Clinical Updates: By Carol A. Kemper, MD, FACP

Anthrax Vaccine Program Bombs

Source: ProMED mail post, Jan. 9, 2002.

The federally sponsored effort to provide postexposure anthrax vaccine to more than 5100 individuals potentially exposed to the deadly organism last fall has met with significant resistance and disinterest. Lacking union support, postal workers uniformly eschewed vaccination, including those workers at the New Jersey facility that experienced 2 deaths and 2 non-fatal cases of infection. Only 152 people, many of whom are congressional staffers, agreed to participate in the program. The controversial program was intended to thwart concerns regarding the possible risk of "reactivation" of anthrax despite receipt of prophylactic antimicrobials. In addition, adherence to the prophylactic regimen was amazingly poor. Reports suggest that half of those receiving prophylaxis did not complete their course of therapy.

Voriconazole vs. Liposomal Ampho in Neutropenic Fever

Source: Walsh TJ, et al. N Engl J Med. 2002;346:225-234.

Voriconazole, an experimental second-generation azole with a broader spectrum of in vitro activity than fluconazole, is likely to be available for use in the United States within the next couple of months. This open-label, international multicenter study by the Mycoses Study Group compared the efficacy of voriconazole vs. liposomal amphotericin B (LA-B) in patients with neutropenia and fever. A total of 837 patients were randomly assigned (1:1) to voriconazole or LA-B. Eligible patients were at least 12 years old, had received chemotherapy for various malignacies (mostly leukemia and lymphoma) or bone marrow transplants, were neutropenic and had persisting fever (> 38 C), despite at least 4 days of systemic antibacterial therapy. Patients with active fungal infection at the time of enrollment were excluded, although 13 patients in the voriconazole group and 6 patients in the LA-B group were diagnosed with fungal infection within 24 hours of randomization. Voriconazole was administered as a loading dose (6 mg/kg Q12 hrs) and then 3 mg/kg Q12 hrs; LA-B was administered 3 mg/kg daily. The dosages of both drugs could be increased as needed in the event of fungal infection, and were continued for at least 3 days beyond neutrophil recovery or up to 12 weeks.

Success was measured by the use of a composite score based on 5 different outcomes, including resolution of fever, prevention of breakthrough fungal infection, response to treatment in those with documented fungal infection at entry, premature discontinuation of therapy for toxicity or lack of response, and survival. Based on these 5 measures, the overall success of voriconazole vs. LA-B therapy was 26.0% vs. 30.6% (P = NS). Breakthrough fungal infection was significantly less frequent in patients receiving voriconazole (1.9%) vs. LA-B (5%) (P = .02). In patients at especially high risk for fungal infection (relapsed leukemia or allogeneic transplants), breakthrough fungal infection occurred in only 1.2% of voriconazole patients and 9.2% of LA-B patients. However, in patients with documented fungal infection at entry to study, there was a trend toward better response in patients receiving LA-B than voriconazole (4 of 6 vs 6 of 13;P = .63). There was no difference in mortality between the 2 treatment groups.

Patients receiving LA-B were more likely to experience infusion reactions and renal insufficiency, whereas patients receiving voriconazole more commonly experienced abnormal vision and visual hallucinations (4.3%), most of which were transient. In addition, 22% of patients receiving voriconazole were able to switch over to the oral formulation, allowing quicker discharges from the hospital in some patients. Voriconazole appears to be an excellent alternative to LA-B for the empiric treatment of fever and neutropenia. In addition, the availability of an oral formulation will greatly add to our ability to treat many fungal infections without the need for parenteral access or hospitalization.

Ebola Spreads to the Congo

Source: ProMED-mail post, Jan. 24, 2002.

An outbreak of ebola hemorrhagic fever, which has been brewing for weeks in Eastern Gabon near Mekambo, has spread into the adjacent Republic of Congo. As of January 20, at least 42 cases have been confirmed, resulting in 34 deaths—11 of which have occurred in the Congolese villages bordering Gambon. Officials admit that the situation was initially not well contained as angry villagers in Mekambo scared off international medical workers. This part of the French Equatorial Africa is rich in oil, timber, and minerals, but political turmoil and graft continue to hamper access to medical care.

Dr. Kemper, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor of Infectious Disease Alert.