What are the treatment options for enterococcal prosthetic valve endocarditis (PVE)?

Updated: Jan 03, 2019
  • Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
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Enterococcal PVE generally responds as well as disease involving native valves. Six weeks of treatment is recommended for patients with symptoms of enterococcal IE of more than 3 months’ duration, with relapsed infection, or with PVE.

A combination of an inhibitor of cell wall synthesis (ie, penicillin, vancomycin) with an aminoglycoside (ie, gentamicin, streptomycin) is necessary to achieve bactericidal activity against the enterococci. Tobramycin or amikacin does not act synergistically with antibiotics active against the bacterial cell wall.

Increasing numbers of enterococci have aminoglycoside-inactivating enzymes that make them relatively resistant to the usual synergistic combinations. These aminoglycoside-resistant strains have an MIC of 2000 mcg/mL or more for streptomycin and 500 mcg/mL or more for gentamicin. Of gentamicin-resistant enterococcal strains, 25% are susceptible to streptomycin.

Continuously infused ampicillin (serum level of 16 mcg/mL) is probably the best therapy for aminoglycoside-resistant enterococci. Alternative choices are imipenem, ciprofloxacin, or ampicillin with sulbactam. Vancomycin does not appear to be as useful as the aforementioned antibiotics.

Enterococcus faecalis may become resistant to the penicillins because of their production of beta-lactamases. These strains can be treated with ampicillin combined with sulbactam or with vancomycin combined with gentamicin.

Double beta-lactam therapy (ampicillin 2 g IV every 4 hours and ceftriaxone 2 g IV every 12 hours) is recommended for treatment of enterococci susceptible to penicillin and gentamicin when the creatinine clearance is less than 50 mL/min. This combination may be effective against enterococcal isolates that are resistant to high doses of gentamicin.

High peak levels of gentamicin are not necessary to establish synergistic bactericidal activity against enterococci. Peak gentamicin levels of 3-5 mcg/mL, with a trough of less than 2 mcg/mL, frequently can be obtained with a dose of gentamicin of 1 mg/kg IV every 8 hours. Once-a-day gentamicin dosing should not be used because a prolonged postantibiotic effect against gram-positive organisms does not occur, and synergistic killing requires the simultaneous presence of an agent active in the cell wall and an aminoglycoside.

A study indicates that gentamicin usage, even for synergy, is associated with decreasing renal function. However, overall mortality does not appear to be increased. Certainly, gentamicin therapy should be continued to achieve synergy against enterococci, but the practice of administering gentamicin for 5 days in the treatment of S aureus IV drug abuse (IVDA) IE should be questioned.

Vancomycin-resistant isolates of Enterococcus faecium and Enterococcus faecalis (ie, vancomycin-resistant enterococci [VRE]) produce some of the most challenging nosocomial infections. Presently, no therapy has been proven highly effective for IE caused by strains of VRE.

Quinupristin/dalfopristin (ie, Synercid) may suppress E faecium bacteremia but frequently is not bactericidal. Other options for therapy include linezolid, a combination of ampicillin and imipenem, and chloramphenicol. In one small series, the combination of ampicillin and ceftriaxone was found to be useful against VRE. Often, the valve must be replaced to achieve a cure.

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