What are the symptoms of a fungal lung infection

In persons with endemic mycoses, spontaneous recovery usually occurs without treatment, especially in patients who are mildly affected and immunocompetent without dissemination; otherwise, administer treatment as outlined in the table below.

In cases in which aspergillosis, mucormycosis, and candidiasis occur in an immunocompromised host, reversing the factors affecting the patient's immune status is linked to successful recovery from the infection. Attempt ancillary interventions that may help to promote recovery from the opportunistic infection. These include (1) ensuring, with the use of growth factors, neutropenia recovery in patients receiving chemotherapy and bone marrow transplants; (2) withdrawing or tapering immunosuppressive drugs and steroids; and (3) removing infected or highly colonized catheters in patients with candidiasis.

Table. Medical and Surgical Fungal Therapy (Open Table in a new window)

When treatment is indicated, initiate antifungal agents as appropriate. Amphotericin B is the mainstay of initial therapy in many cases, especially for patients who are acutely ill. More expensive liposomal preparations of amphotericin B offer equal efficacy with less toxicity. In patients with invasive aspergillosis, including pulmonary aspergillosis, voriconazole is the new standard of care, based on its superiority over amphotericin B as primary therapy. [5, 12, 40, 41, 42] Vary the dose and treatment duration depending on the underlying pathogen causing the pneumonia.

Care should be taken regarding patients on long-term voriconazole treatment. Bone pain with radiologic evidence of periostitis and 10-fold increased fluoride levels have been reported in allogeneic stem cell transplant patients taking the drug for at least 3 months. Symptoms and findings were reversed with discontinuation of voriconazole. [43]

There is a possible association between the use of voriconazole in markedly immunosuppressed patients as prophylactic agent and the development of mucormycosis, but this matter is still controversial. [5]

Amphotericin B is available in a variety of formulations. Conventional amphotericin B injection contains amphotericin B and sodium deoxycholate as the solvent vehicle.

Amphotericin B cholesteryl sulfate complex (ABCD, Amphotec) consists of a 1:1 molar ratio of amphotericin B to cholesteryl sulfate in a colloidal dispersion, forming a bilayer in microscopic, disk-shaped particles that have a diameter of approximately 115 nm and a thickness of 4 nm.

Amphotericin B lipid complex (ABLC, Abelcet) is composed of amphotericin B and phospholipid complex, with a microscopic, ribbonlike structure having a diameter of approximately 2-11 µm.

Liposomal amphotericin B (L-AmB, AmBisome) contains amphotericin B intercalated in a unilamellar bilayer liposomal membrane; has a liposomal membrane diameter of less than 100 nm; and consists of hydrogenated soy phosphatidylcholine, cholesterol, distearoyl phosphatidylglycerol, and alpha tocopherol.

Some clinicians offer empiric therapy with conventional amphotericin B or liposomal amphotericin B for presumed fungal infections in patients who are febrile and neutropenic (eg, cancer, bone marrow transplantation, solid organ transplantation) and whose febrile state persists after receiving broad-spectrum antibiotics for a few days. Other agents that could be used in this setting are itraconazole and an echinocandin, namely, caspofungin. [44] The therapy is continued until the neutropenia resolves and the patient does not show a documented fungal infection or radiographic infiltrate.

Prophylactic therapy (suppressive therapy) with amphotericin B is used against recurrence or relapse of coccidioidomycosis, cryptococcosis, or histoplasmosis in individuals infected with the human immunodeficiency virus (HIV) who have received adequate treatment for the infection.

Other formulations, however, are starting to replace amphotericin B because of their ease of use (oral formulations) and lower toxicity for more long-term suppression. Posaconazole is used in the prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised patients receiving hematopoietic stem cell transplants who have graft versus host disease and in patients with hematologic malignancies who have chemotherapy-induced neutropenia. [45] While it used to be available only as an oral suspension given thrice daily, a delayed-release tablet formulation of posaconazole for once-daily administration allows for better bioavailability without being affected by food. The intravenous formulation is also administered once daily, but it has to be through a central line because of the presence of a solubilizing excipient SBECD (sulfobutylether-β-cyclodextrin), which can be potentially renal toxic and can accumulate in patients with moderate-to-severe renal failure. [46] Because of the large interindividual and intraindividual variations in bioavailability and drug-to-drug-interactions, therapeutic drug monitoring is recommended for posaconazole, especially if used in the therapeutic setting to treat invasive aspergillosis or zygomycosis.

Other antifungal agents used in the treatment of fungal pneumonia are fluconazole (Diflucan), itraconazole (Sporanox), flucytosine (Ancobon), and ketoconazole (Nizoral). Newer antifungal agents, such as the third-generation triazoles or the echinocandins, are more tolerable than amphotericin B or its liposomal preparations are and may even be more effective in first- or second-line treatment.

Isavuconazole has been approved by the FDA and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. Studies have shown it to be not inferior to voriconazole for aspergillosis and comparable to amphotericin B and posaconazole for mucormycosis. [38]

There have been increasing reports of azole resistance in Aspergillus species. This might be the result of the increasing use of these agents for prophylaxis and treatment of fungal infections; also there are associations with exposure to azole-like compounds used in the agricultural industry in some countries. In addition, some species have intrinsic resistance to various azoles. [5]

Caspofungin is approved for the treatment of invasive Aspergillus infections in patients unresponsive to or unable to receive amphotericin B. Combinations of a triazole with an echinocandin with or without amphotericin B have been anecdotally reported to be effective in some cases of resistant organisms, such as Mucor or Zygomycetes species. [44]

Echinocandins such as caspofungin, micafungin, and anidulafungin [47, 48, 49] offer a broad spectrum of activity for the many Candida species, including fluconazole-resistant strains. They also show effectiveness in Aspergillus infections alone or in combination with an azole.

Because of the introduction of these safer and (possibly) more potent agents, and owing to the ability to combine them together, the outlook for patients with invasive pulmonary infections, especially immunocompromised hosts, may be improving.

The role of combination therapy has been studied only in small retrospective studies with very unclear results. Combination therapy is usually not indicated in first-line treatment. In rare cases, it might be offered with a great deal of caution as second-line or salvage treatment. [39]

The establishment of neutrophil recovery or engraftment and the reduction of immunosuppression in certain patients who are at risk for fungal infections are likely to improve the chances of a successful treatment outcome. Granulocyte-macrophage colony-stimulating factor can theoretically augment pulmonary host defenses against A fumigatus infection.

Surgery may be indicated in invasive aspergillosis. [50]  Surgery is indicated in patients with documented invasive aspergillosis who have been treated with antifungal agents but who have residual lesions. The surgery is performed to prevent disease relapse when additional immunosuppression is required. Surgery is also indicated as a means to prevent or treat massive bleeding, especially when the lung lesion is contiguous with a large blood vessel.

In cavitary pulmonary sporotrichosis, surgical management should be considered in the course of the disease, even for bilateral presentation, providing that the patient has adequate predicted respiratory reserves post-surgery, as delayed surgery may result in complications and poorer outcomes. [16]