Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization

To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR). Susceptibility testing by broth microdilution was performed on 30 MRSA...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2012-12, Vol.67 (12), p.2814-2820
Main Authors: REMY, Joan M, TOW-KEOGH, Cheryl A, MCCONNELL, Timothy S, DALTON, James M, DEVITO, Joseph A
Format: Article
Language:English
Subjects:
Agar
Anti-Bacterial Agents - pharmacology
Antibiotics
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacterial diseases
Biological and medical sciences
Cell migration
Cells
Clinical isolates
DNA Mutational Analysis
DNA, Bacterial - genetics
Drug resistance
Drug Resistance, Bacterial
Fitness
Growth rate
Human bacterial diseases
Humans
Infection
Infectious diseases
Medical sciences
Methicillin-Resistant Staphylococcus aureus - drug effects
Methicillin-Resistant Staphylococcus aureus - growth & development
Microbial Sensitivity Tests
Minimum inhibitory concentration
Mutation
Pharmacology. Drug treatments
Polymerase Chain Reaction
Quinolones
Quinolones - pharmacology
Resistant mutant
Selection, Genetic
Staphylococcal infections, streptococcal infections, pneumococcal infections
Staphylococcus aureus
Staphylococcus infections
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Summary:To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR). Susceptibility testing by broth microdilution was performed on 30 MRSA clinical isolates. For four of these isolates, the presence or absence of mutations in the QRDR was characterized. Resistance selection was performed on these four isolates by spreading cells on drug-containing agar plates followed by incubation for 48 h. Resistance frequencies and mutant prevention concentrations (MPCs) were calculated for each; PCR amplification and sequencing were performed using standard methods to characterize mutations in the QRDR. Growth rate analysis was performed and relative fitness was determined. Delafloxacin demonstrated potent in vitro activity against this set of MRSA isolates, with MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L, respectively. Spontaneous delafloxacin resistance frequencies for the MRSA strains were 2 × 10(-9) to
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dks307