Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2
| Autor: | Brian J. Morrow, A. Simon Lynch, Darren Abbanat, Wenping He, Ellen Z. Baum, Todd A. Davies, Wenchi Shang, Anne Marie Queenan, Steven M. Crespo-Carbone |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
DNA Topoisomerase IV
Methicillin-Resistant Staphylococcus aureus Staphylococcus aureus medicine.drug_class Microbial Sensitivity Tests Biology JNJ-Q2 medicine.disease_cause DNA gyrase Microbiology chemistry.chemical_compound Methicillin Moxifloxacin Ciprofloxacin Drug Resistance Bacterial medicine Humans Pharmacology (medical) Serial Passage Mechanisms of Action: Physiological Effects Pharmacology biochemical phenomena metabolism and nutrition Quinolone bacterial infections and mycoses Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents Infectious Diseases chemistry DNA Gyrase Biofilms Mutation Vancomycin medicine.drug Fluoroquinolones |
| Zdroj: | Antimicrobial agents and chemotherapy. 55(12) |
| ISSN: | 1098-6596 |
| Popis: | The new broad-spectrum fluoroquinolone JNJ-Q2 displays in vitro activity against Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and ciprofloxacin-resistant MRSA isolates. Tested with isogenic methicillin-susceptible S. aureus (MSSA) and MRSA strains bearing quinolone-resistant target mutations, JNJ-Q2 displayed MICs ≤ 0.12 μg/ml, values 16- to 32-fold lower than those determined for moxifloxacin. Overexpression of the NorA efflux pump did not impact JNJ-Q2 MICs. Inhibition of S. aureus DNA gyrase and DNA topoisomerase IV enzymes demonstrated that JNJ-Q2 was more potent than comparators against wild-type enzymes and enzymes carrying quinolone-resistant amino acid substitutions, and JNJ-Q2 displayed equipotent activity against both enzymes. In serial-passage studies comparing resistance selection in parallel MRSA cultures by ciprofloxacin and JNJ-Q2, ciprofloxacin readily selected for mutants displaying MIC values of 128 to 512 μg/ml, which were observed within 18 to 24 days of passage. In contrast, cultures passaged in the presence of JNJ-Q2 displayed MICs ≤ 1 μg/ml for a minimum of 27 days of serial passage. A mutant displaying a JNJ-Q2 MIC of 4 μg/ml was not observed until after 33 days of passage. Mutant characterization revealed that ciprofloxacin-passaged cultures with MICs of 256 to 512 μg/ml carried only 2 or 3 quinolone resistance-determining region (QRDR) mutations. Cultures passaged with JNJ-Q2 selection for up to 51 days displayed MICs of 1 to 64 μg/ml and carried between 4 and 9 target mutations. Established in vitro biofilms of wild-type or ciprofloxacin-resistant MRSA exposed to JNJ-Q2 displayed greater decreases in bacterial counts (7 days of exposure produced 4.5 to >7 log 10 CFU decreases) than biofilms exposed to ciprofloxacin, moxifloxacin, rifampin, or vancomycin. |
| Databáze: | OpenAIRE |
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