Cutaneous Anaphylaxis Induced by 4-Quinolone Antibacterials in Guinea Pigs

Abstract

Several 4-quinolone antibacterials (norfloxacin HCl, enoxacin, ofloxacin, cinoxacin, ciprofloxacin, and nalidixic acid) were administered intradermally to male and female hairless guinea pigs (Crl:IAF(HA)BR). Immediately prior to the intradermal injection, the guinea pigs were given an intravenous injection of Evans blue dye. The diameter of the blue spots at the sites of intradermal injection 15 to 30 minutes after intradermal injection were used as a measure of cutaneous anaphylactoid activity. The quinolones were given in concentrations ranging from 0.009 to 4.0 mg/mL. Compound 48/80 was used as a positive control, and saline was used as the negative control. All the 4-quinolones tested, except nalidixic acid, were positive for cutaneous anaphylactoid activity. Norfloxacin, enoxacin, and ciprofloxacin were positive at concentrations of 0.13 mg/mL or higher. Ofloxacin and cinoxacin were positive at concentrations of 2.0 mg/mL or higher. Pretreatment with the H1 blocker, chlorpheniramine maleate, resulted in diminished responses. These results demonstrate the potential for adverse cutaneous anaphylactoid reactions, presumably due to release of vasoactive mediators, with 4-quinolone antibacterials, and illustrate a simple method to screen new compounds for this activity.

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