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Saturday, March 18, 2000

The emergence of vancomycin-resistant bacteria

Background

Orthopaedic surgeons are among the heaviest users of prophylactic antibiotics. Multiple bacterial species have developed resistance to these commonly used antibiotics.

In addition to infections with methicillin-resistant organisms, vancomycin-resistant enterococci have occurred in orthopaedic patients. Enterococci are the second most common cause of nosocomial infection in the U.S.1

They are ubiquitous in intestinal flora and rapidly acquire resistance to antimicrobials. Since 1989 there has been a rapid increase in the reported incidence of infection and colonization with vancomycin-resistant enterococcus (VRE).2 The U.S. Centers for Disease Control and Prevention National Nosocomial Infections Surveillance system reported an increase in the rate of VRE among all enterococcus infections from 0.3 percent in 1989 to 7.9 percent in 1993.3 Intensive care units were the primary focus with rates increasing from 0.4 percent to 13.6 percent over the same period. VRE has become a common intestinal colonizer with hospital point prevalence rates reported up to 20 percent.4 Prosthetic joint infections with VRE have been reported.5 In multiple studies, exposure to vancomycin is reported as a risk factor in the development of VRE colonization and infection.

Both coagulase-negative staphylococci, e.g., S. epidermidis and S. hemolyticus, and coagulase-positive S. aureus have demonstrated the capacity to develop resistance to each new generation of antimicrobials. Clinical use of penicillin began in 1940. Penicillinase was described in 1944 and by the late 1950s, 50 percent of the strains of S. aureus were resistant. Methicillin was released in 1960 followed rapidly by the development of resistant strains in 1961. Thirty-five percent to 80 percent of all coagulase-negative staphylococci are now resistant to all beta-lactam antibiotics often leaving vancomycin as the last line of defense.6 Over the last decade vancomycin-resistant strains of S. epidermidis (VRSE) and S. hemolyticus have been reported.6,7 In 1997, two patients were reported with S. aureus demonstrating intermediate resistance to vancomycin (VISA).8,9,10 It is anticipated that full resistance (VRSA) will follow. There is experimental evidence that vancomycin resistance can be transferred from enterococcus to S. aureus.11,12 It is essential that all appropriate measures be taken to reduce the spread of VRE, VRSE and VISA, and to slow the evolution of VRSA.

Recommendations

Recommendations fall into two categories: reduction in the use of vancomycin and measures to reduce the nosocomial spread of staphylococci and enterococci.

Recommendation 1

Vancomycin should be reserved for the treatment of serious infection with beta-lactam-resistant organisms or for treatment of infection in patients with life-threatening allergy to beta-lactam antimicrobials.

Vancomycin may be appropriate as a prophylactic antimicrobial for patients undergoing joint replacement at institutions that have identified a significant prevalence (e.g., >10-20 percent) of methicillin-resistant S. aureus (MRSA) and S. epidermidis among orthopaedic patients. Prophylaxis should be discontinued after a maximum of two doses.2 Recommendation 2

Hand washing with antibacterial soaps is highly effective and one of the simplest methods to prevent nosocomial spread.

Many studies have shown that physicians often do not regularly comply with recommendations for hand washing before contact with patients with open or healing wounds. Forty percent of the general population carry S. aureus in their anterior nares and 50 percent of those have positive cultures from their hands.13,14 Daily cleaning of horizontal surfaces with antimicrobial agents and thorough cleaning of patient rooms on discharge should be standard policy, especially in intensive care units.

Recommendation 3

Patients infected with strains of VRE, VRSE or VISA require contact isolation.

From an infection control standpoint, it is better for all patients with resistant strains to be located in a confined section of the hospital and cared for by dedicated staff that do not cross over to other patient care areas "Non-sterile gowns and gloves should be put on when entering the room of a patient infected with resistant strain". They should be removed in the room just prior to exit. Hands should be washed immediately after exit. Noncritical items such as stethoscopes and monitoring equipment should be dedicated to a single room. Equipment that must be brought to the patient should be thoroughly cleaned on exiting the room. Moving the patient out of the room to fixed diagnostic and therapeutic sites should be avoided whenever possible.2

Recommendation 4

The identification of a strain of S. aureus demonstrating reduced sensitivity to vancomycin should be reported to state and local health departments and to CDC's Investigation and Prevention Branch, Hospital Infections Program, telephone (404) 639-6413.

Recommendation 5

In the event that a patient with VISA is identified, all health care personnel and other patients who have had potential contact should have cultures of anterior nares and hands.

Health care personnel with positive cultures for VISA should be removed from patient care and treated until cultures are negative. If transfer of patients with colonization or infection with VISA or VRE to another institution is necessary, the receiving institution should be fully advised of the situation and recommended precautions.8,9 Continuing education programs for house staff and health care personnel are an essential component of this effort.

Pharmaceutical companies have begun developing new antibacterial agents. Information on investigational drug therapies may be obtained from the Food and Drug Administration's Division of Anti-infective Drug Products, telephone (301) 827-2120. The need for intensive research in this area will continue for the foreseeable future.

References

  1. Brandt CM, Rouse MS, Laue NW, et al: Effective treatment of multidrug-resistant enterococcal experimental endocarditis with combinations of cell wall-active agents. J Infect Dis 1996;173:909-913.

  2. Centers for Disease Control and Prevention: Recommendations for preventing the spread of vancomycin resistance. Recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR 1995;44(Rr-12):1-13.

  3. Centers for Disease Control and Prevention: Nosocomial enterococci resistant to vancomycinžUnited States, 1989-1993. MMWR 1993;42(30):597-599.

  4. Morris JG Jr, Shay DK, Hebden JN, et al: Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center. Ann Intern Med 1995;123:250-259.

  5. Holtom P: Personal communication with James V. Luck Jr., MD.

  6. Schwalbe RS, Stapleton JT, Gilligan PH: Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 1987;316:927-931.

  7. Veach LA, Pfaller MA, Barrett M, et al: Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. J Clin Microbiol 1990;28:2064-2068.

  8. Centers for Disease Control and Prevention: Interim guidelines for prevention and control of staphylococcal infection associated with reduced susceptibility to vancomycin. MMWR 1997;46(27):626-628.

  9. Centers for Disease Control and Prevention: Reduced susceptibility of Staphylococcus aureus to vancomycin-Japan, 1996. MMWR 1997;46(27):624-626.

  10. Centers for Disease Control and Prevention: Staphylococcus aureus with reduced susceptibility to vancomycin-United States, 1997. MMWR 1997;46(33):765-766.

  11. Noble WC, Virani Z, Cree RGA: Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992;72:195-198.

  12. Leclercq R, Derlot E, Duval J, Courvalin P: Plasmid-mediated resistance to vancomycin and teicoplaninin in Enterococcus faecium. N Engl J Med 1988;319:157-161.

  13. Casewell MW, Hill RL: The carrier state: methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 1986;18(suppl A):1-12.

  14. Reagan DR, Doebbeling BN, Pfaller MA, et al: Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment. Ann Intern Med 1991;114:101-106.

MAY 1998

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Last modified 28/February/2000 by IS