Testing the sterility of injection preparations of penicillin series antibiotics]

The efficiency of 3 variants of the method for determination of microbial flora was compared on the injection preparation of potassium benzylpenicillin artificially infected with Staph. aureus 209P and the spores of Bac. subtilis ATCC 6633 in different doses and with different amounts of the preparation in the vials. The procedure of the preparation dissolution in the vial with the thioglycol medium containing penicillinase proved to be most effective. The microbe detection amounted to 100 per cent. The procedure was less labour- and time-consuming since addition of penicillinase to each vial with the thioglycol medium was excluded. The risk of the medium occasional infection with microbial flora during the assay was decreased.     

Effect of penicillin on the antigenic properties of serum beta-lipoproteins]

Peculiar characteristics of the antigenic properties of penicillin compounds with heterological and homological beta-lipoproteids of the blood serum were investigated. The beta-lipoproteids isolated from the blood serum of humans (donors) and rabbits were mixed with potassium benzylpenicillin (10000 and 50000 gamma/ml). Twenty seven rabbits were immunized with such compounds and solutions of beta-lipoproteids without addition of the antibiotic. The antisera obtained from the animals were used in the reaction of precipitation and immunoelectrophoresis, the results of which were densitometrized. Some physico-chemical properties of the preparations, such as pH, electrokinetic features were also studied. It was shown that the immunochemical properties of heterological beta-lipoproteids, i.e. precipitation bands changed due to the effect of penicillin. They differed from the control by compactness and contrastness, their amounts decreased, a separate band not identical to that of the control antigen appeared. A separate or intermediate antigen was found in the experiments with serum exhaustion. The peculiarities of the precipitation reaction were confirmed by the immunoelectrophoregrams. These differences were also registered on the densitograms. The compounds of penicillin with homological beta-lipoproteids of the rabbit blood serum induced formation of specific precipitins in the animals. Some physico-chemical properties of beta-lipoproteids also changed under the effect of penicillin.     

Nerve-blocking properties of antibiotics]

Comparative data on the neuroblocking activity of antibiotics of various groups in acute experiments on albino mice and narcotized cats are presented. It was found that according to the impairments in the neuro-muscle conductivity the drugs were arranged in the following descending order: polymyxin B, neomycin, gentamicin, streptomycin, lincomycin and kanamycin. The streptomycin derivatives were approximately 2 times less toxic than streptomycin. The problems of the mode of action of the antibiotics on conductivity of excitation in the neuro-muscle synapses are discussed.     

Effect of tetracycline group antibiotics on the barrier properties of the small intestine epithelium]

The effect of 5 tetracyclines on the barrier and transport properties of the small intestine epithelium was studied. The barrier properties were estimated by a change in the ionic selectivity and conductivity of the epithelium, as well as by enterocyte linkage. The current of the short circuit served the characteristics of the Na transport system state. Dimethylchlortetracycline, methacycline and oxytetracycline in concentrations of 10(-7) g/ml decreased the epithelium conductivity and increased the cell linkage. Tetracycline and methacycline in concentrations of 10(-9) g/ml had an analogous effect. The effect was observed 10--20 minutes after the start of incubation with the substance. No effect on the current of the short circuit was observed within the concentrations of 10(-4) to 10(-9) g/ml. It is suggested that the decreased conductivity and increased linkage are due to adsorption of the tetracycline molecules in the region of close cell contacts.     

Effect of gamma-irradiation on some biological and physico-chemical properties of polyene antibiotics]

Deep effect of gamma-rays on polyenic antibiotics was studied. It was shown that gamma-radiation induced radiation-chemical oxidation of the substances. The chromatographic analysis showed that the levorin degradation products were identical to the polyenic products of the antibiotic oxidative destruction. As for mycoheptin and amphotericin B, destruction of their molecules to non-polyenic products was observed. It was found that toxicity of the levorin aromatic heptaen did not practically change after gamma-irradiation in high doses. The toxicity of mycoheptin and amphotericin B, non-aromatic heptaens increased after exposure to high doses of gamma-rays.     

Elaboration of a rapid method of determining the sensitivity of Brucella to antibiotics]

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.     

Effect of antibiotics on Francisella tularensis]

The minimum inhibitory concentrations of rifampicin, doxycycline, sisomicin, ciprofloxacin and phosmidomycin for various strains of Francisella tularensis were 0.5 to 2.0, 0.5 to 2.0, 0.125 to 0.4, 0.625 to 0.125 and 2.0 to 12.5 micrograms/ml, respectively. Ciprofloxacin and sisomicin had a marked bactericidal effect. The bactericidal effect of rifampicin was insignificant. Doxycycline and phomidomycin had practically no such effect. All the antibiotics had a post effect. The level of the post-antibiotic effect was different and depended on the antibiotic concentration.     

Determination of the microbial contamination of tablets of tetracycline series antibiotics]

The experiments showed that the method of direct plating of tetracycline tablet suspensions on solid nutrient media containing magnesium sulfate may be used for determination of microbial contamination. The method provided determination of both the antibiotic resistant and the antibiotic sensitive organisms which may be present in the drug. Dilution of the basic suspensions increased the probability of the microbe detection in the tablets.     

