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Development of rapid and sensitive procedures for determination of microbial resistance to antibiotics is one of the most urgent trends in microbiology. The problem is shown to be solved by using electrooptical assay based on change of the electrophysical properties of suspended bacterial cells exposed to antibiotics with different mechanisms of action. Possible determination of the microbial cell susceptibility to antibiotics and their antibacterial activity is demonstrated. The results showed the procedure of electrooptical assay to be prospective in solving the problem of the microbiol cells antibiotic susceptibility in microbiology, medicine and veterinary.

High resistance of enterococci to the currently used antibacterials, such as tetracycline, ciprofloxacin and ampicillin was observed. Streptomycin, gentamicin and vancomycin showed the highest activity against the clinical isolates of Enterococcus spp. Streptomycin and gentamicin showed the highest activity against the intestinal enterococci. The PCR revealed the presence of the genetic determinants of resistance to aminoglycosides, glycopeptides and tetracycline in the isolates. The comparison of the results of the bacteriological and genetic tests provided detection of fecal and clinical isolates of Enterococcus spp. possessing the genes of resistance to aminoglycosides and glycopeptides, still without the finally developed significant clinical resistance to the above antibacterials.

The effect of chloramphenicol and tetracycline, as inhibitors of protein synthesis, on electrophysical properties of Escherichia coli K-12 cells was investigated. Significant changes in the orientation spectra (OS) of the cell suspensions incubated with various concentrations of chloramphenicol were observed only at the first five frequencies of the electric field (10-1000 kHz). When the cells were exposed to chloramphenicol (1.5 mcg/ml) or tetracycline (1.7 mcg/ml), no changes in the OS were recorded. Significant changes in the electrooptic signal were observed, when the K-12 cells were simultaneously incubated with chloramphenicol (1.5 mcg/ml) and tetracycline (1.7 mcg/ml), that could be due to the synergistic action of the antibiotics. Therefore, the electrooptic analysis provided registration of higher antibacterial effect with the simultaneous use of chloramphenicol and tetracycline. Additional control experiments with the cell culture on the LB nutrient medium containing chloramphenicol and tetracycline were performed. The results suggested that the use of electrophysical methods for investigation of antibiotics effect on microorganisms was rather efficient.

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.

The effect of the enzyme complex from Vobenzin on transfer of plasmid genes in biofilms of gramnegative bacteria was studied. The extracellular matrix of the bacterial biofilms was shown to contain extracellular DNA carrying the antibiotic resistance markers. The action of the enzyme complex resulted in lower frequency of the antibiotic resistance genes transfer in mixed bacterial biofilms.

The hepatoprotective action of Hepatophyt was studied on Wistar rats with experimental hepatitis caused by exposure of the animals to tetracycline. Hepatophyt was administered per os in a dose of 0.1 g/kg. Its significant pharmacotherapeutic action was due to the content of biologically active substances, mainly of polyphenol nature. As natural antioxidants, they provided stabilization of the biomembranes and increased the energetic potential of the hepatic cells and the contractile capacity of the pericanal microfilaments, thus stimulating the synthesis and transport of the cholates and excretion of bilirubin and cholesterol with bile.

During the 6-year observation period from 1998 to 2003 in Moscow there was recorded in 2000-2001 a decrease in the emergence of Streptococcos pneumoniae resistance to many antibacterials, while during the following years the respective index increased. The above dynamics in the resistance emergence was likely due to a decrease in the use of antibiotics in 1998-1999. In 2003 the rate of resistance to penicillin was 18.6%, 0.4 and 2.1% of the isolates were resistant to amoxicillin and cefotaxime respectively, the rate of resistance to erythromycin reached 19%, 65.4% of the resistant strains showed M phenotype. High rates of resistance were as well observed with respect to tetracycline (40.1%), co-trimoxazole (29.1%) and chloramphenicol (18.6%). Resistance to levofloxacin and moxifloxacin was detected only in rare strains.

