Emerging resistance to antimicrobial agents in gram-positive bacteria. Enterococci, staphylococci and nonpneumococcal streptococci.

Staphylococci (Staphylococcus aureus and coagulase-negative Staphylococcus species) and enterococci are the aetiological organisms in 47 to 52% of nosocomial blood stream infections and approximately 30% of all nosocomial infections in the US. In European intensive care units, almost half of all infections are attributed to staphylococci. The streptococci have also become increasingly important because of the modified virulence of Streptococcus pyogenes strains, and the emerging role of the viridans group streptococci as a cause of potentially fatal bacteraemia in the neutropenic host. Resistance to available antimicrobial agents is increasing and includes, in particular, resistance to the glycopeptides (vancomycin and teicoplanin) amongst enterococci, resistance to penicillinase-resistant penicillins (oxacillin and methicillin) and fluoroquinolones (ciprofloxacin and ofloxacin) amongst staphylococci, and resistance to penicillin and some other beta-lactams amongst viridans group streptococci. New compounds for effective therapy of infection with antimicrobial-resistant Gram-positive species are needed urgently. To this end, the streptogramin combinations [quinupristin/dalfopristin (RP 59500; Synercid)], everninomycin derivatives (SCH 27899), oxazolidinones (U-100572, U-100766) and several newer fluoroquinolones (clinafloxacin, DU 6859a, grepafloxacin, levofloxacin, sparfloxacin, trovafloxacin) are under rapid development and clinical investigation.