Candida and Aspergillus are the most common causes of invasive fungal infections in immunocompromised patients. Over the past two decades, there has been a substantial rise among cancer patients in the incidence of life-threatening invasive fungal infections that pose significant clinical challenges for the oncology community (N Engl J Med 348:1546-1554, 2003).
Brahm H. Segal, MD, chief of infectious diseases at Roswell Park Cancer Institute in Buffalo, N.Y., explained that the increased incidence of IFIs correlates with today’s growing high-risk patient population.
“We now have significantly more stem cell and solid organ transplant recipients and greater numbers of patients receiving intensive chemotherapy for acute leukemia,” Dr. Segal told Oncology News International.
“Candidiasis, which can present with a spectrum of diseases from mucosal infection to disseminated and invasive disease, is the central IFI caused by endogenous flora that have colonized in the gastrointestinal tract,” Dr. Segal added.
Major risk factors for candidal infections include neutropenia, mucositis, use of broad-spectrum antibiotics, chemo-induced immune dysfunction, GI surgery, indwelling catheters, and total parenteral nutrition.
“Aspergillus and other mold infections are generally contracted from environmental exposure, inhalation of airborne spores,” continued Dr. Segal. Aspergillus and other mold infections pose a greater threat than invasive candidiasis in patients with acute leukemia and allogeneic hematopoietic stem cell transplantation when prophylaxis with fluconazole (an agent active against yeasts but not molds) is used, he explained.
Understanding how IFIs can be acquired requires clear review of both endogenous and environmental sources leading to transmission of these infections. In-patient environmental exposure has a well-documented association with Aspergillus infection; in fact, molecular testing of fungal strains from patients and their corresponding hospital environment has found that perhaps 40% of cases of invasive aspergillosis are nosocomial (Clin Microbiol Infect 12[Supplement 7]:77-83, 2006).
Up to 90% of invasive aspergillosis presents with pneumonia; inhalation of Aspergillus spores is presumed to be the causative agent in this syndrome. High-efficiency particulate air (HEPA) filters have been shown to reduce the number of airborne spores and the incidence of invasive aspergillosis. However, studies show that HEPA filters do not completely eliminate risk of infections, which suggests exposure from alternate sources such as in-hospital water systems. Construction, ventilation and air-conditioning systems, flower arrangements, dust, carpets, and computer fans are also potential sources of environmental-related transmission of aspergilli, especially in an outpatient setting.
Empirical treatment varies
Populations at high risk for fungal infections require diagnostic approaches, such as radiologic imaging, culture, and histopathology of fluids or tissue biopsies. “There have also been novel advances in early diagnostic methods of invasive fungal infections, which include galactomannan and β-glucan antigen detection and polymerase chain reaction using fungal-specific primers,” said Dr. Segal. Polymerase chain reaction-based diagnosis of IFIs is promising, but still considered investigational.
Three lipid formulations of amphotericin B are now available for treating invasive fungal infections: amphotericin B lipid complex, amphotericin B cholesteryl sulfate, and liposomal amphotericin B. However, despite the availability of emerging antifungal drugs, the overall mortality in immunocompromised patients remains high, with large variations according to underlying disease.
Because diagnosing a fungal infection is difficult to establish with certainty, antifungal prophylaxis is increasingly being used to prevent these infections. But, according to Michael G. Ison, MD, “Many of the medicines used to prevent fungal infections reduce the incidence of these pathogens, but—with the exception of posaconazole and a subset of situations and patients—they haven’t been shown to markedly reduce mortality.”
Dr. Ison noted that prophylactic measures reduce hospitalizations and lengths of stays, and in that way, they add to patients’ quality of life and reduce healthcare costs. Dr. Ison is director of the transplant and immunocompromised host infectious diseases service at Chicago’s Feinberg School of Medicine at Northwestern University.