Vancomycin-resistant Enterococcus (VRE)

Infection Control - Prevention of Spread

by

Raymond B. Otero, Ph.D.  
Consultant  

Introduction  

Enterococci are the second most commonly isolated organism in nosocomial infections^1. Enterococci are a therapeutic challenge because of their intrinsic resistant to many antibiotics. Recent reports of enterococci with high-level resistance to multiple antibiotics have highlighted the rapidly decreasing therapeutic options for these organisms. As we enter into a new millennium and an era of decreased antibiotic effectiveness, it becomes more imperative to develop appropriate infection control procedures to decrease the transmission of these organisms in the health care setting.

History  

Vancomycin-resistant enterococci (VRE) was first documented in Europe in the 1980’s and is now a major problem in healthcare facilities in the United States². Since 1989, there has been a rapid increase in the incidence of infection and colonization with VRE³. There have been numerous reports of VRE outbreaks in hospitals^1,4-6. Rapid detection of VRE has to be accompanied by effective containment and control measures with prompt initiation of an effective strategic plan that requires alert, well-trained individuals in infection control, epidemiology and microbiology⁷.

Antimicrobial resistance in Enterococci

The mechanism by which the enterococci resist vancomycin is complex and includes a number of phenotypes. Strains that exhibit the VanA phenotype show a high level resistance to vancomycin and teicoplanin, and VanB strains exhibit a moderate to high level resistance to vancomycin but remain susceptible to teicoplanin. The genes for both phenotypes have been cloned and sequenced and have also been shown to be transferable^8,9.

The following agents have shown intrinsic (always present and not acquired) resistance to enterococci⁷:

Aminoglycosides (low level)

Cephalosporins

Clindamycin

Trimethoprim/sulfamethoxa-zole

The following agents have shown acquired (developed over time) resistance to enterococci⁷:

Macrolides

Tetracycline

Lincosamides (high levels)

Chloramphenicol

Aminoglycosides (high level)

Penicillin and ampicillin (beta-lactamase)

Rifampin

Vancomycin

Quinolones

Reservoirs

Enterococci are normal inhabitants of the human gastrointestinal tract^10,11. Other major sites of colonization that may act as reservoirs for enterococci in hospitalized patients or nursing home residents include wounds and chronic decubital ulcers⁷. Enterococci are seldom found in pure culture in wounds, but when they are, the wounds usually have no clinical evidence of infection¹². Generally, enterococci are present in mixed culture in soft tissue wounds. Asymptomatic women may also carry enterococci in high numbers in their vaginas¹³, while 60% of men in hospitals may carry enterococci in their perineal or meatal areas¹⁸.

Enterococci are also hardy organisms, which allows them to survive well on environmental surfaces². Resistant enterococci have been isolated from surrounding areas of infected patients². Instruments such as electronic thermometers have been implicated in spreading this organism¹⁴.

Health care providers may also become colonized with resistant enterococci and contribute to their spread by poor hygiene^15,16. Recently, the role of elderly patients residing in extended care facilities as sources of resistant enterococci has been addressed²³. In one VA medical center, several of the patients were colonized with resistant enterococci in their rectum or urine. These studies suggest that the community and extended care facilities may provide a continuous source for reintroduction of VRE in hospitals¹⁷.

Modes of transmission

The source of enterococcal infections was always felt to be the resident’s/patient’s own flora. Some studies have strongly suggested that enterococci isolated from infections were from the host’s own gastrointestinal tract¹⁸. Possible environmental contamination may lead to the spread of the organism².

Contact spread is the primary means of transmission by health care workers¹⁵. There are no reported cases in the literature that suggests that enterococci are spread by respiratory droplets. Good handwashing practices must be part of the employee’s orientation program³.

Risk factors

Various studies have examined the reasons for the development of enterococcal urinary tract infections and have identified urinary tract instrumentation or catheterization, genitourinary pathology, and the use of antibiotics, especially cephalosporins, as significant risk factors¹⁹. Imipenem was also found to significantly predispose patients in acquiring ampicillin-resistant enterococci²⁰, while previous use of vancomycin was also important for acquiring vancomycin-resistant strains (i.e., treating MRSA colonized patients with vancomycin)²¹.

Pathogenesis

As mentioned above, the enterococci are part of the human endogenous flora. In the elderly or immunocompromised patient, these organisms can become opportunistic. Studies have shown that enterococci frequently colonized the meatus and perineum of hospitalized men, but infections would develop predominantly when they were catheterized or had genitourinary pathology¹⁹. Little is known about the virulence factors in enterococci. There is a hemolysin factor (destroys red cells) which has been shown to contribute to the disease process²². No other factors have been described.

