ICPs told to heed 'early warning' of Japan's new resistant staph
ICPs told to heed early warning’ of Japan’s new resistant staph
Bolster your program support now, the CDC cautions
Recent confirmation of intermediate vancomycin-resistant Staphylo coccus aureus in Japan should be taken as an early warning that cases may begin appearing in the United States, and that higher levels of resistance may only be a matter of time, public health officials tell Hospital Infection Control.
Infection control professionals in the United States should heighten surveillance for vancomycin resistance in S. aureus isolates, redouble antibiotic control efforts, and be on the alert for patients with non-responsive infections, officials advise.
"Hopefully, this early warning will provide the infection control community with the ammunition needed to get better administrative support to enhance their infection control programs, enhance their laboratories, and basically make their surveillance systems sentinel systems,’ so we would recognize this if it came in and respond to it very quickly," says William Jarvis, MD, chief of the investigations and preventions branch of the hospital infections program at the Centers for Disease Control and Prevention in Atlanta.
As reported in HIC, public health officials in Japan asked the CDC to confirm vancomycin resistance in the isolate. The prime concern was that dreaded vancomycin-resistant S. aureus (VRSA) which would be resistant to all commonly used antibiotics in the United States had finally emerged in a clinical setting. (See story in HIC, June 1997, pp. 81-83.) Instead, the isolate tested had an intermediate level of vancomycin resistance with a minimum inhibitory concentration (MIC) reading of 8. By definition, an MIC level of 32 is needed for an organism to be classified as fully vancomycin-resistant. Thus the CDC is referring to the emerging pathogen as vancomycin-intermediate S. aureus (VISA), Jarvis explains.
Regardless, the CDC is taking the situation seriously and maintains contingency plans to go to the site of the first U.S. case to implement strict infection control measures. As soon as any institution or laboratory identifies such an isolate, it should notify its infection control department, which in turn should alert local health authorities and the CDC, Jarvis says.
"We would try to work out an arrangement to send a team there immediately," he says.
Pathogen could arise anywhere
However, the CDC does not advise screening incoming patients from Japan for the organism, he says. A similar strain could arise under antibiotic pressure in the U.S. and even go undetected without careful laboratory scrutiny of isolates, he adds.
"To our knowledge there has not been a report of any such isolate here," he says. " Whether [VISA] from Japan will end up getting over here ultimately? Maybe. Rapidly? Hopefully not. It may just be that the Japanese have been more astute at picking this up. There is no reason to believe it might not come from somewhere else or even from within the United States."
Though the worst-case scenario of VRSA was not realized, the CDC’s confirmation of an intermediate level of resistance may prove to be a harbinger of greater levels of vancomycin resistance in the future.
"Every class of drugs is unique, but my guess is that at some point in the future we will see higher levels of resistance in staph," says Fred Tenover, PhD, chief of the CDC nosocomial pathogens laboratory branch, who tested the Japanese isolate at the CDC.
The isolate came from an infant who developed a methicillin-resistant S. aureus (MRSA) surgical site infection following heart surgery in May 1996 at a Tokyo hospital. The patient recovered after being treated with streptomycin, a drug that is currently available in the U.S. only on an emergency basis for patients with non-responsive infections, and was discharged last September. (See related story, p. 99.) Japanese researchers detected a low level of vancomycin resistance in the isolate and sent it to the CDC for confirmation.
"It looks like the initial MRSA isolate was the same as the isolate that subsequently was a VISA," Jarvis says.
Health officials in Japan subsequently began conducting surveillance at other hospitals, and have now identified the VISA strain at a total of six hospitals in Tokyo and Nagasaki, Tenover reports. Though the CDC does not have complete information about the extent of the problem, the agency is in discussions with Japanese health officials in hopes of participating in the investigation, Jarvis says.
Japanese infection control limited
"We’re hoping in working with the Japanese that they will contain this, but at this point we don’t even know how widespread it is there," Jarvis says.
Indeed, some observers note that the general state of infection control in Japan does not bode well for control of the pathogen in that country. (For one clinician’s observations about infection control in Japan, see guest column, p. 100.)
"Really, in Japan, hospital epidemiology and epidemiology as we know it literally does not exist," Jarvis says. "They are very microbiologically oriented they actually define epidemiology as microbiology. When you look at their [1996] E. coli outbreak when hundreds of people were getting sick, to my knowledge there never was an epidemiologic investigation."
Though conceding that Japan is "some years behind other advanced countries in the field of hospital infection control and prevention," a Japanese clinician and author noted in a 1994 overview article that hospital epidemiology has been rapidly improving in response to sharp increases in MRSA infection cases in the mid-1980s.1
"However, few hospitals have special departments engaged exclusively in infection control activities . . . and the status of infection control nurse practitioners is not yet firmly established," wrote Hiroyoshi Kobayashi, MD, professor and director of the department of infection control and prevention at the University of Tokyo Hospital. He also noted in the article that some 12% to 20% of all bacteria isolated at Japanese hospitals are S. aureus, of which about 60% is MRSA.
