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Antimicrobial Agents and Chemotherapy, August 1999, p. 1914-1918, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Analysis of Vancomycin Population Susceptibility Profiles, Killing Activity, and Postantibiotic Effect against Vancomycin-Intermediate Staphylococcus aureus

Jeffrey R. Aeschlimann,1,2,dagger Ellie Hershberger,1,2 and Michael J. Rybak1,2,3,*

The Anti-Infective Research Laboratory, Department of Pharmacy Services, Detroit Receiving Hospital and University Health Center,1 and College of Pharmacy and Allied Health Professions2 and School of Medicine,3 Wayne State University, Detroit, Michigan 48201

Received 20 November 1998/Returned for modification 15 April 1999/Accepted 27 May 1999

Methicillin-resistant Staphylococcus aureus strains with decreased vancomycin susceptibility have been isolated from patients in the United States and Japan. The impact of decreased vancomycin susceptibility on the drug's pharmacodynamic parameters has not been addressed. We studied the activity of vancomycin against three clinical strains of vancomycin intermediate-susceptible Staphylococcus aureus (VISA) under high- and low-inoculum conditions, with stationary- and logarithmic-growth-phase kill curves, and in postantibiotic effect (PAE) experiments. We also investigated the stability of the decreased vancomycin susceptibility by using population susceptibility profiles. The respective vancomycin microdilution MICs and MBCs for VISA strains HIP5836, 14379, and Mu50 were 8 and 8, 8 and 8, and 8 and 16 µg/ml. HIP5836 had the most homogeneous elevation of vancomycin MICs, because the MIC for nearly all bacteria in the inoculum was 8 µg/ml. The population MICs (defined as the lowest vancomycin concentration inhibiting 99.9% of growth) for the first serial passages of HIP5836, Mu50, and 14379 were 8, 4, and 2 µg/ml, respectively. After 10 passages, they decreased to 4, 2, and 1 µg/ml, respectively. The Mu50 population MIC increased to 12 µg/ml after five serial passages on vancomycin agar. In the low- and high-inoculum kill curves, time to 99.9% killing was significantly (P < 0.05) longer for both Mu50 and HIP5836 than that for 14379 and a control strain. However, colony counts at 24 h were similar to those of the vancomycin-sensitive strain for all VISA strains. The PAE (at 4× MIC) ranged from 1.3 h for 14379 to 2.0 h for HIP5836 and was similar to or greater than the PAE against the vancomycin-sensitive strain. In conclusion, we found that the decreased vancomycin susceptibility increased during persistent exposures to the drug and decreased upon removal of the selective pressure. The decreased vancomycin susceptibility decreased the rate of vancomycin killing, but did not affect the extent of killing or the PAE.

* Corresponding author. Mailing address: The Anti-Infective Research Laboratory, Department of Pharmacy Services (1B), Detroit Receiving Hospital and University Health Center, 4201 St. Antoine Blvd., Detroit, MI 48201. Phone: (313) 745-4554. Fax: (313) 993-2522. E-mail: mrybak{at}dmc.org.

dagger Present address: The University of Connecticut, School of Pharmacy, Storrs, CT 06269.

Antimicrobial Agents and Chemotherapy, August 1999, p. 1914-1918, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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