Treatment of hospitalized patients with complicated Gram-positive skin andskin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin

Citation
Rl. Nichols et al., Treatment of hospitalized patients with complicated Gram-positive skin andskin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin, J ANTIMICRO, 44(2), 1999, pp. 263-273
Citations number
15
Categorie Soggetti
Pharmacology,Microbiology
Journal title
Journal of antimicrobial chemotherapy
ISSN journal
03057453 → ACNP
Volume
44
Issue
2
Year of publication
1999
Pages
263 - 273
Database
ISI
SICI code
Abstract
Quinupristin/dalfopristin (Synercid), the first injectable streptogramin an tibiotic available for the treatment of complicated Gram-positive skin and skin 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% CI, -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 bacteri ological eradication rates were somewhat tower for quinupristin/dalfopristi n (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% a nd 77.7%, respectively). The lower bacteriological response rates in the qu inupristin/dalfopristin group were, in part, due to a higher rate of polymi crobial infections and a higher incidence of patients classified as clinica l failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication ra te for quinupristin/dalfopristin was higher in monomicrobial infections tha n in polymicrobial infections (72.6% versus 63.3%, respectively), whereas t he corresponding rate for the comparator regimens was lower for monomicrobi al infections than polymicrobial infections (70.8% versus 83.1%). This find ing was not unexpected, since the spectrum of quinupristin/dalfopristin is focused on Gram-positive pathogens and additional antibiotics to treat Gram -negative bacteria were not required per protocol. The systemic tolerabilit y of both treatment regimens was qualitatively similar. A higher rate of dr ug-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 quinupristi n/dalfopristin (19.1%), whereas the most common reason for discontinuation among those receiving the comparator regimens was treatment failure (11.5%) . Quinupristin/dalfopristin is an effective alternative for the treatment o f hospitalized patients with complicated skin and skin structure infections due to quinupristin/ dalfopristin-susceptible Gram-positive organisms, inc luding methicillin- and erythromycin-resistant S. aureus.