CQ-397 and CQ-414: Antimicrobial activity and spectrum of two fluoroquinolone-cephalosporin, dual-action compounds with carboxamido bonds

Abstract

Objective: To evaluate the potential spectrum of activity of two novel dual-action compounds with carboxamido bonds (CQ-397 and CQ-414; Laboratories Aranda, San Rafael, Mexico) against human pathogens. Approximately 800 Gram-positive and Gram-negative aerobic clinical bacteria were tested in vitro using the Mueller-Hinton broth microdilution method of the National Committee of Clinical Laboratory Standards. Results: CQ-397 (cefamandole + enrofloxacin) and CQ-414 (cefamandole + norfloxacin) were equally potent against Enterobacteriaceae (MIC90 range, 0.06-0.5 μg/mL and 0.06-1 μg/mL, respectively). Citrobacter freundii (MIC90, 4 μg/mL) and Providencia spp. (MIC90, > 32 μg/mL) exhibited elevated study drug MICs. Enterobacteriaceae resistant to fluoroquinolones generally remained resistant. CQ-397 and CQ-414 were active against Stenotrophomonas maltophilia (MIC90, 4 μg/ml) and oxacillin-susceptible staphylococci (MIC90, 0.25 μg/mL), but not oxacillin-resistant Staphylococcus aureus (MIC90, > 32 μg/ml), Staphylococcus epidermidis (MIC90, 8 μg/mL), and enterococci (MIC90s, 8 to > 32 μg/mL). There was no difference in the dual-action drug activity (MIC90, 2 μg/mL) between penicillin-susceptible and -resistant pneumococci. Haemophilus influenzae and Moraxella catarrhalis were very susceptible (MIC range, ≤ 0.015-0.06 μg/m L) to both compounds. Conclusions: The activity of these novel dual-action compounds, formed from the bonding of older antimicrobials, warrants further investigation for potential human and/or animal health use, including toxicology and pharmacokinetics.