High-Dose Intravenous Fluoroquinolones in the Treatment of Severe Infections

Abstract

A bacterial infection should be considered “serious” in case of underlying disease, nosocomial origin, antibiotic resistant pathogen, and/or poor delivery of antibiotics at the site of infection. Treatment of most serious infections requires parenteral administration of antimicrobial agents. Intravenous fluoroquinolones are a class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most Gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Most clinical trials with ciprofloxacin, ofloxacin, pefloxacin, the fluroquinolones currently available in France for parenteral use, are almost 10 years old. There are few studies with higher dosage and most of them have been carried out with ciprofloxacin. The findings of these studies indicate that higher dosage regimens of i.v. ciprofloxacin are much more effective against severe nososcomial infections than is the dosage of 200 mg twice daily. The higher dosage regimens resulted in greater rates of clinical cure and improvement in both monomicrobial and polymicrobial infections. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use.