Single-Dose Oral Amoxicillin or Linezolid for Prophylaxis of Experimental Endocarditis Due to Vancomycin-Susceptible and Vancomycin-Resistant Enterococcus faecalis

Abstract

Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the UnitedStates and 3 g in the United Kingdom) in moderate-risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin-resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resistant and/or aminoglycoside-resistant isolates. The present study tested oral linezolid as an alternative. Rats with catheterinduced aortic vegetations were given prophylaxis simulating human pharmacokinetics of oral amoxicillin (2-to 3-g single dose), oral linezolid (600 mg, single or multiple oral doses every 12 h), or intravenous vancomycin (1-g single dose). Rats were then inoculated with the minimum inoculum infecting 90% of the animals (90% infective dose [ID 90 ]) or with 10 times the ID 90 of the vancomycin-susceptible E. faecalis strain JH2-2 or the vancomycin-resistant (VanA phenotype) E. faecalis strain UCN41. Amoxicillin was also tested with two additional vancomycin-susceptible E. faecalis strains, 309 and 1209. Animals were sacrificed 3 days later. All the tested bacteria were susceptible to amoxicillin and gentamicin. Single-dose amoxicillin provided 100% protection against all four isolates at both the ID 90 and 10 times the ID 90 . In contrast, linezolid required up to four consecutive doses to provide full protection against the vancomycinresistant isolate. Vancomycin protected only against the vancomycin-susceptible strain. The high efficacy of single-dose oral amoxicillin suggests that this regimen could be used for prophylaxis in both moderaterisk and high-risk patients without additional aminoglycosides. Linezolid appears to be less reliable, at least against the vancomycin-resistant strain.

Methicillin-Resistant Staphylococcus aureus Prosthetic Valve Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management

“…PVE occurs in 1% to 6% of patients after prosthetic valve placement (63), accompanied by an incidence of 0.3% to 1.2% per patient year (6,(64)(65)(66) and accounting for 16% to 31% of IE cases in several studies (1,6,(67)(68)(69)(70). The etiology of 146 early-PVE clinical cases and 140 late-PVE cases was summarized from 17 published reports (32).…”

Impact of AHA’s 2007 guideline change on incidence of infective endocarditis in infants and children

“…[3][4][5][6][7] Despite relatively robust evidence on which the AHA based the guideline change, concerns have arisen that the change might potentially lead to increased incidence of IE, or worse prognosis in the event of infection. [8][9][10] Several studies evaluated guideline change impact on disease incidence in adults. [11][12][13][14][15] Pasquali et al 16 analyzed the impact on the pediatric population in the U.S., but given that the database was limited to children's hospitals in the U.S., their results failed to provide nationally-representative evidence.…”

Dose Optimization of Combined Linezolid and Fosfomycin against Enterococcus by Using an In Vitro Pharmacokinetic/Pharmacodynamic Model

“…In a rabbit endocarditis model, the administration of 10 mg/kg/12 h in simulated humans revealed only a 2 log 10 CFU/mL decrease in colony count even after 4 d ( 36 ). In contrast, in rat peritonitis simulating standard dose administration, linezolid was bactericidal and bacteriostatic against vancomycin-resistant Enterococcus , and the bactericidal effect in vivo may be caused by the synergistic effects of linezolid with intrinsic host defenses (polymorphonuclear leukocytes [PMNs]) or molecules (e.g., host defense peptides and antibodies) in vivo ( 37 ). Because standard dosing in critically ill patients still shows failure, the issue of whether to change the dose of linezolid is still being discussed.…”