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Antimicrobial Agents and Chemotherapy, July 2007, p. 2582-2586, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.00939-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vancomycin In Vitro Bactericidal Activity and Its Relationship to Efficacy in Clearance of Methicillin-Resistant Staphylococcus aureus Bacteremia{triangledown}

Pamela A. Moise,1* George Sakoulas,2 Alan Forrest,3 and Jerome J. Schentag3,4

University of the Pacific School of Pharmacy and San Diego VA Medical Center, San Diego, California 92161,1 Westchester Medical Center and Division of Infectious Diseases, New York Medical College, Valhalla, New York 10595,2 SUNY Buffalo School of Pharmacy, Buffalo, New York 14260,3 CPL Associates, LLC, Buffalo, New York 142264

Received 29 July 2006/ Returned for modification 13 October 2006/ Accepted 12 April 2007

We examined the relationship between the time to clearance of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia while patients were receiving vancomycin therapy and the in vitro bactericidal activity of vancomycin. Vancomycin killing assays were performed with 34 MRSA bloodstream isolates (17 accessory gene regulator group II [agr-II] and 17 non-agr-II isolates) from 34 different patients with MRSA bacteremia for whom clinical and microbiological outcomes data were available. Vancomycin doses were prospectively adjusted to achieve peak plasma concentrations of 28 to 32 µg/ml and trough concentrations of 8 to 12 µg/ml. Bactericidal assays were performed over 24 h with ~107 to 108 CFU/ml in broth containing 16 µg/ml vancomycin. The median time to clearance of bacteremia was 6.5 days for patients with MRSA isolates demonstrating ≥2.5 reductions in log10 CFU/ml at 24 h and >10.5 days for patients with MRSA isolates demonstrating <2.5 log10 CFU/ml by 24 h (P = 0.025). The median time to clearance was significantly longer with MRSA isolates with vancomycin MICs of 2.0 µg/ml compared to that with MRSA isolates with MICs of ≤1.0 µg/ml (P = 0.019). The bacteremia caused by MRSA isolates with absent or severely reduced delta-hemolysin expression was of a longer duration of bacteremia (10 days and 6.5 days, respectively; P = 0.27) and had a decreased probability of eradication (44% and 78%, respectively; P = 0.086). We conclude that strain-specific microbiological features of MRSA, such as increased vancomycin MICs and decreased killing by vancomycin, appear to be predictive of prolonged MRSA bacteremia while patients are receiving vancomycin therapy. Prolonged bacteremia and decreased delta-hemolysin expression may also be related. Evaluation of these properties may be useful in the consideration of antimicrobial therapies that can be used as alternatives to vancomycin for the treatment of MRSA bacteremia.

* Corresponding author. Mailing address: San Diego VA Medical Center (119), 3350 La Jolla Village Drive, San Diego, CA 92161. Phone: (858) 583-1392. Fax: (858) 552-7582. E-mail: p_moise{at}yahoo.com

{triangledown} Published ahead of print on 23 April 2007.

Antimicrobial Agents and Chemotherapy, July 2007, p. 2582-2586, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.00939-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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