An HIV-positive patient with a CD4 count of 120 cells per microlitre develops progressive dyspnoea with bilateral diffuse pulmonary infiltrates. Why are azole antifungal agents ineffective against the causative organism despite it being classified among fungi?

• A It resides exclusively within alveolar macrophages where azoles cannot penetrate
• B It exists only as cysts that lack active sterol biosynthesis
• C It possesses an efflux pump that rapidly expels azoles
• D Its cell membrane contains cholesterol instead of ergosterol ✓

Explanation

Pneumocystis jirovecii pneumonia occurs below a CD4 count of 200 cells per microlitre and causes diffuse bilateral interstitial infiltrates. Unlike true fungi, Pneumocystis has little or no ergosterol in its membranes and instead uses cholesterol, so lanosterol 14-alpha-demethylase inhibitors such as fluconazole have no target. This is also why echinocandins have only partial activity. Trimethoprim-sulfamethoxazole remains first-line therapy. Efflux pumps explain azole resistance in Candida species, and both trophic and cystic forms of Pneumocystis lack the ergosterol target.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.