Serum Concentrations of Penicillin, Doxycycline, and Ciprofloxacin during Prolonged Therapy in Rhesus Monkeys

Kelly, Daryl J.; Chulay, Jeffrey D.; Mikesell, Perry; Friedlander, Arthur M.

doi:10.1093/infdis/166.5.1184

Cited by 51 publications

(37 citation statements)

References 4 publications

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“…In such a scenario, oral antibiotics would be the only efficient way to deliver antimicrobial therapy to large numbers of individuals quickly. Thus, each animal was given 125 mg of ciprofloxacin every 12 h, an oral dose previously shown to provide therapeutic antibiotic levels (12). This was confirmed in the present study in which peak-and-trough serum samples from all animals in both groups had ciprofloxacin concentrations above the minimum inhibitory concentration for B. anthracis (0.06 g͞ml; data not shown).…”

Section: Discussionsupporting

confidence: 85%

Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax

Vietri¹,

Purcell²,

Lawler³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Prevention of inhalational anthrax after Bacillus anthracis spore exposure requires a prolonged course of antibiotic prophylaxis. In response to the 2001 anthrax attack in the United States, Ϸ10,000 people were offered 60 days of antibiotic prophylaxis to prevent inhalational anthrax, but adherence to this regimen was poor. We sought to determine whether a short course of antibiotic prophylaxis after exposure could protect non-human primates from a high-dose spore challenge if vaccination was combined with antibiotics. Two groups of 10 rhesus macaques were exposed to Ϸ1,600 LD 50 of spores by aerosol. Both groups were given ciprofloxacin by orogastric tube twice daily for 14 days, beginning 1-2 h after exposure. One group also received three doses of the licensed human anthrax vaccine (anthrax vaccine adsorbed) after exposure. In the ciprofloxacin-only group, four of nine monkeys (44%) survived the challenge. In contrast, all 10 monkeys that received 14 days of antibiotic plus anthrax vaccine adsorbed survived (P ‫؍‬ 0.011). Thus postexposure vaccination enhanced the protection afforded by 14 days of antibiotic prophylaxis alone and completely protected animals against inhalational anthrax. These data provide evidence that postexposure vaccination can shorten the duration of antibiotic prophylaxis required to protect against inhalational anthrax and may impact public health management of a bioterrorism event.Bacillus anthracis ͉ treatment ͉ vaccine B acillus anthracis infection in humans occurs as cutaneous, gastrointestinal, or inhalational anthrax depending upon the route of exposure. Cutaneous anthrax is rarely fatal and can be effectively treated with antibiotics. Inhalational anthrax, the form likely to occur after a bioterrorist attack, on the other hand, is difficult to diagnose early, and despite antibiotic therapy, has a high fatality rate. Anthrax is rare in industrialized countries, and vaccination with anthrax vaccine adsorbed (AVA) is confined to those who could be potentially exposed to anthrax, such as veterinary workers, woolen mill employees, and laboratory workers (1). Military personnel in the United States are also vaccinated due to the potential threat of B. anthracis being used as a bioweapon.Past experiments have shown that the rhesus macaque is the animal model that most closely mimics inhalational anthrax in humans (2). In both humans and macaques, inhalational anthrax begins with the deposition of 1-to 5-m spores in the alveolar spaces, where spores are thought to be ingested by alveolar phagocytic cells. Some spores survive inside the phagocyte and are transported to the draining pulmonary and mediastinal lymph nodes where germination occurs. Although most spores probably germinate within a few days after inhalation, germination is not synchronous (3). Some spores remain dormant and do not germinate for prolonged periods (4, 5). It is the delayed germination of retained spores into vegetative bacilli that necessitates the prolonged use of prophylactic antibiotics after an inhalational ...

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Section: Discussionsupporting

confidence: 85%

Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax

Vietri¹,

Purcell²,

Lawler³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Data adapted from Kirkwood (1983) Body surface area, calculated using the allometric equation:-Surface area = 11.7 x Weighto. 66 was used to extrapolate doses of antibiotics from man to rhesus monkeys (Kelly et al 1992). However, the surface area method has not been used to any great extent because of controversy over whether it is fundamentally more inaccurate than body weight (Calabrese 1991).…”

Section: Extrapolation Of Antibiotic Dose Information Between Speciesmentioning

confidence: 99%

Antibiotic therapeutics in laboratory animals

Morris

1995

Lab Anim

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SummaryInformation on antibiotic therapeutics in laboratory species, especially in rodents and rabbits, is reviewed. A number of areas are considered: interference by antibiotics with an experiment, antibiotic toxicity, routes of administration, effects of formulation on bioavailability, antibiotic prophylaxis, use of combinations of antibiotics, misuse of antibiotics, regulatory approval for antibiotic use in animals, sources of information on antibiotic indications and dose, and extrapolation of dose information from other species.

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“…Concerns about bioaggression around the time of the 1991 Gulf War resulted in some examination of the effectiveness of more modern antimicrobials both in vitro (10,22) and in vivo in animal models (13,17,20). The "anthrax letter" events of October and November 2001 in the United States further stimulated interest in antimicrobial therapy for anthrax and some debate on the appropriate therapies for different categories of patient infection (5,6,15,16), with further in vitro susceptibility tests being carried out (4,9,12,26).…”

mentioning

confidence: 99%

MICs of Selected Antibiotics forBacillus anthracis,Bacillus cereus,Bacillus thuringiensis, andBacillus mycoidesfrom a Range of Clinical and Environmental Sources as Determined by the Etest

et al. 2004

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Serum Concentrations of Penicillin, Doxycycline, and Ciprofloxacin during Prolonged Therapy in Rhesus Monkeys

Cited by 51 publications

References 4 publications

Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax

Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax

Antibiotic therapeutics in laboratory animals

MICs of Selected Antibiotics forBacillus anthracis,Bacillus cereus,Bacillus thuringiensis, andBacillus mycoidesfrom a Range of Clinical and Environmental Sources as Determined by the Etest

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