Testing a new weapon against nosocomial staph
Testing a new weapon against nosocomial staph
Synercid fares well, but trials will define niche
Source: Sambatakou H, et al. In-vitro activity and killing effect of quinupristin/dalfopristin (RP59500) on nosocomial Staphylococcus aureus and interactions with rifampicin and ciproflox acin against methicillin-resistant isolates. J Antimicrob Chemother 1998; 41:349-355.
Quinupristin/dalfopristin, known previously as RP59500, is a combination of two streptogramins, semisynthetic derivatives of insoluble pristinamycins IA and IIB, respectively. Synercid, (quinupristin/dalfopristin), an IV injectable strepto - gramin, has been used in Europe for years and is expected to be approved by the Food and Drug Administration soon. This study from Athens Medical School in Greece offers some of the most current data for Synercid's activity against nosocomial strains of S. aureus. Sambatakou and colleagues seek to determine three traits of Synercid:
o its in vitro inhibitory activity against 101 methicillin-resistant S. aureus (MRSA) strains and 53 methicillin-susceptible S. aureus (MSSA) isolates;
o its killing effect against 24 MRSA and seven MSSA isolates;
o its interactions with rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant to both.
Killing curves supported the superior activity of quinupristin/dalfopristin against MSSA strains: 50% of MRSA strains were killed by 4 MIC (minimum inhibitory concentration) at 24 hours, compared with 100% of MSSA isolates at the same time and concentration. Three (12.5%) of the 24 MRSA strains tested were not killed after 24 hours incubation at 1 MIC, and two (8.3%) were not after 24 hours at 2 MIC, whereas at 4 MIC, no resistance to killing was observed. The combination of quinupristin/dalfopristin plus ciprofloxacin or rifampicin at 4 MIC was bactericidal in 100% of MSSA isolates at 24 hours. The combination was bactericidal in 75% (ciprofloxacin) and 83% (rifampicin) of MRSA isolates at 24 hours. For one MRSA isolate, neither ciprofloxacin nor rifampicin was bactericidal, but the combination using ciprofloxacin or rifampicin at their mean serum levels was bactericidal at 24 hours for 2 MIC and at 6 hours or less at 4 MIC.
Comment by Joseph F. John, MD, professor of medicine and microbiology, Robert Wood Johnson Medical School in New Brunswick, NJ:
The arrival of quinupristin/dalfopristin (Synercid) has been anticipated for several years. Preliminary data suggest it has good activity against gram-positive bacteria, but few clinical data are published. Although the present study does not use case studies, the in vitro data presented here using only nosocomial strains of S. aureus are reassuring to a certain degree. The combination is highly inhibitory and bactericidal against MSSA. On the other hand, the data for MRSA show less inhibitory effect, and the bactericidal concentration is reduced fourfold (0.25 to 2 mg/L). For 50% of the MRSA isolates that were not killed by 4 MIC of quinupristin/dalfopristin, a synergistic effect was seen with both ciprofloxacin and rifampicin at 2 MIC and 4 MIC, even if the isolates were resistant to ciprofloxacin and rifampicin.
What is exciting about this study is that soon there should be an alternative anti-staphylococcal chemotherapy. For those patients who are intolerant to both penicillin and vancomycin and who have MSSA infections, quinupristin/dalfopristin should prove a reasonable alternative. For those patients who have MRSA infections, perhaps more analysis of such strains will be necessary. If there are no other alternatives for MRSA infections, this study suggests that use of ciprofloxacin or rifampicin in combination with quinupristin/ dalfopristin may be an effective regimen.
In compassionate-use programs, 10 of 11 cases of MRSA bacteremia were successfully treated with the streptogramin in combination. Quinupristin/dalfopristin seems to be generally well-tolerated but has some distinctive adverse effects, including joint and muscle pain and venous intolerance. As Synercid becomes available, clinicians will need to weigh a body of data from in vitro studies like that of Sambatakou et al. - as well as data from uncontrolled trials - to determine the niche that this novel antibiotic will fill.
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