Department of Microbiology The University of Hong Kong Lunch Seminar “Optimizing the Clinical Management of Nosocomial Infections – a Pharmacokinetic/ Pharmacodynamic Perspective” By Prof. William Craig, MD Professor of Medicine & Pharmaceutics, University of Wisconsin, USA Chairman: Dr. P. L. Ho, Dept. of Microbiology, HKU Date: 18 Nov. 05 (Friday) Time: 12:00 – 13:00 13:00 – 13:45 13:45 – 14:00 Venue: Rm. 4, G/F, University Pathology Building, Queen Mary Hospital (To see the location map, click here) Lunch Lecture Q&A All are welcome Enquires: [email protected] Click here for PubMed publication by the speaker Optimizing the Clinical Management of Nosocomial Infections: a PK/PD Perspective Professor William A. Craig, MD, University of Wisconsin, Madison, WI 53711 Abstract PK/PD is interested in the relationship between a drug’s pharmacokinetics and its antimicrobial effect. To improve antimicrobial efficacy in nosocomial infections PK/PD has focused on providing optimal empiric dosing regimens for a variety of different antimicrobials. For beta-lactams, time above MIC is the important PK/PD indice. For gram-negative bacilli, one needs to exceed the MIC for at least 50% of the dosing interval to obtain efficacy in bacteremia and severe pneumonia with penicillins and cephalosporins. Carbapenems appear to require less time above MIC for efficacy. Longer infusions for beta-lactams with faster half-lives can enhance the duration of time serum levels exceed the MIC of less susceptible strains. For fluoroquinolones AUC/MIC ratios of 87-125 have been associated with improved outcome against gram-negative bacillary infections. High AUC/MIC values can also reduce the emergence of resistance during therapy. Fluoroquinolones can vary in their ability to reach these PK/PD goals. PK/PD indices with magnitudes less than those cited above have been associated with a reduced rate of bacterial eradication, a reduced clinical outcome, or the emergence of resistant mutants. For aminoglycosides, peak/MIC ratios of 8 or greater are associated with more rapid response and improved outcomes. Once-daily dosing of aminoglycosides enhance their ability to obtain high peak levels and also delays the onset of any nephrotoxicity. AUC/MIC ratios are also important for linezolid and vancomycin. Values greater than 100 for linezolid are associated with improved outcome in staphylococcal infections. Studies in animal models suggest that efficacy with use of vancomycin could be enhanced by higher doses than currently used. Application of PK/PD principles combined with shorter courses of therapy should be able to assist in optimizing antimicrobial therapy for nosocomial infections and helping to control the rate of increasing drug resistance. Sponsored by: Daiichi Pharmaceutical Co. Ltd. Hong Kong Medical Supplies Ltd.