The role of transport activity of Acholeplasma laidlawii plasmatic membrane in the development of resistance to ciprofloxacin and tetracycline was investigated. It was shown that one of the important steps of resistance development in acholeplasms is a complex of adaptation metabolic reactions providing limited antibiotic accumulation by the cells. In the case of ciprofloxacin resistance metabolism changes concerning transport systems took place before mutations in target genes. Development of tetracycline resistance of mollecutes after incubation in the medium with enhancing antibiotic concentrations and not connected with the presence of tet(M) determinant was demonstrated for the first time.

The role of physico-chemical rearrangements in the cell plasmalemma of Acholeplasma laidlawii in the development of resistance to tetracycline was investigated. The cells of A.laidlawii were shown to be tolerant to tetracycline and to preserve a rather high titre of the cells even at a concentration of the antibiotic in the inoculation medium much higher than the MIC. The results of the investigation of the structural rearrangements in the plasmatic membrane of the cells grown in the presence of tetracycline revealed changes in the lipid flow in the surface layer and an increase in the cholesterol and phospholipid contents. The size of the changes depended on the time of tetracycline addition and the phase of the culture growth.

The influence of exogenous RNAse on the dynamics of the acid formation by the industrial strain 8R-A3 of Lactobacillus plantarum, its antibiotic sensitivity and antagonistic activity was studied. In the presence of the RNAase growth stimulating dose both a decrease of the culture lag-phase and a more intensive accumulation of lactic acid in the incubation medium resulting in an increase of the Lactobacillus antagonistic activity were observed. It was shown that RNAase increased the Lactobacillus stability to tetracycline and erythromycin by 32 to 57 per cent as compared to the control.

Susceptibility of 150 Corynebacterium isolates (91 strains of C.pseudodiphtheriticum and 59 strains of the ANF group corynebacteria) to 21 antibacterial drugs was determined by the method of serial dilutions in a solid medium. It was shown that the MIC of the drugs for the diphtheroids was within the ranges of < 0.015 to > 32.0 micrograms/ml. 66 per cent of the Corynebacterium strains circulating in St. Petersburg was resistant at least to 1 antibacterial drug. The Corynebacterium isolates with moderate resistance to erythromycin and lincomycin (57.3 per cent) and resistant to trimethoprime (16.7 per cent) were the most frequent. 8.0 per cent of the diphtheroids was resistant at least to 4 antibacterial drugs. No significant difference in the susceptibility of the ANF group corynebacteria and C.pseudodiphtheriticum to the drugs was observed. Gentamicin, rifampicin, tetracycline and doxycycline showed high activity against the corynebacteria at present circulating in St. Petersburg. When antibacterial therapy of the infection due to corynebacteria fails it is necessary to estimate antibioticograms of Corynebacterium pure cultures.

Activity patterns of membrane-bound enzymes of an antibiotic sensitive strain of Staphylococcus aureus 8325-4 and its variants containing the plasmids of resistance to penicillin, tetracycline, erythromycin and chloramphenicol were studied. It was shown that acquiring of resistance to the above mentioned antibiotics influenced cellular energy metabolism. The resistant strains exhibited an increase in the specific activity of NADN, malate and succinate oxidases, intensification of the ATP-hydrolyzing activity, changes in the activity of definite dehydrogenases and a decrease in the specific content of cytochromes. No changes in the composition of respiration carriers were detected.

The sensitivity of 235 N. meningitidis strains to 5 antibiotics was estimated by the diameter of growth inhibition zones according to the criteria recommended by a Laboratory (Marseilles, France) collaborating with the WHO. All the strains proved to be sensitive to benzylpenicillin when disks containing 10 and 2 IU of the antibiotic were used. The strains were also shown to be sensitive to chloramphenicol and tetracycline. 95.7 and 7.7 per cent of the strains were sensitive to rifampicin and oleandomycin, respectively. When the strain sensitivity was assayed with the disks containing 10 and 2 IU of benzylpenicillin by the more severe criteria recommended by J. Saez-Nieto et al., significant changes were detected: meningococci with relative resistance to benzylpenicillin were detected in various regions of this country and the number of such strains was found to have a tendency to slightly increase.

