rifampin and Plague

Possible use of ciprofloxacin combinations with some other antibiotics such as rifampicin, ampicillin, cefotaxime, doxycycline and amikacin was studied on albino mice with experimental plague caused by the pathogen strain (approximately 1000 LD50) deprived of the ability to produce the capsular antigen, fraction I (Fra- phenotype). The combination of ciprofloxacin with ampicillin or doxycycline had no effect on the increase of the survival rate (t<2) evident of inexpediency of its use in the infection caused by the Fra- strains of the plague microbe. The combination of ciprofloxacin and cefotaxime used in definite doses had some effect (t=2.6). The most significant synergistic effect was observed with the use of ciprofloxacin in combination with amikacin or rifampicin (t>3.3-9.0) which made the combination most promising.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Ciprofloxacin; Drug Synergism; Drug Therapy, Combination; Mice; Mice, Inbred Strains; Plague; Rifampin; Yersinia pestis

Tetracycline, doxycycline, streptomycin and rifampicin were used for prophylaxis of experimental plague in albino mice (Yersinia pestis 231, approximately 1000 LD50). The antibiotics were administered 5 hours after the infection for 5 days. Tetracycline and doxycycline provided survival of 60 to 75% of the animals, while the respective figure for streptomycin and rifampicin was 100%, but streptomycin and rifampicin inhibited development of plague immunity evident from a lower protection index (PI) by 3-4 orders. The PI for the tetracyclines lowered by 2 orders. Simultaneous prophylaxis with the tetracyclines and immunization by Y. pestis EV Rifr R(SmTc) (10(6) microbial cells) provided not only higher percentage of the animal survival (80-90%) but also development of sufficient plague immunity: PI of 1.0 x 10(5)--5.0 x 10(5). When the animals were infected with Y. pestis 231 R(SmTc) the use of the tetracyclines failed, whereas the use of doxycycline and simultaneous vaccination by EV Rifr R(SmTc) provided survival of 70-85% of the animals. Successive use of inefficient streptomycin (for 2 days) and efficient rifampicin (for 3 days) provided survival only of 30% of the mice. A similar regimen of the successive use of the inefficient and efficient antibiotics (the total term of 5 days) started simultaneously with immunization by EV Rifr R(SmTc) provided survival of 80% of the animals. The use of combined specific and urgent prophylaxis of plague infection due not only to antibiotic susceptible but also to antibiotic resistant strains of the plague pathogen was shown promising.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Immunization; Mice; Plague; Rifampin; Streptomycin; Tetracyclines; Yersinia pestis

Experiments were performed with two strains of plague bacteria--231 (isolated from marmot) and 358 (isolated from human) and their isogenic variants with Fra- and Fra-Tox- phenotype. Mutants resistant to rifampicin (Rifr) and nalidixic acid (Nalr) appeared independently of pathogen phenotype and genotype with frequency n.10(-8)-n.10(-9), subsequently. Rifr mutation influenced on virulence manifestation at albino mice and antigendeficient variants with Fra- and Fra-Tox- phenotype. In every group of strains highly virulent subcultures were registered. Resistance to nalidixic acid mainly was not associated with virulence loss. Nalr mutants of parent and antigenmodified mutants were cross resistant to fluoroqinolones (ciprofloxacin, ofloxacin, pefloxacin, lomefloxacin). LD50 for untreated albino mice did not differ from LD50, for mice treated with rifampicin (when mice were infected with strain resistant to rifampicin) or with nalidixic acid and fluoroquinolones (when animals were infected with Nalr mutants). Antigenmodified strains of plague bacteria and their Rifr, Nalr mutants were able to overcome specific immune reaction. The drugs should be used in synergic combinations (with aminoglycosides or cephalosporines of III generation) to prevent appearance of virulent strains resistant to rifampicin and fluroquinolones.

