Though not often considered as a big threat compared to Gram-negative bacteria, there are different challenges posed by Gram-positive bacteria, E. faecalis and E. faecium, Dr Jose Munita explained at the ECCMID 2019.1
E. faecalis have a high-level of resistance to aminoglycosides, though frequently remain susceptible to ampicillin and vancomycin.
E. faecium are the opposite: they have frequent resistance to ampicillin and vancomycin. Treatment of these vancomycin-resistant enterococci (VRE) infections is difficult in part because there are few therapeutic options, which leads to high mortality rates for patients with VRE. Linezolid is the only FDA approved treatment. There are other agents available for VRE. faecium, including daptomycin, tigecycline, tetracyclines, chloramphenicol, nitrofurantoin, fosfomycin, and oritavancin, though these are not FDA-approved.
To better understand VRE, researchers conducted The Vancomycin-Resistant ENterococci OUtcomes Study (VENOUS 1), a prospective observational cohort study of enterococcal bloodstream infections. Using multivariate analysis to look for factors associated with mortality, researchers found that VRE in the blood was highly associated (odds ratio 4.1; 95% confidence interval 1.06–16.63; p=0.042), along with ICU admissions, neutropenia, Pitt bacteremia, haemodialysis, and microbiological failures.
Munita advised that if the source of infection is not a pneumonia, and money is not a problem, a bactericidal regimen is likely the most effective. Daptomycin, though not FDA approved, has shown strong clinical activity against enterococci.
Based on the literature, there is less mortality with daptomycin compared to linezolid. Although uncertainties in susceptibility testing, breakpoints, and dosing remain, higher doses of daptomycin seem to have higher efficacy compared to linezolid.
For recalcitrant infections, Munita noted that β-lactams were an interesting approach for combination therapies.
“I think we need to keep tetracyclines on the table. For many patients, these drugs will still work, and I like them a lot.”