Importance of understanding pharmacokinetic/pharmacodynamic principles in the emergence of resistances, including community-associated Staphylococcus aureus

Thomas R Fritsche, Ronald N Jones
Journal of Drugs in Dermatology: JDD 2005, 4 (6 Suppl): s4-8
Pharmacologic parameters have been defined to predict efficacy in antimicrobial selection for the treatment of uncomplicated skin and skin structure infections (uSSSIs). Pharmacokinetics (PK) and pharmacodynamics (PD) are the bases for describing the in vivo behavior of antimicrobial agents. T>MIC is the duration of time that a pathogen is exposed to concentrations of antimicrobial agents that exceed the MIC of that particular organism. For antimicrobials with time-dependent activity (eg, penicillin and cephalosporins), the T>MIC needed to eradicate bacteria is generally 40% to 50% of the dosing interval. The most frequently prescribed oral antimicrobials for uSSSI are oral cephalosporins, amoxicillin/clavulanic acid, macrolides, anti-staphylococcal penicillins, and fluoroquinolones. The selected oral agent should display a broad spectrum of antimicrobial coverage, be able to be dosed once, or at most twice, a day, and show high levels of target attainment (> or = 90%) for eradicating the key pathogens associated with uSSSI. The recent emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting (CA-MRSA) is especially troublesome in that oral cephalosporins (and all other beta-lactam agents) are contraindicated, requiring alternative therapeutic approaches. While a common cause of cutaneous disease, including abscess formation, CA-MRSA has caused life-threatening necrotizing fasciitis and pneumonia. Treatment of abscesses produced by this pathogen consists of incision and drainage followed by an appropriate oral antimicrobial, based upon knowledge on the local resistance prevalence rates or as directed by culture and susceptibility testing.

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