TREATMENT OF EXPERIMENTAL ENDOCARDITIS CAUSED BY MULTIDRUG-RESISTANT ENTEROCOCCUS-FAECIUM WITH RAMOPLANIN AND PENICILLIN

Antibiotic resistant strains of enterococci are being isolated with in creasing frequency. Effective treatment of infections caused by Entero coccus faecium resistant to ampicillin, vancomycin and aminoglycosides has not been established. We studied the activity of ramoplanin, a ne w lipoglycopeptide antibiotic, against two strains of multidrug resist ant E. faecium. In time kill studies, ramoplanin was bactericidal agai nst both strains, but not in the presence of 50% serum. The combinatio n of ramoplanin and penicillin was bactericidal even in the presence o f serum. In rabbits with experimental endocarditis neither penicillin nor ramoplanin significantly reduced vegetation colony counts when giv en alone, although ramoplanin significantly reduced spleen and kidney bacterial counts of both strains. The combination of ramoplanin plus p enicillin resulted in a significant reduction of vegetation bacterial counts (-3.2 and -3.7 log(10) cfu/g for strains VA3 and MMC3, respecti vely, P < 0.01). All spleen cultures and 9 out of 10 kidney cultures f rom each strain were sterile following combination therapy. While ramo planin will not be available for parenteral therapy, further research into the development of other lipoglycopeptide antibiotics is warrante d.