Optimal conditions were developed for determination of antibiotic sensitivity in Brucella by using enzyme immunoassay directly in the primary cultures of the material tested. The Brucella concentration in the material tested should be not lower than 1.10(6) microbial cells/ml and the time of culture incubation be 24 hours at 37 degrees C. The obligatory condition is to use a liquid medium, i.e. the Albimi broth with 1% glucose. To inhibit the foreign microflora it is recommended to use polymyxin B and amphoglucamine in a concentration of 3 microgram/ml. The use of enzyme immunoassay was shown that it was possible to determine the antibiotic sensitivity of Brucella in practice.

In vivo and in vitro efficacy of tetracyclines was studied with respect to anthracic infection induced by a tetracycline-resistant resistant strain containing plasmid pBC16. The plasmid-containing strain was resistant to tetracycline, doxycycline and minocycline, the MICs exceeding those for the initial strain 500, 640 and 80 times, respectively. There was no therapeutic effect of tetracycline and doxycycline in the treatment and urgent prophylaxis of anthracic infection caused by the tetracycline-resistant strain of Bacillus anthracis. High therapeutic efficacy of minocycline in the average therapeutic concentrations was shown irrespective of the contaminating doses and strains. Minocycline was recommended for treatment and urgent prophylaxis of anthracic infection caused by tetracycline-resistant B. anthracis strains.

Genetic determinants of tetracycline resistance of classes A, B and C were detected with DNA probes labeled with radioactive phosphorus (32P) in Shigella (44 strains) and Salmonella (50 strains). It was shown that in the Shigella strains the frequency of the Tet A gene amounted to 66 per cent, the frequency of the Tet B gene was equal to 84 per cent, the frequency of their combination was equal to 50 per cent and the frequency of the Tet C gene was nil. In the Salmonella strains the frequency of the Tet A, Tet B and Tet C genes was equal to 0.100 and 20 per cent, respectively, and that of their combination amounted to 20%. Possible use of the DNA probes in epidemiological analysis of outbreaks of Shigella and Salmonella infections is suggested.

The effect of subinhibitory concentrations of antimicrobial agents such as chloramphenicol, tetracycline, rifampicin and nalidixic acid on various factors of virulence in Shigella spp. and enteroinvasive colon bacilli was studied. It was shown that under such conditions changes took place in various events of the interaction with the epithelial cells, i.e. in adhesion, penetration, intracellular multiplication and transfers between contacting cells. The total effect of chloramphenicol resulted in increasing of the virulence while that of nalidixic acid, tetracycline and rifampicin resulted in its decreasing.

It was shown on male rats that like ethanol tetracycline increased lipid peroxidation (LPO) in the hepatocyte membranes, evident from increased levels of diene conjugates and malone dialdehyde in the liver homogenates, especially on their combination. The signal amplitude of the EPR-forms of cytochrome P-450 and Cu-, Mo- and Fe-containing proteins did not change, while the content of the EPR-forms of the free radicals increased. High efficiency of antioxidants, such as tocopherol acetate, sodium selenite and tincture of Astragalus L. is indirect evidence of the role of the free radicals in initiation of LPO in tetracycline affections of the liver.

