Trial reportThe Journal of antimicrobial chemotherapy2023
Exploring the in situ evolution of nitrofurantoin resistance in clinically derived uropathogenic Escherichia coli isolates.
Trial report in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- ESKAPE Pathogens in a Hungarian Emergency Department: A 5-Year Retrospective Observational Study of Prevalence and Resistance Patterns Utilizing the AWaRe Framework.Antibiotics (Basel, Switzerland) · 2026Article
- Antimicrobial strategies for ureteral stent removal after radical cystectomy: a comparative cohort study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Implications for methenamine hippurate use in recurrent urinary tract infection management: Formaldehyde resistance and altered urinary composition.PLoS pathogens · 2026Article
- Poultry-associated nitrofurantoin-resistant and pre-resistantOne health (Amsterdam, Netherlands) · 2025Article
- Nitrofurantoin resistance mechanisms in uropathogenic Escherichia coli isolates from Iran.Annals of clinical microbiology and antimicrobials · 2025Article
- Within-host bacterial evolution and the emergence of pathogenicity.Nature microbiology · 2025Review
- Coevolutionary history of predation constrains the evolvability of antibiotic resistance in prey bacteria.npj antimicrobials and resistance · 2025Article
- Trimethoprim resistance inJournal of medical microbiology · 2025Article
- Use of Machine Learning to Assess the Management of Uncomplicated Urinary Tract Infection.JAMA network open · 2025Article
- Nitrofurantoin as a preferred first-line therapy for urinary tract infection: A comparison using urinary tract infection-specific antibiograms.Bladder (San Francisco, Calif.) · 2025Article
- Unlocking Nitrofurantoin: Understanding Molecular Mechanisms of Action and Resistance in Enterobacterales.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Review
- Predicting future hospital antimicrobial resistance prevalence using machine learning.Communications medicine · 2024Article
- Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance.Nature reviews. Microbiology · 2024Review
- Reassessing the management of uncomplicated urinary tract infection: A retrospective analysis using machine learning causal inference.medRxiv : the preprint server for health sciences · 2024Article
- Improving nitrofurantoin resistance prediction inAntimicrobial agents and chemotherapy · 2024Article
- Overcoming challenges in the economic evaluation of interventions to optimise antibiotic use.Communications medicine · 2024Review
- Insights into durability against resistance from the antibiotic nitrofurantoin.npj antimicrobials and resistance · 2024Review
- Antimicrobial Resistance in Bacteria from Meat and Meat Products: A One Health Perspective.Microorganisms · 2023Review
- ISMicrobial genomics · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNitrofurantoin 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.
objectiveTo 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.
methodsThe investigation of NitR evolution in E. coli used general microbiology techniques and genetics to model known NitR mutations in NitSE. coli strains.
resultsGrowth rate analysis identified a 2%-10% slower doubling time for nitrofurantoin resistant strains: NitS: 20.8 ± 0.7 min compared to NitR: 23 ± 0.8 min. Statistically, these data indicated no fitness advantage of evolved strains compared to the sensitive predecessor (P-value = 0.13). Genetic manipulation of E. coli to mimic NitR evolution, supported no fitness advantage (P-value = 0.22). In contrast, data argued that a first-step mutant gained a selective advantage, at sub-MIC (4-8 mg/L) nitrofurantoin concentrations.
conclusionCorrelation 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.