Pharmacodynamics of Fluoroquinolones

Elshaboury, Ramy H.; Dilworth, Thomas J; Rotschafer, John C.

doi:10.1007/978-1-4939-3323-5_8

Cited by 4 publications

(4 citation statements)

References 82 publications

(90 reference statements)

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“…In a recent study on national antibiotic prescribing trends in outpatient settings, fluoroquinolones were the third most commonly prescribed antibiotic class in the United States, with 115 prescriptions ordered per 1000 adults 2 . The prevalence of fluoroquinolones in clinical practice is likely related to multiple qualities of the drug class—including perceived safety, pharmacokinetics conducive to once or twice daily dosing and bioavailability, and a broad spectrum of antimicrobial activity 3‐5 …”

Section: Introductionmentioning

confidence: 99%

“…2 The prevalence of fluoroquinolones in clinical practice is likely related to multiple qualities of the drug class-including perceived safety, pharmacokinetics conducive to once or twice daily dosing and bioavailability, and a broad spectrum of antimicrobial activity. [3][4][5] Increasing evidence has called into question the safety of fluoroquinolone prescriptions in clinical practice. [6][7][8][9] Prolonged therapy has been linked to the development of antimicrobial-resistant bacteria as well as Clostridioides difficile infection [10][11][12][13][14][15] .…”

mentioning

confidence: 99%

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Outpatient fluoroquinolone prescribing patterns before and after US FDA boxed warning

Bratsman

Mathias

Laubscher

et al. 2020

Pharmacoepidemiology and Drug

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Objectives Fluoroquinolones are routinely overprescribed for uncomplicated urinary tract infection (uUTI), acute sinusitis, and acute bronchitis. In 2016, the United States (US) Food and Drug Administration (FDA) updated the boxed warning on fluoroquinolones, recommending against their use as first‐line agents for the routine pharmacologic management of uUTI, acute sinusitis, and acute bronchitis in patients who have other treatment options. The primary objective of this study was to determine if the 2016 expanded boxed warning was associated with decreased fluoroquinolone prescription rates for these three diagnoses. Methods We retrospectively reviewed antibiotics prescribed at a single, large, academic outpatient center for these three diagnoses between January 2013 and May 2018. Interrupted time series analysis was used to compare the rate of fluoroquinolone prescriptions before and after the May 2016 FDA boxed warning. Results A total of 10 087 antibiotic prescriptions for these three diagnoses were examined. There was no significant change in fluoroquinolone prescription rates after the FDA boxed warning. The majority of inappropriate fluoroquinolone prescriptions were given for the management of uUTI. Conclusion The 2016 US FDA boxed warning against fluoroquinolone use for uUTI, acute sinusitis, and acute bronchitis was not associated with a statistically significant reduction in the rate of fluoroquinolone prescriptions for these diagnoses. Additional research is needed to define how US FDA boxed warnings may be incorporated into broader antibiotic stewardship programs to decrease overuse of fluoroquinolones and avoid adverse effects of the drug class, including Clostridioides difficile infections and emergence of resistant organisms.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Outpatient fluoroquinolone prescribing patterns before and after US FDA boxed warning

Bratsman

Mathias

Laubscher

et al. 2020

Pharmacoepidemiology and Drug

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“…Development of resistance of different uropathogens to fluoroquinolones, mainly due to their inappropriate use, represents a current and alarming unmet clinical need [6]. Given that ciprofloxacin's antibacterial effects are determined by the AUC over the MIC [7], it is fundamental to characterize its pharmacokinetics (PK) in the target populations to optimize drug exposure avoiding toxicity and minimizing resistance. Such characterization is not trivial to achieve in the case of paediatric patients suffering from certain diseases like cUTI, as shown below.…”

mentioning

confidence: 99%

Physiologically-Based Pharmacokinetic model for Ciprofloxacin in children with complicated Urinary Tract Infection

