[In vitro induction of transmissive resistance to tetracycline, chloramphenicol and ampicillin chloramphenicol in Vibrio cholera non-O1/non-O139 serogroups isolated within 1990-2005].

Inducible character of resistance to tetracycline, chloramphenicol and ampicillin was investigated in 20 strains of Vibrio cholera non-O1/non-O139 serogroups isolated from inhabitants of Uzbekistan in 1990 (10 strains, ctx+) and in 2001 (5 strains, ctx-) and from inhabitants of Kalmykiya within 2003-2005 (5 strains, ctx-). Eight of the 20 isolates showed not only capacity for induction of the antibiotic resistance, but also its possible self transfer to Escherichia coli and reverse crosses in El Tor V. cholerae P-5879. It was shown that the effect of the antibacterial on the isolates phenotypic susceptibility could increase the resistance markers expression, when the genomes contained sites responsible for their expression, that required constant bacteriological control of the treatment efficacy and the use of the isolates antibioticograms for early replace of the inefficient drug by the efficient one. The prevalence of V. cholerae O1 and non-O1/non-O13 serogroups with multiple resistance to the antibacterial and the genetic potency for the antibiotic resistance development in the pathogen made difficult the choice of efficient drugs for prophylaxis and treatment of diseases caused by V. cholerae.

[Antibioticograms of Vibrio cholerae non-01/non-0139 strains isolated from humans within 1968-2009].

Analysis of the antibioticograms of the Vibrio cholerae non-01/non-0139 strains showed that in the cultures isolated in the Rostov Region in 1968--1975 there were present markers of resistance to ampicillin (7%), kanamycin (15.8%), rifampicin (3.5%) and trimetoprim/sulfamethoxazole (14%). Among the strains isolated in the Ukraine in 1975 14% was resistant to ampicillin. More than a half of the strains isolated in Uzbekistan in 1990 and 2000-2001, in the Arkhangelsk Region in 1999-2000 and in the Kalmykia in 1999-2005 was antibiotic resistant. In the above regions the strains were resistant to ampicillin (12.5-44.4%), kanamycin (11-55%), rifampicin (1.9-12.5%) and trimetoprim/sulfamethoxazole (25-62.5%). Among the cultures isolated in Uzbekistan in 1990 and 2000-2001 25 and 7.8% were resistant to furazolidone and 31.25% was resistant to streptomycin (1990). All the cultures isolated in the Rostov Region in 2005-2009 were resistant to ampicillin, 50% was resistant to ceftazidim, 57% was resistant to streptomycin and furazolidone, 7.2% was resistant to kanamycin and 14% was resistant to trimetoprim/sulfamethoxazole. The studies revealed an increase of the extent of the V.cholerae non-01/non-0139 resistance spectrum within 1968-2009, simultaneous presence of up to 5 diverse resistance markers and a variety of their combinations, that requires the use of antibacterials for the treatment of the diseases due to the vibrios in strict compliance with the pathogen antibioticogram and their early replace by more efficient drugs.

[Lack of levofloxacin and moxyfloxacin efficacy in experimental plague of albino mice infected with nalidixic acid resistant pathogen (Nal(r))].

The efficacy of levofloxacin and moxyfloxacin vs. the previously tested fluoroquinolones was studied on albino mice with experimental plague due to the Nal(r) mutants of Yersinia pestis 231 and 231 FI-. The plague microbe mutants resistant to nalidixic acid (Nal(r)) generated at a frequency of 10(-10)-10(-9). The resistance to nalidixic acid was not accompanied by the strains loss of the virulence. The Nal(r) mutants were cross resistant to fluoroquinolones (ciprofloxacin, moxyfloxacin). The LD50 for the nontreated animals did not differ from that for the mice treated with nalidixic acid and the fluoroquinolones (when the animals were infected with Nal(r) mutants). The results showed that the criteria of the plague microbe susceptibility/resistance to fluoroquinolones should be revised.

[Infectious-toxic model of plague in mice].

