Expanded activity and utility of the new fluoroquinolones: a review

In general, the fluoroquinolones developed over the past few years have greater potency, a broader spectrum of antimicrobial activity, greater in vitro efficacy against resistant organisms, and a better safety profile than other antimicrobial agents, including the older quinolones. The present review focuses on 4 new quinolones that are commercially available (levofloxacin, trovafloxacin, grepafloxacin, and sparfloxacin) and 3 that are currently undergoing clinical trials (gatifloxacin, moxifloxacin, and clinafloxacin). Examination of the minimum inhibitory concentrations of these drugs against gram-positive, gram-negative, anaerobic, and atypical organisms demonstrates their increased potency in vitro. The available clinical evidence, although sparse, suggests the potential enhanced efficacy of these drugs in the treatment of various community-acquired and nosocomial infections (eg, respiratory, urinary tract, and skin infections and sexually transmitted diseases). Compared with ciprofloxacin, their pharmacokinetic profiles demonstrate equivalent or greater bioavailability, higher plasma concentrations, and increased tissue penetration, as reflected in greater volume of distribution. Adverse events seen with most quinolones are mild. Serious adverse effects that may occur are phototoxicity (particularly with sparfloxacin) and prolongation of the QTc interval (seen with sparfloxacin and grepafloxacin). Drug interactions are possible between multivalent cation-containing compounds and all quinolones and between theophylline and both ciprofloxacin and grepafloxacin. Drugs that prolong the QTc interval should not be coadministered with sparfloxacin and grepafloxacin. Step-down therapy, a therapeutic and cost-saving advantage possible with gatifloxacin, levofloxacin, and moxifloxacin, allows the switching of patients from intravenous to oral therapy without having to change the dosage regimen or class of antibiotics. In addition to shortening the hospital stay and reducing the risk of venous complications, step-down therapy has been shown to cut hospital drug costs by 40% and hospitalization costs by 20%.