Vancomycin-Resistant Staphylococcus aureus — Pennsylvania, 2002
Public Health Dispatch

Morbidity and Mortality Weekly Report v.51, n.40 11oct02

The MMWR series of publications is published by the Epidemiology Program Office, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services, Atlanta, GA 30333.

Staphylococcus aureus is one of the most common causes of hospital- and community-acquired infections (1,2). Since the recognition of vancomycin-resistant enterococci in 1988, the emergence of vancomycin-resistant S. aureus (VRSA) (minimum inhibitory concentration [MIC] >32 µg/mL [3]) has been anticipated. The transfer of the genetic element containing the vanA vancomycin resistance gene from Enterococcus faecalis to S. aureus was demonstrated in the laboratory in 1992 (4); the first clinical infection with VRSA was reported in July 2002 (5). This report describes the second documented clinical isolate of VRSA from a patient.

On September 20, the patient was admitted to a hospital in Pennsylvania and evaluated for a chronic foot ulcer and possible osteomyelitis. A culture of the ulcer grew S. aureus. This isolate was tested for antimicrobial susceptibility by disk diffusion; a vancomycin-agar screen plate (brain heart infusion agar containing 6 µg/mL vancomycin) also was inoculated. Growth on the vancomycin screen plate and a 12 mm zone of inhibition around the vancomycin disk suggested that the isolate had decreased susceptibility to vancomycin. Further testing by Etest® confirmed that the isolate was resistant to vancomycin (MIC=64 µg/mL). Following notification of the Pennsylvania Department of Health (PDH), the isolate was forwarded to CDC, where it was confirmed to be VRSA (vancomycin MIC=32 µg/mL by broth microdilution testing). The isolate contained both the mecA and vanA genes mediating oxacillin and vancomycin resistance, respectively. The isolate was susceptible to chloramphenicol, linezolid, minocycline, quinupristin-dalfopristin, rifampin, and trimethoprim-sulfamethoxazole.

The patient has been discharged from the hospital and is responding to antimicrobial treatment. The patient is receiving home-health care. PDH and CDC are assisting healthcare providers investigating this case of VRSA. The goals of this investigation include assessment of infection-control practices in the hospital and home setting and the possibility of transmission of the organism to other patients, health-care providers, and family or social contacts. Previous investigations of VRSA and vancomycin-intermediate S. aureus in the home setting demonstrated no transmission among family or home health-care contacts (5,6).

The presence of vanA in this VRSA suggests that the resistance determinate was acquired from a vancomycin-resistant enterococcus. Development of this VRSA appears to be unrelated to the previous VRSA identified in Michigan (5). However, because both were probably the result of conjugation events, additional VRSA infections are likely to occur. Therefore, clinical microbiology laboratories must ensure that they are using susceptibility testing methods that will detect VRSA and that they are saving potential VRSA for confirmatory testing. In addition, more systematic surveillance for VRSA will enhance the ability of the public health system and the health-care system to rapidly address this resistant pathogen.

The public health response to this VRSA occurrence is ongoing. Using proper infection-control practices and good antimicrobial agent management will help limit the emergence and spread of antimicrobial-resistant microorganisms, including VRSA. CDC recommends contact precautions when caring for patients with these infections, including placing the patient in a private room, wearing gloves and a gown during patient contact, washing hands after contact with the patient and infectious body tissues or fluids, and not sharing patient-care items with other patients. CDC guidelines for preventing spread of VRSA are available at http://www.cdc.gov/ncidod/hip/10_20.pdf. [also below]

The isolation of S. aureus with confirmed or “presumptive” vancomycin resistance should be saved and reported through state and local health departments to CDC’s Division of Healthcare Quality Promotion, National Center for Infectious Diseases, telephone 800-893-0485.

Reported by: D Miller, V Urdaneta, MD, A Weltman, MD, Pennsylvania Dept of Health. Office of the Director, Div of Healthcare Quality Promotion, National Center for Infectious Diseases; S Park, EIS Officer, CDC.

References

1. CDC. National Nosocomial Infections Surveillance (NNIS) report, data summary from January 1992–June 2001. Am J Infect Control 2001;29: 404–21.

