Page 867 - Basic _ Clinical Pharmacology ( PDFDrive )

48
P
H
C
A
T
E
R
Antifungal Agents

Harry W. Lampiris, MD, &
Daniel S. Maddix, Pharm D

C ASE STUD Y

The patient is a 37-year-old African-American man who with 20% eosinophils, protein 75, and glucose 20. HIV
lives in San Jose, California. He was recently incarcerated test is negative, TB skin test is negative, CSF cryptococcal
near Bakersfield, California and returned to Oakland about antigen is negative, and CSF gram stain is negative. Patient
3 months ago. He is currently experiencing one month of receives empiric therapy for bacterial meningitis with van-
severe headache and double vision. He has a temperature comycin and ceftriaxone, and is unimproved after 72 hours
of 38.6°C (101.5°F) and the physical exam reveals nuchal of treatment. After 3 days a white mold is identified growing
rigidity and right-sided sixth cranial nerve palsy. MRI of from his CSF culture. What medical therapy would be most
his brain is normal, and lumbar puncture reveals 330 WBC appropriate now?

Human fungal infections have increased dramatically in incidence The antifungal drugs presently available fall into the follow-
and severity in recent years, owing mainly to advances in surgery, ing categories: systemic drugs (oral or parenteral) for systemic
cancer treatment, treatment of patients with solid organ and bone infections, oral systemic drugs for mucocutaneous infections, and
marrow transplantation, the HIV epidemic, and increasing use topical drugs for mucocutaneous infections.
of broad-spectrum antimicrobial therapy in critically ill patients.
These changes have resulted in increased numbers of patients at
risk for fungal infections. ■ SYSTEMIC ANTIFUNGAL DRUGS
For many years, amphotericin B was the only efficacious FOR SYSTEMIC INFECTIONS
antifungal drug available for systemic use. While highly effec-
tive in many serious infections, it is also quite toxic. In the last AMPHOTERICIN B
several decades, pharmacotherapy of fungal disease has been
revolutionized by the introduction of the relatively nontoxic Amphotericin A and B are antifungal antibiotics produced by
azole drugs (both oral and parenteral formulations) and the Streptomyces nodosus. Amphotericin A is not in clinical use.
echinocandins (only available for parenteral administration).
The new agents in these classes offer more targeted, less toxic Chemistry & Pharmacokinetics
therapy than older agents such as amphotericin B for patients
with serious systemic fungal infections. Combination therapy Amphotericin B is an amphoteric polyene macrolide (polyene =
is being reconsidered, and new formulations of old agents are containing many double bonds; macrolide = containing a large
becoming available. Unfortunately, the appearance of azole- lactone ring of 12 or more atoms). It is nearly insoluble in water
resistant and echinocandin-resistant organisms, as well as the and is therefore prepared as a colloidal suspension of amphoteri-
rise in the number of patients at risk for mycotic infections, has cin B and sodium deoxycholate for intravenous injection. Several
created new challenges. formulations have been developed in which amphotericin B is

853