ArticleAntimicrobial agents and chemotherapy2009
Pharmacokinetic/pharmacodynamic analysis of the influence of inoculum size on the selection of resistance in Escherichia coli by a quinolone in a mouse thigh bacterial infection model.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed.
- Translational PK/PD for the Development of Novel Antibiotics-A Drug Developer's Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Mutant Prevention Concentration, Frequency of Spontaneous Mutant Selection, and Mutant Selection Window-a New Approach to theAntimicrobial agents and chemotherapy · 2023Article
- PKPD Modeling of the Inoculum Effect ofFrontiers in pharmacology · 2022Article
- Pharmacokinetics and pharmacodynamics of enrofloxacin treatment of Escherichia coli in a murine thigh infection modeling.BMC veterinary research · 2021Article
- Prediction of Minocycline Activity in the Gut From a Pig Preclinical Model Using a Pharmacokinetic -Pharmacodynamic Approach.Frontiers in microbiology · 2021Article
- Murine Thigh Microdialysis to Evaluate the Pharmacokinetic/Pharmacodynamic Integration of Cefquinome AgainstFrontiers in veterinary science · 2020Article
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- Antimicrobial Activity and Resistance: Influencing Factors.Frontiers in pharmacology · 2017Review
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- Pharmacokinetics/pharmacodynamics of marbofloxacin in a Pasteurella multocida serious murine lung infection model.BMC veterinary research · 2015Article
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- In vivo evaluation of mutant selection window of cefquinome against Escherichia coli in piglet tissue-cage model.BMC veterinary research · 2014Article
- Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.Antimicrobial agents and chemotherapy · 2014Article
- Impact of early versus later fluoroquinolone treatment on the clinical; microbiological and resistance outcomes in a mouse-lung model of Pasteurella multocida infection.Veterinary microbiology · 2011Article
- Emergence of resistant Klebsiella pneumoniae in the intestinal tract during successful treatment of Klebsiella pneumoniae lung infection in rats.Antimicrobial agents and chemotherapy · 2010Article
- Influence of inoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of Klebsiella pneumoniae in a rat lung infection model.Antimicrobial agents and chemotherapy · 2009Article
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Abstract
Maintaining quinolone concentrations outside the mutant selection window (MSW) between the MIC and mutant prevention concentration (MPC) was suggested by in vitro and in vivo studies to prevent the selection of resistant mutants. However, selection also may depend on the presence of resistant bacterial mutants at the start of treatment, which is highly dependent on the initial inoculum size. In this study, a mouse thigh bacterial infection model was used to test the influence of different exposures to marbofloxacin on the selection of resistant bacteria after infection with a low (10(5) CFU) or high (10(8) CFU) initial inoculum of Escherichia coli. The inoculum size was shown to influence the exposure to marbofloxacin and the values of pharmacokinetic/pharmacodynamic indices. When the abilities of the indices time within the MSW (T(MSW)), area under the concentration-time curve of 0 to 24 h divided by the MIC, and the maximum concentration of drug in plasma divided by the MIC to predict the selection of resistant bacteria were compared, only T(MSW) appeared to be a good predictor of the prevention of resistance for values less than 30%. When the T(MSW) was higher than 34%, the selection of resistant bacteria occurred less often in thighs initially infected with the low inoculum (11/24; 46%) than in those infected with the high inoculum (30/36; 80%), suggesting that the selection of resistant mutants depends on both the T(MSW) and inoculum size. The relevance of these results merits further investigation to test different strategies of antibiotic therapy depending on the expected bacterial burden at the infectious site.
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