eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Enterococcal Infection

Author: Meera Varman, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Infectious Diseases, Creighton University School of Medicine
Coauthor(s): Archana Chatterjee, MD, PhD, Professor of Pediatrics, Medical Microbiology and Immunology, and Pharmacy, Division of Pediatric Infectious Diseases, Chief of Division of Pediatric Infectious Diseases, Creighton University School of Medicine; Hospital Epidemiologist and Medical Director of Infection Control, Children's Hospital; Walid Abuhammour, MD, FAAP, Associate Professor of Pediatrics, Michigan State University; Director of Pediatric Infectious Disease, Department of Pediatrics, Hurley Medical Center
Contributor Information and Disclosures

Updated: Nov 12, 2009

Introduction

Background

The French word enterocque first was used in 1899 by Thiercelin to describe gram-positive cocci of enteric origin that formed pairs and short chains. Enterococcus species, Streptococcus bovis, and Streptococcus equines originally were grouped together as group D streptococci (Lancefield classification). However, DNA hybridization studies showed that enterococci are biologically, serologically, and genetically different from streptococci, and enterococci now are placed in a separate genus. Enterococcus is currently recognized as one of the most common causes of nosocomial infections and is becoming increasingly resistant to numerous antibiotics, including vancomycin.

Pathophysiology

The genus Enterococcus includes 17 species. Most human clinical isolates are due to either E faecalis (74-90%) or E faecium (5-16%). Occasionally, human infections can be due to Enterococcus raffinosus, Enterococcus casseliflavus, Enterococcus durans, or Enterococcus avium. Enterococci are normal flora of the gastrointestinal tract of humans and animals. They also may be found in oral secretions, the upper respiratory tract, skin, and the vagina.

Enterococci normally inhabit the bowel; thus, determining whether the microbe is a true pathogen or just happens to be associated with an illness is difficult. Enterococcus is frequently isolated from polymicrobial wounds and intra-abdominal and pelvic infections; however, whether enterococci contribute to the pathogenesis of these infections is often uncertain. Clinical trials have demonstrated that patients with such infections recover without any specific antienterococcal therapy. In animal models, injection of enterococci rarely causes peritonitis or subcutaneous infection, but synergy may be observed between enterococci and other organisms (especially anaerobes).

The pathogenesis of enterococcal infections is poorly understood, but several possible virulence factors exist. Hemolysin/bacteriocin is a plasmid-encoded protein that generally is accepted as a virulence factor. Hemolysin causes lysis of human erythrocytes, functions as a bacteriocin, and is active against other gram-positive cocci. This protein has been demonstrated to increase virulence in several animal models.

Aggregation substance is a plasmid-encoded surface protein that causes clumping or aggregation of enterococci. This substance may mediate adherence to urinary tract epithelial cells, resulting in urinary tract infection (UTI), and may promote adherence to endocardial tissue, resulting in endocarditis.

Gelatinase is an extracellular zinc endopeptidase similar to the elastase produced by Pseudomonas aeruginosa and has been found to be produced by a large percentage of Enterococcus faecalis isolates from hospitalized patients and patients with endocarditis. Enterococcus faecium may have a carbohydrate moiety that makes it resistant to phagocytosis. Enterococcus also contains lipoteichoic acid, which may cause an exaggerated host inflammatory response.

During chemotherapy, an imbalance was noted between colonization of anaerobic and aerobic bacteria in the gut. In pediatric patients with acute myeloid leukemia, chemotherapy is associated with a 10,000-fold reduction in fecal anaerobes and 100-fold increase in enterococci.¹

Frequency

United States

Enterococcal infection is the second most common cause of hospital-acquired infection in the United States. Studies have demonstrated an increased incidence of enterococcal bacteremia in the general pediatric population, from 7 cases of bacteremia per 1000 in 1986 to 48 per l000 in 1991. A 12% increase in vancomycin-resistant Enterococcus (VRE) hospital-acquired infections in the ICU was reported in 2004, with a rate of about 28%.²

International

VRE and VRE infection have increasingly become a worldwide public health threat since the condition was first recognized in the mid 1980s. Among 210 bile samples obtained from 2001-2004 from 79 adult liver transplant recipients within 30 days of transplantation, approximately 75% yielded bacterial strains, of which 36% showed enterococci.³ Among this same cohort, gram-positive organisms constituted about 78% of surgical site infections, and aminoglycoside-resistant enterococci was reported in 24%.

Mortality/Morbidity

Neonatal infections are associated with a 6% mortality rate in early onset septicemia, which rises to 15% in late-onset infections associated with necrotizing enterocolitis. In general, enterococcal sepsis is implicated in 7-50% of fatal cases.

Race

No racial predilection is noted.

Sex

No predilection is reported for either sex, although enterococcal endocarditis is more common in adult men.

