Dwight A. Powell
Historically classified as group D streptococci, enterococci are now classified as a separate genus with at least 35 different species.
Only two species, Enterococcus faecalis and Enterococcus faecium, account for all but a rare case of human disease. E faecalis is responsible for about 80% to 90% of human cases, but several studies show a rising proportion of cases due to E faecium. Enterococci are facultatively anaerobic oxidase- and catalase-positive gram-positive cocci that normally inhabit the bowel These very hardy organisms remain viable for weeks on environmental surfaces such as bed rails, sinks, faucets, and doorknobs. Human-to-human spread is common in hospital settings.
Enterococci are generally not highly invasive pathogens and are typically classified as opportunists. Infections are most often associated with prolonged hospitalization particularly in intensive care or hematology/oncology units; use of broad-spectrum antibiotics; indwelling lines; immunocompromised state; or loss of integrity of the gastrointestinal tract, urinary tract, or skin.1
The three most common types of infection associated with enterococci are urinary tract infection (UTI), polymicrobial abdominal infections, and bacteremia or sepsis. Although infrequent, cases of focal organ infection, such as endocarditis, meningitis, and wound infections, may be severe. UTI caused by enterococci are most often associated with indwelling urinary catheters and account for approximately 15% of nosocomial UTIs in children.
Enterococci may be involved in intra-abdominal polymicrobial infections following intestinal perforation such as ruptured appendix or necrotizing enterocolitis. Although there has been controversy regarding the pathogenic role of enterococci in such infections, most authorities recommend adding an antibiotic to cover for enterococci in such infections.3 Enterococcal bacteremia or sepsis in children may not be identified with a specific focus, but common risk factors are use of broad-spectrum antibiotics or intravascular catheters in association with underlying conditions such as surgery, immunosuppression, transplants, or major organ dysfunction.4 Bacteremia without a focal infection may result in a self-limited illness or a severe and life-threatening illness, particularly in newborns or children with underlying disease. Bacteremia is often polymicrobial with other enteric microorganisms. Mortality occurs in up to 25% of cases, but is hard to separate from the underlying health problems.
In newborns, infection may present as early onset sepsis in the first several days of life, similar to early onset group B streptococcal sepsis. However, most neonatal enterococcal infections are nosocomial and occur after the second week of life, typically in the setting of bacteremia attributable to line infection or necrotizing enterocolitis.5,6
Enterococci are easily isolated on standard bacterial culture plates or broth media. They are distinguished from nonenterococcal, catalase-negative, gram-positive cocci by the PYR reaction (hydrolysis of L-pyrrolidinyl-β-naphthylamide), the ability to hydrolyze esculin in the presence of 41% bile salts, and growth in 6.5% NaCl at 10°C to 45°C.
The most important aspect of treating enterococcal infections is determination of antibiotic susceptibility.7 Enterococci have an intrinsic resistance to cephalosporins, monobactams, antistaphylococcal penicillins, clindamycin, and aminoglycosides. For penicillin-susceptible strains, ampicillin is considered more active than penicillin.
In beta-lactam–susceptible enterococci, the combination of ampicillin or penicillin and an aminoglycoside improves aminoglycoside uptake and results in synergistic activity. However, synergy is not possible with high-grade resistant enterococci (minimal inhibitory concentration >2000 mcg/ml).
Resistance to the glycopeptide antibiotics, vancomycin and teicoplanin, is mediated by the production of novel peptidoglycan, with decreased affinity for glycopeptides. This alters the ability of vancomycin and teicoplanin to inhibit cell wall formation. Resistance is transferred by gene clusters Van A, B, C, D, F, and G, carried in transposon 1546. Although the gene clusters vary in the degree of resistance to vancomycin or teicoplanin, for practical clinical purposes they are grouped as vancomycin-resistant enterococci (VRE).8-10
Most enterococci are susceptible to linezolid, the first of a new class of synthetic antibiotics called oxazolidinones. However, there are now reports in the United States and Europe of linezolid-resistant enterococci.11
Ampicillin alone is the antibiotic of choice for UTIs with susceptible enterococci (about 98% of E faecalis and 15% of E faecium). Serious infections such as meningitis, sepsis, and endocarditis must be treated with the addition of an aminoglycoside. For ampicillin-resistant enterococci, vancomycin is the antibiotic of choice. However, vancomycin-resistant strains of enterococci (VRE) are increasing at an alarming rate. The National Nosocomial Surveillance Network Database—USA reported a vancomycin resistance rate of 28.5% among enterococci causing hospital-associated infections in intensive care units in 2004. Some E faecalis VRE retain ampicillin susceptibility, whereas most E faecium VRE do not.1
If linezolid resistance is confirmed in a VRE E faecium strain, it is most likely to remain susceptible to quinupristin-dalfopristin, a combined streptogramin antibiotic (safety and efficacy has not been established in children younger than 16 years). Unfortunately, quinupristin-dalfopristin is not active against E faecalis.
Prevention of further spread of VRE will depend on appropriate control measures such as active surveillance for VRE in intensive care settings, contact isolation to minimize person-to-person transmission, and restriction of the use of vancomycin and other broad-spectrum antibiotics.13,14