Importance of beta-lactamase inactivation in treatment of experimental endocarditis caused by Staphylococcus aureus.
To test the hypothesis that cephalosporins resistant to beta-lactamase are preferred in the treatment of serious staphyloccal infections, the ability of four cephalosporins to eradicate bacteria from the cardiac vegetations of rabbits with experimental endocarditis was examined. Two strains of Staphylococcus aureus were chosen as pathogens: one that rapidly and completely inactivated 50 micrograms of cefazolin in vitro (beta-lactamase-positive) and another that did not inactivate any cephalosporin (beta-lactamase-negative). Rabbits with a polyethylene catheter in the left ventricle were reliably infected witih 10(5) bacteria. Similar numbers of S. aureus were recovered from the cardiac vegetations of rabbits inoculated with the beta-lactamase-positive strain after 24 hr of treatment with each of four cephalosporins. However, when the animals were treated at intervals of 6 hr for four days, significantly fewer rabbits survived after treatment with cefazolin than with cephalothin. No difference in survival was observed in the treatment of rabbits with endocarditis due to the beta-lactamase-negative strain. The failure of cefazolin in the treatment of staphylococcal endocarditis in rabbits may be due to inactivation of the drug by beta-lactamase in vivo.
D000818:Animals; D002437:Cefazolin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D002509:Cephaloridine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D002512:Cephalothin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000209:etiology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008297:Male; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013203:Staphylococcal Infections; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D002511:Cephalosporins; D001618:beta-Lactamases; D002437:Cefazolin; D002509:Cephaloridine; D002512:Cephalothin