
Correlation of these findings to nitrofurantoin pharmacokinetic data suggests that the low incidence of E. coli NitR, within the community, is driven by urine-based nitrofurantoin concentrations that selectively inhibit the growth of E. coli strains carrying the key first-step loss-of-function mutation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones Urinarias
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Infecciones por Escherichia coli
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Escherichia coli Uropatógena
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido