Pharmacodynamics of nitrofurantoin at different pH levels against pathogens involved in urinary tract infections

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

doi:10.1093/jac/dkx313

Cited by 20 publications

(19 citation statements)

References 16 publications

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“…The present study extends the antibiotic potentiating activity of the cinnamon derived proanthocyanidin to nitrofurantoin. Since it was reported that pH plays a vital role in the antibacterial activity of nitrofurantoin (Fransen et al, 2017 ), the synergy studies were conducted in a range of pH from 5.2 to 7.6. In order to establish synergy mathematically, two models were considered—Fractional Inhibitory Concentration Index and Bliss independence model (Kaur et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…The antibiofilm activity at a very low concentration of TAP directed toward the evaluation of potentiating activity of TAP with the known frontline antibiotic, NIT. Previous reports state that the effective pH of nitrofurantoin activity is 5.5-6.5 (Fransen et al, 2017). Thus, the synergy activity was tested in different pH (5.2, 5.8, 6.4, 7.0, and 7.6) in a time-dependent manner.…”

Section: Potentiation Of Nitrofurantoin By Tap-ph-dependent Studymentioning

confidence: 99%

“…Therefore, it is crucial to take into account the pH of the urine before any treatments. The effect of urinary pH in the antimicrobial action of nitrofurantoin is well-documented (Fransen et al, 2017 ). Nitrofurantoin is a broad-spectrum antibiotic, exclusively used as a therapy for uncomplicated UTI–cystitis (Gardiner et al, 2019 ) and a prophylactic agent for recurrent UTI (Muller et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…Nitrofurantoin is a broad-spectrum antibiotic, exclusively used as a therapy for uncomplicated UTI–cystitis (Gardiner et al, 2019 ) and a prophylactic agent for recurrent UTI (Muller et al, 2017 ). It is from the Nitrofurans family of flavonoids and works best at an optimum pH of 5.5–6.5 against UPEC (Fransen et al, 2017 ). A strategy to improve the efficacy of antibiotics in the face of antibiotic resistance and changing pH is to use combinations of plant-derived compounds with antibiotics, which enhances and restores the antibacterial activity of the traditional antibiotics.…”

Section: Introductionmentioning

confidence: 99%

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Reciprocal Cooperation of Type A Procyanidin and Nitrofurantoin Against Multi-Drug Resistant (MDR) UPEC: A pH-Dependent Study

Vasudevan

Selvan

Bhaskaran

et al. 2020

Front. Cell. Infect. Microbiol.

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Uropathogenic Escherichia coli (UPEC) accounts for the majority of complicated and uncomplicated urinary tract infections. The use of phytomolecules in the treatment of UTI is fast gaining attention. The current report identifies a multidrug-resistant strain (QSLUPEC7), which is a strong biofilm producer, among the considered clinical isolates. The antimicrobial and antibiofilm activity was evaluated for the phytomolecule, Type A procyanidin (TAP) from Cinnamomum zeylanicum against QSLUPEC7. TAP treatment did not affect the growth of the MDR strain but affected the biofilm formation (∼70% inhibition). The confocal microscopic examination reveals the biofilm inhibition and the live cells in the biofilm corroborates the antimicrobial results. Further, the synergy studies of TAP and nitrofurantoin (NIT) were carried out at different pH. TAP acts synergistically with nitrofurantoin at different pH considered. A closer look in the results reveals that at pH 5.8, maximum growth inhibition is recorded. The gene expression analysis shows that TAP alone and in combination with NIT downregulates the major fimbriae adhesins of UPEC. The results conclude that the TAP has an antibiofilm activity against the multidrug-resistant strain of UPEC, without affecting the growth. Also, TAP reciprocally cooperates with nitrofurantoin at different pH by downregulating the adhesins of UPEC.

