Combining quinupristin/dalfopristin with other agents for resistant infections

OBJECTIVE: To review the resistance mechanisms of Enterococcus and Staphylococcus spp. and summarize quinupristin/ dalfopristin's (QD's) effects on these resistant organisms when combined with other antibiotics via review of the literature and unpublished data. DATA SOURCES: Data were identified by a PubMed search (1996-May 2003) using the search terms quinupristin/dalfopristin, synergy, in vitro, in vivo, vancomycin-resistant Enterococcus faecium (VREF), methicillin-resistant Staphylococcus aureus (MRSA), and individual antibiotic names. Bibliographies of the resultant PubMed searches were reviewed and included if applicable. STUDY SELECTION AND DATA EXTRACTION: All studies reviewed were analyzed; specific drug data were included only if clinically pertinent. In vitro data from studies with adequate design were discussed, whereas all case reports and clinical trials were utilized. DATA SYNTHESIS: In the treatment of VREF, available information seems conflicting, although some clear differences have become apparent. QD-ampicillin and QD-doxycycline combinations have demonstrated beneficial activity, usually displaying synergistic or additive effects even in macrolide-, lincosamine-, and streptogramin-resistant (MLSB) isolates. Vancomycin and chloramphenicol have shown some efficacy, but antagonistic or null results also have been observed. Regarding MRSA, results from many studies of QD combinations have been ambiguous. More common combinations displayed synergy or additive effects against MRSA, but only QD-rifampin showed consistent beneficial activity against MRSA and MLSB isolates. Most other combinations displayed antagonism when tested in vitro. CONCLUSIONS: Data supporting the use of various QD-antibiotic combinations against VREF and MRSA are increasing, but further in vitro and in vivo data are needed to confirm the findings.