Age

Adults are infected more commonly than children (excepting the neonatal period). Most of the literature regarding invasive enterococcal infections in children focuses on the neonatal period and indicates that approximately 50% of newborn infants are colonized with E faecalis by age 1 week. Older children who develop bacteremia have underlying risk factors.

Clinical

History

• Historical risk factors for acquisition of vancomycin-resistant Enterococcus (VRE) and enterococcal infections include history of the following:
  • Prolonged hospitalization
  • Long stay in ICU
  • Surgical reexploration following liver transplantation
  • Prior use of antibiotics, mainly vancomycin and cephalosporins
  • Immunocompromised state
  • Breakdown of normal physical barriers (eg, GI tract, skin, urinary tract)
  • Neurosurgical procedures and use of neurosurgical devices
• Recent surveillance by perirectal culture for VRE and nasal culture for methicillin-resistant Staphylococcus aureus (MRSA) conducted between 2002 and 2003 revealed a co-colonization rate of 2.7% in 65 of 2,440 patients in an ICU. Significant risk factors included older age, male sex, hospitalization in an ICU, and antibiotic use during previous hospitalization within a year.
• The SENTRY Antimicrobial Surveillance Program, performed between 1997-2002 to assess blood stream infections (BSIs) in the United States, Europe, and Latin America, documented that the incidence of oxacillin-resistant S aureus (39.1%) and VRE (17.7%) were highest in the United States.⁴
• In a review of 451 patients on chronic dialysis, 60 (13%) were found to be colonized with VRE associated with increased mortality of 50%, compared with 10% in noncolonized patients.⁵ This also poses challenges to infection control measures and medical care for these patients.
• In a 2-year study of 1330 ICU admissions, 638 patients were at risk for acquisition; any VRE-colonized room occupants within the previous 2 weeks and a positive room culture result were independent risk factors for the acquisition of VRE.⁶ This reinforces the necessity of thoroughly cleaning rooms prior to admitting new patients.

Physical

• Urinary tract infections: VRE is an infrequent cause of urinary tract infection (UTI) in healthy children. When an enterococcal UTI occurs in children, it is usually acquired nosocomially. Risk factors for UTIs caused by enterococci include the following:
  • Indwelling urinary catheters
  • Instrumentation of the urinary tract
  • Structural abnormalities of the urinary tract: In a retrospective review of 257 episodes of UTI over 5 years, E faecalis was identified in 5.1% (13); 9 of these patients had significant underlying anatomic abnormality.⁷
  • Bacteremia: This may be polymicrobial, probably reflecting the severity of the underlying disease. In adults, the genitourinary tract is the most common entry site for enterococcal bacteremia but is implicated much less frequently in the etiology of enterococcal bacteremia in children. However, in a study by Christie et al, urosepsis was the etiology of 12% of episodes of nosocomial enterococcal bacteremia in hospitalized children.⁸
  • BSI: BSI due to VRE is an independent predictor of mortality, and duration of hospital stay is prolonged in BSI secondary to VRE, compared with vancomycin-susceptible enterococci (VSE) (4.5 d vs <1 d). In a study of more than 2000 hematology-oncology (including transplant) patients, rectal colonization of VRE was close to 5%, of which E faecium constituted 84%.⁹ Among these patients with VRE, 29% eventually developed bacteremia. A negative predictive value as high as 99.9% for the risk of bacteremia was documented in this study.
• Endocarditis: In contrast to adults, in whom enterococci cause as many as 15% of cases of endocarditis, these organisms rarely infect the heart valves of children.
• Intra-abdominal infections: Enterococcus is often isolated from polymicrobial abdominal or pelvic abscesses. In a 1993 study by Bonadio, 5 cases of enterococcal bacteremia occurred in previously healthy infants with gastroenteritis, 6 cases were associated with bowel obstruction, and 1 case was associated with appendicitis without perforation.¹⁰
• Meningitis: Although Enterococcus rarely causes meningitis in otherwise healthy children and adults, it is known to cause meningitis and ventriculitis in children with ventriculoperitoneal (VP) shunts.
• Neonatal infections: Enterococci account for as many as 10% of cases of neonatal bacteremia and septicemia. Incidence of neonatal enterococcal septicemia increased from 0.12 per 1000 live births in 1982 to 0.8 per 1000 live births in 1986. Enterococcus may cause early onset (within 7 d of birth) or late-onset (>7 d) neonatal sepsis. Early onset sepsis caused by enterococci is milder than that caused by group B streptococcal sepsis. Most cases of enterococcal bacteremia in neonates are nosocomial. Central venous catheters, necrotizing enterocolitis, and intra-abdominal surgery are risk factors. Enterococcus may cause focal skin and soft tissue infections, meningitis, and conjunctivitis in the neonate. Most neonatal infections are caused by E faecalis.

Causes

See Pathophysiology.

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