ABSTRACT
The combined effect of doxycycline and microbial peptidoglycan was studied with multifactorial analysis. The drugs were used preventively and therapeutically. The preventive use of doxycycline in the subtherapeutic doses in combination with the immunomodulator resulted in a significant increase in the survival rate rather than the average life-span (ALS) of the experimental animals. The therapeutic use of the drugs was more efficient than the preventive one and resulted in higher survival and ALS. By the results of the experiments polynomial statistic models of the second order were developed and the equal level curves characterizing the survival rate and ALS were plotted. The dose-time regimens of the combined use of doxycycline an peptidoglycan were optimized.
Subject(s)
Disease Models, Animal , Doxycycline/administration & dosage , Peptidoglycan/administration & dosage , Plague/drug therapy , Rhizobium , Animals , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Therapy, Combination , Mice , Plague/mortality , Plague/prevention & controlABSTRACT
Multifactorial analysis of the combined action of rifampicin and a microbial peptidoglycan on the immune response to antigens of the vaccine EV fraction 1 was performed. The results were computer-processed and the second order equations describing delayed hypersensitivity (DH) and antibody titers were derived. Nomographs or equal level curves showing interrelations of the investigated factors were plotted. The character of the combined action on DH and antibody titers was heterogeneous. The peptidoglycan had a pronounced immunostimulant action on DH and, to a lesser extent, influenced the humoral response. Conditions for the peptidoglycan use aimed at immunostimulation were optimized with application of multifactorial analysis.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Hypersensitivity, Delayed/immunology , Models, Biological , Peptidoglycan/administration & dosage , Rifampin/administration & dosage , Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Animals , Computer Graphics , Drug Synergism , Mice , Mice, Inbred CBAABSTRACT
Comparative efficacy of the use of injection and oral dosage forms of rifampicin in the subtherapeutic doses in combination with peptidoglycan , an immunomodulator of microbial origin, was studied in respect to experimental anthracic infection with application of multifactorial analysis. It was shown that the antibiotic and immunomodulator had a pronounced synergistic effect. Polynomial statistic models were developed and nomograms or equal level curves defining the survival rate and average life-span (ALS) of the experimental animals within a wide range of the antibiotic and immunomodulator doses and the peptidoglycan dosing time were plotted. The combined use of the injection rifampicin in the subtherapeutic doses and the immunomodulator provided a significant increase in the survival rate and ALS, whereas the use of the oral antibiotic in combination with the immunomodulator increased only the ALS and not the survival rate. Multifactorial analysis proved to be an optimal methodical approach to comparative study of various antibiotic dosage forms used in combination with immunomodulators under experimental conditions.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Anthrax/drug therapy , Disease Models, Animal , Peptidoglycan/administration & dosage , Rifampin/administration & dosage , Administration, Oral , Animals , Anthrax/immunology , Anthrax/mortality , Drug Therapy, Combination , Factor Analysis, Statistical , Injections, Intraperitoneal , Male , MiceABSTRACT
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.
Subject(s)
Peptidoglycan/therapeutic use , Plague/drug therapy , Rhizobium , Rifampin/therapeutic use , Animals , Anti-Bacterial Agents , Data Interpretation, Statistical , Drug Synergism , Drug Therapy, Combination/therapeutic use , MiceABSTRACT
Multifactorial analysis of the combined action of a microbial peptidoglycan and doxycycline on the immune response to antigens of the vaccine EV fraction 1 was made. Nomograms or equal level curves characterizing delayed hypersensitivity (DH) and antibody titers in various doses of the peptidoglycan and the antibiotic were plotted by the experimental data with a computer. The peptidoglycan had a pronounced immunomodulatory action on DH and antibody titers. However, the types of regulation of the both responses markedly differed. With multifactor analysis, the range of the values of the operating parameters, i.e. the drug doses and the time of their administration providing the required levels of DH and antibodies under the conditions of the combined therapy were defined.
Subject(s)
Antibody Formation/drug effects , Doxycycline/pharmacology , Peptidoglycan/pharmacology , Animals , Drug Interactions , Factor Analysis, Statistical , Hypersensitivity, Delayed/immunology , Immunity, Cellular/drug effectsABSTRACT
The effect of doxycycline combination with a low molecular immunomodulator of microbial origin on the primary immune response to the vaccine EV antigens was studied in multifactor experiments. Mathematical processing of the data provided construction of polynomial statistic models of the second order describing increased delayed type hypersensitivity (IDTH) and the antibody titer. Analysis of the quasimonofactor models revealed different character of regulation of the cellular and humoral response. Nomograms were plotted for precise quantitative estimation of the dose-time parameters of the regimens for combined use of the antibiotic and immunomodulator providing the required levels of IDTH and the antibody titer.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Doxycycline/therapeutic use , Immunity/drug effects , Adjuvants, Immunologic/administration & dosage , Animals , Antigens/immunology , Doxycycline/administration & dosage , Drug Therapy, Combination , Factor Analysis, Statistical , Hypersensitivity, Delayed , Male , Mice , Mice, Inbred CBA , Molecular WeightABSTRACT
A significant decrease in resistance to infections caused by gramnegative pathogens was observed in mice with neutropenia induced by cytostatics. Efficacy of schemes for combined chemotherapy with beta-lactams, aminoglycosides and a novel peptide antibiotic was studied on model infections in mice with neutropenia. In the neutropenic mice with sepsis caused by Pseudomonas the peptide antibiotic administered parenterally in a single dose of 50 micrograms/kg provided high therapeutic activity. In combination with azlocillin, cefotaxime and amikacin the peptide antibiotic has a synergistic therapeutic action.
