Journal Article

Pharmacodynamic Interactions of Antibiotics Alone and in Combination

Jerome J. Schentag, Laura C. Strenkoski-Nix, David E. Nix and Alan Forrest

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 27, issue 1, pages 40-46
Published in print July 1998 | ISSN: 1058-4838
Published online July 1998 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/514621
Pharmacodynamic Interactions of Antibiotics Alone and in Combination

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Clinical trials show that the area under the inhibitory curve (AUIC) is predictive of antibacterial killing rates in patients with nosocomial pneumonia and is useful for predicting clinical or microbiological outcomes and making dosage adjustments with β-lactams, quinolones, aminoglycosides, and vancomycin. The AUIC values of two antibiotics are additive, and since antibiotics are often given in combination, determining the AUIC for antibiotic combinations could potentially predict the microbiological outcomes for patients given these combinations. To further address this question, mathematical modeling was used to study in vitro pharmacokinetic and pharmacodynamic interactions of the antimicrobials piperacillin and ciprofloxacin. These agents were also studied in vivo in healthy volunteers. Blood samples were obtained for analysis of serum drug concentrations, and serum inhibitory titers were determined against eight common bacterial pathogens, chosen to reflect the range of MIC values to ciprofloxacin and piperacillin. Additive AUIC relationships predictive of bacterial killing rates were typical in patients given these antibiotics in combination.

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Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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