Vancomycin Resistant Enterococci Pharmacotherapy

Vancomycin-resistant enterococci (VRE) are enterococci, mainly Enterococcus faecium, with acquired vanA or vanB gene clusters that replace the terminal D-alanyl-D-alanine of peptidoglycan precursors with D-alanyl-D-lactate (vanA, high-level resistance to vancomycin and teicoplanin) or D-alanyl-D-serine (vanB, vancomycin resistance but teicoplanin susceptibility in some). Most E. faecium also resist ampicillin through PBP5 changes. E. faecalis is usually ampicillin-susceptible and remains treatable with ampicillin.

Epidemiology and risk. Gut colonisation precedes infection, promoted by vancomycin, cephalosporins and anaerobe-active antibiotics. Infection occurs in intensive care, haematology, transplant, renal and abdominal surgery patients. Colonisation is not treated.

Treatment principles. Treat only true infection. Remove infected devices and drain collections. Choose agents by site, not by in-vitro susceptibility alone.

• Linezolid: bacteriostatic, active against vanA and vanB strains; first-line oral and IV option for most sites; limited by marrow, neuropathy and serotonergic toxicity.
• Daptomycin: bactericidal, used at high dose (10 to 12 mg/kg); not for pneumonia.
• Tedizolid: potentially fewer marrow effects; limited data.
• Oritavancin and telavancin: variable activity against vanA strains; limited experience.
• Tigecycline, eravacycline: active in vitro; for intra-abdominal infection, not bacteraemia.
• Quinupristin-dalfopristin: active against E. faecium only.
• Urinary agents: nitrofurantoin and fosfomycin for cystitis.
• Ampicillin: for ampicillin-susceptible VRE E. faecalis.

Adult regimens (normal renal function).

• Bacteraemia: linezolid 600 mg IV or orally every 12 hours, or daptomycin 10 to 12 mg/kg IV once daily. Duration depends on source: 7 to 14 days for catheter-related or abdominal sources once the focus is removed.
• Endocarditis: daptomycin 10 to 12 mg/kg once daily, often with ampicillin (if the strain has ampicillin MIC low) or ceftaroline, or linezolid 600 mg every 12 hours; treatment for 6 weeks, with specialist direction and surgical review.
• Intra-abdominal or pelvic infection: linezolid 600 mg every 12 hours or tigecycline 100 mg then 50 mg every 12 hours (with attention to its limitations).
• Urinary infection: nitrofurantoin 100 mg modified-release every 12 hours for cystitis, or fosfomycin 3 g as a single dose; for pyelonephritis, linezolid or daptomycin.
• Meningitis: linezolid 600 mg every 12 hours, with source removal.
• Children: linezolid 10 mg/kg every 8 hours under 12 years; daptomycin weight-based specialist dosing.

Selection. Choose linezolid when oral therapy is possible and marrow function is adequate; choose daptomycin for endovascular infection or when the patient has serotonergic drugs, thrombocytopenia or long therapy planned. Avoid tigecycline as sole therapy for bacteraemia.

Principal risks. Linezolid thrombocytopenia (from days 10 to 14), neuropathy, lactic acidosis and serotonin syndrome; daptomycin myopathy and eosinophilic pneumonia; tigecycline nausea, pancreatitis and mortality signal; C. difficile infection with all.

Monitoring. Full blood count weekly (twice weekly with renal impairment); creatine kinase weekly for daptomycin; repeat blood cultures and echocardiography; drug levels where available.

Infection control. Contact precautions, dedicated equipment, screening in high-risk units, hand hygiene, environmental cleaning, and reduction of vancomycin and cephalosporin use.

Special groups. Pregnancy and breastfeeding: avoid linezolid unless there is no alternative. Renal impairment: daptomycin every 48 hours at creatinine clearance under 30 mL/min; linezolid unchanged. Region: availability of linezolid and daptomycin is limited in East Africa, and VRE detection depends on laboratory capacity; where VRE is suspected, discuss with microbiology and infection control.

Referral and escalation. Infectious diseases consultation for all VRE bacteraemia and endocarditis.