AIM: To develop infectious-toxic model of plague in mice and to assess perspectives of its use for selection of new vaccine preparations. MATERIALS AND METHODS: Cells of virulent strains of Yersinia pestis 231 and 231 FI- incubated in lysates of human erythrocytes for their activation as well as suspensions of these strains in isotonic solution of NaCl were used for subcutaneous inoculation of infection-nanve and immune mice. RESULTS: It was shown that activated cultures were characterized by maximal virulence (LD50 = 1-3 CFU) and caused rapid infection--mean length of survival reduced on 1 - 3 days (P < or = 0.01). Vaccine strain EV used by conventional way of inoculation (suspension in isotonic solution of NaCl) induced strong antibacterial immunity (index of immunity--10(5)), whereas activated (in lysate of erythrocytes) cells of Y. pestis 231 strain overcame it (index of immunity--10(2)). LD50 value of Y. pestis 231 FI- for immune and nanve animals was 3 m.c. (1 CFU), which demonstrates the absence of ability of EV strain to induce antitoxic immunity in the macroorganism. CONCLUSION: Use of two models of infection allows to make more adequate prognosis of efficacy for relevant vaccine preparations.

[Efficacy of levofloxacin, lomefloxacin and moxifloxacin vs. other fluoroquinolones in experimental plague due to FI+ and FI- strains of Yersinia pestis in Albino mice].

Activity of levofloxacin, lomefloxacin and moxifloxacin against 20 FI+ and 20 FI- strains of Yersinia pestis was studied. It was shown that the strains were highly susceptible to the fluoroquinolones. In the experiments on mice subcutaneously infected with suspension of strains 231 FI+ and 231 FI- of Y. pestis in a dose of about 1000 LD50 (10(4) microbial cells) the ED50 of levofloxacin and moxifloxacin was 5.5-14.0 mg/kg independent of the infective culture phenotype and that of lomefloxacin was 18.5 mg/kg. Estimation of the impact of the pathogen infective dose value on the results of the experimental plague treatment with the therapeutic dose equivalent to the human one showed high efficacy of the fluoroquinolones (efficacy index of 10(4)). The treatment for 7 days provided 90-100-percent survival of the animals. The prophylactive use of lomefloxacin (in 5 hours - 5 days) was less efficient (70-80% of the survivals) in the animals infected with the antigen-changed (FI-) variant of the pathogen. Levofloxacin and moxifloxacin provided 90-100-percent survival of the animals treated for a course of 5 days independent of the pathogen phenotype. The study demonstrated that the use oflevofloxacin, lomefloxacin and moxifloxacin was prospective for the prophylaxis and therapy of experimental plague.

[Efficacy of cefixime and cefepime vs. other cephalosporins in experimental plague of albino mice due to variants FI+ and FI- of the plague microbe].

Efficacy of cefixime and cefepime vs. ceftriaxone, cefotaxime, ceftazidime and cefoperazone was studied in vitro and in the treatment of experimental plague of albino mice due to natural, antigen complete strains of the plague microbe and the pathogen variants deprived of the ability to produce the capsule antigen fraction I (FI- phenotype). The MICs of cefixime and cefepime for 20 FI+ and 20 FI- strains of the plague microbe were 0.02-0.08 mg/l, that corresponded to the MICs of ceftriaxone, cefotaxime and ceftazidime. The MICs of cefoperazone were somewhat higher (0.1-0.2 mg/l). The ED50 values of cefixime and cefepime for prevention and treatment of experimental plague in mice statistically did not significantly differ from the ED50 values of ceftriaxone, cefotaxime, ceftazidime and cefoperazone. The efficacy indices (EIs) of cefixime and cefepime were > 10(4) independent of the infective strain phenotype (FI+ or FI-) and did not differ from those of ceftriaxone and ceftazidime. The efficacy of cefotaxime and cefoperazone was somewhat lower (EIs 1.7 x 10(3)-8.9 x 10(3)). Both the antibacterials were shown to provide high protective and therapeutic efficacy (80-100% of the survivors) independent of the phenotype (FI+ or FI-) of the pathogen infective strain. The results allowed to consider the antibiotics prospective in prevention and treatment of plague.

