Are bugs winning the battle with vancomycin?
Bacteria show increased resistance to antibiotics
The bad news for home infusion providers is that home care patients in Michigan and New Jersey with strains of staphylococcus bacteria that showed signs of becoming resistant to vancomycin were not the first such cases in the United States, and they’re not likely to be the last. The good news, says Ronald N. Jones, MD, professor and director of the medical microbiology division at the University of Iowa College of Medicine, is that health care providers have the ability to inhibit such bacteria from becoming resistant through awareness and common sense.
By prescribing antibiotics less frequently and cycling effective drugs rather than exposing a patient for a prolonged time period to one drug, health care providers and physicians can play an integral role in slowing the development of antibiotic-resistant drugs. But because such practices are not currently in widespread use, bacteria are growing more and more resistant to popular antibiotics including vancomycin in large part due to a failure by health care providers to properly use and monitor the use of antimicrobial agents.
"Almost all of the major resistances to antibiotics have emerged in the past 20 years, so this is a recent two-decade phenomenon of escalating resistance," says Jones. "It’s clearly true that the use of antibiotics over a long period of time creates an environment for the bacteria to mutate and evolve themselves so they can survive in a hostile environment of antibiotics, and yet we continue to escalate our prescriptions every year."
Kenneth Wilcox, MD, state epidemiologist with the Michigan Department of Community Health, notes that the Michigan home care patient had a staph infection which, after six months of treatment with vancomycin, showed an increased resistance to the drug. Fortunately, the bacteria was susceptible to chloramphenicol, rifampin, trimethoprim-sulfamethoxazole, and tetracycline. The patient continues to receive antibiotic therapy at home.
The Department of Community Health cultured those who lived with, cared for, and/or had significant contact with the patient, and none had acquired the resistant strain.
Jones says two points are important regarding this specific case:
• "First, this organism was not resistant to vancomycin; it was actually intermediate in its degree of susceptibility, which fully means that it was only one step up in our laboratory tests above susceptible," he says. "So it’s just marginally resistant by laboratory test."
• Second, the care given to the patient provided the perfect opportunity for the strain to mutate.
"This patient that had vancomycin-resistant staphylococci is almost exactly like a patient 10 years before in North Carolina," notes Jones. "Both patients were exposed to months and months and months of continuous vancomycin therapy. These patients are the type that if we had to design an experiment to create a resistance, it would be in these patients."
While it’s no surprise that such patients can become breeding grounds for bacteria that show early signs of full antibiotic resistance, it’s the bigger picture that worries Jones.
"Our concern is that an organism that mutates to this level does not get into the general population of patients," he says. "We’ve got to make sure these continue to be isolated events."
Which isn’t an easy task. A case in point is in Japan, where a patient received vancomycin for several weeks and was cultured with a strain of bacteria identical to that which appeared in the Michigan patient. The problem was the organism had become endemic in the medical center where the Japanese patient was being treated.
"In Japan the barn door is open, and we’ve lost the control in that environment," says Jones. "Here we need to make sure the organism is not spread to the community or hospital, so good infection control policies are needed."
Jones notes that many questions remain unanswered regarding the Japanese patient, such as whether the organism mutated in this individual or if he acquired an already resistant strain from another person in the medical center.
Of worry to William Trick, MD, hospital epidemiologist for the Centers for Disease Control and Prevention in Atlanta, is both the organism and the antibiotic involved in the above examples. Trick tells Home Infusion Therapy Management that the CDC is paying close attention to such cases because staphylococcus is so common, while vancomycin is often the antibiotic of last resort for bacteria resistant to other medications.
In fact, the CDC is so concerned, it has made available its Interim Guidelines for Prevention and Control of Staphylococcal Infection Associated with Reduced Susceptibility to Vancomycin. (See editor’s note at end of article for how to access this report.)
The CDC’s guidelines include the following:
• Using recommended laboratory methods for identifying such strains.
These include media and incubation methods, antimicrobial susceptibility methods, and susceptibility breakpoints.
• Prevent the spread of the bacteria.
CDC suggestions include patient isolation when appropriate, dedicating specific health care workers to provide one-on-one care, and strictly enforcing all infection-control practices.
In reviewing the Michigan patient’s plan of care, Jones says vancomycin was appropriate. However, a different use of the drug could have been just as effective without providing the bacteria the opportunity to mutate.
"In retrospect, this is the kind of setting where people could have suspected such a resistance situation and may have wanted to cycle therapeutic drugs," he says. "Use vanco for a while, then use another drug that would have equal effect. Doing this would not allow the organism the continuous opportunity to mutate."
Situations in which there is a failure to cycle drugs, and the same antibiotic is prescribed over an extended period are when the most resistant organisms emerge. Such resistance comes as no surprise to Jones.
"For almost any drug that I have studied in the last 20 years of my professional career, I can create mutations by passaging in the presence of drugs," he says.
Additional attention needed
Jones is a lead researcher in the Sentry Antimicrobial Surveillance, a program designed by Jones and researchers from the Eijkman-Winker Institute for Microbiology Infection and Inflammation at University Hospital in Utrecht, Netherlands. Funded by Bristol-Myers Squibb Co. of Princeton, NJ, Sentry will monitor antimicrobial resistance patterns and bacterial infections worldwide for the next three to five years.
Such monitoring is needed, says Jones, for many reasons, including the fact that serious resistances are no longer being found exclusively in hospitals.
"Now, many of the serious resistances are not emerging in hospitals but in the community setting," he explains, adding that antibiotic prescriptions written in physician offices are three times more common than those ordered in hospitals.
The study hopes to educate physicians and health care providers on the various resistances that are emerging and educate the public that antibiotics are not always necessary. While the study presently includes South America, the United States, Canada, and 14 European countries, it will expand into the Western Pacific, Africa, and the Middle East next year.
"We have selected medical centers that are geographically located, so if we get important results from a medical center in western Pennsylvania, we will direct reports back to medical professionals in that area and publish these as quickly as we can through national and international meetings and the lay press," says Jones.
Data from the Sentry program will be published in medical journals and geographically appropriate medical publications. Jones adds that there will be an interactive Web page available by year’s end.
(Editor’s note: Interim Guidelines for Prevention and Control of Staphylococcal Infection Associated with Reduced Susceptibility to Vancomycin is available by accessing the CDC’s Web page at www.cdc.gov/ncidod/hip/hip.htm.)
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