Overview of preclinical studies with ciprofloxacin

Abstract

Ciprofloxacin is a new 6-fluoro-7-piperazino-4-quinolone that is highly active against a broad array of microbial pathogens. Minimal inhibitory concentrations (MICs) of ciprofloxacin are generally below 0.5 micrograms/ml for Hemophilus, Neisseria, and Enterobacteriaceae and are 1.0 microgram/ml or less for many non-fermentative gram-negative bacteria. Most staphylococci, including strains resistant to methicillin, are inhibited by 1.0 microgram/ml or less of ciprofloxacin, whereas streptococci are somewhat less susceptible. Obligate anaerobes are generally not susceptible to ciprofloxacin at concentrations below 1.0 microgram/ml. The antimicrobial potency of ciprofloxacin is twofold to fourfold greater than that of norfloxacin and is considerably greater than that of cephalosporins and aminoglycosides in tests with most gram-negative bacteria. Factors diminishing the in vitro activity of ciprofloxacin include acidic pH, high levels of magnesium ions, and an inoculum size of 10(7) colony-forming units/ml or greater. Ciprofloxacin is bactericidal at concentrations near its MIC for most bacteria. In vivo tests with experimentally induced infections in animals confirm the potency of ciprofloxacin. Doses required to protect 50 percent of animals from death are generally less than 2.0 mg/kg for gram-negative infections and range from 0.7 to 7.0 mg/kg for staphylococcal infections. The antimicrobial spectrum and potency of ciprofloxacin demonstrated in these preclinical studies make this quinolone a promising new antimicrobial agent.