Balbas-Martinez

Michelet

Edginton

et al. 2019

European Journal of Pharmaceutical Sciences

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In a recent multicenter population pharmacokinetic study of ciprofloxacin administered to children suffering from complicated urinary tract infection (cUTI), the apparent volume of distribution (V d ) and total plasma clearance (CL) were decreased by 83.6% and 41.5% respectively, compared to healthy children. To understand these differences, a physiologicallybased pharmacokinetic model (PBPK) for ciprofloxacin was developed for cUTI children. First, a PBPK model in adults was developed, modified incorporating age-dependent functions and evaluated with paediatric data generated from a published model in healthy children. Then, the model was then adapted to a cUTI paediatric population according to the degree of renal impairment (KF) affecting renal clearance (CL Renal, ) and CYP1A2 clearance (CL CYP1A2 ). Serum and urine samples obtained from 22 cUTI children were used for model evaluation. Lastly, a parameter sensitivity analysis identified the most influential parameters on V and CL. The PBPK model predicted the ciprofloxacin exposure in adults and children, capturing age-related pharmacokinetic changes. Plasma concentrations and fraction excreted unchanged in urine (f e ) predictions improved in paediatric cUTI patients once CL renal and CL CYP1A2 were corrected by KF. The presented PBPK model for ciprofloxacin demonstrates its adequacy to simulate different dosing scenarios to obtain PK predictions in a healthy population from 3 months old onwards. Model adaptation of CL Renal and CL CYP1A2 according to KF explained partially the differences seen in the plasma drug concentrations and f e vs time profiles between healthy and cUTI children. Nevertheless, it is necessary to further investigate the disease-related changes in cUTI to improve model predictions.

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“…To evaluate antimicrobial treatment with FQs, the pharmacokinetic/pharmacodynamic (PK/PD) parameter that best predicts its microbiological activity and clinical efficacy is the ratio f-AUC 24/MIC, which is generally >30 for Gram-positive microorganisms, >125 for Gram-negative microorganism and ~ 50 for anaerobes, with variations between individual microorganisms. FQs show a concentration-dependent pattern of bactericidal activity for Gram-negative microorganisms, whereas for Gram-positive and anaerobic pathogens it shows a time-dependent pattern of bactericidal activity [ 165 ].…”

Section: Mechanism Of Antimicrobial Activity Of Quinolonesmentioning

confidence: 99%

Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents

et al. 2021

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Broad antibacterial spectrum, high oral bioavailability and excellent tissue penetration combined with safety and few, yet rare, unwanted effects, have made the quinolones class of antimicrobials one of the most used in inpatients and outpatients. Initially discovered during the search for improved chloroquine-derivative molecules with increased anti-malarial activity, today the quinolones, intended as antimicrobials, comprehend four generations that progressively have been extending antimicrobial spectrum and clinical use. The quinolone class of antimicrobials exerts its antimicrobial actions through inhibiting DNA gyrase and Topoisomerase IV that in turn inhibits synthesis of DNA and RNA. Good distribution through different tissues and organs to treat Gram-positive and Gram-negative bacteria have made quinolones a good choice to treat disease in both humans and animals. The extensive use of quinolones, in both human health and in the veterinary field, has induced a rise of resistance and menace with leaving the quinolones family ineffective to treat infections. This review revises the evolution of quinolones structures, biological activity, and the clinical importance of this evolving family. Next, updated information regarding the mechanism of antimicrobial activity is revised. The veterinary use of quinolones in animal productions is also considered for its environmental role in spreading resistance. Finally, considerations for the use of quinolones in human and veterinary medicine are discussed.

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Pharmacodynamics of Fluoroquinolones

Cited by 4 publications

References 82 publications

Outpatient fluoroquinolone prescribing patterns before and after US FDA boxed warning

Outpatient fluoroquinolone prescribing patterns before and after US FDA boxed warning

Physiologically-Based Pharmacokinetic model for Ciprofloxacin in children with complicated Urinary Tract Infection

Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents

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