Neuraminidase inhibitors: zanamivir and oseltamivir.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of zanamivir and oseltamivir for the prophylaxis and treatment of influenza. DATA SOURCES: A MEDLINE search restricted to English-language journals was conducted (1980-May 2000). STUDY SELECTION AND DATA EXTRACTION: All efficacy and safety trials were included if conducted in humans and published in a journal. Abstracts were included if no other data source was available. DATA SYNTHESIS: Zanamivir and oseltamivir block influenza neuraminidase and prevent the cleavage of sialic acid residues, thus interfering with progeny virus dispersement within the mucosal secretions and reducing viral infectivity. The neuraminidase trials for prophylaxis and treatment of influenza enrolled predominantly young (mean age 29-37 y), healthy, mostly unvaccinated individuals who were at the lowest risk of influenza and its complications. When zanamivir 10 mg inhaled twice daily or oseltamivir 75 mg orally twice daily were used for treatment, systemic symptoms such as myalgias, fever, and headache were reduced by approximately 0.7-1.5 days. Greater efficacy (symptom reduction by 1.5-2.0 d) was noted in proven cases of influenza infection, in febrile patients, and in patients who received the treatment medication within 30 hours of symptom onset. Clinical efficacy did not increase when doses higher than the treatment dose approved by the Food and Drug Administration were used. When given for prophylaxis, zanamivir 10 mg inhaled once daily or oseltamivir 75 mg orally once daily was used for four to six weeks and achieved protective clinical efficacy for laboratory-confirmed influenza ranging from 67% to 74%, depending on whether culture or serologic tests were performed. The most common adverse effects (usually < 5%) included upper respiratory tract symptoms. Patients with asthma or chronic obstructive pulmonary disease who received zanamivir had an increased incidence of a > 20% decline in forced expiratory volume in one second or peak expiratory flow rates. Headaches, nausea, and vomiting were more frequent in the oseltamivir groups than in placebo groups. The most common gastrointestinal adverse effects, nausea and vomiting, were reduced to approximately 10% by administering the medication with food. CONCLUSIONS: Zanamivir and oseltamivir are more effective in preventing culture-positive influenza or for treatment of culture-positive influenza in febrile (> or = 37.8 degrees C) individuals. Treatment is more effective if initiated within 30 hours of symptom onset in febrile individuals; however, it is difficult to meet these criteria. More realistically, clinical efficacy is closer to 60-70% and, for treatment started within 48 hours for laboratory-confirmed influenza, symptom reduction is approximately 0.7-1.5 days. If used appropriately to minimize the development of resistance, the neuraminidase inhibitors represent a new and unique class of antiinfluenza agents that can potentially reduce the morbidity associated with influenza.

Malaria epidemiology and economics in a pharmacist-managed international travel clinic.

With high rates of travel and low adherence to malaria prophylaxis, targeting educational efforts to high-risk travelers is vital. We assessed risk factors for acquiring malaria, and resource use and outcomes of these patients in a managed care environment. Patients were identified from January 1, 1994, to December 31, 1997, using microbiology and pharmacy databases, chart reviews, and interviews. Sixteen patients acquired malaria during the study; although only 50% contacted the travel clinic. Only 31% (5) of them had documented adherence. Fifty percent were hospitalized at a cost of $3881/patient. Travelers at greatest risk for nonadherence appear to be expatriates and those visiting Africa. Providers should target these groups with more intensive counseling in an effort to improve therapy adherence and reduce the risk for malaria.

Antiinfectives update: focus on treatment and prevention of viral and associated infections.

OBJECTIVE: To review the clinically significant antiinfectives approved by the Food and Drug Administration (FDA) since 1996, with an emphasis on agents used for treatment, prevention, or suppression of infection in immunocompromised individuals. DATA SOURCES: A MEDLINE search covering November 1994 to March 1998 was conducted to identify all antiinfectives (new medications and old medications with new indications) and the pertinent literature for review. The search was updated in August 1998 and supplemented with an FDA listing of approved drugs to enhance completeness. STUDY SELECTION: Clinically relevant studies were selected to highlight specific points about each medication. Preclinical publications were used when sufficient information was not available from clinical trials and this information was needed for clinical practice. CONCLUSIONS: Several new and promising antiretroviral agents (stavudine, lamivudine, saquinavir soft-gel capsules, nelfinavir, efavirenz) have been approved, which may allow more options to control HIV viremia. New options for treatment, prevention, and suppression of infections in immunocompromised individuals include azithromycin, cidofovir, famciclovir, valacyclovir, and itraconazole suspension. Liposomal-based amphotericin products may be associated with less toxicity than conventional amphotericin B; however, superior efficacy has not been proven.

Pharmacoeconomic analysis of ampicillin-sulbactam versus cefoxitin in the treatment of intraabdominal infections.

We conducted a retrospective pharmacoeconomic analysis of a prospective, multicenter, double-blind, randomized, controlled trial comparing the beta-lactamase inhibitor combination ampicillin-sulbactam (96 patients) and the cephalosporin cefoxitin (101) in the treatment of intraabdominal infections. An institutional perspective was adopted for the analysis. The primary outcomes of interest were cure and failure rates, development of new infection, and antibiotic-related adverse events. Epidemiologic data pertaining to outcomes was retrieved primarily from the trial, although results of other published studies were taken into consideration through extensive sensitivity analyses. Data pertaining to potential resource use and economic impact were retrieved mainly from the University Health Consortium and hospital-specific sources. When considering only costs associated with drug acquisition through cost-minimization analysis, a potential savings of $37.24/patient may be realized with ampicillin-sulbactam relative to cefoxitin based on an average 7-day regimen. Outcome data collected for the entire hospitalization during the trial revealed an approximately 9% greater frequency of failure with cefoxitin relative to ampicillin-sulbactam. When considering all outcomes of interest in the initial base-case analysis, a potential cost savings of approximately $890/patient may be realized with ampicillin-sulbactam relative to cefoxitin. In assessing the impact of the significant variability in probability and cost estimates, Monte Carlo analysis revealed a savings of $425/patient for ampicillin-sulbactam over cefoxitin (95% CI -$618 to $1516 [corrected]). Given the model assumptions, our analysis suggests a 78% certainty level that savings will be experienced when ampicillin-sulbactam is chosen over cefoxitin.

Active immunization in HIV-infected patients.

Patients infected with human immunodeficiency virus (HIV) are at risk for various viral and bacterial infections. Active immunization with currently available vaccines may reduce the risk of some vaccine-preventable diseases in this population. Based on available data, most vaccines used in the United States are safe in HIV-infected adults and children. Their clinical efficacy in these individuals is not well defined, although it appears that patients in the earlier stages of infection are more likely to mount a protective antibody response than those in the later stages. Current guidelines for vaccination in HIV-infected children and adults in the United States have been recommended by the Advisory Committee on Immunization Practices.