In recent years, there has been a dramatic increase in the incidence of hospital-associated (nosocomial) infections caused by strains of Staphylococcus aureus that are resistant to multiple antibiotics; some strains now demonstrate resis-tance to as many as 20 antimicrobial compounds, including antiseptics and disinfectants. The threat to patient care posed by such organisms, largely due to their intransigence to antimicrobial chemotherapy, has stimulated efforts to gain insights into the genetic nature of the determinants encoding antibiotic resistance and the mechanisms by which they spread in staphylococcal populations. Attention is also being directed towards understanding the processes and pathways for the evolution of resistance in S. aureus. These studies have benefited, significantly, from the ap-plication of the powerful techniques of molecular genetics and have led to an explosion in the information on staphylococcal resistance since the last review devoted to this topic appeared in this journal (255). In this article, we have placed greatest emphasis on the molecular and genetic nature of resistance determinants but have also included brief descriptions of the resistance mechanisms they encode. Recent reviews which include some discussion of the genetics of antibiotic resistance in staphylococci are those by Foster (142), Poston and Naidoo (392), Brunton (55), Lacey (259), Kayser et al.(223a), and Gillespie and Skurray (157).

Emergence of Multiresistant S. aureus Staphylococci, together with pneumococci and strepto-cocci, are members of a group of invasive gram-positive pathogens, known as the pyogenic cocci, which cause vari-ous suppurative or pus-forming diseases in humans and other animals. Staphylococci are characteristically non-motile, catalase-positive facultative anaerobes, which grow in" grapelike" clusters and can be divided into pathogenic and relatively nonpathogenic strains on the basis of the synthesis of the enzyme coagulase (19, 360). Coagulasepositive strains, classified as S. aureus, often produce a yellow carotenoid pigment (which has led to them being colloquially referred to as" golden staph") and cause acute to chronic infections including pimples, boils, deep tissue abscesses, enterocolitis, bacteriuria, osteomyelitis, pneumo-nia, carditis, meningitis, septicemia and arthritis. Strains that do not produce coagulase, such as S. epidermidis, are nonpigmented and are generally less invasive but have increasingly been associated, as opportunistic pathogens, with serious nosocomial infections (8, 363). For reviews of biological, clinical, and epidemiological aspects of staphylococci, see references 117 and 118. Before the antibiotic era of medicine began some 40 years ago, the prognosis for patients with severe staphylococcal infections was extremely poor. The introduction of penicillin into clinical use in the early 1940s, though, brought about a dramatic reversal in this situation (386). For the first time, invasive S. aureus infections, such as those that develop from accidental or operative trauma, burns, and other seri-ous skin lesions, could be treated effectively. The period of universally effective penicillin therapy was disconcertingly short-lived, however. Within a few years the