Diseases

The various types of diseases that enterococci can cause are listed below⁷:

Urinary (common)

Bacteremia/septicemia (increasing in incidence)

Endocarditis (3^rd most common organism)

Intra-abdominal/pelvic infections (role controversial)

Skin and soft tissue (rarely found in pure culture, generally mixed)

Neonatal infections (increasing in incidence)

Meningitis (rare)

Otitis media with effusion

Lower respiratory (rare)

Prevention and Risk Reduction of Nosocomial Infections Caused by Enterococci

Enterococci are very tolerant organisms and can survive easily on the hands of health care personnel. Patient-to-patient spread by health care personnel has been documented³. Strict observance of hand-washing policies would then be a key element in controlling the spread of epidemic strains of enterococci or any other organism³.

Cohorting of infected and colonized patients with poor hygiene has been used to prevent the spread of this organism. Proper barriers such as gloves and gowns when soiling is likely are important in preventing dissemination.

Each health care facility through collaboration of its quality improvement and infection control programs such as pharmacy, reference microbiology laboratory, nursing, physicians, housekeeping services should develop a comprehensive, institutional-specific strategic plan to detect, prevent and control infection and colonization withVRE³.

Proper use of vancomycin is very important control measure. Situations in which the use of vancomycin is appropriate or acceptable are³:

1.   treatment of serious infections caused by beta-lactam gram-positive organisms;

2.   treatment of infections caused by gram-positive microorganisms in patients/residents who have serious allergies to beta-lactam antibiotics;

3.   when antibiotic-associated colitis (caused by Clostridium difficile) fails to respond to metronidazole therapy or is severe and potentially life-threatening.

Situations in which the use of vancomycin should be discouraged³:

1.   treatment in response to a single blood culture positive for coagulase negative Staphylococcus;

2.   continued empirical use for presumed infections in patients whose cultures are negative for beta-lactam resistant gram-positive organisms;

3.   eradication of MRSA colonization;

4.   primary treatment of antibiotic-associated colitis;

5.   use of vancomycin solution for topical application or irrigation.

Key parameters of vancomycin use can be monitored through the reference pharmacy and can be part of the quality assurance/improvement process or as part of a drug-utilization review by the pharmacy³.

The following measures should be implemented by all health care facilities³:

1.   reference laboratories should notify appropriate personnel that a vancomycin-resistant enterococcus has been isolated;

2.   alert staff members that such an organism has been isolated from your facility;

3.   establish systems(s) for monitoring appropriate process and outcome measures (e.g., cumulative incidence or incidence density of VRE colonization, rate of compliance with VRE isolation precautions and handwashing, interval between VRE identification by the laboratory and implementation of isolation precautions).

Initiate the following isolation precautions to prevent resident/patient-to-resident/patient transmission³:

1.   place VRE-infected residents (drainage can not be contained) in CONTACT ISOLATION (private room);

2.   place known colonized residents with poor hygiene and with the possibility of spread high in a cohort system or a private room;

3.   wear a gown and gloves when entering the room of a colonized or infected VRE resident/patient if substantial contact with the resident/patient is anticipated or if the resident/patient is incontinent, has had an ileostomy or colostomy, has diarrhea or has a wound drainage not contained by dressing;

4.   remove gloves and gown before leaving room;

5.   wash hands immediately with an antiseptic soap (Note: this is the only time that CDC has recommended the use of an antiseptic soap outside of surgery for patient care);

6.   adopt a policy for deciding when the resident comes out of isolation or a cohort system;

7.   establish a system for highlighting the records of infected or colonized VRE residents/patients so they can be promptly identified and placed in the appropriate setting upon readmission (VRE colonization can persist indefinetly);

8.   dedicate the use of non-critical items such as stethoscope or sphygmomanometer to a single resident/patient or cohort of residents/patients infected or colonized with VRE;

9.   any gross contamination of body fluids (e.g., fecal contamination) should be cleaned up as soon as possible to avoid environmental spread.

Role of the microbiology laboratory³

Microbiology personnel are the first persons to recognize the presence of multiple drug resistant organisms. The laboratory has to have the ability to promptly and accurately identify VRE to help the physicians and nurses in making a judgment whether their resident/patient is colonized or infected. This will avoid costly containment efforts when recognition of the problem is delayed. An example of a microbiology report from an infected site is shown in Table 1.

Educational programs  

Continuing education programs for all physicians, nurses and pharmacists should be provided at least annually or as needed. The program should include information concerning the epidemiology of vancomycin-resistant enterococci and the potential impact that this organism has on the cost and outcome of resident/patient care.

Summation

Standard Precautions (formerly called Universal Precautions) when broadly interpreted (i.e., handwashing before and after all patient/resident contact, use of gloves for all body fluids and secretions/mucous membranes/non-contact skin; use of gowns if soiling is likely to occur and the use of protective eye-wear if splashing of body fluid is likely), are adequate to prevent the spread of VRE when these precautions are applied correctly and consistently.

