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Biomedical subjects

B Wiedemann

Publications and source records attributed to B Wiedemann.

At least 163 records · Page 9Linked to original sources
PubMed1984

The incidence and development of resistance in Staphylococcus aureus from three European countries.

In a multicentre study conducted by the Paul Ehrlich Society we tested 3482 Staphylococcus aureus strains, isolated in different hospitals in West Germany, Austria and Switzerland, against 12 antibiotics with standardized techniques between 1976 and 1982. In order to avoid mistakes in the classification of the strains into sensitive, intermediate and resistant, we adapted breakpoints to the population distribution. There were no marked changes in the incidence of sensitive strains during the period. Striking differences from one hospital to another were observed. The percentage of strains sensitive to penicillin remains low (27%). The other antibiotics studied show activity against 80-100% of strains.

Anti-Bacterial Agents↗
PubMed1984

Transfer of the chromosomal bla gene from Enterobacter cloacae to Escherichia coli by RP4::mini-Mu.

The resistance gene for beta-lactamase-stable cephalosporins from Enterobacter cloacae was transferred to Escherichia coli by the aid of RP4::mini-Mu. The R-prime plasmids generated carried 60 to 80 kilobases (kb) of E. cloacae DNA and coded for the chromosomal E. cloacae beta-lactamase. The gene was fully expressed in the recipient. Restriction endonuclease EcoRI fragments of the R-prime plasmid pBP100 were cloned into the vector pBP328, yielding the plasmid pBP102 with a size of 14 kb. A restriction map of this plasmid was constructed. By digesting pBP102 into seven PstI fragments, ligating the fragments, and looking for the smallest plasmid generated, pBP103 was isolated. It consisted of three PstI fragments, two of them (together 4.2 kb) necessary for resistance. During the experiment (performed in a recA+ background) the largest PstI fragment had undergone a substitution of a 0.3-kb segment of pBP102 by a 0.7-kb segment in pBP103 (as deduced by heteroduplex analysis). The bla gene of resistant E. cloacae strains was dominant over the gene of susceptible organisms.

Cephalosporins↗
PubMed1984

Development of resistance following the use of antibiotics.

There is no doubt that antibiotic usage is related to the development of resistant bacteria. Nevertheless, there is a great deal of confusion about the mechanisms involved in this process and the quantitative aspects. Bacterial genes coding for resistance can be exchanged on a molecular level between different DNA structures and they can spread from one bacterial cell to another. In quantitative terms, however, the selection of resistant bacteria in their natural environment, e.g. in the bowel flora or on mucous membranes, is the most important factor influencing the development and spread of antibiotic resistant microorganisms. The amount of drug incorporated into the bowel or soft tissue flora depends on the route of administration. Even drugs which are related in many respects differ markedly in their ability to select resistant organisms. A selection of resistant organisms from the normal human flora implicates, that primarily a minority of resistant organisms is present and overgrows the sensitive ones which are inhibited by the drug. Usually these resistant strains belong to the resident flora and carry their resistance genes on plasmids. Only rarely resistant mutants can be found, although the mutation rate might be high. The development of resistance from the population of microorganisms causing the infection is rare. This observation can be based on two rationales : 1. The mutation rate from susceptible to resistant in most microorganisms is usually rather low (about 10(-9); thus the number of microbes present on the site of infection is not high enough to allow mutants to arise.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1983

The influence of beta-lactamases on minimal inhibitory concentrations.

The stability towards hydrolysis by beta-lactamases is commonly used as a major criterion for the quality of a beta-lactam antibiotic. The activity of a beta-lactam compound is influenced by many factors, however. After the introduction of third generation cephalosporins, evidence arose that beta-lactamases can be the only reason for resistance, although the drug is not or only slightly hydrolyzed by the corresponding enzyme. Here it seems as if binding of the antibiotic to the beta-lactamase is the main factor which influences the drug's activity. But, in fact, the situation is much more complicated, as at least several different factors must be considered in combination with beta-lactamase activity.