Subject(s)
Agranulocytosis/immunology , Amikacin/administration & dosage , Azlocillin/administration & dosage , Cefotaxime/administration & dosage , Escherichia coli Infections/drug therapy , Klebsiella Infections/drug therapy , Neutropenia/immunology , Pseudomonas Infections/drug therapy , Animals , Drug Synergism , Drug Therapy, Combination/administration & dosage , Escherichia coli Infections/etiology , Escherichia coli Infections/immunology , Immune Tolerance/drug effects , Klebsiella Infections/etiology , Klebsiella Infections/immunology , Mice , Neutropenia/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/etiology , Opportunistic Infections/immunology , Pseudomonas Infections/etiology , Pseudomonas Infections/immunologyABSTRACT
Multifactor analysis was applied to combined effect of a low molecular immunomodulator of microbial origin and rifampicin on the primary immune response (increased delayed type hypersensitivity and antibody titer) to the antigens of vaccine EV fraction I. Computer processing of the experimental data provided construction of the 2nd order polynomial models satisfactorily describing cellular and humoral responses in the combined therapy. For increasing the informative capacity of the analysis of the polynomial statistic models it was proposed to develop quasimonofactor relationships reflecting the factor effect on the output with changing of the other factors within the studied ranges. Nomograms (equal level lines at fixed values of one factor) were constructed which provided rapid and correct estimation of optimal values for the regulating parameters (drug doses and administration time). Immunostimulating activity of the microbial immunomodulator was estimated quantitatively and conditions for selective regulation of the cellular and humoral responses were determined.
Subject(s)
Adjuvants, Immunologic/pharmacology , Bacterial Proteins/pharmacology , Rifampin/pharmacology , Vaccines/immunology , Animals , Factor Analysis, Statistical , Male , Mice , Mice, Inbred CBASubject(s)
Anti-Bacterial Agents/biosynthesis , Gram-Negative Bacteria/metabolism , Anti-Bacterial Agents/pharmacology , Culture Media/metabolism , Gram-Negative Aerobic Bacteria/metabolism , Gram-Negative Anaerobic Bacteria/metabolism , Gram-Negative Bacteria/classification , Gram-Negative Bacteria/drug effects , Spores, BacterialABSTRACT
The effect of rifampicin combination with a natural low molecular immunomodulator on the primary immune response to the antigens of tularemia vaccine was studied with the methods of multifactor designing of the experiment. The dependence of the delayed hypersensitivity and antibody titer on doses of the antibiotic and immunomodulator and the time of the immunomodulator administration was manifested by the second order equation. Nomographs for precise quantitative estimation of the doses and regimens providing the maximal delayed type hypersensitivity and antibody titers were plotted.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antigens, Bacterial/immunology , Francisella tularensis/immunology , Rifampin/pharmacology , Animals , Antibodies, Bacterial/analysis , Antibody Formation/drug effects , Dose-Response Relationship, Drug , Hypersensitivity, Delayed/immunology , Immunity, Cellular/drug effects , Immunization , Male , Mice , Mice, Inbred CBA , Molecular Weight , Research Design , Time FactorsABSTRACT
Glycerol-yeast medium No. 3 may be used as a seed medium in screening of antibiotic-producing strains among Acetobacter, Gluconobacter, Chromobacterium, Agrobacterium, and other genera. The medium is transparent. It provides visual instrumental control of the growth rate of the seed material and estimation of biomass augmentation. The period of the exponential phase growth of the strains tested on medium No. 3 was 2-8 hours. When no growth on medium No. 3 is observed media Nos. 1 and 2 can be used as alternative seed media.
Subject(s)
Acetobacter/growth & development , Chromobacterium/growth & development , Culture Media , Pseudomonadaceae/growth & development , Rhizobium/growth & development , Anti-Bacterial Agents/biosynthesisABSTRACT
A method for selective isolation of gramnegative nonsporulating bacteria from soil substrates was developed. The method consists of plating out the substrates on a glucose-yeast medium with addition of benzylpenicillin and nalidixic acid. The isolation frequency of gramnegative nonsporulating bacteria increased under such conditions from 9-16 (control) to 80-100 per cent. At the same time the isolation frequency of gram-positive bacteria decreased from 88.5 to 9.6 per cent.