The effect of tetracycline hydrochloride on the levels of total protein and separate protein fractions, such as albumins and alpha 1-, alpha 2-, beta- and gamma-globulins in the lymph and blood serum of rabbits was studied. The antibiotic was administered intramuscularly in a single dose of 25 mg/kg or repeatedly for 7 and 20 days. The lymph was collected from the thoracic duct 1, 1.5, 2, 2.5, 3, 3.5, 4 and 24 hours after the antibiotic administration in a single dose. When the antibiotic was used repeatedly, the lymph was collected 24 hours after the last injection. The levels of the total protein were determined colorimetrically and those of the protein fractions were determined turbidimetrically. The results indicated that under the experimental conditions tetracycline induced a marked decrease in the contents of both the total protein and the protein fractions in the lymph and blood serum of the animals. This phenomenon was observed in all periods. Comparative analysis of the data on the lymph and blood serum specimens collected from the same experimental animal revealed a difference in the albumin-globulin ratio, which was higher in the lymph and lower in the blood serum compared to that in the intact animals. This is indicative of the tetracycline capacity for decreasing mainly the levels of the globulin fraction in the lymph and the albumin fraction in the blood serum. The decrease in the level of the gamma-globulin fraction in the lymph and blood serum may be attributed to inhibition of the immune system function due to antibiotic therapy. Since maintenance of the albumin level is one of the liver important functions, the changes in the protein composition of the lymph provide an additional information on the effect of tetracycline on this function of the liver.

The effect of tetracycline, amphotericin B and kefzol on distribution of some proteins between the blood and lymph of the thoracic duct was studied on rabbits. Tetracycline was injected intramuscularly in the form of hydrochloride dissolved in 2% novocain in a dose of 25 mg/kg once or daily for 7 and 20 days. Kefzol (sodium cephazolin) was injected intramuscularly in a single dose of 100 mg/kg. Amphotericin B was injected intravenously in a dose of 1000 Units/kg once or for 5 days. The lymph samples were collected from the thoracic duct of rabbits treated with single doses of the antibiotics 1 and 24 hours after their injection. When the animals were treated with the antibiotics repeatedly the lymph samples were collected 24 hours after the last injection. The level of the total protein and the ratio of the protein fractions, i. e. albumins, alpha 1-, alpha 2-, beta- and gamma-globulins in the lymph and blood serum were determined. On the basis of these findings the protein coefficient (albumin/globulin) of the lymph and blood, the coefficients of the protein permeability of the blood vessels (R) and the constants of selective permeability of the blood capillaries (S) were calculated. It was shown that the shifts in the protein circulation between the blood and lymph had mainly the same trends independent of the antibiotics used and their retention time in the host. A significant decrease in the permeability of the blood vessel walls in respect to the total protein and gamma-globulins and a marked increase in their selectivity in passing of the protein molecules of different size were observed in all cases.

L-forms of bacteria were isolated in 18 out of 300 fever patients with diagnoses of typhoid-paratyphoid fever, grippe, virus respiration disease and others in the Diagnostic Department of an Infection Hospital during bacteriological tests of the blood. Among the cultures tested 13 were instable and reversed to the bacterial form. The type identification showed that only 9 revertants possessed properties characteristic of the typhoid fever microbes and belonged to S. typhi. Sensitivity of the typhoid fever revertants to levomycetin, sintomycin, streptomycin, pencillin and tetracycline was studied. The studies showed that the typhoid fever revertants from the L-forms isolated from the patients were sufficiently sensitive to levomycetin, sintomycin, penicillin and tetracycline. The minimum bactericidal concentrations of the above antibiotics ranged within 12.5--100 gamma/ml.

The effect of tetracycline and tetraolean on the shifts in the plasma-cell elements was studied experimentally on male albino rats of Wister line and rabbits immunized with foreign erythrocytes and typhoid fever vaccine respectively. It was noted that prolonged use of the antibiotics for 10 to 12 days inhibited proliferation of the plasmic cells, the inhibitory effect of tetracycline being more pronounced. At the same time an inhibitory effect of the antibiotics on the antibody formation in the animals was found in the experiments.

