Vancomycin (glycopeptide) intermediate Staphylococcus aureus (VISA)

By Aimee Wilkins, MD and Jason E. Farley, RN, MPH

The Organism

•	Staphylococcus aureus (S. aureus) is a gram-positive coccus that produces a variety of infections in community and institutional settings.
•	The degree of resistance to vancomycin is determined by the MIC (minimum inhibitory concentration) using the breakpoints established by the National Cmmittee for Clinical Laboratory Standards:
	£4 mcg/ml: vancomycin sensitive S. aureus (VSSA)
	8-16 mcg/ml: vancomycin intermediate S. aureus (VISA)
	³32 mcg/ml: vancomycin resistant S. aureus (VRSA) (7,8,10)

•	A more general term for VISA in the literature is glycopeptide intermediate S. aureus (GISA) that reflects resistance to the whole class of glycopeptide antibiotics.

Epidemiology

•	VISA, first reported in 1996 in a Japanese child who developed a nosocomial surgical site infection with methicillin-resistant S. aureus (MRSA). After therapy with glycopeptides subsequent isolates then grew VISA with MICs of 8 mcg/ml.

•	Countries now reporting GISA isolates: (2,4,5,6)
	Japan (Multiple strains)
	United States (Six strains confirmed, others reported)
	Europe (France, UK, Spain)
	Far East (China, Korea)
•	Colonization of health-care workers or family members associated with the case patients has not been reported.

Disease Description

•	Risk factors are not well described except that all cases have received long courses of vancomycin or other glycopeptide antibiotic.
•	Among US cases all have been associated with end stage renal disease with concurrent dialysis.
•	In some cases, antecedent MRSA infection (peritoneal, bloodstream, and/or device-related) was treated repeatedly and for long time periods with a glycopeptide.  Over time, isolates developed reduced susceptibility to vancomycin (8).  Based on genetic typing MRSA and subsequent VISA strains are identical (pulse-field gel electrophoresis).
•	The mechanism of glycopeptide resistance in GISA isolates has not been discovered, but appears to be related to alterations in cell-wall synthesis.
•	The enterococcal vancomycin-resistance genes (vanA, vanB, vanC, or vanD) have not been found in S. aureus clinical isolates to date.

Treatment

•	Indwelling catheters should be removed and any potential source of infection drained.
•	Antibiotic therapy should be based on invitro susceptibility tests.
•	Treatment may include penicillins, rifampin, trimethoprim-sulfamethoxazole, gentamicin and/or chloramphenicol or combination of other antibiotics.
•	The role for newer anti-staphylococcal agents such as quinprisitin/dalfopristin or linezolid has not been defined, but they may be useful.
•	Any treatment decisions should be made in conjunction with infectious disease consultation.

Diagnosis

•	The role of the microbiology laboratory is essential. Appropriate laboratory screening for vancomycin susceptibility is critical.
•	The most accurate method for susceptibility testing is a MIC method (such as broth dilution, agar dilution or agar-gradient diffusion).  Disk diffusion methods are not appropriate since they fail to detect staphylococci with reduced susceptibility to glycopeptides (7,10).
•	A survey of microbiology laboratories participating in the Active Bacterial Core Surveillance/Emerging Infections Program Network found that 84% used appropriate methods to detect reduced susceptibility to vancomycin while 16% did not. Only 59% of labs did confirmatory testing of candidate VISA strains.
•	All suspected VISA strains should have the MIC confirmed in the lab by an appropriate method and at the appropriate reference laboratory (currently CDC).

Infection Control

	Both the Johns Hopkins Hospital and the CDC have guidelines for preventing the spread of VISA (Insert Link to JHH and  CDC VISA Guidelines) which are summarized below (3):
•	Isolation in a private room with Special Precautions (gown, mask, gloves, and handwashing) at JHH
•	Minimize the number of healthcare workers caring for the patient (1:1 Nursing care)
•	Monitor the compliance with isolation precautions and monitor personnel for acquisition of the isolate
•	Use dedicated equipment for patient care
•	Initiate epidemiologic and laboratory investigations
•	Obtain baseline cultures from the hands and nares of people who have had physical contact with the patient, the patient's health care providers, roommates of the patient
•	Report the isolate to the state health department and CDC
•	Consult with the state health department and the CDC before transferring or discharging the patient
•	Transport all specimens in double bags
•	Further information can be obtained through the CDC's Hospital Infection Program, National Center for Infectious Diseases (404) 639-6413 or http://www.cdc.gov/ncidod/hip/vanco/vanco.htm or through the Department of Hospital Epidemiology and Infection Control at Hopkins http://www.hopkins-heic.org

Prevention

•	Vancomycin use should be limited to situations in which it is absolutely indicated and guidelines have been published by the Hospital Infection Control Practices Advisory Committee (1,9).
•	Surveillance should be performed in patients with documented MRSA infections, especially if they have received long-term vancomycin therapy with additional emphasis in the HD and CAPD populations.
•	Laboratories should monitor heterogeneous MRSA populations (i.e. increased MIC).
	Examples of situations when vancomycin is not recommended:
•	Routine prophylaxis for surgical patients without allergy to beta lactam antibiotics, low birth-weight infants, dialysis patients, patients with neutropenia, patients with central venous catheters.

References

1. 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.
2. Reduced susceptibility of Staphylococcus aureus to vancomycin- Japan, 1996. MMWR 1997;46:624-6.
3. Interim Guidelines for prevention and control of Staphylococcal infection associated with reduced susceptibility to vancomycin. MMWR 1997;46:626-8, 635.
4. Staphylococcus aureus with reduced susceptibility to vancomycin-United States, 1997. MMWR 1997;46:765-6.
5. Update: Staphylococcus aureus with reduced susceptibility to vancomycin- United States, 1997. MMWR 1997;46:813-15.
6. Staphylococcus aureus with reduced susceptibility to vancomycin-Illinois, 1999. MMWR 2000;48:1165-67.
7. Laboratory capacity to detect antimicrobial resistance, 1998. MMWR 2000; 48:1167-71.
8. Sieradski K, Roberts RB, Haber SW, et al. (1999). The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. NEJM,340, 517-523.
9. Smith TL, Pearson ML, Wilcox KR, et al. (1999). Emergence of vancomycin resistance in Staphylococcus aureus. NEJM,340, 493-501.
10. Tenover, F.C. (1999). Implications of vancomycin-resistant Staphylococcus aureus. Journal of Hospital Infections,43,S3-S7.