Inactivation of Cefazolin, Cephaloridine, and Cephalothin by Methicillin-Sensitive and Methicillin-Resistant Strains of Staphylococcus aureus

Section: Resultssupporting

confidence: 91%

Characterization of four beta-lactamases produced by Staphylococcus aureus

Zygmunt

Stratton

Kernodle

1992

“…The inactivation of CZ, CF, and M by beta-lactamase produced by the strain of S. aureus was studied in vitro as described by Regamey et al (7). A flask containing HIB with 0.2 ,ug of CZ per ml (to induce beta-lactamase) and an inoculum of 108 S. aureus were incubated overnight at 370C.…”

Section: Methodsmentioning

confidence: 99%

“…Cefazolin (CZ) is much more susceptile to inactivation by Staphylococcus aureus betalactamase than cephalothin (CF) (7), raising doubts about the usefulness of CZ in staphylococcal endocarditis (2). This study compares the efficacy of CZ, CF, and methicillin (M) in the therapy of left-sided endocarditis in rabbits, caused by a highly penicillin-resistant, methicillin-susceptible strain of S. aureus, which rapidly inactivates CZ in vitro.…”

mentioning

confidence: 99%

Treatment of Experimental Staphylococcus aureus Endocarditis: Comparison of Cephalothin, Cefazolin, and Methicillin

Carrizosa

Santoro

Kaye

1978

The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactaase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and oneeighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.Cefazolin (CZ) is much more susceptile to inactivation by Staphylococcus aureus betalactamase than cephalothin (CF) (7), raising doubts about the usefulness of CZ in staphylococcal endocarditis (2). This study compares the efficacy of CZ, CF, and methicillin (M) in the therapy of left-sided endocarditis in rabbits, caused by a highly penicillin-resistant, methicillin-susceptible strain of S. aureus, which rapidly inactivates CZ in vitro. MATERIALS AND METHODSOrganism. A strain of S. aureus obtained from the blood of a patient with endocarditis was used in all experiments. The minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of CZ, CF, M, and penicillin G were determined by using an antibiotic dilution method in both heart infusion broth (HIB; Difco Laboratories, Detroit, Mich.) and pooled rabbit serum (Microbiological Associates, Inc., Bethesda, Md.). The antibiotics were diluted in twofold steps in tubes containing 0.5 ml of HIB or serum. The bacterial inoculum for each tube was 0.5 ml of a 10-2 dilution in HIB or serum of an 18-h HIB culture. The MIC was considered to be the lowest concentration of antibiotic that prevented turbidity after 24 h of incubation at 370C. After the MIC was determined, 0.01 ml of each clear tube was streaked on the surface of a sheep blood agar plate with a sterile platinum loop. The minimal bactericidal concentration was the lowest concentration of antibiotic that resulted in no growth on the plate after 48 h at 370C. Stock cultures were made by incubating the organism in HIB at 37°C for 24 h and storing 1-ml portions at -20°C. For each experiment, a portion was subcultured into HIB, incubated at 37°C for 18 h, and diluted in HIB or serum.In vitro studies. The rate at which the S. aureus was killed was studied in flasks with HIB containing CZ, CF, or M. The inoculum in HIB was added to each flask and incubated at 370...

“…for CF, 6.5 for CX, and 7.2 for CM. After 72 h the mean logio colony-forming units per ml were 5.0 for CZ, 4.1 for CF, 3.6 for CX, and 5.6 for CM.…”

mentioning

confidence: 97%

“…Cefazolin (CZ) is much more susceptible to inactivation by Staphylococcus aureus beta-lactamase (cephalosporinase) than is cephalothin (CF) (6). This has raised doubts about the usefulness of CZ in staphylococcal endocarditis (1).…”

mentioning

confidence: 99%

Treatment of Experimental Staphylococcus aureus Abscesses: Comparison of Cefazolin, Cephalothin, Cefoxitin, and Cefamandole

Kaye

Parsons

Carrizosa

et al. 1979

Cefazolin (CZ), cephalothin (CF), cefoxitin (CX), and cefamandole (CM) were evaluated in therapy of Staphylococcus aureus infection produced in perforated table tennis balls placed intraperitoneally in rabbits. Four weeks after placement of two balls in each rabbit, a beta-lactamase producing strain of S. aureus was injected into one of the balls. Twenty-four hours later therapy was initiated with 40 mg of CZ or 80 mg of CF, CX, or CM per kg intramuscularly every 6 h. After 24 h of treatment, the mean log 10 colony-forming units per ml were 7.1 for CZ, 6.7 for CF, 6.5 for CX, and 7.2 for CM. After 72 h the mean log 10 colony-forming units per ml were 5.0 for CZ, 4.1 for CF, 3.6 for CX, and 5.6 for CM. After 8 days, the titers were 1.6/ml for CZ, 1.0 for CF, 1.9 for CX, and 3.6 for CM. CZ serum levels were about double CF and CX levels and about two-thirds of CM levels. In sterile ball fluid CZ and CM levels were more than double CF or CX concentrations. Concentrations of all four antibiotics were lower in infected balls.