Antibiotic Treatment of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus epidermidis

• Published in: The Journal of infectious diseases Vol. 170; no. 1; pp. 100 - 109
• Main Authors: Entenza, José M., Fluckiger, Ursula, Glauser, Michel P., Moreillon, Philippe
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.07.1994; University of Chicago Press
• Subjects: Amoxicillin - therapeutic use; Animals; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria; Biological and medical sciences; Clavulanic Acid; Clavulanic Acids - therapeutic use; Drug Therapy, Combination - therapeutic use; Endocarditis; Endocarditis - drug therapy; Endocarditis - microbiology; Female; Humans; Infections; Inoculum; Kinetics; Major Articles; Medical sciences; Medical treatment; Methicillin Resistance; Pharmacology. Drug treatments; Phenotype; Rats; Rats, Wistar; Spleen; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus epidermidis - drug effects; Vancomycin - therapeutic use; Vegetation; Rat; Treatment efficiency; Rodentia; Cardiovascular disease; Infection; Penicillin derivatives; Vertebrata; Antibiotic; Chemotherapy; Experimental disease; Mammalia; Staphylococcus epidermidis; Glycopeptide; Polypeptide; Heart disease; Animal; Endocardial disease; Endocarditis; Bacteriosis; Bacteria; Micrococcales; Micrococcaceae; Antibacterial agent; Staphylococcal infection
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/170.1.100

The natural history and treatment of experimental endocarditis due to heterogeneous and homogeneous methicillin-resistant Staphylococcus epidermidis was investigated. Amoxicillin/clavulanate or vancomycin were administered for 3 days via a computerized pump to mimic human drug kinetics in animals. After challenge with the minimum inoculum producing 90% of infections (ID90) , bacteria in the vegetations grew logarithmically for 16 h. Then, bacterial densities stabilized (at ∼108 cfu/g) and growth rates sharply declined. Both regimens cured ⩾60% of endocarditis (due to heterogeneous or homogeneous bacteria) when started 12–16 h after infection, although the bacterial densities in the vegetations had increased by 20 times in between. In contrast, treatment started after 24 h failed in most animals, while bacterial densities had not increased any more. Thus, while both regimens were equivalent, the therapeutic outcome was best predicted by growth rates in the vegetations, not by bacterial densities. These observations highlight the importance of phenotypic tolerance developing in vivo.