[Ceftriaxone in prevention and treatment of experimental plague infection]. / Tseftriakson v profilaktike i lechenii éksperimental'noi chumy.

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.

[Ofloxacin efficacy in the prophylaxis and treatment of experimental plague due to antigen complete and defective strains of the pathogen]. / Effektivnost' ofloksatsina pri profilaktike i lechenii ékperimental'noi chumy, obuslovlennoi prirodnymi i anigenizmennymi shtammami vozbuditelia.

Strains of the plague microbe, antigen complete and defective by fraction I and mouse toxin had the same in vitro susceptibility to ofloxacin (MIC 0.08 mg/L). The drug was superior in its activity to pefloxacin and especially nalidixic acid. In the experiments with albino mice (prophylaxis, 5 days) the ofloxacin efficacy was lower when the infection was due to the plague microbe strains deprived of the ability to produce fraction I and mouse toxin, evident from a statistically significant increase of the drug ED50 and a decrease of the animal survival percentage. When used in the doses corresponding to the human average daily doses, ofloxacin provided effective animal protection (80 to 100 per cent survival) after the prophylaxis for 7 days and the treatment of the plague infection irrespective of the strains, complete or antigen changed. However, when the infection is due to the antigen changed strain, ofloxacin should be used in the maximum daily doses at least for 7 days.

[Third generation cephalosporins (cefoperazone, cefotaxime, ceftazidime and ceftriaxone) in the prevention and treatment of experimental plague in albino mice]. / Tsefalosporiny tret'ego pokoleniia (tsefoperazon, tsefotaksim, tseftazidim, tseftriakson) v profilaktike i lechenii éksperimental'noi chumy belykh myshei.

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.

[Experimental evaluation of prospects for the use of beta-lactams in plague infection caused by pathogens with plasmid resistance to penicillins]. / Eksperimental'naia otsenka perspektiv ispol'zovaniia betalaktamov pri chumnoi infektsii, vyzvannoi vozbuditelem s plazmidnoi ustoichivost'iu k penitsillinam.

High therapeutic efficacies of ceftriaxone, ceftazidime, cefotaxime and azthreonam in the treatment of experimental plague induced by beta-lactamase-producing strains of the plague microbe containing R plasmids RP-1, R57b and R40a were shown to correlate with their in vitro antibacterial activities. The therapeutic efficacy of sulbactam/ampicillin was recorded in the treatment of plague induced by the strain containing R plasmids R57b and R40a (the treatment course of 7 days). However, it was lower when the infection was due to the strain containing plasmid RP-1 (beta-lactamase TEM-2). Cefoperazone was not active in the treatment of experimental plague induced by the strains containing plasmids RP-1 and R57b (beta-lactamases TEM-2 and OXA-3). Ceftriaxone versus the antibiotics tested was considered to be the drug of choice for the etiotropic therapy of plague induced not only by the type strains of the plague microbe but also by its variants with the plasmid pattern resistance to penicillins.

[Beta-lactam antibiotics (ampicillin, cefotaxime) in prevention of experimental plague in albino mice, caused by non-fractioned strains of the pathogen]. / Betalaktamnye antibiotiki (ampitsillin, tsefotaksim) v profilaktike éksperimental'noi chumy belykh myshei, vyzvannoi besfraktsionnymi shtammami vozbuditelia.

The prophylactic action of betalactam antibiotics such as ampicillin and cefotaxime in plague was studied on albino mice infected subcutaneously by Fra+ (Y. pestis 231) and Fra- (Y. pestis 231 Fra-, K-16) variants of the plague microbe. Ampicillin, a semisynthetic penicillin, was prophylactically less active in experimental plague infection induced by the fraction I defect forms of Y. pestis. Cefotaxime, a 3rd generation cephalosporin, was active in experimental plague induced by both the type and the fraction-free strains of Y. pestis.

[Characteristics of etiotropic therapy of plaque infection induced by atypical strains of F1- phenotype plaque microbe]. / Osobennosti étiotropnoi terapii chumnoi infektsii, vyzvannoi atipichnymi shtammami vozbuditelia s F1- fenotipom.

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.

[Cefoperazone in the prevention and treatment of experimental plague caused by typical and fraction-free pathogen strains in white mice]. / Tsefoperazon v profilaktike i lechenii éksperimental'noi chumy belykh myshei, vyzvannoi tipichnym i besfraktionnymi shtammami vozbuditelia.

The high susceptibility of the plague microbe to cefoperazone (MIC of 0.1-0.25 microgram/ml) did not depend on the causative agent ability to produce fraction I. Cefoperazone, a 3rd generation cephalosporin, was highly active in the treatment of experimental plague caused by the plague microbe strain typical in the antigen composition: the drug daily dose of 250-500 mg/kg provided an 80-100 percent survival of the albino mice. The efficacy of cefoperazone lowered when the infection was caused by the strain defective in the capsule antigen. The use of the antibiotic for more prolonged periods provided better results of the etiotropic therapy.

[A comparative study of fluoroquinolones and 3rd-generation cephalosporins in the prevention and treatment of experimental plague caused by Yersinia pestis strains typical and serologically atypical with respect to F1]. / Sravnitel'noe izuchenie ftorkhinolonov i tsefalosporinov III pokoleniia v profilaktike i lechenii éksperimental'noi chumy, obuslovlennoi tipichnym i serologicheski atipichnym po F1 shtammami chumnogo mikroba.