Subject(s)
Gram-Negative Bacteria/isolation & purification , Bacteriological Techniques , Culture Media/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Lincomycin/pharmacology , Nalidixic Acid/pharmacology , Penicillin G/pharmacology , Soil MicrobiologyABSTRACT
The electrophoretic analysis of the plasmid DNA of multiresistant clinical E. coli strains revealed the presence of extrachromosomal DNA in 97% of the strains. The plasmid nature of resistance was established in 88-100% of E. coli strains resistant to chloramphenicol, ampicillin, streptomycin or kanamycin and in 67% of the strains resistant to tetracyclin. 24 out of 40 strains contained conjugative R-plasmids in which the determinants of resistance to kanamycin, ampicillin and chloramphenicol were transferred most frequently (82-93%), while the determinants of resistance to tetracyclin and streptomycin were transferred less frequently (45% and 35%, respectively). Nonconjugative R-plasmids were detected in 15 out of 40 antibiotic-resistant strains; in these plasmids the determinants of resistance to streptomycin (65%) and tetracyclin (22%) were transferred most frequently.
Subject(s)
Anti-Bacterial Agents/antagonists & inhibitors , Escherichia coli/genetics , Plasmids/drug effects , R Factors/drug effects , Chromosomes, Bacterial/drug effects , Conjugation, Genetic , Drug Resistance, Microbial , Escherichia coli/drug effects , Genes, Bacterial/drug effects , Transformation, Bacterial/drug effectsABSTRACT
The gentamicin levels in the lung tissue and blood serum of children operated on for bronchiectasis, destructive pneumonia and pleural tumors were studied. The antibiotic was administered intramuscularly in a dose of 3 mg/kg before the operation. The results showed that intramuscular injections of gentamicin provided the antibiotic levels in the lung tissue sufficient for the growth inhibition of the majority of the microbes isolated from such patients. In the patients with congenital developmental defects of the lungs, the level of the antibiotic in the lung tissue 1 hour after its administration was lower than the therapeutic one, while its blood serum levels were high. By the 2nd hour the gentamicin levels in the lung tissue reached those in the patients with acquired bronchopulmonary disease.
Subject(s)
Bronchiectasis/metabolism , Gentamicins/blood , Lung/metabolism , Pleural Neoplasms/metabolism , Pneumonia/metabolism , Absorption , Adolescent , Child , Child, Preschool , Humans , Injections, Intramuscular , Time FactorsABSTRACT
Pharmacokinetics of gentamicin administered into the eye by means of instillation or hydrophilic contact lenses was studied comparatively. The results of the study showed that gentamicin levels in the humor of the eye anterior chamber after the antibiotic administration with soft contact lenses were higher at all periods than those after instillation. Higher retention time of gentamicin therapeutic doses in the humor of the eye anterior chamber after the antibiotic administration by means of soft contact lenses is also an advantage of this administration route.
Subject(s)
Contact Lenses, Hydrophilic , Eye/drug effects , Gentamicins/metabolism , Animals , Gentamicins/administration & dosage , In Vitro Techniques , Kinetics , Ophthalmic Solutions , RabbitsABSTRACT
Patients with myelotoxic agranulocytosis were treated with gentamicin administered intravenously as drop-wise infusions in a dose of 5 mg/kg body weight a day every 8 hours. The treatment course consisted of 7--24 days. No toxic reactions were observed. The therapeutic efficacy of gentamicin depended on the neutrophilic level and amounted to 50--60 per cent when the drug was used without identification of the causative agent. The prophylactic use of gentamicin decreased the infection incidence in patients with myelotoxic agranulocytosis, while the prophylactic efficacy of gentamicin was evident only when the number of the granulocytes was higher than 100/mm3 of the blood.
Subject(s)
Agranulocytosis/drug therapy , Gentamicins/therapeutic use , Drug Evaluation , Drug Therapy, Combination , Drug Tolerance , Evaluation Studies as Topic , Gentamicins/administration & dosage , Gentamicins/adverse effects , Humans , Leukemia/drug therapy , Lymphoma/drug therapy , Neutropenia/drug therapyABSTRACT
Analysis of 53 antibiotic resistant clinical strains of E. coli isolated from patients with various purulent inflammatory diseases is presented. According to the data of the electrophoretic study 83 per cent of them carried 2 to 6 plasmids. Thirteen of them carried the conjugation R-factor. The antibiotic resistance in the other strains was due to the non-conjugation plasmids.
Subject(s)
Anti-Bacterial Agents/antagonists & inhibitors , Escherichia coli/genetics , Plasmids/drug effects , Conjugation, Genetic/drug effects , Drug Resistance, Microbial , Escherichia coli/drug effects , Microbial Sensitivity Tests , Molecular Weight , R Factors/drug effectsABSTRACT
The results of the study on the pharmacokinetics peculiar properties of carbenicillin premature infants treated with the drug administered intravenously or intramuscularly are presented. The maximum antibiotic blood levels after intravenous administration exceeded the MIC for most of the causative agents isolated from the children. The schemes for the antibiotic use in treatment of purulent septic processes of children are recommended.