The studies on the effect of a number of antibiotics on transfer of R-factors with the use of a kinetic conjugation system showed that rifampicin inhibited the transfer of various R-factors independent of the microbial host strain and R-factor type (the inhibition coefficient of I infinity equals 7.5-16.8). The early conjugation stages preceding the transfer of R-factor DNA were most sensitive to the antibiotic effect. Decreased number of R+ conjugants observed on the donor strain growth in the presence of rifampicin were due rather to selection of spontaneous R- variants with the antibiotic found in our experiments than to its direct effect on the donor competence of R+ cells. It was also found that exposure of E. coli strains to rifampicin for 30 minutes increased their sensitivity to chloramphenicol and tetracycline, this being more pronounced in the cells which not long ago acquired the R-factor. The mechanism of the phenomenon is not clear yet. It was shown to be not associated with the cell permeability impairement under the effect of rifampicin. It was noted that rifampicin combination with neomycin chloramphenicol, tetracycline or streptomycin had a synergistic effect on the strains of E. coli.

Furacillin in combination with such antibiotics as tetracycline, levomycetin or neomycin inhibited the synthesis of proteins in the cells of NAG-vibrios. Combination of 8 gamma/ml of furacillin and 0.125 gamma/ml of tetracycline inhibited the protein synthesis by 58.8 per cent, 8 gamma/ml of furacillin and 0.5 gamma/ml of levomycetin inhibited the synthesis by 61 per cent, 8 gamma/ml of furacillin and 4 gamma/ml of neomycin inhibited it by 59.5 per cent. At the same time furacillin alone in concentrations of 16 and 8 gamma/ml inhibited the protein synthesis by 69.1 and 37 per cent respectively, tetracycline alone in doses of 0.25 and 0.125 gamma/ml inhibited it by 51.3 and 34.7 per cent respectively, levomycetin alone in doses of 1 and 0.5 gamma/ml inhibited it by 54.4 and 33.2 per cent, enomycin in doses of 8 and 4 gamma/ml inhibited it by 54.4 and 22.6 per cent respectively. Therefore, when the above antibiotics were used in combination with furacillin the inhibitory effect of the drugs on the protein synthesis was summarized. When furacillin was combined with tetracycline or levomycetin in the above concentrations, the inhibitory effect on RNA synthesis (42 or 32 per cent respectively) was lower than that of furacillin alone (50.5 per cent). When furacillin was used in combination with neomycin, the inhibition of RNA synthesis increased up to 69 per cent. The increase in the inhibitory effect was also noted with respect to the synthesis of DNA. Combination of furacillin with tetracycline, levomycetin or neomhcin decreased the synthesis of DNA by 79.7, 85 or 85.8 per cent respectively as compared to the inhibitory effect of 8 gamma/ml of furacillin equal to 61 per cent.

The rate of tetracycline hydrochloride transfer into solution from capsules containing different auxiliary substances was studied. It was shown that the dispersity level of tetracycline hydrochloride powder had no significant effect on the capsule disintegration and the rate of the antibiotic transfer into solution. The effect of the auxiliary substance composition on the capsule disintegration and the rate of the antibiotic dissolution was shown. The rate of tetracycline liberation from the capsules containing tetracycline hydrochloride without additives or the antibiotic in combination with 23 per cent of lactose was 4 to 6 times higher than that from the capsules with magnesium carbonate or calcium phosphate as the auxiliary substances.

Development of the tracheobronchial and mesenteric lymph nodes has been studied in fetuses and offsprings of Wistar rats after an intramuscular administration to the female rats therapeutic doses of tetracycline hydrochloride during the first 6 days of pregnancy (preimplantation period of embryogenesis). General histological and morphometrical methods have been applied. Under the experimental conditions certain disorders in formation of functional structures of the lymph nodes have been revealed: differentiation of the parenchyma into the cortical and medullary substance formation of follicles and their germinative centers, development of sinuses, formation of argyrophile stroma architectonics are delayed. Some distrophic and destructive changes of the reticular cells are observed, argyrophilia of the reticular fibers is more evident. Lympho- and plasmocytosis are retarded on the background of an increased eosinophilic and mast cell reaction.

