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The patient should be started on four-drug therapy with rifampin, isoniazid, pyrazinamide, and ethambutol. He should also be started on antiretroviral therapy for HIV. If a protease-inhibitor-based antiretroviral regimen is used to treat his HIV, rifabutin should replace rifampin because of the serious drug-drug interactions between rifampin and protease inhibitors. If dolutegravir is chosen, it must be administered twice daily due to the interaction with rifampin; alternatively, rifabutin can be used in place of rifampin, and dolutegravir can be dosed once daily. The patient is at increased risk of developing hepatotoxicity from both isoniazid and pyrazinamide given his history of alcohol use.
Harry W. Lampiris, MD, & Daniel S. Maddix, Pharm D
The patient is a 37-year-old African-American man who lives in San Jose, California. He was recently incarcerated near Bakersfield, California and returned to Oakland about 3 months ago. He is currently experiencing one month of severe headache and double vision. He has a temperature of 38.6°C (101.5°F) and the physical exam reveals nuchal rigidity and right-sided sixth cranial nerve palsy. MRI of his brain is normal, and lumbar puncture reveals 330 WBC with 20% eosinophils, protein 75, and glucose 20. HIV test is negative, TB skin test is negative, CSF cryptococcal antigen is negative, and CSF gram stain is negative. Patient receives empiric therapy for bacterial meningitis with van-comycin and ceftriaxone, and is unimproved after 72 hours of treatment. After 3 days a white mold is identified growing from his CSF culture. What medical therapy would be most appropriate now?
Human fungal infections have increased dramatically in incidence and severity in recent years, owing mainly to advances in surgery, cancer treatment, treatment of patients with solid organ and bone marrow transplantation, the HIV epidemic, and increasing use of broad-spectrum antimicrobial therapy in critically ill patients. These changes have resulted in increased numbers of patients at risk for fungal infections.
For many years, amphotericin B was the only efficacious antifungal drug available for systemic use. While highly effective in many serious infections, it is also quite toxic. In the last several decades, pharmacotherapy of fungal disease has been revolutionized by the introduction of the relatively nontoxic azole drugs (both oral and parenteral formulations) and the echinocandins (only available for parenteral administration). The new agents in these classes offer more targeted, less toxic therapy than older agents such as amphotericin B for patients with serious systemic fungal infections. Combination therapy is being reconsidered, and new formulations of old agents are becoming available. Unfortunately, the appearance of azoleresistant and echinocandin-resistant organisms, as well as the rise in the number of patients at risk for mycotic infections, has created new challenges.
The antifungal drugs presently available fall into the following categories: systemic drugs (oral or parenteral) for systemic infections, oral systemic drugs for mucocutaneous infections, and topical drugs for mucocutaneous infections.
Amphotericin A and B are antifungal antibiotics produced by Streptomyces nodosus. Amphotericin A is not in clinical use.