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PubMed1998

Evolution of bacterial resistance to antibiotics during the last three decades.

Bacterial resistance to antibiotics is often plasmid-mediated and the associated genes encoded by transposable elements. These elements play a central role in evolution by providing mechanisms for the generation of diversity and, in conjunction with DNA transfer systems, for the dissemination of resistances to other bacteria. At the University Hospital of Zaragoza, extensive efforts have been made to define both the dissemination and evolution of antibiotic resistance by studying the transferable R plasmids and transposable elements. Here we describe the research on bacterial resistance to antibiotics in which many authors listed in the references have participated. The aspects of bacterial resistance dealt with are: (i) transferable resistance mediated by R plasmids in Gram-negative bacteria, (ii) R plasmid-mediated resistance to apramycin and hygromycin in clinical strains, (iii) the transposon Tn1696 and the integron In4, (iv) expression of Escherichia coli resistance genes in Haemophilus influenzae, (v) aminoglycoside-modifying-enzymes in the genus Mycobacterium with no relation to resistance, and (vi) macrolide-resistance and new mechanisms developed by Gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed2001

[Cloning of the sugar related biosynthesis gene cluster from Streptomyces tenebrarius H6].

Streptomyces tenebrarius H6 produces a complex of aminoglycoside antibiotics, such as apramycin, tobramycin and kanamycin B etc. To study the apramycin biosynthetic genes the genomic library from the Streptomyces tenebrarius H6 was established using E. coli/Streptomyces shuttle vector pKC505 by in vitro packing. The probability of finding a specific gene from the library composed of 3,000 colonies was over 99.9%. According to the highly conserved sequence of the genes involved in 6-deoxyhexose biosynthesis, primers were designed and 0.6 kb fragment homologous to strE gene was obtained by PCR. 30 positive clones were found from the genomic library of S. tenebrarius H6 with the 0.6 kb fragment as a probe. Overlapped regions were localized by Southern hybridization and putative sugar related biosynthetic gene cluster was mapped by restriction enzyme digestions. An ORF of dTDP-glucose-4,6-dehydratase gene consisted of 1,132 bp, designated as aprE, was obtained and submitted to GenBank under the accession number of AF306787. A DNA sequence highly homologous to strL coding dTDP-4-dehydrorhamnose reductase was found linked with aprE gene.

Anti-Bacterial Agents↗
PubMed2002

[Establishment of gene replacement/disruption system through homologous recombination in Amycolatopsis mediterranei U32].

A gene replacement/disruption system of Amycolatopsis mediterranei U32 was developed based on the established electroporation conditions as well as appropriate selective markers. Through two-step selection, ahbas gene in U32 was replaced by a promoterless alpha-amylase gene constructed on the plasmid pDK110 of E. coli. The first single-crossover and the second double-crossover frequencies were approximately 0.5%-0.7% and 2%, respectively. Denaturation of the plasmid pDK110 increased the integration frequency about 7-10 folds, while electric shock treatment of the single-crossover recombinants increased the frequency of second crossover recombination about 5 folds. Employing denatured DNA fragments containing an apramycin-resistance gene flanked with regions of the respective genes, One-step disruption of rifO and amrA genes of U32 was also achieved with an efficiency of 30-50 transformants per microgram of DNA.

Actinomycetales↗
PubMed2005

Pretreatment of apramycin wastewater by catalytic wet air oxidation.

The pretreatment technology of wet air oxidation (WAO) and coagulation and acidic hydrolysis for apramycin wastewater was investigated in this paper. The COD, apramycin, NH4+ concentration, and the ratio of BOD5/COD were analyzed, and the color and odor of the effluent were observed. WAO of apramycin wastewater, without catalyst and with RuO2/Al2O3 and RuO2-CeO2/Al2O3 catalysts, was carried out at degradation temperature of 200 degrees C and the total pressure of 4 MPa in a 1 L batch reactor. The result showed that the apramycin removals were respectively 50.2% and 55.0%, COD removals were 40.0% and 46.0%, and the ratio of BOD5/COD was increased to 0.49 and 0.54 with RuO2/Al2O3 and RuO2-CeO2/Al2O3 catalysts in catylytic wet air oxidation (CWAO) after the reaction of 150 min. With the pretreatment of coagulation and acidic hydrolysis, COD and apramycin removals were slight decreased, and the ratio of BOD5/COD was increased to 0.45, and the effluents was not suitable to biological treatment. The color and odor of the wastewater were effectively controlled and the reaction time was obviously shortened with WAO. HO2 may promote organic compounds oxidized in WAO of the apramycin wastewater. The addition of CeO2 could promote the activity and stability of RuO2/Al2O3 in WAO of apramycin wastewater.

