Characterization of isolates associated with emerging resistance to quinupristin/dalfopristin (Synercid (R)) during a worldwide clinical program

Quinupristin/dalfopristin (Synercid(R)) is an i.v. antibiotic active agains t serious Gram-positive infections. Its unique dual mode of action means th at the potential for resistance development is expected to be low. To deter mine the incidence of in vitro emerging resistance in worldwide clinical st udies, susceptibility to quinupristin/dalfopristin was measured for baselin e pathogens and corresponding on- or post-study isolates from 880 evaluable patients. In comparative studies of community-acquired pneumonia, complica ted skin and skin structure infections, and nosocomial pneumonia, the incid ence of emerging resistance was low (1 of 453; 0.22%; 95% CI: 0.01-1.4%). R esistance development occurred in only one pathogen (methicillin-resistant Staphylococcus aureus). In noncomparative studies, six instances (1.8% of 3 38 evaluable cases; 95% CI: 0.7 to 4.0%) of emerging resistance tall vancom ycin-resistant Enterococcus faecium) were confirmed, accompanied by therape utic failure in four cases. Molecular typing did not confirm the identity o f one pair of strains. Overall, the incidence of emerging resistance to qui nupristin/dalfopristin was low. (C) 2000 Elsevier Science Inc. All rights r eserved.