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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
-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
-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
-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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