[Prophylactic use of ceftriaxone in combination with F I antigen immunization in studies on uninbred albino mice infected by Yersinia pestis. Antiplague immunity development].

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.

[Synergistic action of some antibacterial agents in studies on albino mice with experimental plague caused by Fr- phenotype strain of the plague microbe].

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.

[Isepamycin in prophylaxis and treatment of experimental plague due to FI+ and FI- variants of plague microbe].

The efficacy of isepamycin vs. other aminoglycosides was studied in vitro and on albino mice with experimental plague due to natural antigen valuable strains of the plague microbe and the pathogen variants deprived of the ability to produce the capsular antigen fraction I (FI- phenotype). The MICs of isepamycin for the strains of the plague microbe (20 FI+ and 20FI-) were 1.0-4.0 mg\l, that did not differ from those of streptomycin, kanamycin, amikacin and tobramycin. The ED50 of isepamycin in the prophylaxis and treatment of the experimental plague of the mice had no statistically significant differences from the ED50 of the other aminoglycosides. The efficacy index of isepamycin was > 10(4), that did not differ from that of streptomycin, amikacin and gentamicin, irrespective of the strain phenotype (Y. pestis 231 FI+ or Y. pestis 231 FI-). The same as the other aminoglycosides, isepamycin in doses equivalent to the human average daily doses, protected 80-100% of the albino mice from death when used in the prophylaxis and therapy of plague irrespective of the strain phenotype. The results of the study made it possible to consider isepamycin as an agent promising for the prophylaxis and treatment of plague.

[Activity of 22 antibacterials against O1 and O139 serogroup Vibrio cholerae strains isolated from humans within 1927-2005 in various regions of the world].

Analysis of antibioticograms of 390 O1 and O139 serogroup Vibrio cholerae strains isolated from humans within 1927-2005 in various regions of the world showed that the strains of V. cholerae isolated within 1927-1966 were susceptible to 22 antibacterials, the strains isolated within 1938-1993 possessed 1-3 resistance markers and the strains isolated within 1994-2005 had 3-8 resistance markers including resistance to fluoroquinolones. All the strains of O139 serogroup V. cholerae isolated in 1993 and 1994 possessed 3 resistance markers. Studies on albino mice with generalized experimental cholera due to the V. cholerae eltor 1 strain (P-18826, 2005) isolated from a cholera patient, which was highly resistant to nalidixic acid, streptomycin, ampicillin and trimethoprim/sulfamethoxazole and showed cross resistance to fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin and norfloxacin) and moderate resistance to ceftriaxone and cefotaxime, revealed that the only efficient antibiotics were tetracyclines and aminoglycosides (except streptomycin). The investigation demonstrated an extension of the antibiotic resistance spectra of the epidemically significant strains of the cholera pathogen and the necessity of using antibacterial drugs in strict accordance with the antibioticograms in emergent prophylaxis and therapy of cholera and immediate replacement of the drug by a more active one.

[Origin of plague moderate phages of serotype 2]. / O proiskhozhdenii chumnykh umerennykh fagov serotipa 2.

Results of study of the negative colonies morphology, the structure of corpuscles, antigenic properties, specificity, and the action range permitted to refer the phages obtained from 18 E. coli strain, 1 plaque strain, and 1 pseudotoberculosis bacillus strain to the same group and to identify them with plague phages of serological type 2. Isolation of the same phage type from different bacterial species permits to regard them as "polyhostal" ones. E. coli should be considered as the main carrier of phages belonging to serological type 2. It is suggested that phages existing on microbes belonging to different species should be called "polyhostal".

[The possibility of colonizing the intestines of white mice with Lactobacillus acidophilus during bacterial therapy]. / Vozmozhnost' prizhivleniia Lactobacillus acidophilus v kishechnike belykh myshei na fone bakterial'noi terapii.

