Empiric Pharmacodynamic Performance of 9 Antimicrobials Against Pathogens Implicated in the Cause of Complicated Skin and Soft Tissue Infections A Report From the OPTAMA Program

Objective:We compared the probability of achieving bactericidal exposure for commonly used intravenous antibiotics against the pathogens causing complicated skin and soft tissue infections (cSSTIs) to assist in the decision process for initial empiric therapy. Methods: The minimum inhibitory concentration values (MICs) for methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterobacter spp., and Klebsiella spp. were collected from the 2004 MYSTIC surveillance study in US hospitals, and weighted by their prevalence in causing SSTI. Pharmacodynamic exposures were simulated in 5000 subjects receiving imipenem, meropenem, ertapenem, piperacillin-tazobactam, ceftriaxone, ceftazidime, cefepime, ciprofloxacin, and levofloxacin against these pathogens to calculate the cumulative fraction of response (CFR). Pharmacodynamic end points evaluated included fT>(MIC) for the beta-lactams and fAUC/MIC for fluoroquinolones. The prevalence of methicillin-resistant S. aureus (MRSA) was later added into the model at increasing rates to determine its overall effect on CFR. Results: Cefepime 2 g q12h, imipenem 500 mg and 1 g q8h, meropenem 500 mg and 1 g q8h, and piperacillin-tazobactam 3.375 g q6h achieved greater than 90% CFR in the absence of MRSA. Thirdgeneration cephalosporins, quinolones, and ertapenem achieved rates of only 34.8-48.9%, 55.3-75.1%, and 87.8%, respectively. No antimicrobial achieved acceptable CFR when MRSA prevalence exceeded >10% in the model. Conclusion: Due to increasing resistance rates among commonly encountered pathogens and the inability to provide optimal drug exposure, third-generation cephalosporins, fluoroquinolones, and ertapenem should be avoided for the empiric treatment of cSSTIs in place of more broad-spectrum therapy. The addition of an anti-MRSA agent is recommended when this phenotype is suspected.