Staphylococcus aureus is one of the most common causes of hospital-
and community-acquired
infections. Nosocomial methicillin-resistant S. aureus (MRSA)
infections have become common,
and cases of community-acquired MRSA infections also have occurred (1,2).
Since 1996,
vancomycin-intermediate S. aureus (VISA; vancomycin minimum inhibitory
concentration
[MIC]=8-16 µg/mL) has been identified in Europe, Asia, and the United States
(3-5). The emergence of
reduced vancomycin susceptibility in S. aureus increases the
possibility that some strains
will become fully resistant and that available antimicrobial agents will
become ineffective for
treating infections caused by such strains. This report describes the fourth
case of confirmed VISA
from a patient in the United States.
In April 1999, a 63-year-old woman with MRSA bacteremia (MIC less
than 1 µg/mL) was
transferred from a long-term-care facility to an Illinois hospital (hospital
A). The patient had a
history of frequent hospitalizations for complications of hemodialysis-
dependent, end-stage renal
disease, and intravascular access, including two failed arteriovenous grafts,
multiple central
venous catheter-associated infections, and intermittent receipt of vancomycin
therapy through June
1998. Thirteen days after hospital admission and 25 days after initiating
vancomycin therapy (median
vancomycin serum concentration=12.7 µg/mL; range: 12.1 µg/mL-20.9 µg/mL), a
culture from her blood
grew S. aureus with an MIC of 4 µg/mL; the blood culture was tested
using the Vitek® system
(bioMerieux; Hazelwood, Missouri)*. Three subsequent blood specimens drawn
within the next 3 days
grew S. aureus with MICs of 8 µg/mL on confirmatory testing. The
isolates, identical by
pulsed-field gel electrophoresis, were resistant to penicillin, oxacillin,
clindamycin,
erythromycin, ciprofloxacin, and rifampin but susceptible to trimethoprim-
sulfamethoxazole,
tetracycline, gentamicin, and had intermediate susceptibility to
chloramphenicol. No VISA strains
were recovered from other body sites. An echocardiogram demonstrated a mitral
valve vegetation but
the patient declined surgical intervention. Despite treatment with
intravenous vancomycin, rifampin,
and tobramycin, the patient died 10 days after the first VISA blood specimen
was drawn; the cause of
death was endocarditis.
The VISA isolate was interpreted as "susceptible" at 4
µg/mL by the Vitek
system. Because of the increased awareness of VISA strain emergence,
according to laboratory
protocol at hospital A, confirmatory testing was performed on all strains of
S. aureus with
Vitek (MIC greater than or equal to 4 µg/mL) using three additional
independent methods: the Pasco
Gram Positive Microtiter Panel (Pasco Laboratories, Wheatridge, Colorado),
MIC=8 µg/mL; the Etest
(AB Biodisk North America, Inc., Piscataway, New Jersey), MIC=6 µg/mL; and
inoculation into brain
heart infusion (Remel, Lenexa, Kansas) agar with 6 µg/mL of vancomycin (e.g.,
a vancomycin screen
plate indicated growth). Susceptibility results were confirmed by CDC.
After identifying the VISA isolate, hospital A's infection-control
department implemented
CDC's Interim Guidelines for Prevention and Control of Staphylococcal
Infection Associated with
Reduced Susceptibility to Vancomycin (6) and began an epidemiologic
investigation to evaluate
potential transmission. None of 10 family members or 171 health-care workers
screened by nares
culture was colonized with VISA. No other VISA isolates were identified in
other hospitalized
patients.
Reported by: MA Khurshid, MD, T Chou, MPH, R Carey, PhD, R Larsen,
Chicago; C Conover, MD, SL
Bornstein, MD, Acting State Epidemiologist, Illinois Dept of Public Health.
Hospital Infections
Program, National Center for Infectious Diseases; and an EIS Officer, CDC.
Editorial Note:
Since the emergence of nosocomial MRSA infections in the 1980s, and more
recently the emergence
of community-acquired MRSA infections, vancomycin is being used increasingly
as therapy for treating
suspected S. aureus infections. Because few therapies are available to
treat MRSA, the
confirmed reports of VISA strains demonstrating reduced susceptibility to
vancomycin, which has been
the drug of last resort to treat MRSA, is of concern.
The acronyms "VISA" and "GISA" (glycopeptide-
intermediate S.
aureus) have been used in the United States to describe S. aureus
isolates with reduced
susceptibility to vancomycin. The National Committee for Clinical Laboratory
Standards published
interpretive criteria defining both (7). The term "GISA" is a
technically more accurate
description of VISA strains, because all isolates have shown intermediate
level MICs to the
glycopeptide drugs, vancomycin and teicoplanin. However, clinicians may not
recognize the term
glycopeptide, and the acronym VISA is used more frequently.
Laboratorians may not be aware of proper methods for accurately
identifying VISA (8).
Hospital A's laboratory described in this report properly identified this
VISA-infected patient by
using a confirmatory testing protocol consistent with CDC's interim
guidelines (6). This protocol
included an algorithm to identify candidate strains (i.e., vancomycin MIC
greater than or equal to 4
µg/mL) for confirmatory testing. At hospital A's laboratory, the Vitek system
is not used only to
detect intermediate resistance of S. aureus isolates but also to
detect candidate strains for
confirmatory susceptibility testing. Correct and prompt identification of
VISA is critical in
preventing transmission.
If candidate strains are detected, CDC is available to perform
expedited confirmatory
susceptibility testing. CDC is seeking laboratory reports of confirmed cases
of VISA infection for
an ongoing nationwide epidemiologic study. Information on confirmatory
testing, investigation
therapy, and infection-control guidelines can be obtained from CDC's Hospital
Infections Program,
National Center for Infectious Diseases, telephone (404) 639-6413; World-Wide
Web site,