Aminoglycoside avoidance in enterococci endocarditis

One of the joys of being a clinical nephrologist is convincing the infectious disease consultant to treat enterococcus endocarditis without gentamicin. The Infectious Disease Society and the American Heart Association have this table regarding treatment:

From Baddour LM, et al. Circulation 111 e394-e434; 2005

The article states that enterococci are relatively resistant to penicillin, ampicillin and vancomycin compared to streptococci. The antibiotics are bacteriostatic rather than bactericidal in these species. Adding an aminoglycoside restores the lethal activity of the Beta-lactam antibiotics. Interestingly the cell walls of enterococci are highly impermeable to the aminoglycosides and would require plasma concentrations incompatible with human tolerance but the beta-lactams increase cell wall permeability so lower doses are biologically active.

The recommendations advise 4-6 weeks of therapy with the combination beta-lactam and aminoglycoside, however it references an observational study that showed effective therapy with as little as two weeks of aminoglycoside exposure. This was a report on 5-years worth of endocardititis from Sweden. They had 93 cases of enterococcal endocarditis

• Native valve infections: 66 cases
• 54 were cured 
• median duration of beta-lactam therapy: 42 days
• median duration of aminoglycoside exposure: 16 days
• acute valvular surgery: 11
• relapse 2
• deaths 10
• Prosthetic valve endocarditis: 27 cases
• 21 were cured
• median duration of beta-lactam therapy: 42 days
• median duration of aminoglycoside exposure: 15 days
• acute valvular surgery: 8
• relapse 1
• deaths 5

This looks good to my urine stained eyes, it appears that we can comfortably get away with a shorter exposure to gentamicin, but what really caught my eye was this paragraph:

Seven patients without any aminoglycosides, all with good outcomes.

What about avoiding gentamicin altogether?

In 2007 Gavalda published a case series in the Annals of Internal Medicine. He looked at 43 patients with high-level aminoglycoside resistance (HLAR) or renal failure/high risk for renal failure without HLAR. They were treated with ampicillin 2g q4 hours and ceftriaxone 2g q12 hours.

The data was broken down as HLAR and non-HILAR

• HLAR 21 cases
• 6 deaths during treatment
• Non-HILAR 22 cases
• 6 death during treatment
• 2 relapse (one patient received the wrong dose of ceftriaxone)
•  2 death during follow-up

The most recent data comes from the same Spanish group, now with lead author Hidalgo. Published last week they reported on 159 patients treated with ampicillin-ceftriaxone (AC) and compared them to 87 treated with ampicillin-gentamicin (AG). Here are their results from the abstract:

Between AC and AG-treated E. faecalis IE patients, there were no differences in mortality while on antimicrobial treatment (22% vs 21%, P=0.81) or at 3-month follow-up (8% vs 7%, P=0.72), in treatment failure requiring a change in antimicrobials (1% vs 2%, P=0.54), or in relapses (3% vs 4%, P=0.67). However, interruption of antibiotic treatment due to adverse events was much more frequent in AG-treated patients than in those receiving AC (25% vs 1%, P<.001) Conclusions. AC appears as effective as AG for treating EFIE patients and can be used with virtually no risk of renal failure and regardless of the high-level aminoglycoside resistance (HLAR) status of E. faecalis.

I'm going to try this.