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To estimate the in vitro susceptibility of the plague microbe to chemotherapeutics, various experimental models with the maximum closeness to the host conditions were tested. The tests included the assay of the drug antibacterial activity against the plague microbe by the method of two-fold dilutions in biological fluids i.e. human normal (nonimmune) serum (HNS) and guinea pig heparinized blood. Hottinger broth was used as the control. It was shown that any system used for estimation of the drug MIC influenced the plague microbe susceptibility. Thus, the serum complement increased the antibacterial activity of cefotaxime, rifampicin, doxycycline, erythromycin and polymyxin B. In the blood of a susceptible host (guinea pigs) the activity of quinoxydine and dioxydine against the plague microbe markedly increased while the effect of benzylpenicillin, cefotaxime and furazolidone decreased. The data on the in vitro activity of the antibiotics in blood were comparable with those on their in vivo therapeutic efficacy.

In a model of experimental plague of albino mice the prophylactic and therapeutic action of ceftazidime by comparison with that of cefotaxime and the combined action of cefotaxime with other antibiotics were studied. The studies showed that the drugs had a high prophylactic and therapeutic action when used in doses of 200 to 400 mg/kg (ceftazidime) and 400 to 800 mg/kg (cefotaxime). The survival of the animals amounted to 80-100 per cent. The therapeutic effect was defined by the drug dose and the treatment term. When the treatment term was decreased to 3 days, ceftazidime proved to be more advantageous than cefotaxime. When the antibiotic dose was insufficient, the treatment efficacy was shown to depend on the infective dose. The use of cefotaxime in combination with aminoglycosides (gentamicin or sisomicin), rifampicin or doxycycline significantly increased the percentage of the animal survival in comparison to the use of the drugs alone and promoted a rapid elimination of the pathogens in the animals. The combined use of cefotaxime and gentamicin or sisomicin as well as cefotaxime and rifampicin had a synergistic action.

The activity of doxycycline and tetracycline against natural strains of the plague microbe of different origin was studied in vitro. The MICs of doxycycline and tetracycline for the majority of the strains were 0.8 and 3.2 micrograms/ml respectively. The efficacy of doxycycline and tetracycline in the prophylaxis and treatment of experimental plague infection was studied comparatively on albino mice. Doxycycline proved to be superior to tetracycline. By using short-term schemes of the treatment and longer intervals between the drug administrations it was shown that doxycycline had a prolonged action. Moreover, the injectable doxycycline was found to be superior to the oral one. The high efficacy of doxycycline in the treatment of the albino mice with experimental plague infection was confirmed by the pathohistological findings. The pathomorphological changes in the animals were limited by local affections in the site of the contamination and the regional lymph nodes followed by the development of infiltration foci.

The therapeutic effect of azlocillin and its combinations with other antibiotics was studied in a model of experimental plague of albino mice. Azlocillin was shown to be efficient in the prophylaxis and treatment of the experimental plague infection. The optimal doses of azlocillin were determined. The protective action of the drug depended on the dose and the time of its administration. The therapeutic effect was mainly defined by the antibiotic dose. The use of azlocillin in not sufficiently active doses in combination with aminoglycosides (gentamicin, sisomicin and amikacin), rifampicin or doxycycline significantly increased the percentage of the animal survival by comparison with that after the use of every antibiotic alone. A synergistic effect was observed when azlocillin was used in combination with rifampicin or amikacin.