Antibiotic resistance in staphylococci.

When penicillin was introduced in 1944 over 94% of Staphylococcus aureus isolates were susceptible; by 1950 half were resistant. By 1960 many hospitals had outbreaks of virulent multi-resistant S. aureus. These were overcome with penicillinase-stable penicillins, but victory was brief; methicillin-resistant S. aureus (MRSA) were recorded in the year of the drug's launch. MRSA owe their behaviour to an additional, penicillin-resistant peptidoglycan transpeptidase, PBP-2', encoded by mecA. Their spread is clonal, with transfer of mecA being extremely rare. MRSA accumulated and then declined in the 1960s and 1970s, but became re-established in the early 1980s. Some early MRSA strains were colonists rather than invaders and the proportion of MRSA among S. aureus bacteraemias in England remained under 3% until 1992. However, this proportion rose to 34-37% by 1998-1999, reflecting the dissemination of two new epidemic strains, EMRSA 15 and 16. These may be more virulent than earlier MRSA, or their success may reflect changing hospital practice. Until 1996, glycopeptides were universally active against S. aureus; then glycopeptide-intermediate S. aureus (GISA) were found in Japan, France, and the USA. This resistance is associated with increased wall synthesis. Coagulase-negative staphylococci (CNS) are less pathogenic than S. aureus but are important in line-associated bacteraemias and prosthetic device infections. They are even more often resistant than S. aureus, notably to teicoplanin. Few anti-staphylococcal agents were launched from 1970 to 1995, but the situation is now improving. Dalfopristin/quinupristin inhibits virtually all S. aureus, although its bactericidal activity is impaired against strains with constitutive MLSB-type resistance; other new agents are in advanced development. New agents give a renewed opportunity for control, but S. aureus is a resilient foe, able to regain its importance if drugs are used profligately or if hygiene is slackened.