The increase in prevalence of MRSA appears to have been due to spread in hospitals of one or a few clones of S. aureus belonging to phage-type complex 83A and exhibiting multiple antibiotic resistance (27). In Denmark in the 1950s, the S. aureus strains isolated were frequently of the 52/52A/80/81 complex, but these were replaced increasingly in the early 1960s by tetracycline-resistant strains of the 83A complex; 70% of these were multiresistant (45% methicillin resistant). Subsequently, prevalence of strains of phage complex 83A steadily declined until 1980 and has remained at 6% since 1980. Currently, <2% of strains of S. aureus are multiresistant, and even strains of the 83A complex are no longer multiresistant.

Important factors in the control of the Danish outbreak included the extensive and continual monitoring of nosocomial S. aureus isolates and prompt institution of isolation precautions when MRSA was detected. The basis for the increased prevalence of the epidemic clone(s) of MRSA in the Danish outbreak and their subsequent disappearance is unclear. A role for antimicrobial use patterns in the evolution of resistance has been suggested (27). The use of tetracyclines and streptomycin in the 1960s may have provided some selective pressure for the increase in frequency of multiantibiotic-resistant MRSA. Similarly, the considerable reduction in the quantities of these two drugs used during the early 1970s may have lessened the selective pressure for streptomycin- and tetracycline-resistant subtypes of phage 83A complex MRSA.

In the mid 1980s, the newer fluoroquinolone antimicrobials offered considerable initial promise for dealing with both clinical infections due to MRSA and the carrier state (28). The minimum inhibitory concentration (MIC) for 90% of S. aureus isolates (both methicillin-susceptible and methicillin-resistant isolates) was 0.5 µg/ml (29). In the late 1980s and early 1990s, this promise proved disappointing as resistance rapidly developed, particularly among methicillin-resistant strains. In a large tertiary care hospital in New York City, >80% of MRSA had become resistant to the available fluoroquinolones (14).

CNS

By 1971 ≈65% of CNS had become resistant to penicillin at large urban teaching hospitals such as the Massachusetts General Hospital, and from 1979 on ≈80% of isolates have been resistant. Resistance to penicillinase-resistant penicillins, such as methicillin and oxacillin, has steadily increased. At the Massachusetts General Hospital, the percentage of methicillin-resistant isolates among CNS has risen from 8% in 1971 to 54% in 1992.

The increasing role of CNS as a pathogen in infections involving



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