Open AccessIn Vitro Antibacterial Activities of JNJ-Q2, a New Broad-Spectrum Fluoroquinolone
Author(s) -
Brian J. Morrow,
Wenping He,
Karen Amsler,
Barbara D. Foleno,
Mark J. Macielag,
A. Simon Lynch,
Karen Bush
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01374-09
Subject(s) - moxifloxacin , microbiology and biotechnology , broth microdilution , ciprofloxacin , streptococcus pneumoniae , topoisomerase iv , dna gyrase , ofloxacin , staphylococcus aureus , biology , minimum inhibitory concentration , antibiotics , escherichia coli , bacteria , gene , genetics
JNJ-Q2, a novel fluorinated 4-quinolone, was evaluated for its antibacterial potency by broth and agar microdilution MIC methods in studies focused on skin and respiratory tract pathogens, including strains exhibiting contemporary fluoroquinolone resistance phenotypes. Against a set of 118 recent clinical isolates ofStreptococcus pneumoniae , including fluoroquinolone-resistant variants bearing multiple DNA topoisomerase target mutations, an MIC90 value for JNJ-Q2 of 0.12 μg/ml was determined, indicating that it was 32-fold more potent than moxifloxacin. Against a collection of 345 recently collected methicillin-resistantStaphylococcus aureus (MRSA) isolates, including 256 ciprofloxacin-resistant strains, the JNJ-Q2 MIC90 value was 0.25 μg/ml, similarly indicating that it was 32-fold more potent than moxifloxacin. The activities of JNJ-Q2 against Gram-negative pathogens were generally comparable to those of moxifloxacin. In further studies, JNJ-Q2 exhibited bactericidal activities at 2× and 4× MIC levels against clinical isolates ofS. pneumoniae and MRSA with various fluoroquinolone susceptibilities, and its activities were enhanced over those of moxifloxacin. In these studies, the activity exhibited against strains bearinggyrA ,parC , orgyrA plusparC mutations was indicative of the relatively balanced (equipotent) activity of JNJ-Q2 against the DNA topoisomerase target enzymes. Finally, determination of the relative rates or frequencies of the spontaneous development of resistance to JNJ-Q2 at 2× and 4× MICs inS. pneumoniae , MRSA, andEscherichia coli were indicative of a lower potential for resistance development than that for current fluoroquinolones. In conclusion, JNJ-Q2 exhibits a range of antibacterial activitiesin vitro that is supportive of its further evaluation as a potential new agent for the treatment of skin and respiratory tract infections.