In vivo fluoroquinolone concentrations and in vitro selection of resistance in Streptococcus pneumoniae
Abstract number: P1045
De Vecchi E., Nicola L., Zanini S., Drago L.
Objective: To compare the ability to select for resistance in S. pneumoniae of levofloxacin (LVX), ciprofloxacin (CIP), prulifloxacin (PRU) and moxifloxacin (MXF), which are commonly prescribed for treatment of community acquired infections in Italy.
Methods: Fluoroquinolones susceptible S. pneumoniae (n = 30) isolated from lower respiratory tract infections were used. Frequency of spontaneous single-step mutation allowing for bacterial growth in presence of plasma and epithelial lining fluid (ELF) peak and trough concentrations were calculated. Multistep selection of resistance was evaluated by performing 10 serial subcultures on antibiotic-containing agar plates, in which a linear gradient ranging from the peak to the trough concentrations of each drug was obtained, followed by 10 subcultures on antibiotic-free agar. LVX was tested at concentrations obtained with 500 mg and 750 mg dose. MICs were determined after 1, 5, 10 passages on antibiotic-gradient plates and after 10 subcultures on antibiotic free agar. Resistant strains selected after multistep selection were characterised for DNA mutations by sequencing gyrA, gyrB, parC and parE genes.
Results: LVX and MXF showed the lowest frequencies of mutations (median <11-11) at plasma peak and at all ELF concentrations, while medians ranging from 10^-8 to 10^-6 were observed for CIP and PRU. In multi-step selection of resistance, CIP and PRU selected for the highest number of resistant strains (19 and 31, respectively. LVX selected for 2 resistant strains at plasma concentrations. No selection of resistance was observed for LVX ELF concentrations and for plasma and ELF MXF concentrations. Mutations in parC, parE and gyrA genes were found in CIP and PRU resistant strains, while only parC mutations were found for LVX.
Conclusions: LVX and MXF, which are known to possess the highest activity against S. pneumoniae among the tested fluoroquinolones, are also characterised by a lower capacity than CIP and PRU to in vitro select for resistance when tested at concentrations occurring in vivo.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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