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

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.
Method: 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/mL) 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.