Pharmacokinetics and pharmacodynamics of fluoroquinolones

Drusano, George L.; Labro, M. T.; Cars, Otto; Mendes, Paul; Shah, Pramod M.; Sörgel, Fritz; Weber, Willi

doi:10.1111/j.1469-0691.1998.tb00692.x

Cited by 63 publications

(44 citation statements)

References 35 publications

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“…Moreover, a number of clinical studies involving fluoroquinolones have demonstrated similar exposure-response relationships as those derived from animal and in vitro infection models, for both gram-positive and -negative organisms. Findings from in vitro and animals models are in agreement with clinical data, where fAUC 0-24 / MIC ratios of 125 are associated with optimal fluoroquinolone activity for gram-negative bacilli (3,5,6,9,11,16,22,28).…”

Section: Figsupporting

confidence: 76%

Application of an In Vitro Infection Model and Simulation for Reevaluation of Fluoroquinolone Breakpoints for Salmonella enterica Serotype Typhi

Booker

Smith

Forrest

et al. 2005

Antimicrob Agents Chemother

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Salmonella enterica serotype Typhi and nontyphoidal Salmonella remain major causes of morbidity and mortality worldwide. Ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol no longer provide reliable coverage of Salmonella, and fluoroquinoloes have emerged as first-line treatment options. Due to mounting evidence of decreased in vitro susceptibility and diminished clinical response to fluoroquinolone therapy, it has been suggested that the NCCLS breakpoints for the salmonellae be reevaluated. We utilized an in vitro infection model to determine which pharmacokinetic-pharmacodynamic (PK-PD) measure was most closely linked to fluoroquinolone activity against salmonellae and the magnitude that was predictive of efficacy. Monte Carlo simulation was utilized to determine the probability of attaining potential susceptibility breakpoints for three fluoroquinolones. The free-drug area under the concentration-time curve from 0 to 24 h/MIC ratio was the PK-PD measure most predictive of efficacy, and a ratio of 105 corresponded to 90% of maximal activity. Simulation results suggested susceptible breakpoints of 0.12 g/ml for ciprofloxacin and gatifloxacin and 0.25 g/ml for levofloxacin. These proposed breakpoints correspond to the MIC separating the wild-type susceptible organism population from those strains possessing single-step mutations in the quinolone resistance-determining region. These results that integrate PK-PD measures and fluoroquinolone MIC distributions in the genetic context of examined Salmonella isolates clearly demonstrate that the prudent use of a lower susceptibility breakpoint minimizes the probability of clinical failure or delayed response in fluoroquinolonetreated patients.

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Section: Figsupporting

confidence: 76%

Application of an In Vitro Infection Model and Simulation for Reevaluation of Fluoroquinolone Breakpoints for Salmonella enterica Serotype Typhi

Booker

Smith

Forrest

et al. 2005

Antimicrob Agents Chemother

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show abstract

“…Some antimicrobial agents, such as the aminoglycosides, are more effective when they have a high C max : MIC ratio. 8,12 With azithromycin, the fluoroquinolones, the ketolides, daptomycin, and linezolid, it appears that outcome is related to the AUC : MIC ratio. 8,12,13 In these two scenarios, organism eradication is concentrationdependent and the therapeutic goal is to maximize drug exposure.…”

Section: Monte Carlo Analysismentioning

confidence: 97%

“…8,12 In this case, organism eradication is time-dependent and the therapeutic goal is to optimize duration of exposure.…”

Section: Monte Carlo Analysismentioning

confidence: 99%

Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling

Nicolau

2003

Journal of Infection and Chemotherapy

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“…However, a probenecid/ gemfibrozil-inhibitable organic anion transporter may be involved in the efflux of penicillin G and some quinolones (48,332). Most quinolones seem to enter and exit loaded phagocytes by passive diffusion (78,396). The extracellular Ca 2ϩ -induced decrease in levofloxacin uptake could be related to an alteration in the structural conformation of this drug (396).…”

Section: Complex Game For Two or More Players With High Stakesmentioning

confidence: 99%

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Labro¹

2000

Clinical Microbiology Reviews

151

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Pharmacokinetics and pharmacodynamics of fluoroquinolones

Cited by 63 publications

References 35 publications

Application of an In Vitro Infection Model and Simulation for Reevaluation of Fluoroquinolone Breakpoints for Salmonella enterica Serotype Typhi

Application of an In Vitro Infection Model and Simulation for Reevaluation of Fluoroquinolone Breakpoints for Salmonella enterica Serotype Typhi

Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

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