The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium (Reprinted from The Journal Antimicrobial Chemotherapy, vol 44, pg 251-261, 1999)

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 streptogramin: antibiotic, is active in vitro against VREF, with an MIC90 of 1.0 mg/L. We studied the cl inical efficacy:and safety of quinupristin/dalfopristin in the treatment of VREF infection. Two prospective studies were conducted simultaneously. The first enrolled only patients with VREF infection; the second included pati ents with infection caused by other Gram-positive bacterial pathogens in ad dition-to VREF. Patients were enrolled if they had signs and symptoms of ac tive infection and no appropriate alternative antibiotic therapy. The recom mended treatment regimen of quinupristin/daifopristin was 7.5 mg/hg iv ever y 8 h for a duration judged appropriate by the investigator. A total of 396 patients with VREF infection were enrolled. The most frequent indications for treatment included intra-abdominal infection, bacteraemia of unknown or igin, 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-treatmen t was 14.5 +/- 10.7 days (range: 1-108). The majority of patients (82;1%) W ere treated every 8 h, as assessed on day 2 of treatment, while 15.9% were treated every 12 h.,The clinical success rate was 73.6% [142/193 clinically evaluable patients; 95% confidence interval (CI): 67.4%, 79.8%], the bacte riological 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/dalfopuistin 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.