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Enterococcus Species
Historically enterococci, Streptococcus bovis, and S. equinus were grouped together as Lancefield group D streptococci. However, genomic analysis resulted in the reclassification of these organisms, and enterococci now are considered a separate genus ( Table 120.1 ). This chapter focuses on enterococci; the nonenterococcal group D streptococci are discussed in Chapter 121 .
TABLE 120.1
Clinical Significance of Enterococci and Group D Streptococci
| Species | Association With Infection in Children |
|---|---|
| Enterococcus Species | |
| Enterococcus faecalis | Relatively frequent |
| Enterococcus faecium | Infrequent but increasing |
| Other Enterococcus Species | Infrequent |
| E. durans, E. avium, E. casseliflavus, E. dispar, E. flavescens, E. gallinarum, E. hirae, E. malodoratus, E. mundtii, E. pseudoavium, E. raffinosus, E. solitorius |
|
| Non- Enterococcus Species | Infrequent |
| Streptococcus bovis | |
| Streptococcus equinus | |
Enterococci are normal inhabitants of the gastrointestinal tract, with colonization often beginning in the early weeks of life. Invasive disease is uncommon in healthy individuals but prevalent among patients who are exposed to broad-spectrum antibiotics or undergoing therapy for cancer or bone marrow transplantation.
Description of Pathogens
Enterococci are gram-positive, facultatively anaerobic bacteria that grow as diplococci or in short chains. Most isolates are nonhemolytic on sheep blood agar, although some have α-hemolytic or β-hemolytic activity. Unlike other gram-positive, catalase-negative bacteria, enterococci are able to grow at 45°C and withstand temperatures up to 60°C. Other distinguishing features include the ability to grow in bile and hydrolyze esculin, a feature not found in other streptococci of the Lancefield groups (5% of viridans streptococci and most lactococci, aerococci, pediococci, and leuconostocs share this property). Clinical laboratories often use the ability to grow on 6.5% sodium chloride as a means to distinguish enterococci from nonenterococcal group D organisms. The PYR reaction (hydrolysis of L-pyrrolidonyl-P-naphthylamide) is also a rapid means of distinguishing enterococci from S. bovis and S. equinus. S. pyogenes is the only other PYR-positive Streptococcus species and is easily distinguished from enterococci by its positive reaction with group A antiserum and susceptibility to bacitracin. Among enterococci, E. faecalis and E. faecium are the most common human pathogens and are distinguished from each other on the basis of carbohydrate fermentation ( Table 120.2 ).
TABLE 120.2
Biochemical and Growth Characteristics of Clinically Significant Enterococci and Group D Streptococci
| Enterococcus faecalis | Enterococcus faecium | Streptococcus bovis | |
|---|---|---|---|
| Bile esculin | + | + | + |
| PYR reaction | + | + | − |
| Growth in 6.5% NaCl | + | + | − |
| Sorbitol | + | − | +/− |
| Mannitol | + | + | +/− |
| Lactose | + | + | + |
| Starch | − | − | + |
NaCl, sodium chloride; PYR reaction, hydrolysis of L-pyrrolidonyl-P-naphthylamide; +, most isolates demonstrate the characteristic; +/−, occasional isolates test positive for the characteristic; −, most isolates test negative for the characteristic.
Enterococci have several important virulence factors, including adhesive factors called Esp, aggregation substance, and ACE (a collagen-binding protein). Other virulence determinants include a cytolysin and degradative enzymes, such as gelatinase, hyaluronidase, and a serine protease. Many of these virulence factors are encoded on a pathogenicity island that is more commonly found among virulent strains than commensal isolates. The propensity of E. faecalis to cause endocarditis in adults may be related to surface carbohydrates that permit avid adherence to the endothelium of heart valves. Once established on heart tissue, E. faecalis stimulates synthesis of fibrinogen, contributing to vegetation formation. Similarly, infection of the urinary tract may relate to the organism’s ability to adhere to renal epithelial cells. The E. faecalis cytolysin has lethal activity against a broad range of eukaryotic cells and contributes to virulence in experimental models of endocarditis, peritonitis, and endophthalmitis.
Antimicrobial resistance allows the persistence and proliferation of organisms in the gastrointestinal tract despite treatment with broad-spectrum antibiotics. Enterococci have a remarkable propensity to exchange genetic material, both as donor and recipient. Whole genome sequencing has revealed that up to 25% of enterococcal genetic material is composed of mobile or exogenously acquired DNA. The ability to transfer antibiotic resistance genes among species is a major concern.