Air↗
PubMed1988

[Comparative study of apramycin-resistant microorganisms isolated from man and animals].

Apramycin-modifying strains isolated from pigs with coli bacteriosis, from humans and hospital environment were studied comparatively. Production of enzymes modifying the aminoglycoside was estimated with the radioactive cofactor procedure. E. coli isolates from the animals were phenotypically resistant to apramycin and a number of other aminoglycosides. They produced acetyltransferase AAC(3)IV, phosphotransferase APH(3')(5"), APH(3") and other enzymes. Resistance of the strains to gentamicin was also conditioned by AAC(3)IV since these strains did not produce AAD(2") and AAC(6'). In the resistant strains of E. coli and their transconjugates there were detected plasmids with a relative molecular weight of 60-80 MD. Some of the belonged to the compatibility group I1, the others belonged to the compatibility group H1. Strains of S. marcescens, K. pneumoniae. K. oxytoca and S. aureus isolated from humans and hospital environment were sensitive to apramycin. Only isolates of P. aeruginosa were resistant to this antibiotic. However, all the isolates produced AAC(3)IV. Some of them additionally produced AAC(6'), an enzyme modifying amikacin, kanamycin and other antibiotics and not acetylating apramycin. Almost all the strains produced kanamycin- and streptomycin phosphotransferases. Possible coselection of strains resistant to apramycin and gentamicin using one of these aminoglycosides is discussed.

Animals↗
PubMed1987

[Chronic 90-day toxicity of apramycin in chickens].

Investigations were carried out on 72 2-day-old broilers, divided into four groups (one control group--27 broilers and 3 experimental groups--15 broilers in each), treated with apramycin sulphate (AS), which was added to the food in concentration 0, 330, 1000 and 1600 mg/kg (corresponding to 0, 50, 150 and 250 mg/kg m.), in the course of 90 days. It was established that dose of 50 mg/kg m. AS does not causes toxic activities. With doses of 50, 150 and 250 mg/kg m. AS causes reduction of the degree of the pseudo-eosinophilic cells and increase of the percentage of leucocytes--in range similar to the physiological variations, contributes to stimulate the growth and the feed conversion. With doses of 150 and 250 mg/kg m. AS causes reduction of the content of haemoglobin and reduction of the number of erythrocytes; causes dystrophic changes in the internal organs.

Animals↗
PubMed1987

[Apramycin blood concentrations and distribution in the body of calves after different methods of administration].

The serum concentrations of apramycin in calves were studied after i/v application at the rate of 20 mg/kg body mass, after i/m injection at 20-40 mg/kg b. m., and after oral administration (with milk) at 40 mg/kg b. m. in terms of establishing certain pharmacokinetic parameters. It was found that at i/v route of application the concentrations of the antibiotic ranged above 2 micrograms/cm3 within the interval from the 15th min up to the 8h hour. The time of half-distribution (t1/2 alpha) was 0.28 h, while the biologic half-life of half-elimination (t1/2 beta) was 2.31 h. After muscular application of apramycin at 20 and 40 mg/kg it was rapidly adsorbed at the site of injection; the maximum concentrations were 99 micrograms/cm3 and 202 micrograms/cm3, resp., from the first to the second hour. Levels above 2 micrograms/cm3 were found in the blood serum in the course of 8 to 10 hours when the antibiotic was applied at 20 mg/kg b. m., and they have persisted for more than 12 hours when it was administered at the rate of 40 mg/kg. The biologic half-life (t1/2 beta) was 1.63 h and 1.97 h, respectively. Following the oral administration of the antibiotic at 40 mg/kg subtherapeutic levels were established up to the 24 th hour, with the exception of the interval of the 6 th to 8 th when the concentrations were below the minimum therapeutic one (2 micrograms/cm3).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Subchronic toxicity of apramycin in pigs].