Anti-Bacterial Agents↗
PubMed1983

Dissemination of streptomycin and sulfonamide resistance by plasmid pBP1 in Escherichia coli.

About one third of streptomycin resistance in Escherichia coli is mediated by APH-(3''). This enzyme is encoded by the plasmid pBP1 in 80% of all streptomycin resistant strains tested. pBP1, which in addition mediates sulfonamide resistance, has been found to be disseminated in Escherichia coli strains all over the world. It has a molecular weight of 4.0 megadalton and does not seem to be disadvantageous for the metabolism of the bacterial cell. The reason for the slow decrease of resistance to streptomycin and sulfonamide in clinical isolates, despite the restricted use of these drugs, is presumably the survival of bacteria harbouring pBP1 which have been selected by streptomycin and sulfonamides in the early days of chemotherapy.

Anti-Bacterial Agents↗
PubMed1983

Identification of Tn2401, a transposon encoding multiresistance to aminoglycosides.

A transposable element, Tn2401, was found in a clinical isolate of Pseudomonas aeruginosa. Tn2401 had a size of 7190 nucleotides and encoded aminoglycoside 3'-phosphotransferase and aminoglycoside 6'-N-acetyltransferase. The sequence encoding the former enzyme was homologous with that of Tn903. Pseudomonas aeruginosa strains harbouring this transposon were resistant to kanamycin, neomycin, lividomycin, ribostamycin, paromomycin, netilmycin, tobramycin, dibekacin, gentamicin, sisomicin, and butirosin.

Acetyltransferases↗
PubMed1983

Transposition of a gene encoding OXA-2 beta-lactamase.

A bla gene encoding OXA-2 beta-lactamase has been transposed from the Salmonella typhimurium R plasmid R1767. This transposable element which was designated Tn2410 encoded sulphonamide and mercury resistance in addition to the bla gene. It had a size of 18.5 kb and appeared to be flanked by small inverted repeats. Restriction enzyme analysis resulted in a detailed map of Tn2410, which showed a high degree of similarity with the published map of Tn2603, a transposon encoding OXA-1 beta-lactamase. The ampicillin and sulphonamide resistance genes on Tn2410 were mapped in a cluster on the region between the centre and the righ end of the map.

Ampicillin↗
PubMed1983

Chromosomal beta-lactamases of Enterobacter cloacae are responsible for resistance to third-generation cephalosporins.

About 70% of all Enterobacter cloacae strains tested possessed one of two species-specific beta-lactamases. These enzymes, E. cloacae beta-lactamase A and E. cloacae beta-lactamase B, with isoelectric points of 8.8 and 7.8, respectively, had the same pH and temperature optima. Both showed similar enzyme kinetics and were inhibited by cloxacillin but not by p-chloromercuribenzoate. E. cloacae beta-lactamase B appeared to be identical with the enzyme of E. cloacae P99. By a mutation in a regulatory gene, inducible enzyme production could be converted into constitutive expression. In E. cloacae, both enzymes did not hydrolyze third-generation cephalosporins, but they were solely responsible for resistance toward these drugs. This was demonstrated by the characterization of Escherichia coli strains expressing an identical resistance pattern after transfer of the corresponding Enterobacter gene.

Cephalosporins↗
PubMed1983

Amikacin resistance mediated by multiresistance transposon Tn2424.

Tn2424, a multiresistance transposon 25 kilobases long, was isolated from IncFII plasmid NR79. Tn2424 transposed resistance to sulfonamides, streptomycin and spectinomycin, mercuric chloride, chloramphenicol, and amikacin with a frequency of 6 X 10(-5). Resistance to amikacin was mediated by a 6'-N-acetyltransferase, which conferred higher levels of resistance in Pseudomonas aeruginosa than in Escherichia coli. A restriction analysis and cloning experiments resulted in a physical and functional map of Tn2424. Comparison by a heteroduplex technique revealed that Tn2424 includes the total sequence of Tn21 and two additional DNA fragments that are 1.8 and 4 kilobases long.

