It was shown that polyenic antibiotics and their combinations with some other antifungal and antibacterial agents prevented transformation of the C. albicans yeast phase into the tissue one. Moreover, the fungus tissue form proved to be more sensitive than the yeast form to the drugs and especially to their combinations. The in vitro findings were confirmed by the in vivo studies. Combinations of amphotericin B with methacycline, rifampicin, 5-fluorocytosine or polymyxin B were more efficient than the polyene alone. Summation of the drug antifungal effects provided a 4-fold decrease in the polyene quantity required for administration to experimental animals.
Benzylpenicillin interaction with amines in the nonaqueous phase was studied by pH dependence of the coefficient of the antibiotic distribution in the system of amine butyl acetate solution--water. A distribution scheme involving interaction of the amine molecular and cationic forms with benzylpenicillin and amine dissociation equilibrium in organic solution is described. On the basis of the experimental data the interaction and dissociation constants were determined for a number of aromatic and aliphatic amines.
Tissue pharmacokinetics of aclarubicin and its active metabolites was studied with high performance liquid chromatography. The drug was administered to rats intravenously in single doses of 5 and 10 mg/kg and orally in a single dose of 10 mg/kg. With both the administration routes the highest concentrations of the drug and its metabolites were attained in the lymph nodes. Then followed the spleen and lungs. The lowest content of the drug was detected in the heart. The total values of the areas under the concentration/time curves for aclarubicin and its metabolites in the tissues of the heart, lungs, lymph nodes and spleen after oral administration were respectively 2, 3, 4 and 7 times lower than those after the drug intravenous administration in the same dose. The concentrations of the active metabolites MA144N1 and MA144T1 exceeded those of aclarubicin and were detected in the tissues within a longer period as compared to the unchanged drug. With repeated administration preferential accumulation of the metabolites in the tissues and their increased contribution to the aclarubicin antitumor effect could be suspected.
Conditions for cultivation of basidiomycete Coprinus radiatus on agar media and its submersion fermentation were developed. An antibiotic was isolated from the fermentation broth filtrate by extraction with ethyl acetate followed by purification on a column with silica gel. The antibiotic had a pronounced in vivo effect on hemoblastosis La. Spectral analysis of the antibiotic (UV, IR, NMR and mass spectra) showed that it was identical to patulin (a toxin).
It was shown that low molecular peptides Nos. 1 and 2 produced by soil bacteria had a pronounced immunostimulating effect. When the preparations were administered at various periods with respect to immunization the number of AFC in the spleen of immunized animals increased 2-4 times. Preparation No. 2 in a dose of 0.5-25 mg/kg increased delayed type hypersensitivity and hemagglutinin levels in blood serum. The maximum effect was observed when the preparation was administered 24 or 48 hours after immunization. The ability to stimulate immunological processes in animals may probably be attributed to the fact that preparations Nos. 1 and 2 are efficient against carcinoma 755 and not toxic in vitro.
Candida infection caused by intracerebral administration of collection and clinical strains of C. albicans was studied on 1000 albino mice. The infecting doses ranged from 5 X 10(6) to 200 X 10(6) cells. Developing infection might be characterized as Candida encephalomeningitis complicated by generalized candidiasis. Acute purulent inflammations in the tissues of the brain, kidneys and myocardium developing at early periods after the infection were replaced by granulomatous reaction and fibroplastic processes. Generalization of the infection was confirmed by C. albicans isolation from blood and internal organs. Development of multiple microabscesses in the brain tissue and early severe affections in the kidneys and myocardium were a pathomorphological characteristics of the infectious process due to administration of a clinical virulent strain of C. albicans to the brain. Intracerebral administration of various C. albicans strains to mice provided their differentiation by the virulent properties.
Experimental design was used in studying the effect of certain qualitative factors on rheological properties of antibiotic hydrogels. It was shown that water solubility of antibiotics and the procedure of their addition to gel bases were important in developing hydrogels. Scanning electron microscopy was used in comparative analysis of antibiotic hydrogels.
Pharmacokinetics and characteristic features of ampicillin kidney distribution were studied in 21 children with chronic pyelonephritis without signs of renal insufficiency who had undergone urological operations. It was found possible to provide the antibiotic concentrations efficient against ampicillin sensitive and partially middle sensitive microorganisms in the renal parenchyma, pelvis wall, ureterocele, megaureter and urinary bladder. Ampicillin concentrations in tissues of the urinary system were shown to correspond to a higher extent to the concentrations attained in blood than those in urine.