2. Lowy F. Staphylococcus aureus infections. N Engl J Med 1998;339: 520–32.

3. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 4th ed. Approved standard, M7-A4. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1997.

4. 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;93:195–8.

5. CDC. Staphylococcus areus resistant to vancomycin—United States, 2002. MMWR 2002;51:565–7.

6. Hageman, JC, Pegues DA, Jepson C, et al. Vancomycin-intermediate Staphylococcus aureus in a home health-care patient. Emerg Infect Dis 2001;7:1023–5.

source: http://www.cdc.gov/mmwr/PDF/wk/mm5140.pdf  10oct02

Interim Guidelines for Prevention and Control of
Staphylococcal Infection Associated with
Reduced Susceptibility to Vancomycin

Guidelines — Continued Staphylococci are one of the most common causes of community- and hospital-acquired infection. In many U.S. hospitals, strains of staphylococci (i.e., Staphylococcus aureus or coagulase-negative staphylococci) are resistant to all available antimicrobials except vancomycin. Rare cases of infection in the United States ( 1 ) have been caused by coagulase-negative staphylococci with reduced susceptibility to vancomycin (minimum inhibitory concentration [MIC] >=8 mg/mL)* ( 2 ).

* National Committee for Clinical Laboratory Standards breakpoints: susceptible, £4 mg/mL or zone size ³12 mm; intermediate, 8–16 mg/mL or zone size 10–11 mm; and resistant, ³32 mg/mL or zone size £9 mm.

In May 1996, an infection caused by a strain of S. aureus with reduced susceptibility to vancomycin (MIC=8 mg/mL) was diagnosed in a patient in a hospital in Japan ( 3,4); no such infections have been reported in the United States. Although the strain from Japan was not fully resistant to vancomycin (i.e., MIC >=32 mg/mL), its appearance increases the likelihood that fully resistant strains may emerge. Because the occurrence of fully vancomycin-resistant staphylococcal infection in a hospital could result in serious public health consequences, CDC and the Hospital Infection Control Practices Advisory Committee have developed interim guidelines to direct medical and public health responses when isolates of staphylococci with reduced vancomycin susceptibility are identified. This report describes these interim guidelines, which include steps to 1) decrease the likelihood that staphylococci with reduced vancomycin susceptibility will emerge; 2) recognize the occurrence of staphylococci with reduced vancomycin susceptibility; 3) obtain information about investigational antimicrobials for treating either patients infected with fully vancomycin-resistant staphylococci or patients infected with staphylococci with intermediate vancomycin resistance for whom conventional therapy fails; and 4) implement interim infection-control measures. To effectively implement these interim guidelines, each health-care facility should develop a plan based on these guidelines in which responsibilities for critical departments and personnel are clearly delineated.

Preventing the Emergence of Vancomycin Resistance

Antimicrobial use is a major risk factor for the emergence of antimicrobial-resistant pathogens. Reduction of overuse and misuse of antimicrobials will decrease the risk for emergence of staphylococci with reduced susceptibility to vancomycin. Medical and ancillary staff members who are responsible for pharmacy formulary decisions should review and restrict use of vancomycin ( 5 ) and ensure that use of other antimicrobials is appropriate.

Detecting Staphylococci with Reduced Vancomycin Susceptibility

Use of recommended laboratory methods (including media and incubation methods, antimicrobial susceptibility testing methods, and susceptibility breakpoints) for identifying such strains is essential.

1. The most accurate form of antimicrobial susceptibility testing for staphylococci is a minimal inhibitory concentration method (broth dilution, agar dilution, or agargradient diffusion) using a full 24-hour incubation. Strains of staphylococci with a MIC=8 mg/mL (classified as intermediate using National Committee for Clinical Laboratory Standards breakpoints) were not detected by using the current disk diffusion procedure.
2. All strains with a MIC >=4 mg/mL should be considered candidate strains for reduced vancomycin susceptibility. Other than the isolate reported in Japan ( 4 ), all S. aureus strains with putative reduced vancomycin susceptibility sent to CDC for confirmation have been misidentified or mixed with other microorganisms. Therefore, the laboratory should ensure that the strain is in pure culture and reconfirm the genus and species of the organism; then repeat the susceptibility test for vancomycin using a minimal inhibitory concentration method.
3. After repeat testing, if species identification and vancomycin test results are consistent, immediately contact the state health department (SHD) and CDC’s Hospital Infections Program, National Center for Infectious Diseases, telephone (404) 639- 6400, to report the occurrence of a “presumptive” staphylococcal strain with reduced susceptibility to vancomycin and to obtain epidemiologic and laboratory assistance.
4. Retest staphylococci isolated from patients who fail to respond to vancomycin therapy because resistance may have emerged during therapy.