Transmissivity of drug resistance in wild strains of E. coli was shown to be determined not only by the presence of the transmissive factor and r-determinants in the microbial cell, but also by the functional activity of the R-factor. The capacity of the R-factor for transmission depended to a certain extent on the number of the r-determinants in the R-factor and the presence of various r-determinants in the R-factor.

The structure of drug resistance was studied on 2788 clinical strains of staphylococci isolated from various materials of patients with purulent-inflammatory processes, stuff and environment within 12 years from 1968 to 1973. The number of staphylococci resistant to tetracycline increased 13 times among the cultures with resistance marker, while the number of staphylococci resistant to penicillin decreased 1-8 times. The study of the complex resistance revealed the predominance of staphylococci with tetracycline resistance structure (60-5 percent).

It was shown that the conjugation system of Ps. aeruginosa PAO 2604 X PTO 629 rifr used for transfer of the plasmid markers of R-factor RPI was a convenient model for a number of genetic investigations (the rate of transfer of the antibiotic resistance markers was 2.2 X 10(-3) to 8.8 X 10(-5). 80.7 per cent of the exconjugants obtained from this crossing acquired all 3 resistance plasmid markers (carbenicillin tetracycline, neomycin). In 12 per cent of R+-exconjugants transfer of 2 or 1 resistance determinant of R-factor was observed. The use of the above conjugation system revealed the inhibitory effect of bonafton (an antiviral drug), acridine dyes (acrichin, metachrome orange), ethidium bromide and rifampicin. A possibility of intraspecies transfer of resistance plasmid markers was found in crosses Ps. aeruginosa PAO 2604 X X E. coli CSH--2 rifr and Ps. aeruginosa PAO 2604 X E. coli C600 rifr. Transfer of the resistance markers was observed in combinations of carbenicillin, tetracycline, neomycin (Cb, Tc, Nm), tetracycline (Tc) and carbenicillin (Cb).

Administration of tetracycline to rabbits in doses of 10 and 40 mg/kg induced hyperplasia of the reticulo-plasmic tissue of the bone marrow correlating with increased levels of gammaglobulins in the blood serum. The pronounced reticulo-plasmocytal reaction of the bone marrow must be considered as manifestation of hyperplasia of the whole reticulo-histiocytal system of the host with impairement of differentiation of the reticular syncytium of the bone marrow.

The effect of benzylpenicillin and tetracycline on phagocytosis by leukocytes of abdominal cavity exudate, activity of lysozyme and beta-lysines in the blood serum, content of nucleic acids and activity of succinate dehydrogenase and phosphatase (total and acid) in the liver cells was studied on albino mice infected by staphylococci. It was shown that the treatment of the animals with benzylpenicillin and tetracycline for 5 days affected the cellular and nonspecific humoral defence and activity of succinate dehydrogenase and phosphatase. A decrease in the indices of the phagocytosis, activity of lysozyme, beta-lysines, succinate dehydrogenase and phosphatase was observed. Tetracycline had a more pronounced inhibitory effect. Neither benzylpenicillin, nor tetracycline had an effect on the content of nucleic acids in liver cells.