Topics: 4-Quinolones; Animals; Anti-Infective Agents; Drug Resistance, Multiple, Bacterial; Humans; Mice; Mutation; Phenotype; Plague; Rifampin; Virulence; Yersinia pestis

The efficacy of various group antibacterial drugs: aminoglycosides, quinolones, 3rd generation cephalosporins, doxycycline, rifampicin, ampicillin and azthreonam was estimated in the treatment of experimental plague of albino mice induced by antigen complete and atypical strains of the F1- phenotype plague microbe. The in vitro experiments showed that all the strains of the plague microbe irrespective of the phenotype (F1+ or F1-) were highly susceptible to the drugs. The animal experiments demonstrated that aminoglycosides (streptomycin, kanamycin, tobramycin, gentamicin and amikacin) and cephalosporins (ceftriaxone and ceftazidim) were highly efficient in the prophylaxis and treatment of plague due to F1+ and F1- strains. In experimental plague due to F1- phenotype plague microbe the prophylactic effects of cefotaxime, cefoperazone, sulbactam/ampicillin, azthreonam, ciprofloxacin and rifampicin were lower. However, increase of the daily doses of the drugs and prolongation of the treatment course up to 7 days made it possible to increase the protective effects up to 80-100 per cent. Doxycycline and ampicillin were not sufficiently efficient even when used for 10 days in the prophylaxis of plague due to F1- strains.

Topics: Aminoglycosides; Ampicillin; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antigens, Bacterial; Aztreonam; Bacterial Proteins; Cephalosporins; Disease Models, Animal; Doxycycline; Fluoroquinolones; Mice; Monobactams; Penicillins; Phenotype; Plague; Rifampin

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.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Complement Activation; Doxycycline; Erythromycin; Furazolidone; Guinea Pigs; Humans; Microbial Sensitivity Tests; Penicillin G; Penicillins; Plague; Polymyxin B; Quinoxalines; Rifampin; Yersinia pestis

Therapeutic efficacies of various drugs were studied comparatively in the treatment of experimental plague in albino mice at the stage of the infection generalization. It was shown that out of the tested drugs such as ciprofloxacin, amikacin, gentamicin, rifampicin and polymyxin B only ciprofloxacin provided a rather high therapeutic effect in the treatment of the plaque septic form. The in vitro and in vivo experiments demonstrated that ciprofloxacin had an antitoxic action on lipopolysaccharide (LPS) and the plague microbe toxin. In comparison to ciprofloxacin, polymyxin B had a higher neutralizing activity. It was found that the efficacy of the experimental plague treatment at the stage of the infection generalization increased with the use of combinations of the drugs with antitoxic and antibacterial activities (ciprofloxacin and polymyxin B).

Topics: Amikacin; Animals; Anti-Infective Agents; Ciprofloxacin; Disease Progression; Drug Evaluation, Preclinical; Gentamicins; Mice; Plague; Polymyxins; Rifampin

The therapeutic effects of parenteral and oral rifampicins were studied comparatively in a model of experimental plague of albino mice infected subcutaneously and by aerosol. The study showed that in a dose of 25 mg/kg rifampicin was highly efficient in the treatment of the albino mice with experimental glandular plague when the drug was administered either parenterally or orally for 7 days (100-percent survival). The parenteral rifampicin was advantageous when used in lower doses (6.25-12.5 mg/kg) or for a shorter period (3-5 days): 70-100-percent survival against not more than 30 per cent with the oral administration of the drug. It was especially evident when the animals were infected by aerosol. The results made it possible to recommend rifampicin injections in the treatment of the most severe forms of pneumonic plague.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Injections; Mice; Plague; Rifampin; Survival Rate

