Former CDC investigator throws down the gauntlet

With VRSA on rise, time for aggressive strategy

A former top public health investigator who has now become an independent infection control consultant has thrown down the gauntlet to his former colleagues at the Centers for Disease Control and Prevention (CDC).

Fueled in part by the third case of vancomycin-resistant Staphylococcus aureus (VRSA) in the United States, William Jarvis, MD, urges more aggressive hospital surveillance measures than those currently recommended nationally by the CDC.

Echoing the main theme recently in Philadelphia at the annual conference of the Society for Health Care Epidemiology of America (SHEA), Jarvis called for hospitals to conduct active surveillance cultures to rapidly identify and isolate patients with methicillin-resistant Staphylococcus aureus (MRSA).

The CDC has not pushed active surveillance cultures, and the practice has not been widely adopted in U.S. hospitals. Now Jarvis is calling his old colleagues on it.

"In ICU patients, approximately 60% of the isolates causing infections in U.S. hospitals are MRSA strains," he said. "In non-ICU patients, it is over 50%, leading to over 70,000 MRSA infections and many deaths [annually] . . . Active cultures and contact precautions do work. We should not give up on MRSA."

Such approaches have dramatically reduced resistant staph strains in other countries, with Denmark the most often cited example.

"National guidelines in the United States should recommend this comprehensive approach," Jarvis said.

"The [patient] isolation guideline is currently being revised by the CDC. If they don’t recommend this approach, I think we all have to ask, Why not?’ It is an evidenced-based guideline. I think we should be recommending it in the United States nationally that which the western Europeans, the Danes, and SHEA have recommended," he noted.

Indeed, SHEA broke ranks with the CDC last year in urging the active surveillance practice, which calls for culturing patients on admission or periodically to detect and eradicate the reservoir of resistant organisms.1

The guidelines recommend the practice, so colonized or infected patients can be placed in contact isolation rather than serving as an undetected source to spread the pathogens to other patients.

The CDC has long recommended contact precautions for patients colonized or infected with such pathogens, but not active screening to detect them. The CDC currently does not advocate routinely adopting the screening practice but does allow it as an option to control multidrug-resistant pathogens.

The CDC is revising its isolation practices, and SHEA is lobbying the agency to adopt a more aggressive strategy. One factor cited for not going to active surveillance cultures appeared in an early draft of the CDC guidance, which stated, "in acute care, an overemphasis on additional transmission-based precautions . . . can diminish the adherence to standard precautions."

In addition to compliance issues raised by putting more patients in isolation, arguments against the practice also typically have cited cost and lack of efficacy.

Concerning the latter, there even have been suggestions that some studies reflect an inherent bias because many researchers already have adopted the policy and are in favor of it. Jarvis strongly dismissed such criticisms in presenting his case to SHEA attendees, thundering like an attorney making his closing arguments before the jury.

"I would like anyone in this room who had endemic MRSA in their institution and it went away on its own to please raise their hand," he said to a smattering of laughter and not a single raised hand.

"I have never had anybody come up to me anywhere in the world and say that they had a 50% MRSA prevalence [for example] and it disappeared by doing nothing. I don’t believe it. We now have almost 80 to 90 studies showing that with active surveillance cultures and contact isolation that you can dramatically decrease or even eradicate MRSA. It is hard for me to believe that [so many] studies showing an effect in one direction are all absolutely biased, and that for some reason — perhaps chance — those of you who have eradicated MRSA by doing nothing have not reported your data yet. I suspect the New England Journal of Medicine would be more than happy to hear from you," Jarvis added.

See your VRE and MRSA, and raise you VRSA

The latest VRSA case raises the stakes on the issue, in part because controlling MRSA is one of the keys to blocking the emergence of VRSA. There still are drugs that work against the pathogen, but losing vancomycin as a weapon against S. aureus has long been considered a milestone for an approaching post-antibiotic era.

Though the mechanism of resistance in the latest VRSA case in New York is a little unclear in the initial report, it appears to again involve genetic transfer.2

The first two cases in Pennsylvania and Michigan were the result of a "conjugation event": a genetic transfer from vancomycin-resistant enterococci (VRE) to S. aureus.3,4 The vancomycin-resistance determinant vanA, typically found in VRE but never in a clinical staph strain, was found in the VRSA isolates in both cases. The telltale sign was discovered again in the New York case, not surprisingly since it was shown to be possible years ago in lab experiments.5

"This is just one more showing up," said Barry Farr, MD, epidemiologist at the University of Virginia in Charlottesville. "We’ve expected to see these in the last decade ever since studies showed you could put MRSA and VRE together in a test tube or on a rabbit and end up with VRSA."

