ICPs may be missing resistant staph cases
Infection cleared with new drug linezolid
Underscoring that the level of emerging resistance to vancomycin in staph strains is greater than that being reported by the nation’s microbiology laboratories, an investigator emphasizes that a recently reported case of vancomycin-intermediate S. aureus (VISA) may have gone undetected at many labs. In particular, infection control programs that rely on commercial labs or do not routinely keep isolates for later subculturing could have missed the case, which occurred with a 27-year-old home care patient in Las Vegas.
"Commercial labs that may only look at a culture plate for 24 hours and chuck it would not have made the observation [of the case]," says David Pegues, MD, one of the principal investigators in the case and hospital epidemiologist at the University of California Los Angeles (UCLA) Medical Center.
While no evidence of VISA was found in culture at 24 hours, lab technologists at UCLA did a subculture at 48 hours and found "multiple pinpoint colonies" of the emerging pathogen, he says "That is an important point," he tells Hospital Infection Control. "Labs that don’t hold onto cultures, reexamine them, and work up all staph strains for different colony morphologies may fail to detect this phenomenon. We may be missing strains."
Recently reported in Toronto at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the case involved VISA with a minimum inhibitory concentration (MIC) of eight for vancomycin. That is the same level of intermediate resistance detected in the first documented case in Japan in 1996 and in subsequent cases in the United States and other countries. The pathogen also has been described as "GISA" (glycopeptide intermediate S. aureus), a technically more accurate description because all isolates have shown intermediate-level MICs for the glycopeptide drugs vancomycin and teicoplanin.
There have been six confirmed cases of VISA in the United States since 1997, and investigators also are reporting numerous infections with so-called reduced-susceptibility staph strains. (See related story on staph strains with reduced susceptibility.) Pegues investigated the VISA home care case along with epidemiologists from the Centers for Disease Control and Prevention.
Factors that should heighten the suspicions of infection control professionals looking for such cases include the presence of a deep-seated, recalcitrant infection with methicillin-resistant S. aureus (MRSA), where dosage and penetration of an antimicrobial into the infection site may be inadequate, Pegues says. In addition, while previous cases have occurred in dialysis patients and acute-care settings, the case establishes that VISA can occur in home care.
"In anyone with a deep-seated infection caused by MRSA requiring prolonged therapy with vancomycin, the possibility exists for the emergence of these resistant mutants," Pegues says. "When you see a methicillin-resistant staph strain with a vancomycin MIC value that is greater than .5 micrograms per milliliter — something with relative’ resistance [like] one or two — that is a situation where you may want to hold onto a culture longer and do more formal susceptibility testing."
Another key finding is that the patient may have received subtherapeutic doses of vancomycin in home care, contributing to the rise of the resistant pathogen. "It appears as though her trough vancomycin levels were consistently subtherapeutic," Pegues says. "She may have been underdosed on her vancomycin therapy, [which] may have ultimately contributed three months later to the identification of these GISA strains."
The patient’s medical history in Nevada included a laparoscopic cholecystectomy that was complicated by cystic duct laceration in February 2000. She was discharged to home
care in the Las Vegas area and developed multiple liver abscesses. She had subsequent placement of bile duct stents and drains in March
and June at UCLA. After MRSA was isolated from bile, a regimen of metronidazole, fluconazole, and vancomycin was begun. After home infusion of vancomycin for nine weeks, S. aureus was still cultured from bile.
On subculture at UCLA, large and small S. aureus colonies were seen at 24 hours. At 48 hours, however, multiple colonies were subcultured, and two different VISA strains were identified. Somewhat surprisingly, one of the VISA strains was methicillin-susceptible, while the other fit the typical profile of previous cases as an MRSA. Of note, the infection cleared after vancomycin was replaced with combination therapy that included the new drug linezolid.
"She was treated with linezolid, tremethoprim sulfa, and doxycycline," Pegues says. "Within 10 days of beginning that combination therapy and getting off of vancomycin, her biliary drainage cultures were negative."
Some labs cannot detect strains
Are other cases going undetected? Certainly that’s true at 16% of labs responding to a CDC survey by clarifying that they do not have the capacity to detect VISA. Most of those labs were using disk diffusion testing methods that will not detect the pathogen, Scott Fridkin, MD, a medical epidemiologist in the CDC’s hospital infections program, reported at ICAAC. The survey drew respondents from eight states with a total population of about 21 million people. In addition some 60% of the respondents were not aware that confirmatory testing was needed to detect VISA.
That said, Fridkin cited other isolate "look-back" studies that suggest the pathogen is not going undetected. "The incidence of vancomycin intermediate Staph aureus is still unknown, but I have to admit I believe it’s a rare event currently," he said. "I think as we start to look more, we will find it more. How do we know it’s still relatively rare? There have been several published studies that essentially have gone back through their freezers to look at Staph aureus isolates and see if they had any VISAs. One review of 530 isolates from 33 hospitals found zero."
Nevertheless, Fridkin also said it is "quite concerning" that so-called "hetero-resistant" strains of VISA have been reported as high as 20% at some hospitals. "Essentially, it’s an organism that has subpopulations, or daughter cells, that have higher MICs than the parent strain," he said.
"The parent strain’s MICs may be usually between 1 and 4 µg/ml, but after propagating these strains on vancomycin-containing agar, we are able to identify these subpopulations [with higher MICs]," he explained.
Also issuing a warning about that organism at ICAAC was Mary Rogeman, MD, hospital epidemiologist at the VA Medical Center in Baltimore and professor of Medicine at the University of Maryland. "When people go back retrospectively to look at their isolate collections, we’re seeing a frightening amount of "hetero-VISA," she said. "These are colonies of MRSA, which are susceptible to vancomycin on conventional testing, but they contain subpopulations of cells with vancomycin MICs of approximately eight to 16, so they fall into the intermediate susceptibility. . . . Again, none of these isolates conventionally tested as being resistant to vancomycin, but with specialized testing designed to bring out these subpopulations of cells, they were able to find it. So, with time, I’m afraid that we’re going to be not only talking about MRSA in the future, but we’ll be talking about VRSA as well."
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content