prosthetic devices (artificial heart valves, cardiac pacemaker leads, joint replacements, nervous system ventricular shunts, peritoneal dialysis catheters, and polyethylene intravenous catheters) has occurred contemporaneously with development of increasing methicillin-resistance. Staphylococcus epidermidis, a common commensal on human skin, is frequently the species infecting foreign body implants or indwelling venous catheters, but other CNS species may also be involved. Binding of such organisms to foreign-body surfaces and their intercell adherence is enhanced by a biofilm matrix (extracellular "slime layer" consisting of exopolysaccharides) they produce. Colonization within a biofilm appears to protect S. epidermidis cells against opsonization and phagocytosis by polymorphonuclear leukocytes, and it may afford protection against the bactericidal action of antibiotics by acting as a barrier to the latter's penetration (30).
CNS (and S. aureus) have developed resistance mechanisms for evading the inhibitory action of many antimicrobials previously useful in treating infections due to these microorganisms (14). They have acquired plasmid genes encoding β-lactamase production that render them (>90%) resistant to penicillin G. MRSA are resistant to methicillin and other penicillinase-resistant penicillins, cephalosporins, carbapenems, and penems by virtue of a chromosomal gene (mecA) that encodes a new PBP (PB2a) with reduced affinity for all β-lactam antibiotics. Fluoroquinolone resistance in clinical isolates of S. aureus is associated with mutations in the A subunit of the DNA gyrase (31). A second form of resistance to fluoroquinolones in S. aureus is due to a mutation (norA) in the chromosomal gene that codes for a membrane transporter effecting fluoroquinolone efflux driven by the proton gradient across the cell membrane (32). Rifampin resistance in S. aureus is encoded on the chromosomal gene for the DNA-dependent RNA polymerase and involves an alteration in the B subunit to which rifampin binds. Rifampin is not used alone to treat staphylococcal infections because of rapid emergence of resistance.
Staphylococcal infections are not ordinarily treated with aminoglycosides, but a drug in this class is sometimes combined with a penicillinase-resistant penicillin in the treatment of life-threatening infections. Plasmid-mediated aminoglycoside-modifying enzymes (phosphotransferase, adenylylating enzyme, and acetyltransferase) alter the conformation of these antibiotics and interfere with binding of the aminoglycoside to the 30S ribosomal subunit, a necessary step in aminoglycoside action (formation of an unstable initiation complex, thus blocking translation and exerting a bactericidal effect).
Resistance in staphylococci to tetracyclines is encoded on plasmids or transposons that cause synthesis of a new membrane protein that