Fluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin.

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LaPlante KL, Rybak MJ, Tsuji B, Lodise TP, Kaatz GW

Fluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin.

Antimicrob Agents Chemother. 2007 Apr;51(4):1315-20. Epub 2007 Feb 12.

PubMed ID

17296740 [ View in PubMed

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Abstract

The potential for resistance development in Streptococcus pneumoniae secondary to exposure to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin at various levels was examined at high inoculum (10(8.5) to 10(9) log10 CFU/ml) over 96 h in an in vitro pharmacodynamic (PD) model using two fluoroquinolone-susceptible isolates. The pharmacokinetics of each drug was simulated to provide a range of free areas under the concentration-time curves (fAUC) that correlated with various fluoroquinolone doses. Potential first (parC and parE)- and second-step (gyrA and gyrB) mutations in isolates with raised MICs were identified by sequence analysis. PD models simulating fAUC/MICs of 51 andgatifloxacin>moxifloxacin=gemifloxacin, which may be related to structural differences within the class.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Gemifloxacin	DNA topoisomerase 4 subunit A	Protein	Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)	Yes	Inhibitor	Details