Thus, the argument is that the failure to identify and control these pathogens will only lead to more commingling and genetic transfer of their resistant components.

"The thing that accentuates the importance of this is studies by the CDC that show that even when strains of Staph aureus have intermediate susceptibility to vancomycin, those isolates that cause infection were associated with significantly higher mortality in patients than the ones that were fully susceptible to vancomycin," Farr said. "So we are not even talking about those that are frankly resistant like these [three VRSA cases]. We haven’t seen enough of these to see that same epidemiologic pattern, but all of the prior data suggests that we may see [similar mortality] problems."

Farr is a longtime advocate of active surveillance cultures and cited the increasing preponderance of evidence for the method at the studies presented at the SHEA meeting.

"I think I have seen about 15 or more different studies here showing the success of switching from standard precautions to active surveillance cultures and contact precautions," he said in an interview at the SHEA conference. "Every time, what didn’t work were standard precautions. If [the CDC is] still going to recommend that as its main measure in most facilities, we know what the message is: This is not going to be controlled. It is going to stay bad and probably get worse."

VRSA emergence called a nightmare

One definition of getting worse would be for VRSA to find its own niche, proliferate, and no longer need the genetic transfer from VRE to defeat vancomycin.

"If we look at the pattern of the use of the antibiotic and the emergence of resistance, there is oftentimes a two- to three-year delay before you have widespread growth in that resistant organism," Jarvis said.

"We have seen that with MRSA and VRE, and we may well see that — and it is going to cause us a great deal of difficulty — with VRSA," he continued.

Showing a graphic slide of an unhealed foot wound of one of the first patients with VRSA, Jarvis said, "I think you can imagine a wound such as this being an ideal source for transmission for VRSA to other patients and health care workers and causing a nightmare."

The emergence of MRSA in the community has been a legitimate and widely reported phenomenon, but the fact is about 99% of MRSA infections still are linked to hospitals, he said. As community and strains mix, the current marked differences in their antibiotic susceptibility profiles will gradually disappear, he predicted.

"There is an urgent need worldwide to control this pathogen," Jarvis told SHEA attendees. "We can look to our Danish colleagues to show that if there is a will there is a way."

Indeed, the oft-cited Danish experience shows that the MRSA proportion of all staph infections was running at about 35% in the mid-1960s in that country.

"They, as a country, decided that this was unacceptable. They instituted a number of interventions including infection control surveillance cultures, antimicrobial controls, and hand hygiene," Jarvis said. "They were able within a decade to decrease that rate to close to zero and have maintained that for nearly 30 years."

Other countries have followed suit, adopting a policy that has become popularly known as "search and destroy." Why is it important to identify colonized patients on admission and get them into prompt isolation? Jarvis cited studies that indicate a fourfold to sixteenfold reduction in transmission by isolating a colonized patient.

Moreover, one study showed active surveillance cultures are cost-effective even if you only prevent 14% of subsequent infections.5

"I think I can show you from virtually every type of paper, where this type of intervention has been included, that everyone has prevented much more than 14% of infections," he said.

While advocating active surveillance cultures, Jarvis said the selection of the patient population screened should be left to the local hospital. At the time of hospital admission or periodically thereafter, infection control professionals can culture high-risk patients such as those on antibiotics or with a history of prior admission to an area of the hospital or another facility with endemic MRSA.

"I am hopeful that the CDC will adopt this policy and will recommend it for long-term care," he said. "Because, otherwise, all of you in acute care are going to have to label every long-term care patient as a high-risk patient.

"If you look at several studies that are out there, long-term care facilities end up as one of the high-risk populations that are constantly giving you MRSA patients. So you will to have to do what they are not doing and control it at the door," Jarvis concluded.

References

1. Muto CA, Jernigan JA, Ostrowsky BE, et al. Special report: SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and Enterococcus. Infect Control Hosp Epidemiol 2003; 24:362-386.

2. Centers for Disease Control and Prevention. Brief report: Vancomycin-resistant Staphylococcus aureus — New York, 2004. MMWR 2004; 53(15):322-323.

3. Centers for Disease Control and Prevention. Public health dispatch: Vancomycin-resistant Staphylococcus aureus — Pennsylvania, 2002. MMWR 2002; 51:902.

4. Centers for Disease Control and Prevention. Staphylococcus aureus resistant to vancomycin, United States, 2002. MMWR 2002; 51:565-567.

5. Noble WC, Virani Z, Cree RG. Cotransfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992; 93:195-198.

6. Chaix C, Durand-Saleski I, Alberti C, et al. Control of endemic methicillin-resistant Staphylococcus aureus: A cost-benefit analysis in an intensive care unit. JAMA 1999; 282 1,745-1,751.