What question did this study set out to answer?

To evaluate the mutant selection window hypothesis in an experimental rabbit pneumonia model and assess how low-level fluoroquinolone resistance affects the emergence of resistant Streptococcus pneumoniae mutants during gatifloxacin therapy.

August 19, 2004Journal of Antimicrobial ChemotherapyOpen Access

In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants

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Authors

DCDelphine CroisierIDEXX Laboratories (France)MEManuel EtienneInserm LPLionel PirothInserm

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Implication

Animal experimental study demonstrates that low-level fluoroquinolone resistance drives resistant mutant enrichment under gatifloxacin treatment, highlighting mutant selection window dynamics.

Key Points

To evaluate the mutant selection window hypothesis in an experimental rabbit pneumonia model and assess how low-level fluoroquinolone resistance affects the emergence of resistant Streptococcus pneumoniae mutants during gatifloxacin therapy.
Inoculated rabbits with five Streptococcus pneumoniae strains displaying distinct fluoroquinolone resistance profiles (wild-type, efflux mutant MS1A, parC S79F, parC S79T, and gyrA S81F).
Administered a 48-hour human-equivalent gatifloxacin regimen (equivalent to 400 mg once daily) and analyzed bacterial killing and resistance enrichment using classification and regression tree (CART) modeling.
Gatifloxacin achieved >6 log10 killing against the wild-type strain and >5 log10 killing against the efflux strain, but parC-gyrA resistant mutants emerged in 26% of animals infected with the efflux strain.
Treatment failed to produce significant bacterial reduction against both parC-mutated strains due to 100% enrichment of highly resistant mutants, with no bacterial count reductions observed against the gyrA-resistant strain.
CART analysis identified time inside the mutant selection window (T(MSW)) and area under the curve within the window (AUC(MSW)) as the primary variables driving the selection of resistant pneumococci.

Cite This Study

Croisier et al. (2004) studied this question.

synapsesocial.com/papers/6a81921769a8c95c3f3cbcf5 https://doi.org/10.1093/jac/dkh393

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Implication

Animal experimental study demonstrates that low-level fluoroquinolone resistance drives resistant mutant enrichment under gatifloxacin treatment, highlighting mutant selection window dynamics.

In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants

Discussion

Member takes

Implication

Key Points

Cite This Study

In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants

Discussion

Member takes

Implication

Key Points

Cite This Study

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