References  

1.   Christenson, J. C., et al. Detection of vancomycin-resistant enterococci colonization in a children’s hospital. Am J of Infect Cont. 26(6):569-571. 1998.

2.   Weber, D. J., et al. Role of environmental contamination in the transmission of vancomycin-resistant enterococci. Infect Cont Hosp Epid. 18(5):306-309. 1997.

3.   Centers for Disease Control and Prevention. Recommendations for preventing the spread of vancomycin resistance. MMWR. 44(No. RR-12):1-13. 1995.

4.   Jarvis, W. r., Martone, W. J. Predominant pathogens in hospital infections. J Antimicrob Chemothera. 29(Suppl A):19-24. 1992.

5.   Spera, R. V., Farber, B. F. Multiply-resistant Enterococcus faecium: the nosocomial pathogen of the 1990’s. JAMA. 268:2563-2564. 1992.

6.   Centers for Disease Control and Prevention. Nosocomial enterococci resistant to vancomycin, United States – 1989-1993. MMWR 42:597-599. 1993.

7.   Chenowerth, C. E., Schaberg, D. Enterococcus species. In: Hospital Epidemiology and Infection Control. Williams and Wilkins. Pp. 334-345. 1996.

8     Arthur, M., Courvalin P. Genetics and mechanism of glycopeptide resistance in enterococci. Antimicrob Agents Chemother. 37:1563-71. 1993.

9.   Quintiliani, R., et al. The VanB gene confers various levels of self-transferable resistance to vancomycin in enterococci. J Inf Dis. 167:1220-1223. 1993.

10. Gray, J. W., et al. Fecal carriage of antibiotic-resistant Enterococcus in hospitalized and non-hospitalized individuals J Antimicrob Chemother. 30:110-112. 1992.

11. Facklam, R. R., Sahm, D. F. Enterococcus. In: Manual of Clinical Microbiology. ASM Press. Pp. 308-314. 1995.

12. Horvitz, R. A., von Graevenitz, A. A clinical study of the role of enterococci as sole agents of wound and tissue infection.Yale J Biol Med. 50:391-395. 1977.

13. Chenowerth, C., Schaberg, D. The epidemiology of enterococcus. Eur J Clin Microbiol Infect Dis. 9:80-89. 1990.

14. Livornese, L. L., et al. Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers. Ann Intern Med. 117-112-116. 1992.

15. Rhinehart, E., et al. Rapid dissemination of B-lactmase-producing aminoglycoside resistant Enterocccus faecalis amongpatients and staff on an infant-toddler surgical ward. New Engl J Med. 323-1814-1818. 1990.

16. Noskin, G. A., et al. Recovery of vancomycin-resistant enterococci on finger tips and environmental surfaces. Infect Cont Hosp Epid. 16(10):577-581. 1995.

17. Terpenning, M.S., et al. Enterococcal infections: an increasing problem in hospitalized patients. Infect Cont Hosp Epid. 9:457-461. 1988.

18. Gross, P. A., et al. The epidemiology of nosocomial enterococcal urinary tract infections. Am J Med Sci. 272:75-81. 1976.

19. Morrison, A. J., Wenzel, R. P. Nosocomial urinary infections due enterococcus: ten years experience at a university hospital. Arch Intern Med. 146:1549-1551. 1986.

20. Boyce, J. M., et al. Emergence and nosocomial transmission of ampicillin-resistant enterococci. Antimicrob Agents Chemother. 36:1032-1039. 1992.

21. Karanfil, L. V., et al. A cluster of vancomycin-resistant Enterococcus faecium in an intensive care unit. Infect Cont Hosp Epid. 13:195-200. 1992.

22. Ike, Y., et al. High incidence of hemolysin production by Enterococcus faecalis strains associated with human parenteral Infection. J Clin Micro. 24:1524-1528. 1987.

23. Byers, K. E., et al. A hospital epidemic of vancomycin-Resistant Enterococcus: risk factors and control. Infect Cont Hosp. Epid. 22(3):140-147. 2001.  

Table 1 – Microbiology Laboratory Report

Source: Right ankle drainage

Status: Final

Gram stain: Numerous WBC, many gram positive cocci predominantly in chains, some single

Isolate #1: Heavy growth of Enterococcus faecalis

Isolate #2: Light growth of skin flora

Antimicrobial Susceptibility Report

Enterococcus faecalis

*Minimal inhibitory concentration

**S = susceptible; R = Resistant

-End of Report-

Note: the presence of WBC’s indicates infection and not colonization. The presence of numerous cocci in chains verifies the culture of Enterococcus faecalis.

The manner in which a specimen is taken will reflect the outcome of the final report. Always check with the microbiology laboratory on how a specimen should be taken, especially from a wound drainage. Swabs are generally useless for this type of specimen. It is always better to aspiriate fluid using a syringe whenever possible.