Use was made of four groups of six pigs each, weighing 40 to 50 kg to follow up the toxicity of Pharmachim's apramycin in the form of water-soluble powder of apramycin sulfate, given at the rate of (nil), 300, 500, and 1,000 mg per liter of drinking water in the course of 35 days. It was found that such treatment did not lead to changes in the general status of the animals. On the contrary, apramycin sulfate stimulated growth and improved feed conversion. In concentrations of up to 300 mg/l the preparation did not produce an essential effect on the clinico-laboratory indices, and did not lead to toxic alterations of the viscera. In concentrations of 500 and 1,000 mg/l and extending the period to more than 15 days an occasional drop of the percent of lobular neutrophilic leukocytes and rise of the percent of lymphocytes in the blood might occur. This could lead to dystrophic processes in the liver and to negligible changes of the same character in both the kidneys and the heart.

Animals↗
PubMed1983

[A comparison of the effectiveness of furazolidone and apramycin in the control of colibacillosis in weaned piglets].

To compare the effectiveness of furazolidone and apramycin (Apralan) in the treatment of oedema disease in pigs, a trial was made on a commercial farm on which colibacillosis was a recurrent problem. Medicated feed containing 100 ppm of apramycin and 400 ppm of furazolidone respectively was given for three weeks after weaning. 112 Piglets were distributed over 10 battery houses at random. Results are summarized in Figure 1.

Animals↗
PubMed1984

[The effect of apramycin on bacterial contamination and the survival of boar semen during a short preservation period].

264 ejaculate samples taken from seven boars were tested for the bacteriostatic action of apramycin and for its effect on some sperm quality parameters during 96-hour storage. Apralan soluble powder, produced by Elanco Products Limited, was used in the trials at the concentrations of 2.5 to 500 mg per 1000 ml of diluent. The preparation was evaluated according to sperm motility during storage, according to the concentration pattern of hydrogen ions, morphological changes in spermatozoa, thermoresistance test, bacteriological tests and other examinations. The concentrations of 200 to 250 mg of apramycin in combination with 500 000 i. u. of G-penicillin potassium salt had a statistically significantly more favourable effect on the survival of boar sperm, as compared with the combination of streptomycin with penicillin.

Animals↗
PubMed1996

[Characteristics of Streptomyces kanamyceticus mutants resistant to aminoglycoside antibiotics].

The influence of the antibiotic activity level in strains of S. kanamyceticus on their resistance to kanamycin and other aminoglycosides was studied. Correlation between the activity of the strains and their resistance was observed. A collection of induced mutants of S. kanamyceticus with increased resistance to kanamycin, gentamicin, neomycin and apramycin was set. Cross resistance in the mutants to the aminoglycosides under different conditions (fermentative and not fermentative) was characterized. An increase in the resistance to gentamicin, neomycin and apramycin correlated with an increase in the resistance to kanamycin. The effect of the mutations of resistance to the aminoglycosides on the antibiotic activity of S. kanamyceticus was investigated. It was found that the population of the gentamicin resistant mutants was characterized by an increased average antibiotic activity and a higher number of the plus variants which is promising for the improvement of the strains with respect to higher levels of the kanamycin synthesis. The dynamics of the kanamycin synthesis in the initial strain of S. kanamyceticus was compared with that in its aminoglycoside resistant mutants. The apramycin resistant mutant was characterized by a significant delay in the beginning of the kanamycin synthesis.

Anti-Bacterial Agents↗
PubMedDate not supplied

Determination of apramycin in swine kidney tissue by liquid chromatography with fluorescence detection.

A liquid chromatographic method for determining apramycin in swine kidney tissue is described. Apramycin is extracted from tissue with basic methanol and purified by ion-pair extraction. By using an automated derivatization and injection procedure, the purified extract is derivatized with o-phthaldehyde, separated on a C18 column, and detected with a fluorescence detector. For fortified kidney samples, between-run coefficients of variation ranged from 4.8 to 7.1% at 1.00 ppm and from 9.6 to 14.3% at 0.50 ppm. Recoveries ranged from 76 to 86%. Standard curves were linear over the range 10-100 ng/mL.

Acetates↗