The effect of antibiotics was estimated by inhibition of the protein increase in the broth culture of Staph, aureus during incubation at a temperature of 37 degrees for 18 hours. In some experiments preincubation of the antibiotic solutions with the vitamins for 2 hours at light and in dark was used. The antibiotic concentrations in gamma per 1 ml were equal to those of the vitamins. In the experiments with tetracycline and 2-hour preincubation at light the antibiotic in a concentration of 0.1gamma ml inhibited for certain the protein increase by 58.9%, in combination with thiamin it inhibited the protein by 60 per cent and in combination with ascorbic acid by 59%. Riboflavin lowered the activity of tetracycline to a value not differing for certain from the control one. In the experiments with preincubation in dark tetracycline inhibited the protein increase by 55.2%, in combination with thiamin it inhibited the protein increase by 50.5%, in combination with riboflavin by 53% and in combination with ascorbic acid by 57.2%. Erythromycin in a concentration of 0.03gamma/ml when preincubated at light inhibited the protein increase by 48.8% and in combinations with thiamin, riboflavin or ascorbic acid by 23, 27, 47.2% respectively. When preincubated in the darkness erythromycin alone inhibited the protein increase by 47.8% and in combinations with thiamin, riboflavin or ascorbic acid by 32.5, 51.1 or 49.8% respectively. The above vitamins has no effect on levomycetin activity.

Relation between the rate of tetracycline dissolution from tablets and capsules and the biological acceptibility of the antibiotic in the host was studied. The antibiotic dissolution rate from the pharmaceutical forms was determined in a modernized apparatus "Rotary basket" in water, the speed of the basket rotation was 200 r.p.m. In addition the tetracycline blood levels in patients treated with the drug in the above pharmaceutical forms were estimated. It was found that the rate of the antibiotic dissolution characterized the antibiotic biological acceptibility. A test for the dissolution rate was developed. It may be used for estimation of production batches of tetracycline tablets.

The experiment was carried out with 252 albino rats of Wistar line immunized with Candida albicans vaccine under conditions of treatment with tetracycline, streptomycin and penicillin in doses of 40000-50000 Units/kg body weight. In the first part of the experiment the animals were immunized with a single dose of dead carpuscular vaccine and treated with the antibiotics for 10 days. In the second part of the experiment the animals were immunized 3 times, and 2nd and 3rd immunizations being with live cultures of C. albicans and the antibiotics were used for 20 days. The results of the experimental showed that repeated administrations of the antibiotics to the albino rats during immunization decreased the animal immune reactivity and aggravated the experimental candidosis: the rate of semination with the fungus increased and excretion of the fungus from the organism decreased.

The study of the process of tetracycline base crystallization showed that with an increase in the rate of pH, temperature and mixed rotation changes, the specific surface of the crystalline precipitate increased with a simultaneous decrease in the bulk weight, looseness and volume density of the powder. The residual content of tetracycline in the mother solution decreased. The level of the effect of various parameters on the final results was different.

The experiments showed that among 110 Salmonella strains resistant to 1 or more antibiotics 54.5 per cent of the cultures transfered their resistance to E. coli when grown in vitro. The frequency of the transmissive drug resistance in Salmonella was directly proportional to the number of r-determinants in R-factor. The cultures resistant to ampicillin and kanamycin proved to be the most competent donors.

The effect of combinations of penicillin, tetracycline and rifampicin on R. prowazekii (the causative agent of typhus) and R. sibirica (the causative agent of tick-borne rickettsiosis of the North Asia) was studied. It was shown that tetracycline and penicillin used in combination had a summation effect on both R. sibirica and R. prowazekii. The dose of each antibiotic was 2 times lower than the doses of the antibiotics used alone. However, R. sibirica was less sensitive to this combination than R. prowazekii: the minimum rickettsiocidic doses of the combination were 0.5 mg of tetracycline + 10000 units of penicillin per embryo with respect to R. sibirica and 0.1 mg of tetracycline + 10000 units of penicillin per embryo with respect to R. prowazekii. The combinations of rifampicin with penicillin or tetracycline in the concentrations used had no rickettsiocidic effect on either R. sibirica or R. prowazekii. However, it should be noted that these combinations had a synergistic action and provided a rickettsiostatic effect on R. prowazekii: the dose of rifampicin in its combination with penicillin was decreased 10 times and in the combination of rifampicin with tetracycline the doses of both rifampicin and tetracycline were decreased 10 times. Still, penicillin even in a dose of 20000 units per embryo had only a rickettsiostatic effect on R. sibirica and R. prowazekii.