Treatment of staphylococcal infection is dependent on the site involved, the severity of infection, and the antibiotic susceptibility pattern of the organism causing the infection. Although most serious staphylococcal infections are due to coagulase-positive staphylococci (Staphylococcus aureus), infections due to coagulase-negative staphylococci (e.g., Staphylococcus epidermidis) are increasing and may also be life threatening. S. aureus is a highly invasive pathogen, able to spread hematogenously to many organs, leading to metastatic foci of infection. Coagulase-negative staphylococci are generally healthcare-associated infections that require the presence of prosthetic material to gain a foothold and cause infection.

Susceptibility to antibiotics

Staphylococci have a propensity to develop resistance to antibiotics relatively quickly. Most staphylococci are no longer susceptible to the effects of penicillins alone because the bacteria produce enzymes or penicillinases that inactivate many of those drugs. One approach to the problem of antibiotic resistance in staphylococci has been the use of penicillinase-resistant penicillins, e.g., nafcillin, oxacillin, and methicillin. Alternatively, penicillins have been combined with inhibitors of penicillinase. Examples of penicillin–penicillinase-inhibitor combinations include: amoxicillin-clavulanate (Augmentin), ampicillin–sulbactam (Unasyn), piperacillin–tazobactam (Zosyn), and ticarcillin–clavulanate (Timentin). The penicillinase-resistant penicillins and penicillin–penicillinase-inhibitor combinations are effective for the treatment of penicillin-resistant, but methicillin-susceptible, staphylococci.

Other β-lactam antibiotics are also useful for the treatment of methicillin-susceptible staphylococci. First-generation cephalosporins (cefazolin, cephalexin) are the most active, followed by secondgeneration agents (cefuroxime, cefotetan, cefoxitin).