Pharmacodynamics and differential activity of nitrofurantoin against ESBL-positive pathogens involved in urinary tract infections

Fransen, Fiona; Melchers, Maria J.; Meletiadis, Joseph; Mouton, Johan W.

doi:10.1093/jac/dkw212

Cited by 25 publications

(10 citation statements)

References 16 publications

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“…Nitrofurantoin is a valuable antibiotic used to treat acute uncomplicated urinary tract infections [83]. Resistance to nitrofurantoin in E. coli was primarily due to mutations in the nitroreductase genes ( nfsA and nfsB ), which participated in the converting of antibiotics into toxic intermediate compounds [84].…”

Section: Role Of Oqxab Efflux Pump In Nitrofurantoin Resistancementioning

confidence: 99%

The nature and epidemiology of OqxAB, a multidrug efflux pump

Li¹,

Zhang²,

Ning³

et al. 2019

Antimicrob Resist Infect Control

109

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Background OqxAB efflux pump has been found to mediate multidrug resistance (MDR) in various bacteria over the past decades. The updates on the nature and epidemiology of OqxAB efflux pump need to be fully reviewed to broaden our understanding of this MDR determinant. Methods A literature search using the keyword of “oqxAB” was conducted in the online databases of Pubmed and ISI Web of Science with no restriction on the date of publication. The 87 publications were included into this review as references due to their close relevance to the nature and/or epidemiology of OqxAB efflux pump. Results The oqxAB gene generally locates on chromosome and/or plasmids flanked by IS26-like elements in clinical isolates of Enterobacteriaceae and Klebsiella pneumoniae , conferring low to intermediated resistance to quinoxalines, quinolones tigecycline, nitrofurantoin, several detergents and disinfectants (benzalkonium chloride, triclosan and SDS). It could co-spread with other antimicrobial resistance genes ( bla CTX-M , rmtB and aac(6′)-Ib etc.), virulence genes and heavy metal resistance genes ( pco and sil operons). Both RarA (activator) and OqxR (repressor) play important roles on regulation of the expression of OqxAB. Conclusions The dissemination of oqxAB gene may pose a great risk on food safety and public health. Further investigation and understanding of the natural functions, horizontal transfer, and regulation mechanism of the OqxAB efflux pump will aid in future strategies of antimicrobial usage.

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Section: Role Of Oqxab Efflux Pump In Nitrofurantoin Resistancementioning

confidence: 99%

The nature and epidemiology of OqxAB, a multidrug efflux pump

Li¹,

Zhang²,

Ning³

et al. 2019

Antimicrob Resist Infect Control

109

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“…In particular, recent findings indicate that efficacy of fosfomycin might be more related to Area under the concentration-time curve for some strains, and more time-dependent for others. [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Fosfomycin therapeutic drug monitoring in real-life: development and validation of a LC-MS/MS method on plasma samples

Baldelli

Cerea

Mangioni

et al. 2021

Journal of Chemotherapy

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“…However, multiple studies have isolated resistant mutants from growth conditions where antibiotic concentrations were low enough for the proliferation of sensitive isolates [28][29][30] . For most antibiotics, bacterial isolates experience some degree of growth reduction even at concentrations just below their MIC [31][32][33] . Growth analysis data relating to 1646 BASE and W3110 strains and their genetic variants in the presence of Nitrofurantoin support this observation (Tables 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

Exploring the in-situ evolution of Nitrofurantoin resistance in clinically derived Uropathogenic Escherichia coli isolates

Vallée

Harding

Hall

et al. 2022

Preprint

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BACKGROUNDNitrofurantoin has been re-introduced as a first-choice antibiotic to treat uncomplicated acute urinary tract infections in England and Wales. Its mode of action involves initial reduction by nitroreductases, to generate electrophilic intermediates that inhibit protein and nucleic acid synthesis. 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, longitudinal uropathogenic E. coli isolates recovered from two rUTI patients.RESULTSGrowth rate analysis identified a 2-10% slower doubling time for Nitrofurantoin resistant strains, but statistically, these data suggested there was no fitness advantage of evolved strains over their sensitive predecessor (ANOVA P-value = 0.13). Genetic manipulation of E. coli to mimic nitrofurantoin resistance evolution, again confirmed no fitness advantages (ANOVA P-value = 0.22). Rather, further analysis 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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Pharmacodynamics and differential activity of nitrofurantoin against ESBL-positive pathogens involved in urinary tract infections

Cited by 25 publications

References 16 publications

The nature and epidemiology of OqxAB, a multidrug efflux pump

The nature and epidemiology of OqxAB, a multidrug efflux pump

Fosfomycin therapeutic drug monitoring in real-life: development and validation of a LC-MS/MS method on plasma samples

Exploring the in-situ evolution of Nitrofurantoin resistance in clinically derived Uropathogenic Escherichia coli isolates

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