The choice of treatment for the management of adult pulmonary fungal infections should be based on diagnostic findings and individual risk factors, according to a new policy statement issued by the American Thoracic Society. "In most cases, treatment of fungal infections must be based on the causative fungus, the severity of disease, and the clinical features of each patient," the authors wrote.
The policy statement provides organism- and infection-site specific guidelines for therapy, including dosing recommendations, and incorporates the range of novel antifungal medications, such as the extended-spectrum triazoles and echinocandins, that have been introduced since the previous guidelines were published in 1988, according to Dr. Andrew Limper of the Mayo Clinic in Rochester, Minn., and his colleagues on the American Thoracic Society (ATS) Fungal Infections Working Group.
In particular, the recommendations outline the management of endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections with increased prevalence in immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections, such as zygomycoses, hyalohyphomycoses, the phaeohyphomycoses, and infections related to Trichosporon species (Am. J. Respir. Crit. Care. Med. 2011;183:96-128).
Endemic Mycoses. The guidelines recommend treatment with itraconazole for mild to moderate histoplasmosis, sporotrichosis, and blastomycosis, and treatment with amphotericin B for severe disease (followed by itraconazole in patients with sporotrichosis). Patients with severe histoplasmosis with diffuse pulmonary infiltrates and critically ill patients with severe pulmonary blastomycosis may require systemic steroid therapy, as well. Further, for patients with pulmonary blastomycosis and concomitant CNS involvement, combination therapy with liposomal amphotericin B (vs. amphotericin B deoxycholate) and fluconazole "should be considered due to theoretic better CNS penetration," the authors wrote.
Antifungal therapy is not recommended for primary pulmonary coccidioidomycosis in immunocompetent patients who have no risk factors for dissemination, while patients with disseminated infection should be treated with an extended-spectrum triazole, according to the guidelines, which also specify that critically ill patients with disseminated paracoccidioidomycosis should be treated initially with amphotericin B, followed by ketoconazole, itraconazole, or sulfadiazine.
Immunocompromised Patients. The treatment options for fungal infections in patients with compromised immune systems, including transplant patients, those being treated for autoimmune inflammatory conditions, and HIV-infected patients, include oral trimethoprim and sulfamethoxazole, oral primaquine plus clindamycin, or oral atovaquone for mild to moderate Pneumocystis pneumonia. Patients with moderate to severe disease should be given trimethoprim, sulfamethoxazole, and possibly prednisone, the guidelines recommend.
Emerging Fungal Infections. "The management of emerging or rare fungi is supported by limited evidence-based studies with no randomized, blinded comparative studies," the authors wrote, noting that treatment recommendations are thus based on clinical experience and in vitro susceptibility testing. Because the majority of affected patients are immunocompromised, "a primary strategy for management of these infections with underlying diseases is to maximally reduce immunosuppressive drugs, provide immunostimulants, and/or rapidly control the underlying diseases or conditions, such as HIV infection, diabetes, and/or chemotherapy-induced neutropenia," they stated.
Secondarily, particularly in the angioinvasive zygomycoses, necrotic tissues, cysts, or true abscesses should be debulked or debrided, they emphasized.
The third management strategy includes specific antifungal recommendations, such as amphotericin B for zygomycosis; voriconazole, posaconazole, or lipid formulations of amphotericin B for fusariosis; voriconazole or posaconazole for scedosporiosis; itraconazole, voriconazole, or posaconazole for phaeohyphomycoses; and, possibly, voriconazole, posaconazole, or itraconazole for trichosporonis and Paecilomyces infections.
"The exact dosing and duration of treatment for these emerging, rare infections are not precise, and consultation with an expert in infectious disease regarding these clinical decisions should be considered," the authors stressed.
The policy statement also includes recommendations for the treatment of Candida and Aspergillus infections, which are becoming increasingly common in the intensive care unit, the authors stated. For candidemia, the guidelines recommend that all existing central venous catheters should be removed, if possible, or a new placement site should be obtained and initial antifungal treatment should be with fluconazole, an amphotericin B formulation, an echinocandin, or a combination of fluconazole and amphotericin. With respect to Aspergillus infections, the guidelines recommend intravenous voriconazole or liposomal amphotericin B for invasive pulmonary aspergillosis; voriconazole or itraconazole for mild to moderate chronic necrotizing aspergillosis; and liposomal amphotericin B or intravenous voriconazole for severe chronic necrotizing aspergillosis.
The authors reported financial relationships with AlphaMed Pharmaceuticals, Pfizer, Ortho-McNeil, MiraBella Technologies, AstraZeneca, GlaxoSmithKline, Bayer, Novartis, Aradigm, Astellas, Enzon, Merck, and Schering-Plough.