The study revealed the possibility, on principle, for L. acidophilus strain VKM V-2020 D to colonize the intestine of white mice with the preservation of the viability of lactobacilli subjected to the action of antibiotics. The culture of this strain, isolated from the animals, showed the stability of its biological properties: resistance to polymyxin M, kanamycin, cyprofloxacin, nalidixic acid (including acquired resistance to rifampicin), as well as pronounced antagonism with respect to Vibrio cholerae. Good prospects for the use of L. acidophilus strain VKM V-2020 D for further studies regarding its use for prophylaxis and therapy were noted.

[Experimental evaluation of efficacy of Lactobacilli in prophylaxis and treatment of cholera]. / Eksperimental'naia otsenka éffektivnosti laktobatsill dlia profilaktiki i lecheniia kholery.

Investigations on experimental models of cholera ("sealed" mice and suckling rabbits) demonstrated that previous daily oral administration of the ferment culture of Lactobacillus acidophilus BKM B-2020[symbol: see text] in a dose of 3.0 x 10(8) microbial cells/ml daily for 5-7 days prevented to the development of Vibrio cholerae infection. The curative effect observed after 3 administrations of lactobacilli within 48 hours after infection with V. cholerae was registered in 50% of cases. This strain of lactobacilli was found to be suitable for use as the basis component of probiotic, an additional remedy for the prophylaxis and treatment of cholera.

[Characterization of Vibrio cholerae eltor in the city of Kazan in 2001]. / Kharakteristika kholernykh vibrionov él'tor, vydelennykh v g. Kazan' v 2001 g.

Information on V. cholerae eltor isolated in the focus of cholera in Kazan in 2001 at different periods of the outbreak is presented. The identity of strains isolated from patients, vibriocarriers and environmental objects, including their antibioticograms (sensitivity to cyprofloxacin and resistance to trimethoprim--sulfamethoxazole, streptomycin, furazolidone and nalidixic acid, which may be regarded as markers), is shown. Variable tandem repetitions in the DNA of 30 isolates strains of different origin have been determined. The results of this determination make it possible to classify all these strains as one genotype, which confirms the suggestion on the circulation of one subclone of the infective agent of cholera in the focus. As revealed in this investigation, the isolated strains are labile with respect to diagnostic phage eltor, while ctx+ strains are resistant to phage eltor ctx+.

[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.

[Combined use of quinolones with other antibiotics in treatment of experimental plague infection]. / Kombinirovannoe ispol'zovanie khinolonov s drugimi antibiotikami v lechenii éksperimental'noi chumnoi infektsii.

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.

[Comparative study of the effectiveness of amikacin and streptomycin in experimental tularemia]. / Sravnitel'noe izuchenie éffektivnosti amikatsina i streptomitsina pri éksperimental'noi tuliaremii.

In vitro study on antibacterial activity of amikacin in comparison to that of streptomycin revealed a high sensitivity of tularemia microbes of three geographical races to it. Amikacin showed a high therapeutic activity in treatment of albino mice infected with tularemia. The prospects of amikacin use in prophylaxis and treatment of tularemia are defined by its antibiotic activity against streptomycin-resistant forms of the tularemia causative agent.

[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.

[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.

[Detection of persistent resistance to antibacterial drugs in various strains of Francisella tularensis]. / Obnaruzhenie persistiruiushchei ustoichivosti k antibakterial'nym preparatam u nekotorykh shtammov Francisella tularensis.

Under natural conditions, the Francisella tularensis strains AE-261 and P-13864 capable of forming the persist type of resistance to antibacterial drugs and being the cause of the infection in laboratory animals not responding to monotherapy with antibiotics were detectable. The antibioticograms of strains AE-261 and P-13864 under the in vitro conditions did not differ from those of the other studied strains responding to the antibiotic therapy. The observed phenomenon could be associated with individual peculiarities of the strains and their phenotypic variation in the host. Combinations of aminoglycoside antibiotics (streptomycin, gentamicin and amikacin) with rifampicin were shown to be highly active in the treatment of general forms of the infection due to such strains. The combined therapy of tularemia was also considered promising because of its high efficacy when the treatment was started at late periods as well as because unlike the monotherapy with the aminoglycoside antibiotics it provided complete elimination of the pathogen from the host.