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Section: Discussionmentioning

confidence: 99%

Section: Potentiation Of Nitrofurantoin By Tap-ph-dependent Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reciprocal Cooperation of Type A Procyanidin and Nitrofurantoin Against Multi-Drug Resistant (MDR) UPEC: A pH-Dependent Study

Vasudevan

Selvan

Bhaskaran

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Maximum urine concentrations are around 100 mg/L, but vary between 15-230 mg/L, occurring 3-10 h after dosing, but heavily dependent on formulation and fasting status [165]. Activity is enhanced under acidic conditions [166]. Nitrofurantoin is well tolerated with mild gastrointestinal side effects (in 5-16%).…”

Section: Nitrofurantoinmentioning

confidence: 99%

Antimicrobial pharmacokinetics and preclinicalin vitromodels to support optimized treatment approaches for uncomplicated lower urinary tract infections

Abbott

Roberts

Meletiadis

et al. 2020

Expert Review of Anti-infective Therapy

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Introduction: Urinary tract infections (UTIs) are extremely common. Millions of people, particularly healthy women, are affected worldwide every year. One-in-two women will have a recurrence within 12-months of an initial UTI. Inadequate treatment risks worsening infection leading to acute pyelonephritis, bacteremia and sepsis. In an era of increasing antimicrobial resistance, it is critical to provide optimized antimicrobial treatment.Areas covered: Literature was searched using PubMed and Google Scholar (up to 06/2020), examining the etiology, diagnosis and oral antimicrobial therapy for uncomplicated UTIs, with emphasis on urinary antimicrobial pharmacokinetics (PK) and the application of dynamic in vitro models for the pharmacodynamic (PD) profiling of pathogen response.Expert opinion: The majority of antimicrobial agents included in international guidelines were developed decades ago without well-described dose-response relationships. Microbiology laboratories still apply standard diagnostic methodology that has essentially remained unchanged for decades. Furthermore, it is uncertain how relevant standard in vitro susceptibility is for predicting antimicrobial efficacy in urine. In order to optimize UTI treatments, clinicians must exploit the urine-specific PK of antimicrobial agents. Dynamic in vitro models are valuable tools to examine the PK/PD and urodynamic variables associated with UTIs, while informing uropathogen susceptibility reporting, optimized dosing schedules, clinical trials and treatment guidelines.

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Physiologically based pharmacokinetic model to predict drug concentrations of breast cancer resistance protein substrates in milk

Zhang

Zou

Fang

et al. 2022

Biopharm & Drug Disp

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Many mothers need to take some medications during breastfeeding, which may carry a risk to breastfed infants. Thus, determining the amount of a drug transferred into breast milk is critical for risk–benefit analysis of breastfeeding. Breast cancer resistance protein (BCRP), an efflux transporter which usually protects the body from environmental and dietary toxins, was reported to be highly expressed in lactating mammary glands. In this study, we developed a mechanistic lactation physiologically based pharmacokinetic (PBPK) modeling approach incorporating BCRP mediated transport kinetics to simulate the concentration–time profiles of five BCRP drug substrates (acyclovir, bupropion, cimetidine, ciprofloxacin, and nitrofurantoin) in nursing women’s plasma and milk. Due to the lack of certain physiological parameters and scaling factors in nursing women, we combine the bottom up and top down PBPK modeling approaches together with literature reported data to optimize and determine a set of parameters that are applicable for all five drugs. The predictive performance of the PBPK models was assessed by comparing predicted pharmacokinetic profiles and the milk‐to‐plasma (M/P) ratio with clinically reported data. The predicted M/P ratios for acyclovir, bupropion, cimetidine, ciprofloxacin, and nitrofurantoin were 2.48, 3.70, 3.55, 1.21, and 5.78, which were all within 1.5‐fold of the observed values. These PBPK models are useful to predict the PK profiles of those five drugs in the milk for different dosing regimens. Furthermore, the approach proposed in this study will be applicable to predict pharmacokinetics of other transporter substrates in the milk.

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Pharmacodynamics of nitrofurantoin at different pH levels against pathogens involved in urinary tract infections

Abstract: Nitrofurantoin bactericidal activity against Enterobacteriaceae significantly increases at lower pH levels. Bactericidal activity of nitrofurantoin may be overestimated or underestimated, which may have implications for therapy and the interpretation of clinical breakpoints.

Cited by 20 publications

References 16 publications

Reciprocal Cooperation of Type A Procyanidin and Nitrofurantoin Against Multi-Drug Resistant (MDR) UPEC: A pH-Dependent Study

Reciprocal Cooperation of Type A Procyanidin and Nitrofurantoin Against Multi-Drug Resistant (MDR) UPEC: A pH-Dependent Study

Antimicrobial pharmacokinetics and preclinicalin vitromodels to support optimized treatment approaches for uncomplicated lower urinary tract infections

Physiologically based pharmacokinetic model to predict drug concentrations of breast cancer resistance protein substrates in milk

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