Source: Lancet  |  Posted 10 years ago

Quinupristin-dalfopristin, the first formulation of a distinct class of antibiotics known as the streptogramins, is effective in the management of documented severe infections caused by vancomycin-resistant []E. faecium[], nosocomial pneumonia and infections related to the use of intravascular catheters.

The widespread use of antibiotics in community and hospital settings has led to a steady increase in resistant organisms. In intensive care units, for example, the percentage of vancomycin-resistant enterococcal isolates had risen 35-fold, from 0.4 percent to almost 14 percent.

For these reasons, there is a need for new therapies, including treatments for infections caused by antibiotic-resistant gram-positive organisms.

Quinupristin-dalfopristin has activity against a range of gram-positive bacteria that are usually resistant to other agents. It had been shown to be effective in the management of severe infections caused by vancomycin-resistant enterococcus faecium, nosocomial pneumonia and infections related to the use of intravascular catheters.

Of more than 4,000 isolates of S. pneumoniae that were tested, 98 percent were susceptible to quinupristin-dalfopristin, irrespective of resistance to beta-lactam or macrolide antibiotics.

Similarly, 97 percent of streptococcal species besides S. pneumoniae were susceptible to quinupristin-dalfopristin. Other organisms against which the formulation showed in vitro activity included []haemophilus influenzae[], []legionella species[], []mycoplasma species[], []clostridium species[] and []Chlamydia pneumoniae[]. Aerobic gram-negative enteric bacilli were not, however, susceptible to quinupristin-dalfopristin.

The pharmacodynamic (post-antibiotic effect) and pharmacokinetic characteristics of quinupristin-dalfopristin allowed dosing at intervals of eight to 12 hours. The safety profile of the formulation was generally favourable, with no demonstrable ototoxicity, nephrotoxicity, bone marrow suppression or adverse cardiovascular adverse effects.

Reversible arthralgias (9 percent) and myalgias (6 percent) were the most common side-effects and had led to the discontinuation of quinupristin-dalfopristin in up to one half of affected patients. Pain and inflammation at the infusion site were common but required discontinuation of treatment in fewer than 10 percent of patients.

However, there was a potential for drug interactions with quinupristin-dalfopristin because it significantly inhibited the cytochrome P450-3A4 enzyme system. Among drugs whose plasma concentrations were predicted to increase after quinupristin-dalfopristin, cyclosporine in particular should be monitored when used with quinupristin-dalfopristin.

Dr. John P. Manzella, of the Division of Infectious Diseases, York Hospital, York, Pennsylvania, United States, led this study.