Epidemiology
Enterococci are ubiquitous inhabitants of the gastrointestinal tract in humans and animals. E. faecalis is the predominant enterococcal species and is found in the feces of more than 90% of adults and nearly 50% of neonates by 1 week of age. Colonization with E. faecium is less common but appears to be increasing in frequency and is present in approximately 25% of adults. Enterococci account for a minor fraction of the microbes in the intestinal microbiota of healthy individuals but are often abundant in hospitalized patients exposed to antibiotics. Although the gastrointestinal tract is the predominant habitat of enterococci, these organisms can also be found in oral secretions and dental plaque, the upper respiratory tract, the skin, and the vagina. Enterococcal infections are generally presumed to arise from the patient’s indigenous flora. Direct spread from person to person (i.e., by droplet or fecal-oral transmission) is not considered an important means of transmission, although evidence for nosocomial transmission has been reported. ,
E. faecalis accounts for approximately 75% of pediatric enterococcal infections. E. faecium is responsible for most of the remaining enterococcal infections in children; however, infection with other species such as E. gallinarium and E. casseliflavus account for up to 10% of enterococcal infections in some children’s hospitals.
Clinical Manifestations
Most enterococcal infections occur in individuals in whom a surface physical barrier breaks down, such as in the gastrointestinal tract, the integument, or the urinary tract. Other factors associated with enterococcal infections in children are prolonged hospitalization, treatment with antibiotics, and a compromised immune system. In neonates, enterococci are commonly associated with septicemia, whereas in older children and adults these organisms are most commonly associated with bacteremia, intra-abdominal abscess, and urinary tract infection (UTI). Among hospitalized adults, enterococci account for approximately 10% of bloodstream infections (BSIs) and are associated with mortality in one third of affected patients.
Neonatal Infections
Enterococci account for up to 10% of all cases of neonatal BSI, trailing only E. coli , group B streptococci, and methicillin-susceptible Staphylococcus aureus. Neonatal enterococcal infections are most commonly caused by E. faecalis and much less commonly by E. faecium .
Two distinct syndromes of neonatal enterococcal BSI have been described. Early-onset BSI (within 7 days of birth) presents like early-onset group B streptococcal septicemia but tends to be milder. Early-onset infection occurs most often in full-term infants who are otherwise healthy. Late-onset infection (after 7 days of age) accounts for the majority of neonatal enterococcal infections. Prematurity, invasive procedures, necrotizing enterocolitis, and receipt of total parenteral nutrition are major risk factors for neonatal enterococcal infection. The symptoms of late-onset disease are more severe than those of early-onset disease and include apnea, bradycardia, and deteriorating respiratory function. Focal infections such as a scalp abscess or a catheter-related infection are also common. Mortality rates range from 6% in early-onset septicemia to 15% in late-onset infections associated with necrotizing enterocolitis. Enterococci cause approximately 5% of bacteremia episodes in previously healthy young infants who come to medical attention with a fever.
Enterococci are an occasional cause of meningitis, usually as a complication of BSI. Alternatively, enterococci can gain access to the central nervous system by means of contiguous spread, such as through a neural tube defect, a neurenteric cyst, an intrathecal injection, or a ventricular shunt placed for the management of hydrocephalus. Enterococcal meningitis can be associated with minimal abnormality of the cerebrospinal fluid.
Infections in Older Children
Enterococcal BSI is generally an infection of hospitalized children and is not limited to a particular age group. Predisposing factors include an indwelling central venous catheter, gastrointestinal disease, immunodeficiency, cardiovascular abnormalities, and hematologic malignancy. Genitourinary disease is a frequent predisposing factor in adults but is less common in children. Children with community-acquired enterococcal infection are generally younger than 1 year of age; as in adults, BSI caused by enterococci is commonly polymicrobial, probably reflecting the severity of underlying disease and the bowel as the source.
Enterococci rarely cause UTIs in healthy children but account for approximately 15% of healthcare associated UTIs in both children and adults. Placement of an indwelling urinary catheter is the major risk factor for a nosocomial UTI, and early removal of urinary catheters reduces the incidence of infection. Enterococci are often present in intra-abdominal abscesses after intestinal perforation; however, the significance of enterococci in these polymicrobial infections has been questioned because an antimicrobial regimen with poor activity against enterococci is often an effective treatment. Enterococci are frequently part of polymicrobial chronic infections in patients with neurologic deficits, pressure ischemic osteomyelitis, and soft tissue necrosis. These organisms cause up to 15% of cases of endocarditis in adults but rarely infect the heart in children.
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