Pharmacokinetic-pharmacodynamic assessment of faropenem in a lethal murine Bacillus anthracis inhalation postexposure prophylaxis model.

There are few options for prophylaxis after exposure to Bacillus anthracis, especially in children and women of childbearing potential. Faropenem is a beta-lactam in the penem subclass that is being developed as an oral prodrug, faropenem medoxomil, for the treatment of respiratory tract infections. Faropenem was shown to have in vitro activity against B. anthracis strains that variably express the bla1 beta-lactamase (MIC range,

An ounce of prevention is worth a pound of cure: improving communication to reduce mortality during bioterrorism responses.

OBJECTIVE: To identify communication needs and evaluate the effectiveness of alternative communication strategies for bioterrorism responses. METHODS: We provide a framework for evaluating communication needs during a bioterrorism response. Then, using a simulation model of a hypothetical response to anthrax bioterrorism in a large metropolitan area, we evaluate the costs and benefits of alternative strategies for communication during a response. RESULTS: Expected mortality increases significantly with increases in the time for attack detection and announcement; decreases in the rate at which exposed individuals seek and receive prophylaxis; increases in the number of unexposed people seeking prophylaxis; and increases in workload imbalances at dispensing centers. Thus, the timeliness, accuracy, and precision of communications about the mechanisms of exposure and instructions for obtaining prophylaxis and treatment are critical. Investment in strategies that improve adherence to prophylaxis is likely to be highly cost effective, even if the improvement in adherence is modest, and even if such strategies reduce the prophylaxis dispensing rate. CONCLUSIONS: Communication during the response to a bioterror attack must involve the right information delivered at the appropriate time in an effective manner from trusted sources. Because the response system for bioterror communication is only fully operationalized once an attack has occurred, tabletop planning and simulation exercises, and other up-front investments in the design of an effective communication strategy, are critical for effective response planning.

Reducing mortality from anthrax bioterrorism: strategies for stockpiling and dispensing medical and pharmaceutical supplies.

A critical question in planning a response to bioterrorism is how antibiotics and medical supplies should be stockpiled and dispensed. The objective of this work was to evaluate the costs and benefits of alternative strategies for maintaining and dispensing local and regional inventories of antibiotics and medical supplies for responses to anthrax bioterrorism. We modeled the regional and local supply chain for antibiotics and medical supplies as well as local dispensing capacity. We found that mortality was highly dependent on the local dispensing capacity, the number of individuals requiring prophylaxis, adherence to prophylactic antibiotics, and delays in attack detection. For an attack exposing 250,000 people and requiring the prophylaxis of 5 million people, expected mortality fell from 243,000 to 145,000 as the dispensing capacity increased from 14,000 to 420,000 individuals per day. At low dispensing capacities (<14,000 individuals per day), nearly all exposed individuals died, regardless of the rate of adherence to prophylaxis, delays in attack detection, or availability of local inventories. No benefit was achieved by doubling local inventories at low dispensing capacities; however, at higher dispensing capacities, the cost-effectiveness of doubling local inventories fell from 100,000 US dollars to 20,000 US dollars/life year gained as the annual probability of an attack increased from 0.0002 to 0.001. We conclude that because of the reportedly rapid availability of regional inventories, the critical determinant of mortality following anthrax bioterrorism is local dispensing capacity. Bioterrorism preparedness efforts directed at improving local dispensing capacity are required before benefits can be reaped from enhancing local inventories.

The cost-effectiveness of strategies to reduce mortality from an intentional release of aerosolized anthrax spores.

BACKGROUND: Intentional exposures to aerosolized Bacillus anthracis spores have caused fatalities. OBJECTIVE: To evaluate the cost-effectiveness of strategies to reduce mortality from future inhalational anthrax exposures. METHODS: Computer cohort simulation of a 100,000-person single-site exposure (worst-case scenario) and a 100-person multiple-site exposure (resembling the recent US attack). For each scenario, universal vaccination and an emergency surveillance and response (ESR) system were compared with a default strategy that assumed eventual discovery of the exposure. RESULTS: If an exposure was unlikely to occur or was small in scale, neither vaccination nor an ESR system was cost-effective. If an exposure was certain and large in scale, an ESR system was more cost-effective than vaccination ($73 v. $29,600 per life-year saved), and a rapid response saved more lives than improved surveillance. CONCLUSIONS: Strategies to reduce deaths from anthrax attacks are cost-effective only if large exposures are certain. A faster response is more beneficial than enhanced surveillance.

Is it influenza or anthrax? A decision analytic approach to the treatment of patients with influenza-like illnesses.

STUDY OBJECTIVE: We analyze the risks and benefits of alternative treatment strategies for non-septic-appearing febrile patients with influenza-like illnesses and possible exposure to anthrax. METHODS: We used a decision analytic model to evaluate 6 testing and treatment strategies in an emergency department. Patients were non-septic-appearing and had influenza-like illnesses but low likelihood of exposure to anthrax. The following interventions were used: (1) no empiric antibiotics; (2) blood culture and treatment only if the result was positive; (3) rapid testing for influenza and, for those who tested negative, treatment with 60 days of ciprofloxacin; (4) a two-test strategy in which all patients were first tested for influenza; those who tested negative had a blood culture test and were treated empirically with ciprofloxacin for 3 days while waiting for blood culture results; (5) culture test for all patients and treatment with ciprofloxacin for up to 3 days while waiting for blood culture results; and (6) treatment of all patients with ciprofloxacin empirically for 60 days. Main outcome measures were deaths, complications from anthrax, adverse events from ciprofloxacin, and ciprofloxacin patient-days. RESULTS: For nonzero probabilities of anthrax, patient mortality was always lowest in the strategies in which all patients were treated empirically for anthrax either for 60 days or for 3 days pending blood culture results. These strategies, however, were associated with more morbidity (more ciprofloxacin patient-days and more antibiotic adverse events) than were strategies without empiric treatment. The numbers of adverse events and antibiotic patient-days were reduced substantially with the two-test strategy, in which patients with influenza were identified early and not treated. In general, for probabilities of anthrax equaling or exceeding 2%, treating all patients empirically for 60 days was best, but for probabilities between 0.1% and 2%, the sensitivity of blood culture for anthrax determined the optimal strategy: when the sensitivity exceeded 95%, a short course of empiric ciprofloxacin until blood culture results became available was best, but for sensitivities below 95%, more aggressive empiric antibiotics use was warranted. The proportion of patients with influenza in the community affected the choice of strategy, so that seasonal variation exists. CONCLUSION: During influenza season, our findings support rapid testing for influenza, followed by empiric treatment for anthrax pending blood culture results for those who test negative for influenza. Our results help to highlight the importance of developing rapid and sensitive tests for anthrax and of developing improved surveillance and methods to calculate the previous probability of attacks.

An outbreak of anthrax in pigs: a practitioner's account.

An outbreak of anthrax occurred in a 500 sow unit at Singret Farm, Llay, during the summer of 1989. This paper describes the sequence of events leading up to the depopulation of the farm, as seen and recorded by a veterinary surgeon in the practice involved. Some of the problems encountered and their significance for the future are discussed.