Ciprofloxacin: chemistry, mechanism of action, resistance, antimicrobial spectrum, pharmacokinetics, clinical trials, and adverse reactions

Abstract

Ciprofloxacin, considered a benchmark when comparing new fluoroquinolones, shares with these agents a common mechanism of action: inhibition of DNA gyrase. While ciprofloxacin demonstrated a fairly good activity against gram-positive bacteria, it is against gram-negative organisms that it proved to be more potent than other fluoroquinolones. It is the most active quinolone against Pseudomonas aeruginosa, with MIC90s on the order of 0.5 micrograms/ml. When given orally, ciprofloxacin exhibited 70% bioavailability and attained peak serum levels ranging between 1.5 and 2.9 micrograms/ml after a single 500-mg dose. Nineteen percent of an oral dose was excreted as metabolites in both urine and feces. In most cases, body fluids and tissue concentrations equaled or exceeded those in concurrent serum samples. In clinical trials, oral and intravenous ciprofloxacin yielded similar clinical and bacteriologic results compared to standard therapy in a wide array of systemic infections, including lower and upper urinary tract infections; gonococcal urethritis; skin, skin structure, and bone infections; and respiratory tract and gastrointestinal tract infections. Major benefits with the oral form of this quinolone are expected in chronic pyelonephritis and bone infections, and in pulmonary exacerbations in patients with cystic fibrosis. Emergence of ciprofloxacin-resistant microorganisms has been noted in clinical practice, primarily Pseudomonas aeruginosa and Staphylococcus aureus. The most frequent side effects are related to the gastrointestinal tract; but attention should be given to adverse central nervous system effects.