Biological counterstrike: antibiotic resistance mechanisms of Gram-positive cocci

The development of antibiotic resistance by bacteria is an evolutionary inevitability, a convincing demonstration of their ability to adapt to adverse environmental conditions. Since the emergence of penicillinase-producing Staphylococcus aureus in the 1940s, staphylococci, enterococci and streptococci have proved themselves adept at developing or acquiring mechanisms that confer resistance to all clinically available antibacterial classes. The increasing problems of methicillin-resistant S. aureus and coagulase-negative staphylococci (MRSA and MRCoNS), glycopeptide-resistant enterococci and penicillin-resistant pneumococci in the 1980s, and recognition of glycopeptide-intermediate S. aureus in the 1990s and, most recently, of fully vancomycin-resistant isolates of S. aureus have emphasised our need for new anti-Gram-positive agents. Antibiotic resistance is one of the major public health concerns for the beginning of the 21st century. The pharmaceutical industry has responded with the development of oxazolidinones, lipopeptides, injectable streptogramins, ketolides, glycylcyclines, second-generation glycopeptides and novel fluoroquinolones. However, clinical use of these novel agents will cause new selective pressures and will continue to drive the development of resistance. This review describes the various antibiotic resistance mechanisms identified in isolates of staphylococci, enterococci and streptococci, including mechanisms of resistance to recently introduced anti-Gram-positive agents.