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