The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium

A progressive increase in the incidence of vancomycin resistance in strains of Enterococcus faecium (VREF) has severely constrained treatment options for patients with infection caused by this emerging pathogen. Quinupristin/ dalfopristin (Synercid), the first injectable strepto-gramin antibiotic, is active in vitro against VREF, with an MIC90, of 1.0 mg/L. We studied the c linical efficacy and safety of quinupristin/dalfopristin in the treatment o f VREF infection. Two prospective studies were conducted simultaneously. Th e first enrolled only patients with VREF infection; the second included pat ients with infection caused by other Gram-positive bacterial pathogens in a ddition to VREF. Patients were enrolled if they had signs and symptoms of a ctive infection and no appropriate alternative antibiotic therapy. The reco mmended treatment regimen of quinupristin/dalfopristin was 7.5 mg/kg iv eve ry 8 h for a duration judged appropriate by the investigator. A total of 39 6 patients with VREF infection were enrolled. The most frequent indications for treatment included intra-abdominal infection, bacteraemia of unknown o rigin, urinary tract infection, catheter-related bacteraemia, and skin and skin structure infection. This patient population had a high prevalence of severe underlying illness, including a history of diabetes mellitus, transp lantation, mechanical ventilation, dialysis, chronic liver disease with cir rhosis and oncological disorders. The mean (+/- S.D.) duration of treatment was 14.5 +/- 10.7 days (range: 1-108). The majority of patients (82.1%) we re treated every 8 h, as assessed on day 2 of treatment, while 15.9% were t reated every 12 h. The clinical success rate was 73.6% [142/193 clinically evaluable patients; 95% confidence interval (CI): 67.4%, 79.8%], the bacter iological success rate 70.5% (110/156 bacteriologically evaluable patients; 95% CI: 63.4%, 77.7%) and the overall success (both clinical and bacteriol ogical success) rate 65.8% (102/156 bacteriologically evaluable patients; 9 5% CI: 57.9%, 72.9%). VREF bacteraemia at entry, mechanical ventilation and laparotomy were associated with a worse outcome. Quinupristin/dalfopristin was generally well tolerated. The most common systemic adverse events rela ted to treatment were arthralgias (9.1%) and myalgias (6.6%). Related labor atory abnormalities were infrequent. In these severely ill patients with VR EF infection and no other clinically appropriate therapeutic alternatives, quinupristin/dalfopristin demonstrated substantial efficacy and a good nerv ous system, cardiovascular, gastrointestinal, renal and hepatic tolerabilit y.