Effect of antibiotics on the absorption of basic nutrients]

The impact of tetracycline, gentamicin, streptomycin, erythromycin, oxacillin, benzylpenicillin and sulfanilamides on the absorption function of the small intestine was studied in 79 patients with chronic bronchitis. The drugs were shown to mainly inhibit fat absorption: on the average, by 87 per cent in all the patients treated with tetracycline, on the average, by 89 and 36 per cent in 80-70 per cent of the patients treated with gentamicin and streptomycin, respectively, and, on the average by 26 and 16 per cent in 20-25 per cent of the patients treated with erythromycin and oxacillin, respectively. The absorption of protein decreased, on the average, by 23-74 per cent in all the patients treated with tetracycline, gentamicin and streptomycin. As for the other drugs, they had, on the average no significant effect on protein absorption. The absorption of carbohydrates (d-xylose) significantly decreased under the effect of these three drugs (by 21, 34 and 36 per cent, respectively). The analysis revealed a relation of absorption function to the presence and degree of intestinal dysbacteriosis.     

Characteristics of determining the microbial contamination of penicillin series antibiotic powders and tablets]

Optimal conditions for determination of microbial contamination of drugs were studied on artificially contaminated powders and tablets of phenoxymethylpenicillin, ampicillin, oxacillin and dicloxacillin. The method of membrane filtration was the best for determination of the microbial contamination of the powders. However, it was not possible to wash out completely the antibiotic from the membrane filter. To prevent this it was necessary to add penicillinase into the nutrient medium onto which the filter was put for providing the microbial growth. For determination of microbial contamination of tablets direct plating of 3 per cent suspension of the tablet mass onto the surface of the nutrient medium with penicillinase was the best.     

Immunocorrecting properties of antibiotics in secondary immunodeficiency]

The study investigated immunocorrecting properties of penicillin G, streptomycin, gentamycin in cyclophosphamide--induced immunodeficiency in mice. It was determined, that antibiotics in sub-bactericidal doses possess pronounced immunocorrecting properties. This effect was observed in both humoral and cell-mediated immune response.     

Preparation and kinetic properties of immobilized benzyl penicillin acylase]

An active insoluble preparation of immobilized benzyl penicillin acylase (IBA) EC 3.5.1.11 has been obtained by its entrapping into polyacrylamide gel lattice. Due to immobilization the preparation maintains up to 87% of its initial activity. The kinetics of IBA at low substrate concentrations obeys the Michaelis-Menten law; however, the apparent KM value decreases and the temperature optimum elevates. The inhibition by the reaction products--6-aminopenicillanic acid and phenylacetic acid--has been found to be 4.3 mM. The resultant IBA preparation proves to be suitable for hydrolysis of 5% benzyl penicillin solutions.     

Effect of penicillin precursors on antibiotic biosynthesis in various strains]

The regularities of biosynthesis of 6-aminopenicillanic acid (6-APA), benzylpenicillin (BP) and phenoxymethylpenicillin (PMP) by the strains under the investigation did not significantly differ. In the absence of the precursor both the strains mainly synthesized 6-APA. Phenylacetic acid (PAA) and phenoxyacetic acid (POAA) provided directed biosynthesis: the fungus synthesized BP or PMP depending on the precursor nature. When the amount of the precursors was not sufficient, 6-APA was synthesized along with the penicillins. PAA proved to be a more active precursor than POAA. When both precursors were present in the fermentation broth, only BR was synthesized. An important distinction of strain 316A was its increased sensitivity to PAA especially in the initial period. After an increase in the PAA concentration the growth rate of strain 316A lowered to a greater extent than that of strain 284A. This was likely to determine the higher levels of penicillin production by strain 316A in the presence of POAA, a nontoxic precursor. A procedure for supplying the precursors was developed. Under the laboratory conditions it provided high levels of the penicillin production.     

Early discoveries in the penicillin series.

It is now 50 years since the therapeutic potential of penicillin was first demonstrated. This first antibiotic and the series of compounds derived from it have been of immense importance in modern medicine. This article describes the early search for more potent penicillin derivatives, culminating with the discovery of an intermediate of penicillin biosynthesis, 6-beta-amino penicillanic acid (6-APA). A companion article in next month's TIBS will chart the subsequent exploitation of 6-APA and the preparation of a range of clinically important semi-synthetic penicillins.     

Effect of chymotrypsin on the urinary excretion of antibiotics in rabbits]

The effect of cymotrypsin on excretion of penicillin, methicillin, oxacillin, streptomycin and gentamycin with urine including the kidney clearance was studied on rabbits. It was found that the enzyme introduced intramuscularly in a dose of 20 mg/kg increased excretion of penicillin, methicillin, oxacillin and gentamycin by 37, 24, 26 and 16 per cent respectively. The only exclusion was streptomycin. Chymotrypsin increased the kidney clearance of penicillin, methicillin, oxacillin, streptomycin and gentamycin by 1.7, 1.9, 2.2, 1.2 and 1.5 times respectively.