Obtaining Investigational Antimicrobials

The susceptibility pattern of a particular staphylococcus strain, the site of infection, and the response to conventional therapy is important in determining the need for investigational antimicrobials to treat infections caused by staphylococci with reduced vancomycin susceptibility. Several antimicrobial agents in clinical development may be useful in treating vancomycin-resistant enterococci and methicillinresistant S. aureus. Some of these agents also may be useful in treating infections with S. aureus with reduced susceptibility to vancomycin. The usefulness of any antimicrobial agent will depend on the resistance mechanism and susceptibility pattern of the S. aureus strain. CDC and the Food and Drug Administration (FDA) are working to improve access by clinical providers to investigational agents that may be useful for treating patients with confirmed infections with S. aureus strains with reduced susceptibility to vancomycin. Physicians treating infections caused by staphylococci with reduced vancomycin susceptibility can obtain information about investigational drug therapies from FDA’s Division of Anti-Infective Drug Products, telephone (301) 827-2120. The physician will be requested to send the isolate to CDC for microbiologic and epidemiologic evaluation.

Preventing the Spread of Staphylococci with Reduced Vancomycin Susceptibility

To prevent the spread of staphylococci with reduced susceptibility to vancomycin within and between facilities and to minimize the potential for the organism to become endemic, the following steps should be taken whenever such an organism is isolated:

1. The laboratory should immediately notify infection-control personnel, the clinical unit, and the attending physician.
2. Infection-control personnel, in collaboration with appropriate authorities (including the SHD and CDC), should initiate an epidemiologic and laboratory investigation.
3. Medical and nursing staff should
   1. isolate the patient in a private room and use contact precautions (gown, mask, glove, and antibacterial soap for handwashing) as recommended for multidrug-resistant organisms ( 6 );
   2. minimize the number of persons with access to colonized/infected patients; and
   3. dedicate specific health-care workers to provide one-on-one care for the colonized/infected patient or the cohort of colonized/infected patients.
4. Infection-control personnel should
   1. inform all personnel providing direct patient care of the epidemiologic implications of such strains and of the infection-control precautions necessary for their containment;
   2. monitor and strictly enforce compliance with contact precautions and other recommended infection-control practices;
   3. determine whether transmission has already occurred by obtaining baseline cultures (before initiation of precautions) for staphylococci with reduced susceptibility to vancomycin from the anterior nares and hands of all health-care workers, roommates, and others with direct patient contact;
   4. assess efficacy of precautions by monitoring health-care personnel for acquisition of staphylococci with reduced susceptibility to vancomycin as recommended by consultants from SHD or CDC;
   5. avoid transferring infected patients within or between facilities, and if transfer is necessary, fully inform the receiving institution or unit of the patient’s colonization/infection status and appropriate precautions; and
   6. consult with SHD and CDC before discharge of the colonized/infected patient.

Reported by: Hospital Infection Control Practices Advisory Committee. Div of Anti-Infective Drug Products and Div of Special Pathogens and Immunologic Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration. Hospital Infections Program, National Center for Infectious Diseases, CDC.

References

1. Garrett DO, Jochimsen E, Murfitt K, et al. The impending apocalypse: the emergence of vancomycin resistance in Staphylococcus spp. [Abstract S1]. Infect Control Hosp Epidemiol 1997; 18:P32.

2. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically—fourth edition: approved standard, M7-A4. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1997.

3. Hiramatsu K, Hanaki H, Ino T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997 (in press).

4. CDC. Reduced susceptibility of Staphylococcus aureus to vancomycin—Japan, 1996. MMWR 1997;46:624–6.

5. Hospital Infection Control Practices Advisory Committee. Recommendations for preventing the spread of vancomycin resistance. MMWR 1995;44(no. RR-12).

6. Garner JS, Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol 1996;17:53–80.