Quinupristin/dalfopristin: therapeutic potential for vancomycin-resistant enterococcal infections

Vancomycin-resistant Enterococcus faecium (VREF) is an opportunistic pathog en, which causes infections among severely ill, hospitalized patients, in w hom it is likely to increase the risk of progressive local or systemic dise ase and to worsen the prognosis. Because these organisms are often highly r esistant to penicillin, ampicillin and many other antimicrobials including the glycopeptides, there are few proven therapeutic alternatives for the tr eatment of infection caused by VREF. Quinupristin/dalfopristin is highly ac tive against VREF in vitro. A prolonged post-antibiotic effect, good polymo rphonuclear leucocyte/macrophage penetration and slow release, and active m etabolites allow this agent to be used with an 8 or 12 h dosing interval. T he combined results from a Phase III non-comparative study and an emergency -use study of quinupristin/dalfopristin for the treatment of VREF infection produced a clinical response rate (cure or improvement) in 142 (73.6%) of 193 clinically evaluable patients. The baseline pathogen was eradicated or presumed eradicated from 110 of 156 (70.5%) bacteriologically evaluable pat ients. Fifty-two per cent of the severely ill patients in these two studies died, but no death was attributed to quinupristin/dalfopristin therapy. Th e most common adverse event was arthralgia (9.1%). Quinupristin/dalfopristi n has demonstrated efficacy for the treatment of serious VREF infections, i ncluding those that have failed conventional therapy.