The efficacy of combinations of fluoroquinolones (ciprofloxacin and pefloxacin) with betalactams (ampicillin, azlocillin and cefotaxime), aminoglycosides (amikacin) and rifampicin was studied on albino mice infected subcutaneously with plague. The drugs were used in deliberately ineffective or insufficiently effective doses. Synergism was observes with the use of ciprofloxacin and pefloxacin in combinations with amikacin, cefotaxime or rifampicin. The combinations of ciprofloxacin with ampicillin or azlocillin had no synergistic action though the therapeutic effect was not lower. With using the specifically determined doses the efficacy of the combinations could be increased by comparison with that of the drugs used alone.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Drug Synergism; Drug Therapy, Combination; Lactams; Mice; Pefloxacin; Plague; Rifampin

Combination of a betalactam antibiotic (ampicillin or azlocillin) or polymyxin B with rifampicin were studied with their administration in succession at various intervals in an experimental model of plague infection of albino mice. It was shown that when the administration of the betalactams or polymyxin B preceded the administration of rifampicin, the efficacy of the preventive therapy considerably increased. The time of the intervals was noted to be of importance and should be predetermined for every subsequent administration.

Topics: Ampicillin; Animals; Azlocillin; Drug Administration Schedule; Drug Therapy, Combination; Mice; Plague; Polymyxin B; Rifampin

The effect of rifampicin on the plague microbe was studied in vitro and in albino mice with experimental plague infection. The rifampicin MIC with respect to 50 strains of the plague microbe of different origin in the tests on the Hottinger agar ranged from 1.6 to 6.4 micrograms/ml. High efficacy of rifampicin was shown in the prophylaxis and treatment of experimental plague when used in doses of 25 and 50 mg/kg once every 24 hours for 5 to 7 days. Rifampicin prevented the development of plague in at least 80 per cent of the albino mice when it was administered 1, 3, 6 and 24 hours prior to the infection. The antibiotic had a prolonged action and preserved its high efficacy after the administration at intervals of 48 and 72 hours.

Topics: Animals; Mice; Microbial Sensitivity Tests; Plague; Rifampin; Yersinia pestis

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.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Azlocillin; Dose-Response Relationship, Drug; Doxycycline; Drug Therapy, Combination; Mice; Plague; Rifampin

The combined effect of rifampicin and a microbial peptidoglycan was studied in multifactorial experiments on noninbred mice with plague infection. The effect of rifampicin and the immunomodulator was shown to be synergistic. The results of the multifactorial experiments provided designing of polynomial statistic models of the second order characterizing the animal survival rate and mean life-span and plotting of nomograms or equal level lines useful in optimization of the combined therapy parameters.

Topics: Animals; Anti-Bacterial Agents; Data Interpretation, Statistical; Drug Synergism; Drug Therapy, Combination; Mice; Peptidoglycan; Plague; Rhizobium; Rifampin

Multifactorial analysis was applied to the study of the combined effect of rifampicin and a microbial polysaccharide in experimental plague infection. The effect of the antibiotic and immunomodulator was shown to be synergistic. On the basis of the study results polynomial statistic models of the second order were designed and nomograms or equal level lines were plotted which provided optimization of the combined chemo- and immunotherapy.

Topics: Animals; Anti-Bacterial Agents; Data Interpretation, Statistical; Drug Synergism; Drug Therapy, Combination; Mice; Plague; Polysaccharides, Bacterial; Rhodococcus; Rifampin

Multifactorial analysis of the combined effect of rifampicin and a low molecular immunomodulator of microbial origin in experimental plague infection was performed. Synergism of the antibiotic used in the subtherapeutic doses and the immunomodulator was shown. By the results of the study polynomial statistic models of the second order describing the survival rate and average life-span of the experimental animals were developed and nomographs (equal level curves) were plotted for rapid estimating the therapy quantitative parameters. Optimization of the combined use of rifampicin and the immunomodulator on the basis of the multifactorial analysis was achieved.

Topics: Adjuvants, Immunologic; Animals; Bacteria; Drug Synergism; Drug Therapy, Combination; Factor Analysis, Statistical; Life Expectancy; Mice; Models, Statistical; Molecular Weight; Plague; Rifampin; Survival Rate