Where does lipid amphotericin-B fit in?

Despite a dearth of clinical data, clinicians seem to be warming to the use of lipid formulations of amphotericin-B (AB) for severe fungal infections — perhaps because there’s nowhere else to go with drug therapy until newer agents come on line.

The main appeal of lipid AB is that it’s less toxic to the kidneys than standard amphotericin. It can be dosed higher, and some studies at least suggest it may be more effective than the older product — for example, in the emergency treatment of aspergillosis. John R. Wingard, MD, of the University of Florida in Gainesville, summarized what is known about lipid AB: "Efficacy has not been compromised by the lipid formulation; nephrotoxicity is less; perhaps there’s a greater response rate. But it needs further study."

There’s one more thing known about lipid AB: It’s expensive. A day of lipid AB therapy might cost hundreds of dollars compared to less than $10 for the regular solution.

Still, there are some situations in which the lipid product might be cost-effective, such as in liver transplant patients who develop disseminated fungal disease, suggests Victor L. Yu, MD, of the University of Pittsburgh/VA Medical Center.

"Start out immediately with lipid amphotericin-B." Yu says. "My reason: The incidence and frequency of renal dysfunction are very high in these patients."

He says the lipid formulations also are a good choice in bone marrow transplants: A recent study showed that as a group, bone marrow transplant patients with fungal infections did better using lipid AB than regular.

But for some transplant patients — heart and lung, for example — cost outweighs benefits when it comes to lipid AB — at least until more studies come along. These patients respond well to plain amphotericin-B, Yu says.

Even though amphotericin-B is highly toxic, there is some interest in using it prophylactically — albeit in unusual forms and doses. Ben E. dePauw, MD, of the University Hospital in Nijmegen, Netherlands, says two studies showed fewer fungal infections with a prophylaxis of amphotericin-B nasal spray. Studies also have shown lower rates of infection with an inhalation form of the drug. The rationale behind using these dosage forms is simple: Fungi are usually breathed in, and the nasal passages often are the first site of colonization. On the other hand, dePauw says the impact of low-dose intravenous amphotericin-B on preventing fungal infections is "doubtful."

For pharmacists, one of the problems with amphotericin-B is that blood levels of the drug don’t correlate well with effectiveness or toxicity, according to Thomas C. Hardin, PharmD, of the University of Texas Health Science Center in San Antonio. Hardin says things don’t improve much on the monitoring end when it comes to the lipid formulations, either. Levels of these agents tend to differ with brand.

In fact, about the only two places in antifungal therapy where therapeutic drug monitoring can provide meaningful data are with fluocytosine (where levels should remain below 100 mcg/ml) and with itraconazole, which is poorly absorbed. While no "target" serum concentration has been defined for fluconazole yet, average doses produce blood levels of 10 to 30 mcg/ml, Hardin says.