Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published November 17, 2021


Should patients being treated with methotrexate routinely receive prophylaxis against P. jirovecii pneumonia?

Pneumocystis jirovecii is a fungus with a complex life cycle and cannot be grown under standard culture conditions. Read the NEJM Case Records of the Massachusetts General Hospital here.

Clinical Pearls

Q: How is P. jirovecii identified?

A:jirovecii is identified either with the use of direct microscopic visualization, such as with highly specific direct immunofluorescence staining, or with a polymerase-chain-reaction (PCR) test. As compared with direct visualization, a PCR test is more sensitive but less specific owing to its greater ability to detect asymptomatic carriage.

Q: Are there any indirect methods for detection of P. jirovecii?

A: In addition to the direct-detection methods described above, a blood test for 1,3-β-d-glucan (a cell-wall polysaccharide found in most fungi, including P. jirovecii) is often used as a noninvasive diagnostic test for P. jirovecii pneumonia. The test has an overall sensitivity of 91% and an overall specificity of 79%. The 1,3-β-d-glucan blood test is less sensitive in persons without HIV infection than in those with HIV infection or acquired immunodeficiency syndrome (AIDS), probably owing to a lower fungal burden, and must be interpreted within the context of the pretest probability of P. jirovecii pneumonia.

Morning Report Questions 

Q: How is P. jirovecii pneumonia treated?

A:P. jirovecii is an atypical fungus that scavenges host cholesterol for its membranes rather than synthesizing ergosterol; therefore, treatment with azole antifungal agents or amphotericin is not effective. Caspofungin and micafungin inhibit 1,3-β-d-glucan synthetases and are effective against the cystic form of P. jirovecii. However, these agents are ineffective against the trophic form of P. jirovecii and thus do not fully eradicate the infection. Trimethoprim–sulfamethoxazole is the cornerstone of pneumocystis pneumonia treatment. This antibiotic combination disrupts folate synthesis crucial to the growth and reproduction of the organism by blocking two enzymes that are not expressed in humans (dihydrofolate reductase and dihydropteroate synthase). The intravenous route of administration of trimethoprim–sulfamethoxazole is standard in critically ill patients with P. jirovecii pneumonia, but oral therapy is acceptable in patients with mild disease.

Q: Should patients being treated with methotrexate routinely receive prophylaxis against P. jirovecii pneumonia?

A: For some patients, such as those who have AIDS and CD4+ T-cell counts of less than 200 per microliter, use of prophylaxis against P. jirovecii pneumonia is standard practice. Among patients without HIV infection, guidelines exist for those with hematologic cancers, for those with solid cancers who are being treated with cytotoxic chemotherapy, and for those undergoing organ or stem-cell transplantation. For patients who are immunosuppressed because of inflammatory conditions, it is a more nuanced decision. There is no consensus regarding the routine use of prophylaxis against P. jirovecii pneumonia for patients being treated with methotrexate. Historically, the incidence of P. jirovecii pneumonia among patients treated with methotrexate monotherapy has been quite low, and many physicians do not prescribe prophylaxis against P. jirovecii pneumonia in such a scenario. However, the American Thoracic Society guidelines recommend prophylaxis against P. jirovecii pneumonia for patients treated with methotrexate.

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