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Antimicrobial Agents and Chemotherapy, July 1999, p. 1747-1753, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Combinations of Vancomycin and beta -Lactams Are Synergistic against Staphylococci with Reduced Susceptibilities to Vancomycin

Michael W. Climo,1,2,* Roberto L. Patron,1 and Gordon L. Archer1,3

Departments of Medicine1 and Microbiology/Immunology,3 Medical College of Virginia Campus of Virginia Commonwealth University, and the Hunter Holmes McGuire Veterans Affairs Medical Center,2 Richmond, Virginia

Received 7 December 1998/Returned for modification 26 February 1999/Accepted 6 April 1999

Evidence of synergism between combinations of vancomycin and beta -lactam antibiotics against 59 isolates of methicillin-resistant staphylococci (Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus) for which vancomycin MICs ranged from 1 to 16 µg/ml were tested by broth microdilution checkerboard, disk diffusion, agar dilution, and time-kill antimicrobial susceptibility tests. The combination of vancomycin and oxacillin demonstrated synergy by all test methods against 30 of 59 isolates; no antagonism was seen. Synergy with vancomycin was also found by modified disk diffusion testing for ceftriaxone, ceftazidime, cefpodoxime, and amoxicillin-clavulanate but not for aztreonam. Evidence of synergy correlated directly with vancomycin MICs. The efficacy of vancomycin given alone and in combination with nafcillin was tested in the rabbit model of experimental endocarditis caused by three clinical isolates of glycopeptide-intermediate-susceptible S. aureus (GISA) (isolates HIP5827, HIP5836, and MU50). Two of the GISA isolates (isolates MU50 and HIP5836) were extremely virulent in this model, with 27 of 42 (64%) animals dying during the 3-day trial. Therapy with either vancomycin or nafcillin given as a single agent was ineffective for animals infected with HIP5827 or MU50. However, the combination of vancomycin and nafcillin resulted in a mean reduction of 4.52 log10 CFU/g of aortic valvular vegetations per g compared to the reduction for controls for animals infected with HIP5827 and a reduction of 4.15 log10 CFU/g for animals infected with MU50. Renal abscesses caused by HIP5827 were sterilized significantly better with the combination of vancomycin and nafcillin than by either treatment alone. We conclude that the combination of vancomycin and beta -lactams with antistaphylococcal activity is an effective regimen for the treatment of infections with clinical strains of staphylococci which demonstrate reduced susceptibility to glycopeptides.


* Corresponding author. Mailing address: McGuire Veterans Affairs Medical Center, 1201 Broad Rock Blvd., Section 111-C, Richmond, VA. Phone: (804) 675-5018. Fax: (804) 675-5437. E-mail: Climo.Michael{at}Richmond.va.gov or MWCLIMO{at}aol.com.


Antimicrobial Agents and Chemotherapy, July 1999, p. 1747-1753, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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