Cefamandole-aminoglycoside therapy of experimental enterococcal endocarditis

Cephalosporin-aminoglycoside therapy of human enterococcal endocarditis has been associated with a high incidence of clinical failure. The comparative efficacy of three cephalosporin antibiotics (cefamandole, cefazolin, and cephalothin), in combination with gentamicin, was studied in a rabbit model of enterococcal endocarditis. The cefamandole-gentamicin combination produced higher rates of cure, despite the administration of comparatively lower doses. Studies of antibiotic penetration into a fibrin thrombus indicated that cefamandole penetrated the thrombus readily. The greater efficacy of the cefamandole-gentamicin combination may be related to the superior penetration of cefamandole into the fibrin-rich vegetations of endocarditis.