Antimicrobial Agents and Chemotherapy: Potent Antibiotic Combination for Resistant S. aureus Bacteremias
Speaker: Joseph L. Gugliotta, MD, Infectious Disease Specialist, Hunterdon Medical Center, Flemington, New Jersey.
The combination of quinupristin/dalfopristin (Synercid, Aventis) and vancomycin (Vancocin, Lilly) proved to be highly effective in the treatment of bacteremias caused by oxacillin-resistant Staphylococcus aureus (ORSA) strains, demonstrating enhanced bactericidal activity compared with either antibiotic tested alone.
Two patients with oxacillin-resistant S. aureus bacteremias remained blood culture positive with vancomycin and then with quinupristin/dalfopristin therapy, in both cases alone or with rifampin. Within 48 hours of switching to a combination of quinupristin/dalfopristin and vancomycin, the bacteremias were cleared, with all subsequent blood cultures being negative.
Two ORSA isolates from the two patients with sepsis and S. aureus ATCC 43300 were studied in vitro in a time-kill synergy assay (a>100-fold or 2 log10 decrease in the viable cell count at 24 hours for the combination of quinupristin/dalfopristin and vancomycin compared with the most active agent). The two antibiotics were tested alone and in combination at 0.25, 0.5, and 1 times the minimum inhibitory concentration (MIC) with samples taken at 0, three, six, and 24 hours to determine viable cell counts.
Quinupristin, at 1 times MIC, was more effective than vancomycin in suppressing bacterial regrowth after 24 hours, whereas the combination of quinupristin/dalfopristin plus vancomycin was bactericidal (>99.9% reduction from the initial inoculum) for both isolates and a control isolate (ORSA ATCC 43300) at 1 times MIC after 24 hours. Using this time-kill synergy methodology, the combination of quinupristin/dalfo-pristin and vancomycin achieved synergy for one clinical isolate and approached synergy for another clinical isolate, demonstrating that quinupristin/dalfopristin used in combination with vancomycin is more effective than either agent alone to treat ORSA infections.
Improved Treatment for Hospitalized Gram-Positive Infections
Speaker: Mark Wilcox, MD, Staff Physician and Lead Investigator, Leeds General Infirmary & University of Leeds Old Medical School, Leeds, United Kingdom.
Linezolid (Zyvox drug, Pharmacia), a novel oxazolidinone antibiotic available as an intravenous (IV) or oral dosage form, has been shown to have a significant advantage over teicoplanin for the treatment of gram-positive infections in hospitalized patients, being especially superior for the treatment of nosocomial gram-positive bacteremias.
In this study, 430 hospitalized patients with suspected or proven gram-positive infections were enrolled into a phase IIIb, randomized, open-label, comparator-controlled, multinational, multicenter study. Patients were randomly assigned to receive either linezolid 600 mg every 12 hours IV or orally, or teicoplanin IV or intramuscularly (IM) as per approved prescribing information, for seven to 28 days. Clinical and microbiological efficacy, safety, and tolerability were assessed at the end of the treatment period.
Linezolid demonstrated a significantly better success rate overall than teicoplanin in the treatment of all gram-positive-infected patients, with clinical success rates of 95.5% on line-zolid compared to 87.6% for those on teicoplanin. In patients with gram-positive bacteremias, the clinical success rate with linezolid was 88.5% versus a clinical success rate of 56.7% with teicoplanin. Furthermore, when other specific sites of infection were considered, such as pneumonia and skin or soft tissue infections, linezolid demonstrated comparable rates of success. More than half (54%) of patients receiving IV linezol-id could be switched to oral linezolid therapy, which makes canadian linezolid particularly valuable economically.