Actinomycete plasmid pSB24.1 was cloned on vector of the E. coli pBR325 system. The following bireplicon plasmids were obtained: pSU501 and pSU502 (by XhoI site of pSB24.1 and SalGI site of pBR325), pSU503 (by Bg1II (c) site of pSB24.1 and BamHI site of pBR325) and pSU504 (by Bg1II(b) site of pSB24.1 and BamHI site of pBR325). In the cells of E. coli C600 plasmids pSU501-504 determined phenotype AprCmrTcs and were stable. In the cells of Str. lividans the initial structure pSU501 selected by Ltz+ phenotype was maintained at a frequency of 12.5 per cent. Analysis of the deletion variants of pSU501 isolated from Str. lividans showed that the deletions were induced by both the pBR325 region and the pSB24.1 DNA fragment near XhoI site. The region from SacII(a) site to Bg1II(b) site clockwise in the map of plasmid pSB24.1 was not significant for its replication and maintenance in Str. lividans. There were detected unique sites of pSB24.1 and its derivatives useful for cloning. Possible shortening of plasmid pSB24.1 by 567 kb (the length between the terminator of the open frame reading translation and XhoI site) was revealed.
Development of rational antibiotic dosing is mainly limited by the absence of a clear conception of the minimum efficient concentration. Studies on antimicrobial effect kinetics in dynamic models in vitro simulating pharmacokinetic profiles observed in humans markedly promote the problem solution. Such an approach enabled one to reveal a relationship between duration or intensity of the antibiotic effect and the area under the concentration/time curve. This relationship depends on the antibiotic pharmacokinetic profile. It is advisable to evaluate antibiotic efficacy against microorganisms by the minimum efficient area under the concentration/time curve and not by the antibiotic minimum efficient concentration. Thus, it is possible to estimate simultaneous contribution of two factors to the antimicrobial effect: drug concentration and exposure time.
Sensitivity of 201 S. typhi strains to antibiotics and chlorine containing disinfectants was studied. The strains were isolated in the regions of the Left Bank Ukraine. Among the typhoid cultures the proportion of R+ strains was on the whole equal to 29.3 per cent. Chloramine resistant strains amounted to 21.8 per cent. Among chloramine resistant strains the number of the cultures carrying R plasmids was 3 times higher than that of the strains sensitive to disinfectant. Simultaneous transfer of the R plasmid and chloramine resistance to the recipient strain suggested that resistance of the S. typhi strains to chloramine was of plasmid nature.
A procedure for indicating strict anaerobes in microbial associations was developed. The indication is performed with two disks: aminoglycoside (amikacin, 10-micrograms disk) (A) and metronidazole aminoglycoside (metronidazole + amikacin, 5- and 10-micrograms disks respectively) (MA). Colonies growing in zone A and absent in zone MA are considered to be strictly anaerobic. The procedure is characterized by high reliability: false positive results are practically not recorded and the frequency of false negative results does not exceed 5-10 per cent. The rate of detecting anaerobes in clinical materials is significantly increased (by 1-3 days) as compared to that with the use of the routine bacterial methods. The indication procedure markedly simplifies laboratory diagnosis of anaerobic infections at the account of clear differentiation of microorganisms grown on the primary plate and possible directed selection of anaerobic colonies for further investigation which excludes the necessity of rejecting or studying other colony types. This leads to economy of nutrient media and increasing labor productivity.
Microscopic examination of native bile and smears stained with the Gram procedure rapidly provided information on the presence of bactericholia and the necessity of antibacterial therapy prior to closing of the postoperative wound in accordance with the drug spectrum. Determination of the phagocytic and bactericidal activity of the bile leukocytes was a significant adjuvant to routine microscopic examinations, whereas evaluation of the average cytochemical coefficient and phagocytosis intensity was an important factor in prognosis of postoperative pyoinflammatory complications. Gram-negative bacteria were the predominating causative agents of acute cholecystitis and cholangitis (89 per cent). Among them Escherichieae, Klebsielleae and P. aeruginosa were isolated most frequently (32.4, 31.1 and 16.4 per cent, respectively). Amikacin, tobramycin, sisomicin, gentamicin and cefotaxime showed the highest activity against the above pathogens. However, comparative analysis of the antibioticograms revealed differences in antibiotic sensitivity of separate bacterial species.
Data on laboratory studies with real liquid sewage from antibiotic manufacture are presented. Two schemes are discussed: treatment of the sewage in an electrolysis plant followed by its afterpurification either in a column with pyrolusite or during a joint process of electrochemical purification with catalyst location on the plant bottom under the electrodes. The afterpurification of electrochemically treated liquid sewage on waste pyrolusite can provide and additional effect i.e. lower consumption of oxygen and decoloration at average by 15 and 25 per cent respectively.
The parameters of additional treatment of biologically pure antibiotic production sewage in winter were studied on a pilot model of a 3.72 m3 biopond with higher aquatic plants (Phragmites communis). Sufficiently high efficiency of the process of possible provision of the required sewage quality were shown. A mathematical model of the process based on the first order reaction equation was developed. Its application was estimated and the values of the equation constants were measured.
