Treatment of hospitalized patients with complicated Gram-positive skin andskin structure infections - Two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin (Reprinted from The Journal of Antimicrobial Chemotherapy, vol 44, pg 263-273, 1999)

Quinupristin/dalfopristin (Synercid), the first injectable streptogramin an tibiotic available for the treatment of complicated Gram-positive skin and shin structure infections, was compared with standard comparators (cefazoli n, oxacillin or vancomycin) in one USA and one international trial. These t wo randomized, open-label trials of virtually identical design enrolled a t otal of 893 patients (450 quinupristin/dalfopristin, 443 comparator). The m ajority of patients had erysipelas, traumatic wound infection or clean surg ical wound infection. Staphylococcus aureus was the most frequently isolate d pathogen in both treatment groups and polymicrobial infection was more co mmon in the quinupristin/dalfopristin group than in the comparator group. T he clinical success rate (cure plus improvement) in the clinically evaluabl e population was equivalent between the two treatment groups (68.2% quinupr istin/dalfopristin, 70.7% comparator; 95% Cl, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacterio logical eradication rates were somewhat lower for quinupristin/dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% an d 77.7%, respectively). The lower bacteriological response rates in the qui nupristin/dalfopristin group were, in part, due to a higher rate of polymic robial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rat e for quinupristin/dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas th e corresponding rate for the comparator regimens was lower for monomicrobia l infections than polymicrobial infections (70.8% versus 83.1%). This findi ng was not unexpected, since the spectrum of quinupristin/dalfopristin is f ocused on Gram-positive pathogens and additional antibiotics to treat Gram- negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of dru g-related venous adverse events was reported for quinupristin/dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin /dalfopristin (19.1%), whereas the most common reason for discontinuation a mong those receiving the comparator regimens was treatment failure (11.5%). Quinupristin/dalfopristin is an effective alternative for the treatment of hospitalized patients with complicated skin and skin structure infections due to quinupristin/dalfopristin-susceptible Gram-positive organisms, inclu ding methicillin- and erythuomycin-resistant S. aureus.