Susceptibility and synergy studies of methicillin-resistant Staphylococcus epidermidis.
Methicillin-resistant Staphylococcus epidermidis is an important cause of cerebrospinal fluid shunt infections and prosthetic valve endocarditis. Agar dilution minimum inhibitory concentrations were determined for 100 strains of methicillin-resistant S. epidermidis which were isolated from clinical specimens. Vancomycin inhibited all 100 strains at </=3.12 mug/ml, whereas clindamycin inhibited only 46 strains at </=12.5 mug/ml. Methicillin-resistant S. epidermidis strains were resistant to achievable levels of erythromycin, with 90 strains having a minimum inhibitory concentration of >/=3.12 mug/ml. Of the five cephalosporins and one cephamycin tested, cefamandole was the most active in vitro, inhibiting 97 strains at </=25 mug/ml. Antibiotic synergism was examined by a quantitative bacterial time-kill method. Synergism (>/=10(2) kill by the combination over the most effective single antibiotic at 24 h) was demonstrated with vancomycin (1.56 mug/ml) plus cefamandole (6.25 mug/ml) in 14 of 14 strains, vancomycin plus cephalothin (6.25 mug/ml) in 14 of 14 strains, vancomycin plus rifampin (0.008 to 0.012 mug/ml) in 6 of 12 strains, rifampin plus cefamandole in 9 of 12 strains, and rifampin plus cephalothin in 10 of 12 strains. The emergence of populations of bacteria resistant to 0.2 mug of rifampin per ml developed in three of five methicillin-resistant S. epidermidis strains tested. The addition of either vancomycin, cephalothin, or cefamandole to the rifampin prevented the emergence of resistance in these three strains. Clinical trials of synergistic antibiotic combination therapy for serious methicillin-resistant S. epidermidis infections are indicated.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002435:Cefamandole / Q000494:pharmacology; D002512:Cephalothin / Q000494:pharmacology; D004357:Drug Synergism; D008712:Methicillin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D012293:Rifampin / Q000494:pharmacology; D013210:Staphylococcus / Q000187:drug effects*; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002435:Cefamandole; D014640:Vancomycin; D008712:Methicillin; D002512:Cephalothin; D012293:Rifampin
Can Med Assoc J. 1965 Jul 3;93:8-16
14308909
J Infect Dis. 1975 May;131(5):543-52
1127260
J Thorac Cardiovasc Surg. 1977 Apr;73(4):625-9
839852
JAMA. 1978 Oct 27;240(18):1963-5
249793
South Med J. 1978 Nov;71(11):1353-5
251348
J Infect Dis. 1979 Apr;139(4):452-7
438546
Antimicrob Agents Chemother. 1978 Sep;14(3):353-9
708013
J Infect Dis. 1978 Mar;137(3):245-50
632623
Compr Ther. 1978 Jan;4(1):53-60
620513
J Pediatr. 1973 Feb;82(2):222-7
4265196
Lancet. 1974 Jun 8;1(7867):1155-8
4136804
J Bone Joint Surg Am. 1972 Mar;54(2):257-75
4631242
Circulation. 1973 Jun;47(6):1319-26
4709547
Nature. 1969 May 10;222(5193):533-7
4891831
Proc Natl Acad Sci U S A. 1965 Apr;53:881-9
14324547