Correlates of Therapeutic Efficacy in Experimental Methicillin-Resistant <i>Staphylococcus aureus</i> Endocarditis

Abstract

Seventy animals with experimental aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) were randomized to receive: no therapy; pefloxacin 40 or 80 mg/kg/day i.v.; or vancomycin 30 mg/kg/day i.v. Vancomycin caused a more rapid decrease in intravegetation MRSA counts than pefloxacin at 40 or 80 mg/kg/day (p < 0.001, p < 0.05, respectively, therapy day 3). The major correlate of therapeutic efficacy in this study was the significantly higher mean intravegetation levels achieved by vancomycin (16.8 ± 6.1 μg/g) versus those attained by pefloxacin therapy at either 40 (1.6 ± 0.13 μg/g) or 80 mg/kg/day (2.8 ± 0.53 μg/g, p < 0.005, p < 0.025, respectively).

Chemoprophylactic efficacy against experimental endocarditis caused by beta-lactamase-producing, aminoglycoside-resistant enterococci is associated with prolonged serum inhibitory activity

“…The PAE duration (in hours) was defined as the difference in the time required for the antibiotic-exposed and unexposed HH22 cells to increase in counts by 1 log10 CFU/ml above the number present just after the centrifugation-washingresuspension step (1). For each antibiotic regimen tested, four separate PAE experiments were performed to generate a mean + standard error of the mean PAE.…”

Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-ResistantStaphylococcus aureus(MRSA)

“…Briefly, an indwelling transcarotid artery-to-left ventricle catheter was inserted under general anesthesia with xylazine and ketamine to induce sterile aortic vegetations. At 48 h after catheter placement, IE was induced by an iv challenge of ~ 2 x 10 5 cfu, an inoculum, which induces IE in >95% of catheterized rabbits with this strain based on extensive prior data (8,9,(16)(17)(18). One group of untreated animals (controls) were humanely sacrificed by iv pentobarbital at ~24 h postinfection, target organs sterilely removed and quantitatively cultured to establish the baseline MRSA bioburden in these tissues (vegetations; kidneys; and spleen).…”