Since vancomycin is a common first-line therapy for MRSA infection, it is possible that VISA appeared in Japan due to selective pressure for resistant strains to emerge and proliferate. Still, the resistance did not arise via a transmitted gene from vancomycin-resistant enterococci (VRE), a scenario proven possible in lab experiments.2
"This isn’t any of the known enterococcal genes, and it does not look like it is [genetically] transmissible," Tenover says. "It looks like it is some sort of change in the cell wall. It looks thicker by electron microscopy, but that is really all we know now."
Though the direct transfer of resistant genes from VRE to S. aureus was considered by some a more dire scenario possibly signaling a more rapid emergence of a pathogen with full antibiotic resistance Jarvis said a more gradual appearance of resistance in staph is hardly comforting.
"I think from what the Japanese have found in their laboratory studies and what Fred [Tenover] has confirmed here, it looks like the best hypothesis right now is the pressure of vancomycin use led to increased resistance in this strain," he says. "Now if it can jump from an MIC of 2 to 4 to an MIC of 8, I am not sure it can’t then jump to 16 and then to 32 as time goes on. So I am not sure that this is better [than genetic transfer from VRE]. They’re both bad."
Indeed, the finding suggests that the same strain could eventually appear elsewhere in patients with MRSA being treated with vancomycin, as is frequently the case in U.S. hospitals even rural facilities like Holzer Medical Center in Gallipolis, OH.
"That worries me a great deal because we do have high usage of vancomycin, and I know that every time vancomycin is given it increases the risk of bugs becoming resistant,"says Nancy Childs, RN, BSN, CIC, infection control practitioner at the medical center. "But it is hard in our area because we have a high community rate of MRSA. Every day I get a list of the antibiotics ordered from the pharmacy, and any time there is vancomycin ordered I go up and look at the chart and see why it was ordered. Most of the time it is because there is a resistant organism like staph."
Failed therapy may precede first case here
A key point to remember about the first case in Japan is that the clinical "red flag" event was that the patient with MRSA infection did not respond to therapy with vancomycin. For that reason, it is unlikely cases have occurred in the U.S. and been missed because no such patient has been reported, Tenover says.
"We would have expected to have seen this similar sort of occurrence in our patients and we simply haven’t had that," he says. "The major message [for U.S. infection control practitioners] is if they hear of or are aware of an apparent patient failure with vancomycin particularly for an MRSA infection that would certainly be the time to look at that strain more closely or let us know so we could test it or have a reference laboratory test it. I think that is really the critical issue now, looking for the potential patient failures."
Likewise, clinical labs in the U.S. should now be routinely screening staph isolates for vancomycin resistance, he adds. Though the CDC receives about two isolates a month of suspected VRSA from U.S. hospitals, none of which have been confirmed in subsequent testing, there is a perception that many hospitals are not trying to find the pathogen because it has never been reported.
"One of the issues that we have heard people say is, There is no resistance described up to this point; therefore, we are not going to test,’" Tenover says. "[Now] they need to be looking for this type of resistance in staphylococci."
The CDC is in the process of drafting infection control measures for the first U.S. cases of VISA or VRSA, and expects to issue them in the near future. In general, the measures are expected to be similar to guidelines already published by clinicians and to the existing CDC guidelines for VRE.3,4 In that regard, the CDC is hopeful that the news from Japan will bolster compliance with existing infection control recommendations and antibiotic control measures for VRE, which is increasingly becoming endemic in U.S hospitals.
"It is just going to set the stage for the genetic [resistance] material to be transferred," Jarvis says. "That did not happen this time, but I think it is a forewarning of what can happen in the future. If this organism or a more highly resistant staphylococcal organism is introduced into a U.S. hospital, infection control departments are going to have to have better administrative support and better compliance by their health care workers to prevent spread. Hopefully, this forewarning from Japan will bring the message home."
References
1. Kobayashi H. Overview of [the] health care system. Asepsis 1994; 16:4-6.
2. Noble WC, Virani Z, Cree RG. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992; 72:195-198.
3. Edmond MB, Wenzel RP, Pasculle AW. Vancomycin-resistant Staphylococcus aureus: Perspectives on measures needed for control. Ann Intern Med 1996; 124:329-334.
4. Centers for Disease Control and Prevention. Hospital Infection Control Practices Advisory Committee. Recom mendations for preventing the spread of vancomycin resistance. Infect Control Hosp Epidemiol 1995; 16:105-113.
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