Emerging resistant fungal infections pose treatment problems

April 2006

CHICAGO — New fungal strains are emerging, causing serious infections and unpredictable response to currently available antifungal agents, Michael A. Pfaller, MD, said at the 16th Annual Meeting of the Society for Healthcare Epidemiology of America, held here.

“We clearly have an ever-expanding spectrum of opportunistic fungal pathogens that go beyond the common standard of species. We have to realize that many of these are inherently nonsusceptible to these antifungal agents that we have and they may require use of alternative approaches, possibly combinations,” said Pfaller, professor and director of molecular epidemiology and fungus testing laboratory in the department of pathology and epidemiology at the University of Iowa College of Medicine and College of Public Health.

Aspergillus terreus, Candida krusei, Scedosporium apiosperum and Scedosporium prolificans are fungi that may have intrinsic resistance to antifungal agents. Many of these organisms are poorly understood by medical professionals working in the laboratory and clinic, and may require new treatment methods. Pfaller discussed some of the unusual fungal organisms.

“We need to be very aggressive in making an etiologic diagnosis if at all possible,” he told Infectious Disease News.

Treatment resistance

More than 17 different species of candidemia are known to cause bloodstream infections, 95% of which are due to four specific species — C. albicans, C. glabrata, C. parapsilosis and C. tropicalis. Several rare species occur in nosocomial clusters and exhibit innate or acquired resistance to one or more established antifungal agents: C. krusei, C. lusitaniae, C. guilliermondii, C. rugosa and C. dubliniensis.

Many strains are developing resistance to treatment options. A. terreus is intrinsically resistant to amphotericin B, but susceptible to most others, according to Pfaller. S. apiosperum is well known for amphotericin B resistance, but can be treated with an extended- spectrum azole and S. prolificans is resistant to almost all treatment options.

“We know with all these invasive fungal infections mortality is high,” he said.

Studies indicate that delay in treatment is an independent determinant of hospital mortality. For treatment of candidemia, “if you don’t start therapy early, the results are poor,” Pfaller said. “That’s the importance of getting appropriate therapy, not only the right drug but the right dose.”

From 1998 through 2000, the CDC conducted population-based surveillance studies in Connecticut and Baltimore. Published in Infection Control and Hospital Epidemiology, the studies showed that if patients received adequate treatment — a systemically active antifungal for at least seven days — the mortality was lower than those treated inadequately.

“We have problems getting drugs on board and then continuing them long enough, which is one of the reasons why we are continuing to see a high mortality with bloodstream infections,” he said.

Increasing prevalence

C. krusei is more common in Europe than other areas of the world and C. guilliermondii is considered an emerging pathogen in Latin America. C. glabrata is the major organism in the United States that researchers are concerned, with respect to antifungal resistance to fluconazole and other azoles, and the extended-spectrum triazoles as well, according to Pfaller. C. glabrata is a major cause of bloodstream infections; however, the frequency varies.

Pfaller and colleagues conducted surveillance studies, which are published in Clinical Microbiology and Infection, and from 1992 through 2004, they collected C. glabrata bloodstream infection isolates from several geographic regions to determine variation. The data show that in 2004, 19.7% of isolates were C. glabrata in North America compared with 8.8% in Europe, 7.2% in Asia Pacific and 4.7% in Latin America.

Yeasts other than candida include the trichosporons such as Trichosporon asahii and T. mucoides, which are known to cause deep invasive infections, catheter-associated fungemia and hematogenous dissemination of positive blood cultures and multiple skin lesions.

“We have an ever-increasing array of patients with various pathogenic insults to them that are at risk for invasive fungal infection,” concluded Pfaller. “You have to think fungus when confronting a possible infection. There are no non-pathogenic fungi. Any organism can cause invasive and fatal disease.”

For more information:

• Pfaller MA. New developments in fungal disease. Symposium 20-17. Presented at: 16th Annual Meeting of Society for Healthcare Epidemiology of America; March 18-21, 2006; Chicago.
• Morgan J, Meltzer MI, Plkaytis BD, et al. Excess mortality, hospital stay, and cost due to candidemia: a case-control study using data from population-based candidemia surveillance. Infect Control Hosp Epidemiol. 2005;26:540-547.
• Pfaller MA, Diekema DJ. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol. 2004;42:4419-4431.