Traditionally, B. Ciprofloxacin is similarly potent in inhibiting the growth of B. Comparison of animal and human pharmacokinetics. These values can be compared with those obtained from pharmacokinetic studies in adults and children who received ciprofloxacin at the dosages approved for managing postexposure inhalational anthrax. Serum concentrations of ciprofloxacin across these 3 populations were found to be comparable.
The maximum concentration C max was 1. The minimum concentration C min was 0. Inhalational anthrax: animal models and human pathology. Since the s, studies of inhalational anthrax have been conducted in a number of animal species. The study of human disease resulting from sporadic industrial exposure and from the outbreak in Sverdlovsk has provided an understanding of inhalational anthrax that demonstrates that the rhesus monkey is a relevant animal model of this disease [ 2 , 3 ].
The applicability of this model is based on data attesting to the similarities in pathogenesis, clinical course, and tissue pathology in rhesus monkeys and humans with inhalational anthrax. Animal model: study supporting the indication of ciprofloxacin. There were 6 groups of 10 animals each. One group received human anthrax vaccine only on days 1 and 14 after exposure. Three groups received a day regimen of antimicrobials that was started 24 h after exposure. The antibiotics administered were penicillin, doxycycline, and ciprofloxacin.
One group received both doxycycline and vaccine, and a control group of 10 monkeys received saline intramuscularly. After this exposure, animals were observed for a total of 90 days. All animals had serial blood specimens obtained for culture. Animals that died or were sacrificed underwent necropsy; tissue specimens were cultured and examined histologically [ 11 ]. Results were reported as mortality rates or postexposure survival curves [ 11 ].
Inspection of the data presented in figure 1 demonstrates markedly different survival curves for the animals that received postexposure ciprofloxacin for 30 days, compared with those animals that received saline control. Survival curves for rhesus monkeys administered either ciprofloxacin Cipro or saline Control after exposure to aerosolized Bacillus anthracis. End of treatment occurred at 30 days after exposure; test of cure TOC occurred 90 days after exposure.
Adapted from [ 11 ]. Inspection of the survival curves in figure 2 shows the results for all 6 groups of monkeys. The animals in the control and in the postexposure vaccine groups demonstrated a rapid decrease in survival and a high mortality rate, and those that received 30 days of antimicrobial therapy or therapy with antimicrobials plus vaccine demonstrated markedly improved survival.
These data suggest that a number of different regimens that were studied in this experiment afford comparable protection after the first challenge. Table 2 presents a statistical analysis of the mortality rates for animals receiving ciprofloxacin, compared with that for animals in the control group.
P values demonstrate that, for the evaluable study population, mortality rates for the ciprofloxacin cohort are significantly less than the mortality rate for the control cohort and are similar to mortality rates for the cohorts that received penicillin, doxycycline, or doxycycline plus vaccine.
Evaluable population analysis for proven cases of death due to anthrax in a rhesus-monkey model. Underlying the consideration of a postexposure regimen of ciprofloxacin was the question of the duration of drug administration. The discussion below describes the approach taken by the FDA in the review of the ciprofloxacin application. Animal models. Early work by Henderson et al. They hypothesized that inhaled spores were phagocytosed by pulmonary macrophages and transported to the mediastinum, where they germinated and produced toxin.
The results of this study [ 12 ] are presented in figure 3. Survival curves for rhesus monkeys administered either penicillin or saline after exposure to aerosolized Bacillus anthracis. The control group received saline. Adapted from [ 12 ]. Henderson et al. Penicillin administration that began 24 h after exposure to aerosolized spores of B. When the duration of penicillin therapy was extended to 10 or 20 days, a similar delay of death was observed, and the length of time by which death was delayed was generally proportional to the duration of antimicrobial administration figure 3 ; groups B and C.
Using pathologic specimens, they also quantified the proportion of spores that were found in the lungs after exposure and produced the results presented in table 3. Retention of Bacillus anthracis spores in the lung after aerosol challenge in a rhesus-monkey model.
Thus, the idea of spore attrition was introduced. Small numbers of spores could be found as long as days after exposure.
Other early studies of inhalational anthrax in the guinea pig by Ross [ 13 ] permitted direct observation of spores that were deposited on pulmonary alveolar epithelium and provided insight into possible mechanisms of spore attrition.
Ross [ 13 ] noted that the number of spores that reached regional lymph nodes was substantially less than the number of spores deposited on the alveolar epithelium. Using differential staining techniques, she provided histological evidence that not all inhaled spores develop into vegetative organisms that produce systemic disease [ 13 ]. Early studies by Henderson's group demonstrated that regimens of 5, 10, and 20 days of postexposure antibiotic administration were too short; high mortality rates in the study cohorts were only delayed [ 12 ].
However, among the animals that received ciprofloxacin, 1 in 10 was not sufficiently protected from inhalational anthrax after 30 days of therapy.
This suggests that, after 30 days of antimicrobial therapy, there remained an adequate number of inhaled spores to progress to the vegetative phase, produce toxin, and cause disease. The largest human epidemic of inhalational anthrax ever reported occurred in Sverdlovsk in Data from this outbreak, for which data from a series of 42 necropsies were reported [ 1 ], show that 1 patient developed disease 43 days after the presumed exposure. If such a lower limit exists, is there a period of antimicrobial administration that will eradicate enough of the developing vegetative organisms such that the risk of disease is minimized?
The discussion below addresses these questions. Human epidemiology. A rough approximation of spore load according to the amount of time after exposure to aerosolized B. However, it neither quantifies the spore load nor does it speculate about the number of spores that are sufficient for the development of clinical disease.
The findings of epidemiological studies of mill workers with industrial exposure to anthrax spores provide some insight into this question. Other investigators recovered B. Thus, the possibility exists that there is a low organism load that is not associated with clinical disease.
One might consider repeated low-level exposures in the workplace a different immunological challenge than that resulting from an intentional exposure to aerosolized anthrax spores. Perhaps the occupational exposures present enough antigen to elicit a protective immune response over time. Epidemiological studies suggest that this is not the case. Brachman and Fekety [ 17 ] compared the length of employment in goat-hair processing mills of a group of employees without a history of anthrax with that of a group of employees who had a history of anthrax.
They found that the likelihood of the development of anthrax was independent of the length of time of employment in the mill. Jun 14, Share this page:. Sign up now». Related News All news. Sep 21 GAO says Defense Department lagging on lab biosecurity. Aug 22 Infectious disease field loses 'commander-in-chief' D.
Jul 30 Cipro is specifically indicated for the following: adult female patients with acute uncomplicated cystitis caused by Escherichia coli or Staphylococcus saprophyticus.
Mechanism of Action Ciprofloxacin is a member of the fluoroquinolone class of antibacterial agents. Side Effects Adverse effects associated with the use of Cipro may include, but are not limited to, the following: nausea diarrhea abnormal liver function tests vomiting rash The Cipro drug label comes with the following Black Box Warning: Fluoroquinolones, including Cipro have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including: 1 Tendinitis and tendon rupture, 2 Peripheral neuropathy, 3 Central nervous system effects.
Clinical Trial Results No trial data posted on prescription drug label.
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