Cross-resistance analyses and molecular typing of Staphylococcus aureus and Streptococcus spp. isolates resistant to quinupristin/dalfopristin

Sir, During the past two decades Gram-positive bacteria, predominantly staphylococci and streptococci, have reemerged as important pathogens. Staphylococci, in particular, have demonstrated a remarkable propensity for acquiring mechanisms of resistance to every new antimicrobial to become available and for spreading among patients, institutions and communities. More recently, there have also been increasing concerns about -lactam resistance in Streptococcus pneumoniae and other streptococci. Clearly, there is a pressing need to identify novel compounds that can be used as therapy for patients with infections caused by these organisms. Quinupristin/dalfopristin, a combination of two streptogramins, is one such agent. It has been shown to have excellent activity in vitro against a broad range of staphylococci and streptococci, including strains that exhibit multidrug r e s i s t a n c e . Resistance to streptogramins can develop through one of several mechanisms—alteration of the target site (the most common mechanism), active transport or e f flux mediated by an ATP-binding protein and enzyme m o d i fic a t i o n . The aims of the present study were to determine the antibiotic susceptibilities of strains of S t a p h y l o c o c cus aureus and S t r e p t o c o c c u s spp. exhibiting intermediate susceptibility or resistance to quinupristin/dalfopristin and to investigate the clonal relatedness of these strains. The bacteria studied were identified from among a total of 2393 strains of S. aureus (574 of which were resistant to methicillin), 963 of S. pneumoniaeand 486 of other Strepto coccus spp. isolated in 24 university hospitals participating in the European SENTRY antimicrobial surveillance programme between April 1997 and February 1999. MICs of quinupristin/dalfopristin for the isolates were determined by a microbroth dilution method recommended by the NCCLS. The susceptibilities of strains for which the MICs of quinupristin/dalfopristin were 2 mg/L to several antibiotics were then determined by the same microbroth dilution method. The antibiotics were as follows: penicillin, oxacillin, ciprofloxacin, gentamicin, erythromycin, clindamycin, teicoplanin, vancomycin and the novel oxazolidinone, linezolid. In addition, the S. aureus strains were typed by a PFGE method described previously. Of the 3842 non-replicate strains submitted, 21 (0.9%) S. aureus isolates, one (0.1%) S. pneumoniae isolate and six (1.2%) other Streptococcus spp. isolates (comprising one strain each of Streptococcus mitis, Streptococcus oralis, Streptococcus bovis, Streptococcus porcinus, Streptococcus intermedius and Streptococcus sanguis) exhibited intermediate susceptibility or resistance to quinupristin/ dalfopristin. Of the 21 S. aureus isolates, 18 were methicillin-resistant (MRSA) and three were methicillin-susceptible (MSSA); therefore 3.1% of MRSA isolates and 0.2% of MSSA isolates were non-susceptible to quinupristin/ dalfopristin. Most (16) of the 21 S. aureusstrains that were resistant to quinupristin/dalfopristin were referred from three hospitals in France, one of which contributed 14 strains. The remainder came from hospitals in Spain (three strains), Austria (one) and the UK (one). The single quinupristin/ dalfopristin-resistant S. pneumoniae isolate was isolated in Germany and the six Streptococcus spp. isolates were from France (two strains), Austria (one), Italy (one), The Netherlands (one) and Turkey (one). Twenty-three (82%) of the 28 isolates were recovered from patients with bacteraemias, the remaining strains being isolated from patients with wound infections (three strains) or nosocomial pneumonias (two). The susceptibilities of the 28 strains are summarized in the Table. All 21 quinupristin/dalfopristin-resistant S. aureus isolates expressed the MLSB resistance phenotype and were resistant to penicillin and ciprofloxacin. The 18 MRSA isolates were also resistant to gentamicin (with 16 exhibiting high-level resistance) and five exhibited intermediate susceptibility to vancomycin (MICs 4 mg/L). The single quinupristin/dalfopristin-resistant S. pneumoniae