Oral β-lactams applied to uncomplicated infections of skin and skin structures

Abstract

Uncomplicated skin and skin structure infections (uSSSIs) include impetigo, erysipelas, folliculitis, simple abscesses, and cellulitis. Their common bacterial causative agents include Staphylococcus aureus and Streptococcus pyogenes. Current guidelines predate the widespread occurrences of methicillin-resistant S. aureus (MRSA) as a community-acquired pathogen and include dicloxacillin, cephalexin, erythromycin, clindamycin, and amoxicillin/clavulanic acid, all orally, or mupirocin ointment applied topically, for impetigo. For other uSSSI, recommendations are based on the probability of the infection being caused by MRSA. If methicillin-susceptible S. aureus (MSSA) are known or suspected, the oral agents recommended include clindamycin, dicloxacillin, cephalexin, doxycycline, minocycline, and trimethoprim–sulfamethoxazole (SXT). For MRSA, recommended oral agents are linezolid, clindamycin, doxycycline, minocycline, and SXT. Because community-acquired MRSA infections now predominate in patients with abscesses in the United States, agents recommended for MRSA should be used for this indication. Local susceptibility patterns should guide empiric therapy. However, no placebo-controlled trials of uSSSI are available, and the evidence used to generate these recommendations is based on comparative noninferiority studies, often with wide noninferiority margins and confidence intervals. The evidence used in developing current guidelines therefore has significant limitations. Further studies, such as superiority outcome studies, placebo-controlled studies, measurement of time to resolution, or other novel approaches, are needed to resolve these treatment dilemmas. Until such studies are performed, the best surrogate available for predicting clinical outcome is application of pharmacokinetic and pharmacodynamic principles; these describe in vivo drug behavior and allow determination of susceptibility breakpoints for predicting in vivo antimicrobial efficacy via attainment of antimicrobial targets.