Guideline sources The following summarized guidelines for the evaluation and management of pulmonary cryptococcosis are prepared by our editorial team based on guidelines from the Infectious Diseases Society of America (IDSA/CDC/NIH/HIVMA 2023), the American Thoracic Society (ATS 2011), and the Infectious Diseases Society of America (IDSA 2010). 1 2 3 Guidelines 1. Diagnostic investigations Evaluation for CNS involvement: As per ATS 2011 guidelines, perform a lumbar puncture with analysis of CSF for the presence of Cryptococcus species in patients with pulmonary cryptococcosis and any concern of dissemination, neurologic symptoms, or positive serum cryptococcal antigen titers. A As per IDSA 2010 guidelines: Consider performing a lumbar puncture to rule out asymptomatic CNS involvement in nonimmunocompromised patients with pulmonary cryptococcosis. Consider omitting lumbar puncture in normal hosts with an asymptomatic pulmonary nodule or infiltrate, no CNS symptoms, and negative or very low serum cryptococcal antigen. C Consider performing a lumbar puncture to rule out meningitis in immunosuppressed patients with pulmonary cryptococcosis. C https://web.pathway.md/diseases/recHPMwnytVeVwwqv 1/4 6/29/23, 11:35 PM Pulmonary cryptococcosis Pathway 2. Medical management General principles: As per NIH 2023 guidelines, treat patients with diffuse pulmonary disease similarly to CNS disease. B As per IDSA 2010 guidelines, treat nonimmunosuppressed patients with severe pulmonary cryptococcosis similarly to CNS disease. B Show 2 more Antifungal therapy: As per NIH 2023 guidelines, initiate fluconazole 400-800 mg/day for 10 weeks, followed by 200 mg/day for a total of 6 months, combined with effective antiretroviral therapy in patients with mild-to-moderate symptoms and only focal pulmonary infiltrates. B As per ATS 2011 guidelines, initiate fluconazole 400 mg/day in immunocompetent patients with pulmonary cryptococcosis and no evidence of other organ involvement. Taper the dose to 200 mg/day after clinical improvement is assured and with total treatment for 6 months. B Consider initiating itraconazole 400 mg/day for 6 months as an alternative option. B Show 4 more As per IDSA 2010 guidelines, initiate oral fluconazole 400 mg/day for 6-12 months in nonimmunosuppressed patients with pulmonary cryptococcosis with mild-to-moderate symptoms. Consider initiating oral itraconazole 200 mg BID, voriconazole 200 mg BID, or posaconazole 400 mg BID as alternatives if fluconazole is unavailable or contraindicated. Do not regard persistently positive serum cryptococcal antigen titers as criteria for the continuance of therapy. B Show 2 more Management of increased intracranial pressure: manage patients with cryptococcosis and raised ICP in conjunction with clinicians with appropriate expertise in the treatment of cryptococcosis of the CNS, and obtain neurosurgical consultation as indicated. B Show 3 more Management of immune reconstitution inflammatory syndrome: As per NIH 2023 guidelines, continue both antiretroviral and antifungal therapy and reduce elevated ICP, if present, for the management of immune reconstitution inflammatory syndrome. B Escalate antifungal therapy, such as restarting amphotericin B therapy or increasing the fluconazole dose to 1,200 mg/day, while diagnostic tests are pending. B Show 2 more As per ATS 2011 guidelines, consider administering adjunctive systemic corticosteroids (prednisone 40-60 mg/day, or equivalent, for 1-2 weeks) in patients with inflammatory response syndrome. C As per IDSA 2010 guidelines, consider administering corticosteroids in patients with ARDS in the context of immune reconstitution inflammatory syndrome. C 3. Surgical interventions Indications for surgery: https://web.pathway.md/diseases/recHPMwnytVeVwwqv 2/4 6/29/23, 11:35 PM Pulmonary cryptococcosis Pathway As per ATS 2011 guidelines, consider performing surgical resection in selected patients with pulmonary cryptococcosis and large mass lesions or areas refractory to medical therapy. C As per IDSA 2010 guidelines, consider performing surgery for either diagnosis or persistent radiographic abnormalities and symptoms not responding to antifungal therapy. C 4. Specific circumstances Pediatric patients: initiate oral fluconazole 6-12 mg/kg/day for 6-12 months in pediatric patients with cryptococcal pneumonia. B Pregnant patients: Obtain close follow-up in pregnant patients with limited and stable pulmonary cryptococcosis. Initiate fluconazole after delivery. B Monitor for immune reconstitution inflammatory syndrome in the postpartum period. B Asymptomatic patients: do not initiate antifungal treatment in asymptomatic immunocompetent patients with respiratory tract colonization by Cryptococcus neoformans. D Patients with Cryptococcus gattii infection: As per ATS 2011 guidelines, consider continuing fluconazole treatment > 6 months in patients with documented Cryptococcus gattii infection, at least in part because of the slightly reduced susceptibility to fluconazole displayed by Cryptococcus gattii compared with Cryptococcus neoformans. C As per IDSA 2010 guidelines, treat patients with pulmonary cryptococcosis caused by Cryptococcus gattii similarly to disease caused by Cryptococcus neoformans. B Clinical findings Symptoms Past medical history Chest pain Diabetes mellitus Cough Human immunodeficiency virus infection Fever Immunocompromising condition Shortness of breath Liver cirrhosis Sputum production Pneumonia Medication history Solid organ transplantation Corticosteroids Social history Lab findings Living in or travel to subtropical regions serum cryptococcal antigen Living in or travel to tropical regions Imaging findings Lung mass Lung nodule https://web.pathway.md/diseases/recHPMwnytVeVwwqv 3/4 6/29/23, 11:35 PM Pulmonary cryptococcosis Pathway Pulmonary cavity References 1. Andrew H Limper, Kenneth S Knox, George A Sarosi et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011 Jan 1;183 1 96 128. Open 2. Perfect JR, Dismukes WE, Dromer F et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010 Feb 1;50 3 291 322. Open 3. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Department of Health and Human Services. 2023. Open https://web.pathway.md/diseases/recHPMwnytVeVwwqv 4/4