Enterococcus (VRE)

Vancomycin-resistant enterococci (VRE) are increasingly common, particularly in high-level tertiary care hospitals. Difficulties in antibiotic killing and immunocompromising medical conditions of many VRE patients make these infections some of the most challenging to treat. Robust clinical trial data for optimal VRE therapy are lacking, and clinical decision-making is frequently based on published small case series, data from animal models of infection, or simple in vitro studies.

The Pathogen

Enterococcus species are Gram-positive cocci whose close resemblance to streptococci had them initially categorized in that genus. E. faecalis and E. faecium are the most common species that infect humans, with E. faecium being more antibiotic-resistant and less virulent than E. faecalis. Enterococci can persist even under antibiotic selection pressure, allowing them to acquire additional genetic elements encoding virulence and antibiotic resistance. Virulence in E. faecalis involves adherence to host tissues and host immune modulation. 

VRE Infections

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Due to their colonization of the gut, enterococci are frequent causes of urinary tract infections (UTI). In complicated patients with anatomic abnormalities, indwelling catheters, or immunosuppressed hosts, enterococcis are the 2nd leading UTI agent. VRE become enriched in antibiotic exposed patients, causing UTI, complicated intra-abdominal infections such as tertiary peritonitis and necrotizing pancreatitis. In patients with community-onset Enterococccus bacteremia, the probability of bacterial endocarditis is quite high. Overall, enterococci are the 3rd most common causes of endocarditis behind Staphylococcus aureus and viridans streptococci, necessitating prolonged combination drug therapy.

VRE Antibiotic Resistance

E. faecalis is typically 10-100 times less susceptible to penicillin than most streptococci, while E. faecium is at least 4-16 times less susceptible than E. faecalis. First identified in the mid-1980s, VRE are a major problem in tertiary hospitals around the world, with >90% of strains being E. faecium. The vanA and vanB operons modify the peptidoglycan target of vancomycin, markedly decreasing its binding affinity.  Transfer of vanA from VRE to MRSA has occurred in several cases. 

 

New Drug Combo for VRE 

CHARM investigators found that oritavancin plus ampicillin continuous infusion combination therapy could successfully treat a deep spine VRE infection associated with hardware. Checkerboard and time-kill assays confirmed synergy between these two antibiotics, and synergies of oritavancin and ampicillin with endogenous human antimicrobial peptide cathelicidin LL-37 were also demonstrated.  

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