Coagulase-negative staphylococci are natural inhabitants of human skin, but virtually all infections (except native endocarditis and infections of peritoneal dialysis catheters) are acquired in the hospital.

Colonization of patients precedes infection, and patients and hospital personnel are the reservoir of potential pathogens.

Potential sites of colonization with resistant S. epidermidis are not as widespread as for S. aureus, but colonization of the intestine has been documented.

Hospital-acquired isolates of S. epidermidis are invariably resistant to multiple antibiotics by plasmid-mediated mechanisms, although conjugative resistance was believed to be a factor in the rapid increase in resistance observed during the 1980s.

More than 70% of isolates in the United States are now resistant to methicillin.

Most strains of S. epidermidis are also resistant to chloramphenicol, clindamycin, macrolides, and tetracyclines.

In addition to dependable vancomycin therapy, many S. epidermidis strains remain susceptible to rifampacin and ciprofloxacin, although resistance to both agents can develop rapidly.

Resistance to vancomycin has been confirmed for Staphylococcus haemolyticus.