ro13-9904 and Plague

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing contagious disease. In the plague mouse model, a single immunization with the EV76 live attenuated Y. pestis strain rapidly induced the expression of hemopexin and haptoglobin in the lung and serum, both of which are important in iron sequestration. Immunization against a concomitant lethal Y. pestis respiratory challenge was correlated with temporary inhibition of disease progression. Combining EV76-immunization and second-line antibiotic treatment, which are individually insufficient, led to a synergistic protective effect that represents a proof of concept for efficient combinational therapy in cases of infection with antibiotic-resistant strains.

Topics: Animals; Anti-Bacterial Agents; Bacterial Vaccines; Ceftriaxone; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Haptoglobins; Hemopexin; Iron; Mice; Mice, Inbred C57BL; Plague; Post-Exposure Prophylaxis; Treatment Outcome; Vaccines, Live, Unattenuated; Yersinia pestis

Administration of highly immunogenic (ED50 12.6 mcg/mouse) F I antigen (100 mcg/mouse) to albino mice 5 hours after their contamination approximately with 1000 LD50 of Yersinia pestis 231 provided 99-percent survival of same animals (17-50%) and 2-5-day prolongation of the life-span, that was indicative of the phenomenon analogous to the survival phenomenon observed in infected animals immunized by immunogenic strains of the plague microbe. The experiment on the mice confirmed high efficacy of ceftriaxone (100-percent survival) when used prophylactically for 5 days 5 hours after the contamination by Y. pestis 231 (approximately 1000 LD50) in the dose equivalent to the daily dose for humans. However, no antiplague immunity developed in the survivors: the immunity index (II) of 1.5x10. The use of ceftriaxone according to the same scheme simultaneously with single immunization by F I antigen in a dose of 100 mcg/mouse resulted not only in 100-percent survival of the animals but also in development of expressing antiplague immunity (II 2.2x10(5)). The protection level corresponded to the control with the same live-stock of the animals after a single immunization in the analogous dose of F I antigen (II 3.2x10(4)) and the ceftriaxone use (II 1.0x10(5)), as well as after immunization of the mice by 10(6) microbial cells of Y. pestis EV NIIEG (II 1.2x10(5)). The results of the study are indicative of the prospective use of subsingle vaccines of the new generation based on F I antigen for combined specific and urgent prophylaxis.

Topics: Animals; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Proteins; Bioterrorism; Ceftriaxone; Immunization; Injections, Intramuscular; Injections, Subcutaneous; Lethal Dose 50; Mice; Plague; Plague Vaccine; Time Factors; Vaccines, Synthetic; Yersinia pestis

Topics: Animals; Ceftriaxone; Cephalosporins; Liver; Mice; Microscopy, Electron; Plague; Yersinia pestis

Strains of the plague microbe of different origin were found to by highly susceptible to the third generation cephalosporins such as cefoperazone, cefotaxime, ceftazidime and ceftriaxone. The MICs ranged form 0.012 to 0.5 microgram/ml. A comparative study on the efficacy of the 3rd generation cephalosporins in the treatment of experimental plague in albino mice revealed that the use of cefoperazone, cefotaxime, ceftazidime and ceftriaxone in the therapy of etiotropic plague was promising. Ceftriaxone, an antibiotic with prolonged action, which was the most efficient in the experiments on the laboratory animals was shown to be the drug of choice among the 3rd generation cephalosporins.

Topics: Animals; Cefoperazone; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Drug Evaluation, Preclinical; Mice; Microbial Sensitivity Tests; Plague; Treatment Outcome; Yersinia pestis

Ceftriaxone (rocefin), a 3rd generation cephalosporin with prolonged action, was highly efficient (ED50 0.12 to 0.38 mg/mouse) against experimental plague in albino mice infected either by Fra+ or Fra- strains of the plague microbe. The daily doses of the antibiotic (0.5-1.0-2.0 mg/mouse) provided 85-100 per cent survival of the animals. All the strains (15) of the plague microbe isolated from different natural foci and different objects were highly sensitive to ceftriaxone. The MIC was 0.02 to 0.05 microgram/ml.

Topics: Animals; Ceftriaxone; Mice; Plague; Yersinia pestis