New VISA case raises questions about pathogen's potential virulence
Renal failure patients appear to be at greatest risk
The third patient in the United States to develop infection with vancomycin-intermediate resistant Staphylococcus aureus (VISA) died shortly after admission to a New York hospital, raising new questions about the potential virulence posed by the emerging pathogen.
A hemodialysis outpatient with "very serious pre-existing medical problems" developed VISA infection last March and died 12 hours after being admitted to the United Hospital Medical Center in Port Chester, Westchester County, NY, the New York State health department announced on April 23. Though primarily investigated and reported by state health officials, the New York case was confirmed by the Centers for Disease Control and Prevention in Atlanta.
"It certainly is of concern to us in that it's the third one in this country," says William Jarvis, MD, acting director of the CDC's hospital infections program. "Patients who are either receiving hemodialysis, have renal failure, or are receiving peritoneal dialysis [are the] population that seems to be at real great risk here, since literally all three of these [U.S.] patients have had some form of that. Review of use of vancomycin and antimicrobials in general in this population is indicated."
Hospital officials declined to provide additional information, but Barbara DeBuono, MD, state health commissioner, says the New York case appears to fit the pattern of those reported previously. Prior cases have involved methicillin-resistant S. aureus (MRSA) infections that develop intermediate resistance to vancomycin after prolonged or intermittent treatment with the antibiotic. The New York patient was treated with vancomycin for six weeks after developing MRSA bacteremia in December 1997 and developed VISA infection three months later, DeBuono says.
"We do think the previous experience with vancomycin treatment for such an extended period of time was related to his coming in months later with an infection with an intermediately resistant organism," she says. "It was not nosocomial, [and] we are totally convinced that this was not in any way community-acquired. This was internal to his own microbiology and flora."
Originally picked up by the hospital lab, the VISA isolate from the patient was confirmed by state pathologists and the CDC. No evidence of transmission to others was found in subsequent cultures of contacts that included 23 health care workers, 13 other patients, and two family members.
The CDC has placed great emphasis on identifying and controlling the pathogen to prevent the beginning of the kind of endemic presence in clinical settings now widely seen with MRSA and vancomycin-resistant enterococci (VRE).
"We don't believe it was transmitted to anyone," DeBuono says.
Synercid-sensitive, MIC of 8
Though the full antibiogram was not reported for the New York isolate, the CDC has determined that the VISA strain - as with the other cases reported so far - is susceptible to quinupristin/dalfopristin, the new drug Synercid.
The New York patient had a VISA strain with a minimum inhibitory concentration (MIC) of 8, the same level of intermediate resistance to vancomycin detected in the first documented case in Japan in 1996 and the two subsequent U.S. cases in Michigan and New Jersey last year.1-4
None of the cases appear to be epidemiologically related, however, as all involve distinct VISA strains that arose independently after exposure to vancomycin for treatment of MRSA, public health officials report. The mechanism of resistance is still under study by the CDC, but it has generally been described as an apparent thickening of the cellular material in VISA isolates.
"I'm not sure you can actually say it's the cell wall," explains Fred Tenover, PhD, chief of the CDC nosocomial pathogens laboratory branch, who has been studying the isolates from the first cases.
"There is a thick layer of extra-cellular material around those cells, but we don't actually have any information that says it is cell-wall precursors or not. On electron microscopy, the organism looks like it has a thickened coat around it. I don't want to call it a capsule [either] . . . but I can't tell you exactly what it is," Tenover says.
It may have lost virulence
There have been some early indications that staph organisms may sacrifice some measure of virulence in developing vancomycin resistance, as the New York patient is the first reported patient to die while actually infected with VISA. However, whether VISA directly caused the death or was merely a contributing factor with other medical conditions remains under discussion.
"My understanding of it is that the patient had severe underlying disease, was elderly, and came in and died rather rapidly," Jarvis says. "So it's not clear whether VISA being virulent is what caused the death."
Staph network formed
Such issues as virulence and patient mortal -ity in VISA cases are among the questions investigators will try to answer in the newly formed staph investigative network at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, MD, says Stephen Heyse, MD, MPH. Heyse is program officer in the NIAID's medical bacteriology and antibacterial resistance branch.
"The [NY] patient appears to have died of sepsis, which means more than likely the staph was probably the offending agent," he says. "But without a whole lot more information, it is really hard to guess."
The question will remain somewhat unresolved because an autopsy was not performed, but it appears VISA infection was the cause of death, DeBuono says. "We will never absolutely know with certainty, but he was admitted for respiratory distress, for sepsis work-up, and he expired 12 hours after he came into the hospital."
"It is likely that the scenario [is that] a fulminant infection due to the intermediate resistant organism overtook him," she explains.
At the same time, officials underscored that prior cases also have involved patients with underlying medical conditions, and the organism appears to pose little threat of infections in the community.
"I would be surprised if people anytime soon started coming into hospitals with VISA pneumonias who are otherwise completely healthy," DeBuono says.
State establishes monitoring system
The New York state health department has established a statewide monitoring system to rapidly identify VISA, and it has distributed CDC guidelines on the pathogen to all hospitals in the state. Likewise, hospitals and kidney dialysis facilities were notified of the confirmed case of VISA.
"We want to get the message out to report to us," she says. "We absolutely have to know when something like this happens. On the other hand, we also want to practice education and send the message out about good infec t ion control techniques, handling equipment, gloves, hand washing, etc. We're letting them know that this has occurred, and they have to be vigilant."
References
1. Centers for Disease Control and Prevention. Staphylococcus aureus with reduced susceptibility to vancomycin - United States, 1997. MMWR 1997; 46: 765-766.
2. Centers for Disease Control and Prevention. Update: Staphylococcus aureus with reduced susceptibility to vancomycin - United States, 1997. MMWR 1997; 46: 813-814.
3. Centers for Disease Control and Prevention. Reduced susceptibility of Staphylococcus aureus to vancomycin - Japan, 1996. MMWR 1997; 46:624-626.
4. Centers for Disease Control and Prevention. Interim guidelines for prevention and control of staphylococcal infection associated with reduced susceptibility to vancomycin. MMWR 1997; 46:626-628.
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