ArticleAntimicrobial agents and chemotherapy2009
Influence of inoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of Klebsiella pneumoniae in a rat lung 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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Who cites it
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
- A New Pharmacokinetic-Pharmacodynamic Model To Characterize the Inoculum Effect of Acinetobacter baumannii on Polymyxin BAntimicrobial agents and chemotherapy · 2022Article
- Prediction of Minocycline Activity in the Gut From a Pig Preclinical Model Using a Pharmacokinetic -Pharmacodynamic Approach.Frontiers in microbiology · 2021Article
- Effect of drug dose and timing of treatment on the emergence of drug resistanceEvolution, medicine, and public health · 2020Article
- Time inside the mutant selection window as a predictor of staphylococcal resistance to linezolid.The Journal of antibiotics · 2018Article
- Antimicrobial Activity and Resistance: Influencing Factors.Frontiers in pharmacology · 2017Review
- Article
- Implementing Precision Antimicrobial Therapy for the Treatment of Bovine Respiratory Disease: Current Limitations and Perspectives.Frontiers in veterinary science · 2017Article
- Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica.Frontiers in microbiology · 2016Article
- Pharmacokinetics/pharmacodynamics of marbofloxacin in a Pasteurella multocida serious murine lung infection model.BMC veterinary research · 2015Article
- Article
- Evaluation of meropenem regimens suppressing emergence of resistance in Acinetobacter baumannii with human simulated exposure in an in vitro intravenous-infusion hollow-fiber infection model.Antimicrobial agents and chemotherapy · 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
- Experimental model for treatment of extended spectrum betalactamase producing-Klebsiella pneumoniae.Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgeryArticle
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7 authors.
Funding
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Abstract
We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after infection with a low (10(5) CFU) or a high (10(9) CFU) inoculum of Klebsiella pneumoniae. For daily fractionated doses of marbofloxacin, prevention of resistance occurred for an area-under-the-concentration-time-curve (AUC)/MIC ratio of 189 h for the low inoculum, whereas for the high inoculum, resistant-subpopulation enrichment occurred for AUC/MIC ratios up to 756 h. For the high-inoculum-infected rats, the AUC/MIC ratio, C(max)/MIC ratio, and time within the mutant selection window (T(MSW)) were not found to be effective predictors of resistance prevention upon comparison of fractionated and single administrations. An index corresponding to the ratio of the time that the drug concentrations were above the mutant prevention concentration (MPC) over the time that the drug concentrations were within the MSW (T(>MPC)/T(MSW)) was the best predictor of the emergence of resistance: a T(>MPC)/T(MSW) ratio of 0.54 was associated with prevention of resistance for both fractionated and single administrations. These results suggest that the enrichment of resistant bacteria depends heavily on the inoculum size at the start of an antimicrobial treatment and that classical PK/PD parameters cannot adequately describe the impact of different dosage regimens on enrichment of resistant bacteria. We propose an original index, the T(>MPC)/T(MSW) ratio, which reflects the ratio of the time that the less susceptible bacterial subpopulation is killed over the time that it is selected, as a potentially powerful indicator of prevention of enrichment of resistant bacteria. This ratio is valid only if plasma concentrations achieve the MPC.
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