What are the causes and treatments of pulmonary fungal infection (PFI)?

From the Guidelines

Fungal lung infections should be treated with antifungal medications, with voriconazole being the first-line treatment for Aspergillus infections at 6 mg/kg IV twice daily on day 1, followed by 4 mg/kg twice daily, or 200-300 mg orally twice daily for 6-12 weeks, as it has been shown to improve survival and response rates compared to other treatments 1.

Treatment Options

• Voriconazole is the recommended treatment for invasive pulmonary aspergillosis, with a loading dose of 6 mg/kg IV twice daily on day 1, followed by 4 mg/kg twice daily, or 200-300 mg orally twice daily for 6-12 weeks 1.
• For patients who are intolerant of or refractory to voriconazole, a formulation of amphotericin B (AMB) is an appropriate alternative, with lipid formulations being less nephrotoxic than conventional AMB 1.
• Caspofungin and itraconazole are also options for salvage therapy, with response rates of around 40% 1.

Diagnosis and Monitoring

• Diagnosis of fungal lung infections requires sputum cultures, bronchoscopy, or lung biopsy to identify the specific fungus and guide appropriate treatment.
• Serial clinical evaluation and radiographic imaging, usually with CT, should be performed at regular intervals to monitor the response to treatment.
• Serial serum galactomannan assays may be useful for therapeutic monitoring, but their prognostic and therapeutic value is still investigational 1.

Specific Fungal Infections

• Candida pneumonia may require fluconazole 400 mg daily for 2-3 weeks.
• Cryptococcal pneumonia is treated with amphotericin B (0.7-1 mg/kg/day) plus flucytosine (100 mg/kg/day) for 2 weeks, followed by fluconazole 400 mg daily for 8 weeks.
• Histoplasmosis often requires itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily for 12 months.

Severe Infections

• Severe fungal lung infections may require hospitalization for IV antifungals and respiratory support.
• Patients with underlying hepatotoxicity or other contraindications to voriconazole may require alternative treatments, such as lipid formulations of AMB or itraconazole 1.

From the FDA Drug Label

1. 1 Invasive Aspergillosis Voriconazole tablets are indicated in adults and pediatric patients (aged 12 to 14 years weighing greater than or equal to 50 kg and those aged 15 years and older regardless of body weight) for the treatment of invasive apergillosis (IA). In clinical trials, the majority of isolates recovered were Aspergillus fumigatus There was a small number of cases of culture-proven disease due to species of Aspergillus other than A. fumigatus

The treatment for fungal lung infection includes voriconazole for invasive aspergillosis.

• The recommended dosing regimen for invasive aspergillosis is a loading dose of 6 mg/kg every 12 hours for the first 24 hours, followed by a maintenance dose of 4 mg/kg every 12 hours 2.
• Voriconazole is effective against Aspergillus fumigatus and other species of Aspergillus.
• Amphotericin B may also be used to treat fungal infections, but its use requires caution due to potential side effects 3.

From the Research

Fungal Lung Infection Treatment

• The treatment of fungal lung infections, such as invasive pulmonary aspergillosis (IPA), typically involves the use of antifungal drugs like voriconazole, isavuconazole, and amphotericin (AmB) formulations 4.
• A systematic review and network meta-analysis found that second-generation triazole antifungal drugs, including voriconazole, isavuconazole, and posaconazole, exhibited superior overall response to dAmB and ABCD in the treatment of IPA 4.
• Voriconazole was ranked as the best drug in network rank analysis, and combination therapy with voriconazole and anidulafungin may serve as an alternative option for IPA patients with limited drug tolerance 4.

Clinical Approach and Management

• Fungal lung infections present both diagnostic and therapeutic challenges, and the increasing prevalence of these infections is correlated with increasing numbers of immunocompromised patients 5.
• The clinical approach to fungal lung infections involves the use of antifungal agents, and the choice of agent depends on the specific type of infection and the patient's underlying condition 5.
• For chronic cavitary pulmonary aspergillosis (CCPA), the mainstay of treatment is oral triazoles, with itraconazole and voriconazole being commonly used options 6.

Antifungal Agents

• Voriconazole has been shown to be effective in the treatment of invasive aspergillosis, with better responses and improved survival compared to amphotericin B 7.
• Inhaled antifungal therapy may provide an attractive option for the treatment of pulmonary fungal infections, with benefits including reduced adverse events and improved exposure to the lung lumen 8.
• However, challenges remain in the development of inhaled antifungal agents, including required preclinical studies, appropriate clinical design, pharmacokinetics, delivery system(s), and regulatory process 8.