Clinical significance of enterococci

Enterococcal pathogenicity was initially addressed at the end of the 19^th  century by MacCallum and Hastings, who isolated an organism from a case of acute endocarditis, and designated it Micrococcus zymogenes based on its fermentative properties. The organism was shown to be resistant to dessication, heating to 60°C, and several antiseptics, including carbolic acid and chloroform. It was also found to be lethal when injected intraperitoneally in white mice, and capable of producing endocarditis in a canine model.

For a long time, enterococci were thought to be unimportant from a medical point of view. Over the past two decades, enterococci have been identified with increasing frequency as agents of nosocomial infections. At the same time, there has been a corresponding accretion of antimicrobial resistance to most currently approved agents. As a result, enterococci have emerged as one of the leading clinical challenges when identified as the cause of serious or life-threatening infections. In humans, about 90% of the enterococcal infections are caused by E. faecalis and the remaining 10% by E. faecium. A century later, enterococci are prominent among nosocomial pathogens, ranking second only to Escherechia coli in total nosocomial infections, accounting for more than 12% of all cases.

Nosocomial infections are infections that patients acquire in a health-care institution. These infections can be caused by transmission of the bacterium from patient to patient or from the health care worker to the patient. Nosocomial infections with enterococci are frequently seen in critically ill patients at intensive care units, for example in liver transplant patients, which are often considered especially vulnerable to enterococcal infections. The problem of nosocomial enterococcal infection is compounded by emerging antibiotic resistance. Enterococci have a limited potential for causing disease as they lack potent toxins and other significant virulence factors. Despite this fact, they can cause bacteraemia, surgical wound infections, urinary tract infections and endocarditis. Infections caused by the genus Enterococcus (most notably E. faecalis, which accounts for ~80% of all infections) include urinary tract infections, bacteremia, intra-abdominal infections, and endocarditis.

Since the late 1980s, enterococci, and mainly E. faecium, have emerged as important nosocomial pathogens with the ability to acquire resistance to almost all known classes of antibiotics. In a point-prevalence study on nosocomial urinary tract infection in 228 European hospitals during 1999, enterococci were the second most commonly isolated microorganisms (15.8%).

Emerging nosocomial enterococcal infections include bacteremia, surgical site and intra-abdominal infections, and more rarely central nervous system, neonatal and pulmonary infections. Of all the species that have been proposed to belong to the genus, only   (E. avium, E. casseliflavus, E. durans, E. dispar, E. faecalis, E. faecium, E. gallinarum, E. hirae, E. mundtii, E. pseudoavium, and E. raffinosus) have been described as associated with human disease. E. faecalis accounts for 80-90% of enterococcal isolates of clinical origin, with E. faecium the second most prevalent enterococcal species.

Enterococci are also associated with obligate anaerobes in mixed infections that result in intra-abdominal abscesses. Typically, enterococci cause infections in debilitated and hospitalized patients that often have been treated with broad-spectrum antibiotics. An explanation for their involvement in disease may thus be a combination of “virulence” factors that enhances their ability to colonize, adhere and induce tissue damage.

The underlying condition of the patient seems to play an important role for the outcome of enterococcal infections. Patients with hematological malignancies, a history of transplantation or severe burns have been more readily colonized with multi-resistant strains and have also been more likely to experience bacteremia and subsequent serious outcome than non immunocompromised patients. Different studies describe a longer length of stay in hospital and increased mortality due to vancomycin-resistant E. faecium compared to vancomycin-susceptible E. faecium. However, resistance alone does not explain the increase of enterococci in nosocomial infections. Although resistance is relatively uncommon among E. faecalis isolates compared to resistance among E. faecium isolates, E. faecalis currently accounts for the majority of clinical enterococcal isolates (up to 90 %), followed by E. faecium.

A comparison of outcomes for patients with bacteremia due to vancomycin-resistant E. faecium or vancomycin-susceptible E. faecium in United State (U.S.) found a median length of stay of 46 days after the first episode of bacteremia in the group of patients with vancomycin-resistant E. faecium, as compared to 19 days for patients infected by a susceptible strain.

The presence of VRE in the bloodstream has also been associated with increased mortality. Although normally commensal in nature, enterococci are responsible for approximately 10% of urinary tract infections and 16% of nosocomial urinary tract infections. They are also commonly isolated from wound infections of the abdominal area as well as those from crushing injuries.

Enterococcal bacteremia is the third leading cause of nosocomial bacteremia. Enterococci are also responsible for between 5 and 20% of cases of bacterial endocarditis. Enterococci have been described as one of the most destructive agents that cause postoperative complications of cataract surgery. Those who are elderly or have an underlying compromising situation are predisposed to enterococcal infection, especially in the hospital environment. This is a significant observation given the ability of enterococci to colonize surfaces of the hospital environment and persist on fingertips and dry surfaces. As a result, enterococci seeding the clinical environment may be more easily spread if infection control measures are poorly implemented.