Vancomycin-resistant Enterococcus (VRE) emerged in the late 1980s and now represents 30-50% of healthcare-associated enterococcal infections in many regions. Enterococci are gram-positive cocci, normal gut commensals that became pathogens through hospital ecology and antibiotic selection pressure. Enterococcus faecium accounts for >90% of VRE clinical isolates (intrinsically more resistant); E. faecalis is less commonly resistant but more pathogenic. Resistance mechanisms involve van gene clusters: vanA (high-level resistance to both vancomycin and teicoplanin, transposon Tn1546, most clinically important), vanB (vancomycin only, variable inducibility), vanC (intrinsic in E. gallinarum/casseliflavus, low-level), vanD/E/G/L/M/N (uncommon).
Clinical syndromes: bloodstream infection (most common, often catheter-associated, mortality 30-50%), endocarditis (challenging due to limited bactericidal options), urinary tract infection, intraabdominal infection (peritonitis, abscess), surgical site infection, meningitis (rare). Risk factors: prolonged hospitalization, ICU stay, prior antibiotic exposure (especially vancomycin, cephalosporins, fluoroquinolones), severity of illness, indwelling devices, immunosuppression (transplant, hematologic malignancy), and proximity to colonized patients or contaminated environment. Asymptomatic colonization (gastrointestinal, ~10x more common than infection) is reservoir for transmission.
Treatment: linezolid (PO/IV, oxazolidinone protein synthesis inhibitor, bacteriostatic, generally first-line for non-bacteremic infections, 600 mg q12h, monitor for thrombocytopenia, peripheral/optic neuropathy with prolonged use, serotonin syndrome with SSRIs); daptomycin (lipopeptide, bactericidal, high-dose 8-12 mg/kg/day for serious infections including bacteremia and endocarditis, often combined with ceftaroline or ampicillin for synergy in E. faecium endocarditis, monitor CK for myopathy); tigecycline (bacteriostatic, not for bacteremia or UTI due to low serum/urine levels); oritavancin and dalbavancin (long-acting lipoglycopeptides); quinupristin-dalfopristin (E. faecium only, IV, infusion reactions, myalgias, requires central line); newer agents: lefamulin, omadacycline. Combination therapy considered for endocarditis and persistent bacteremia. Infection control: active surveillance cultures of high-risk patients, contact precautions for known VRE carriers, hand hygiene with alcohol-based rubs, environmental cleaning (Enterococcus survives weeks on surfaces), and antimicrobial stewardship limiting unnecessary vancomycin and broad-spectrum antibiotic use.