Pharmacodynamic Performance of Tigecycline versus Common Intravenous Antibiotics for the Empiric Treatment of Complicated Skin and Skin Structure Infections

Background: In clinical trials tigecycline was similar to vancomycin/aztreonam for complicated skin and skin structure infections, but data comparing it with other widely used antibiotics are lacking. We predicted the pharmacodynamic cumulative fraction of response (CFR) of tigecycline against bacteria implicated in complicated skin and skin structure infections and compared it with the CFRs for piperacillin/tazobactam, ceftriaxone, levofloxacin, and imipenem/cilastatin. Methods: A 5,000-patient Monte Carlo simulation using a two-compartment intravenous infusion model was used to simulate steady-state concentrations for common dosages of these antibiotics. Population pharmacokinetics data from infected patients were employed. The CFR was calculated against Staphylococcus aureus (42% methicillin-resistant S. aureus [MRSA]), streptococci, coagulase-negative staphylococci, Escherichia coli, Enterobacter, enterococci, Proteus mirabilis, Klebsiella, and Pseudomonas aeruginosa collected from worldwide surveillance (TEST and SENTRY) and weighted by prevalence of involvement in complicated skin and skin structure infections. Results: Excluding MRSA, the weighted CFR was greatest for imipenem/cilastatin and piperacillin/tazobactam regimens (93.9%-95.9%). With 42% MRSA added to the model, only tigecycline monotherapy achieved a high CFR (88.2%). The addition of vancomycin raised the CFR to 91.0%, 89.5%, 88.3%, 82.9%, and 78% for imipenem/cilastatin 500 mg q6h, imipenem/cilastatin 500 mg q8h, piperacillin/tazobactam, levofloxacin, and ceftriaxone regimens, respectively. Conclusion: Tigecycline monotherapy had a likelihood of achieving its requisite pharmacodynamic exposure similar to that of combinations of piperacillin/tazobactam or imipenem/cilastatin plus vancomycin for the empiric treatment of complicated skin and skin structure infections.