Prepositioning Antibiotics for Anthrax (2012) / Chapter Skim
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2 Antibiotics for Anthrax Postexposure Prophylaxis
2 Antibiotics for Anthrax Postexposure Prophylaxis
Pages 41-68
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From page 41... ...
The remainder of the chapter examines two issues related to when antibiotics should be dispensed: first, the incubation period of inhalational anthrax (time from exposure to appearance of symptoms) and second, the delay from the time of an attack until the attack is detected and the decision to begin dispensing antibiotics is made.
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From page 42... ...
for a detailed presentation of the antibiotics that were ap proved by the Food and Drug Administration for anthrax postexposure prophylaxis as of 2001.
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From page 43... ...
analysis of tissue samples (meninges, spleen, lymph node) from 11 autopsy-proven inhalational anthrax cases from the 1979 accidental release of anthrax in Sverdlovsk, Russia,6 revealed at least four strains of B
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From page 44... ...
• A s laboratory testing of antibiotic susceptibility is likely to take more than 2 days, antibiotic distribution and dispensing efforts in response to an anthrax attack would be initiated before the suscep tibility profile of the attack strain was known. • A nthrax vaccine and antitoxin will likely be in even greater demand following an attack with an antibiotic-resistant anthrax strain as compared with a susceptible strain.
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From page 45... ...
The result could be a much 8 As laboratory testing of antibiotic susceptibility is likely to take more than 2 days, antibiotic distribution and dispensing efforts in response to an anthrax attack would be initiated before the susceptibility profile of the attack strain was known. If the strain were ultimately determined not to be susceptible to the antibiotic dispensed, an alternative MCM would have to be dispensed, provided one was available in the quantities needed.
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From page 46... ...
Furthermore, although some information about planned responses is already available in the public domain, prepositioning antibiotics in the home would provide a greater degree of certainty about the planned response and, therefore, could conceivably increase the probability of release of a resistant strain of anthrax. INCUBATION PERIOD OF INHALATIONAL ANTHRAX: EXISTING DATA AND AREAS OF UNCERTAINTY Data on human exposure to aerosolized B
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From page 47... ...
. Brachman notes that "the projected incubation period of six days resembled those of previous cases" (Brachman, 1980, p.
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. None of the three individuals infected had a clear-cut incubation period that could be calculated definitively.
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From page 49... ...
following the incident. To this day, it remains impossible to verify precise and comprehensive specific clinical and epidemiological data, including incubation periods, for many of the individuals suspected to have contracted inhalational anthrax.
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Importantly, in its analysis of previous anthrax incidents, the committee required either microbiologic or histopathologic confirmation of infection with B anthracis when determining the minimum incubation period of patients with inhalational anthrax.
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Examples are the apparent rapid progression to death after symptom onset without effective treatment, the existence of a wide range of incubation periods, and the consistent finding of large volumes of pleural fluid that contributed to respiratory failure and death (Walker, 2000)
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From page 52... ...
state that the highly virulent anthrax strain 836 was used in the former Soviet Union, including at Sverdlovsk in 1979, and that the anthrax released contained chemical additives. Theoretical Modeling of the Incubation Period for Human Inhalational Anthrax As discussed above, some of the data on the incubation period for inhalational anthrax considered by the committee were based on statistical analyses.
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From page 53... ...
, 16 of 70 fatal cases included did not have a known incubation period; instead, the end of the incubation period for these 16 patients was estimated by subtracting 3 days from the date of death. This paper was published prior to the 2001 U.S.
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From page 54... ...
assesses the accuracy of four models of inhalational anthrax dose-response and incubation period distribu tion using the Sverdlovsk data. He concludes that: -- "Dose-response functions that exhibit a threshold for infectivity are contraindicated by the Sverdlovsk data" (Wilkening, 2006, p. 7589)
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From page 55... ...
. In other words, the time from exposure to death in rhesus monkeys is similar to the time from onset of symptoms to death in humans, consistent with the view that the incubation period is longer in humans than in these commonly employed animal models.
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From page 56... ...
. The effectiveness of antibiotics begun later in the incubation period is supported by some data from the 2001 anthrax attack, although notably not from a prospective, controlled experiment: Brentwood postal facility in Washington, DC19 -- More than 2,000 • postal workers were potentially exposed to spores reportedly aero solized from the letter-sorting machine after two letters passed through the facility on Friday morning, October 12, until the facility was closed on Sunday morning, October 21 (Dewan et al., 2002)
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From page 57... ...
To ensure that potentially exposed people receive antibiotics during the time window in which the antibiotics effectively prevent the appearance of anthrax symptoms, the total time for these three stages should be less than the minimum incubation period (approximately 4 days, as discussed above)
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From page 58... ...
CDC's Cities Readiness Initiative (see Chapter 3) has set a goal for state and local health departments to have systems in place to complete dispensing of the initial course of PEP antibiotic(s)
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From page 59... ...
Factors that might immediately be considered include, for example, the number and locations of the BioWatch filters testing positive, intelligence and law enforcement information, evidence of human or animal illnesses consistent with the biological agent detected, and additional environmental testing apart from the BioWatch filters. Thus, it is difficult to predict in advance of a specific event the time period that would be required before the decision to dispense PEP antibiotics could be made by government officials.
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From page 60... ...
However, the incubation period of cutaneous anthrax (exposure via skin) is significantly shorter, approximately 1-3 days (CDC, 2002, 2006a; Freedman et al., 2002; Jernigan et al., 2002)
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From page 61... ...
Finding 2-2: Review of the limited available data on human inhalational anthrax shows that people exposed to aerosolized anthrax have incubation periods of 4 to 8 days or longer. Much of the modeling used to derive shorter estimates is based on data from the Sverdlovsk incident, and the assumptions made potentially lead to an underestimate of the minimum incubation period.
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From page 62... ...
2005. No evidence of a mild form of inhalational Bacillus anthracis infection during a bioterrorism-related inhalational anthrax outbreak in Washington, D.C., in 2001.
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Morbidity and Mortality Weekly Report 5(13) :279-281, http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5113a4.htm (accessed July 21, 2011)
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1993. Postexposure prophylaxis against experimental inhalation anthrax.
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Emerging Infectious Diseases 8(10)
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Emerging Infectious Diseases 8(10)
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From page 67... ...
2008. Modeling the incubation period of inhalational anthrax.
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