Fluoroquinolones (ciprofloxacin and pefloxacin) and 3rd generation cephalosporins (cefoperazone, cefotaxime, ceftazidime and ceftriaxone) were comparatively studied in the prevention and treatment of experimental plague in albino mice caused by F1+ and F1- strains of the plague microbe. Despite the phenotype of the strain which caused the infection, the drugs were highly efficient in the etiotropic therapy. However, in the experimental plague due to F1- strains it was needed to use the maximum mean daily doses of the fluoroquinolones, cefoperazone and cefotaxime. For the prevention of the infection such doses should be used for not less than 7 days. By the efficacy ceftriaxon was superior to the other cephalosporins and should be considered as a drug of choice.

[Virulence of rifampicin and quinolone resistant mutants of strains of plague microbe with Fra+ and Fra- phenotypes]. / Virulentnost' ustoichivykh k rifampitsinu i khinolonam mutantov iz shtammov chumnogo mikroba s Fra+ i Fra- fenotipom.

Experiments with 15 highly virulent antigenically typical strains (Fra+) and 3 fraction-free strains (Fra-) of the plague microbe were conducted. It was demonstrated that a single exposure of the plague microbe to rifampicin or nalidixic acid (100 micrograms/ml) resulted in the formation of mutants (Rifr or Nalr) resistant to the drugs. The mutation frequency was 10(-10)-10(-8). All the Nalr mutants showed cross resistance to ciprofloxacin, a 3rd generation quinolone. A comparative study of the virulence of the clones in the population of the initial strains of the plague microbe and the cultures of the Rifr and Nalr mutants revealed that the predominating majority of the variants resistant to rifampicin and the quinolone preserved their high virulence. The resistance level of the mutants was sufficient for inducing the infection development in the albino mice at the background of the therapy with rifampicin, nalidixic acid or ciprofloxacin: no statistically significant differences in the values of the LD50 of the culture for the treated and nontreated animals were recorded. The Rifr and Nalr variants of the fraction-free strains of the plague microbe preserved their ability to overcome the specific immunity in the albino mice. The experimental data indicated that the rifampicin or quinolone monotherapy required a caution and the combined etiotropic therapy was more advantageous since it decreased the risk of the complications due to the drug resistant virulent variants of the plague microbe forming during the treatment.

[The experimental validation of the advantages of combined emergency (fluoroquinolones) and specific (EV Nalr) prevention of plague versus their sequential use]. / Eksperimental'noe obosnovanie preimushchestv kombinirovannoi ékstrennoi (ftorkhinolony) i spetsificheskoi (EV Nalr) profilaktiki chumy pered ikh posledovatel'nym primeneniem.

Mice immunization with reference vaccine at the early stage of plague infection provided animals survival and prolonged mean survival period up to 2-5 days. Ciprofloxacin, ofloxacin and pefloxacin prevents development of post vaccine immunity at white mice, immunized by reference vaccine strain EV. Nalidixic acid and norfloxacin effect on post vaccine immunity was lower. Use of immunogenic strain EV Nafr (resistant to nalidixic acid and fluoroquinolones) provided antiplague immunity formation at the background of fluoroquinolones prophylaxis. Ciprofloxacin, ofloxacin and pefloxacin used for plague prophylaxis at white mice infected with Yersinia pestis (about 1000 LD50) inhibited postinfective immunity development. Nalidixic acid and norfloxacin didn't demonstrate such effect. Urgent (fluoroquinolones) and specific (EV Nalr) combined prophylaxis was evaluated as more effective for a 5-day period and provided the development of antiplague immunity.

[Doxycycline in the prevention of experimental plague induced by plague microbe variants]. / Doksitsiklin v profilaktike éksperimental'noi chumy, obyslovlennoi variantami shtamma vozbuditelia.

A comparative study was performed on the efficacy of doxycycline in experimental plague infection induced in albino mice by strain 231 of the plague microbe and its variant 231 Fra- deprived of the ability to produce the fraction I antigen. It was shown that the LD50 for strain 231 during animal treatment with doxycycline was significantly higher than that for variant 231 Fra-. Prophylaxis of the plague infection caused by the Fra- forms of the plague microbe required significantly higher doses of doxycycline (ED50) than that of the infection caused by the Fra+ forms. The use of the daily maximum permissible doses of doxycycline (50 to 100 mg/kg a day) for 10 days in treatment of albino mice infected with the strain Fra- did not provide animal survival at the level higher than 60 to 70 per cent while the survival rate in the animals infected with the strain Fra+ of the plague microbe and treated according to the same scheme amounted to 90-100 per cent. The lower therapeutic efficacy of doxycycline in the treatment of the infection caused by the fractionless variant of the plague microbe should be considered in development of rational schemes for prophylaxis and treatment of plague.

[Experimental resistance of Vibrio cholerae el tor to nalidixic acid and fluoroquinolones]. / Eksperimental'naia ustoichivost' kholernogo vibriona biotipa él'tor knalidiksovoi kislote i ftorkhinonam.

It was shown that sensitivity of Vibrio cholerae eltor P-5879 to tetracycline, levomycetin, furazolidone, trimethoprim/sulfamethoxazole, aminoglycosides, beta-lactams, rifampicin, quinolones in vitro correlated with drugs efficacy in the treatment of experimental cholera of albino mice. Mutants of V. cholerae eltor P-5879 Nalr resistant to nalidixic acid (MIC 160-200 mg/l) formed with frequency 10(-9)-110(-8) had no cross resistance to fluoroquinolones. But the efficacy of ofloxacin, lomefloxacin, norfloxacin against these mutants in vivo reduced, though it was not changed in vitro. Mutants of V. cholerae eltor P-5879 resistant to fluoroquinolones and selected after culturing in the presence of the drugs had cross resistance to all quinolones studied. Infection caused by Cpfr mutant could not be treated with nalidixic acid and fluoroquinolones, therapeutic efficacy of rifampicin and beta-lactams, also reduced though sensitivity in vitro was not changed. The results of investigation proves the necessity of quinolones use for cholerae treatment as it is recommended for other severe enteric infections.