Vancomycin-Resistant Enterococci: A Growing Threat

These days, when the subject turns to antibiotic-resistant infections, vancomycin-resistant enterococci (VRE) remains one of the pathogens that comes up most often.

The US Centers for Disease Control and Prevention (CDC) considers VRE to be a “concerning threat,” and estimates that the bug sickens some 20,000 Americans annually, causing death in roughly 1300 people per year. Not surprisingly, given these sobering figures, VRE was included on the World Health Organization’s (WHO) “priority pathogens” list, which was released initially in 2017 and crafted to push for the development of new antibiotics.

Indeed, it is understandable how infections caused by VRE garner so much attention, given the increasingly challenging management conundrum they pose. Daptomycin has been used to treat these infections, with some success, in the past; however, in recent years, investigators have identified VRE strains, particularly in patients with osteomyelitis, that are nonsusceptible to the antibiotic.

Several drug manufacturers seem to be answering the WHO’s call. Among the drugs being evaluated for VRE are:

Telavancin, a bactericidal lipoglycopeptide, has been tested against a worldwide collection of 967 gram-positive pathogens isolated from bone and joint infections. Notably, Staphylococcus aureus (66.4%) was the most common pathogen, and the investigators noted that 35.7% of the strains identified were methicillin-resistant (MRSA), yet 100% susceptible to telavancin (minimum inhibitory concentration [MIC]_50/90 of 0.03/0.06μg/mL). Overall, enterococci had telavancin MIC_50/90 at 0.12/0.25μg/mL, but the drug inhibited vancomycin-susceptible isolates at ≤0.25μg/mL.

Dalbavancin, a lipoglycopeptide antibiotic approved by the United States Food and Drug Administration (FDA) in 2015 for acute bacterial skin and skin structure infections (ABSSSIs), has been found to be active against gram-positive pathogens, including MRSA, and MICs have been reported to be “consistently <0.125 µg/ml, much lower than most other anti-MRSA agents.” The drug has an extended half-life of more than 1 week, allowing an initial dose of 1000 mg followed by 500 mg 1 week later to complete a course of therapy for ABSSSI. Against MRSA, it is 4 to 8 times more potent than vancomycin in vitro, and limited data suggest it possesses activity against MRSA with reduced susceptibility to vancomycin. Dalbavancin also possesses in vitro activity against streptococci and enterococci, although activity against VRE has yet to be confirmed.

Oritavancin, a semisynthetic lipoglycopeptide structurally related to vancomycin, has also been approved for the treatment of ABSSSIs. The drug has a unique mechanism of action (and a prolonged half-life of 200 to 300 hours) that greatly enhances its antimicrobial potency against multidrug-resistant pathogens such as VRE. Specifically, it has been suggested for use in osteomyelitis caused by VRE. A case report published in March 2018 describes a 57-year-old male patient who presented with daptomycin-nonsusceptible VRE and Pseudomonas aeruginosa femoral osteomyelitis secondary to an ongoing right hip infection following multiple surgical procedures. After unsuccessful treatment with daptomycin plus ciprofloxacin for 3 weeks, an infectious diseases specialist was consulted and oritavancin 1200 mg IV once weekly was initiated for a target duration of 6 weeks. Bone cultures obtained 6 days into treatment revealed no bacterial growth, and the patient tolerated the 6-week course of oritavancin with no adverse events. Ultimately, 9.5 months after the completion of oritavancin therapy, the patient was deemed to be infection-free and underwent completion of 2-stage hip revision. According to the investigators, he remained infection-free 5 months postoperatively.

Sadly, VREs are not going anywhere anytime soon. In fact, an analysis presented recently at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2019) in Amsterdam looked at 1521 samples from privacy curtains in 625 hospital rooms and found that 334 (22%) tested positive for multidrug-resistant organisms, the most common of which was VRE (210 cultures; 13.8%). According to the investigators, in the 210 sampling visits during which VRE was detected, 57.6% of patients were also colonized with VRE.