Amikacin↗
PubMed1983

Characterization of Tn2411 and Tn2410, two transposons derived from R-plasmid R1767 and related to Tn2603 and Tn21.

Two transposable elements, Tn2410 and Tn2411, were isolated from Salmonella typhimurium R-factor R1767. They have sizes of 18.5 and 18.0 kilobases, respectively. Tn2411 mediates resistance to streptomycin, sulfonamides, and mercury. In Tn2410, the streptomycin resistance gene was replaced by a gene coding for the production of the beta-lactamase OXA-2, which is responsible for ampicillin resistance. Physical and functional maps of both transposons were compared with those of Tn21, Tn4, and Tn2603. From these data it appeared that Tn21 could be an ancestral transposon from which Tn2411, Tn2410, Tn2603, and Tn4 were evolved by the addition or deletion of small DNA segments.

Ampicillin↗
PubMed1983

[Comparison of the activity of cefaclor with amoxicillin, erythromycin and doxycycline in an in vitro model].

Bactericidal antibiotics like cefaclor and amoxicillin do have a better and prolonged effect on the reduction of the viable cellcount than bacteriostatic ones like erythromycin and doxycyclin, as has been demonstrated in the in vitro model. The influence of the production of beta-lactamases on the kill-kinetics could be studied in this model. While amoxillin became ineffective by the production of beta-lactamases of E. coli and S. aureus the activity of cefaclor was generally maintained. Only a marginal destruction of the drug by the enzymes was observed.

Amoxicillin↗
PubMed1982

Correlation of beta-lactamase production and resistance to beta-lactam antibiotics in Enterobacteriaceae.

Incidence of beta-lactamase production (using the Nitrocefin test and isoelectric focusing) was evaluated on 284 strains of ampicillin-resistant Enterobacteriaceae. Production of the various beta-lactamases was correlated with the resistance to different beta-lactam antibiotics. No obvious correlation between the beta-lactamase production and the resistance pattern was found. The most striking result was the lack of beta-lactamase production in 42.6% of the strains. About 50% or more of the Proteus morganii, Proteus vulgaris, Serratia and Enterobacter strains produced no beta-lactamases, in contrast to E. coli, Klebsiella, and Proteus rettgeri strains which produced beta-lactamases extensively. The predominant enzyme was TEM 1, while TEM 2 enzyme was extremely common in Proteus mirabilis and Proteus rettgeri. Finally, it can be concluded from our results that the production of beta-lactamases can be regarded as an important but not the sole determinant of resistance of beta-lactam antibiotics.

Ampicillin↗
PubMed1981

Molecular nature of a streptomycin and sulfonamide resistance plasmid (pBP1) prevalent in clinical Escherichia coli strains and integration of an ampicillin resistance transposon (TnA).

A small, nonconjugative plasmid, designated pBP1, was originally found in different fecal Escherichia coli serotypes isolated from a healthy proband. Of a total number of 130 hospital strains of E. coli subsequently studied, 8.5% yielded plasmid of the pBP1 type. This R plasmid specifies resistance to streptomycin (Sm) and sulfonamides (Su) and has a mass of 4.0 megadaltons. Inactivation of streptomycin is due to the aminoglycoside phosphotransferase APH-(3 "). A physical map was constructed by analysis with restriction endonucleases. Another small plasmid, pBP1-1, was isolated from one of the hospital strains and characterized as an enlarged pBP1 replicon containing an additional deoxyribonucleic acid sequence identified as a transposable element for ampicillin resistance (TnA). Plasmid pBP1-1 was cleaved by restriction enzymes for identification of the transposon sequence which codes for a TEM 1 beta-lactamase. The sequence organizations in the Sm Su plasmids RSF1010 and pBP1 were shown to be identical for regions specifying streptomycin and sulfonamide resistance, but different for the region containing the origin of replication and genes for replicative functions. Thus, RSF1010, which has been considered as the prototype of Sm Su plasmids, and pBP1, which is at least as frequent in clinical isolates as RSF1010, do not have a single common ancestor.

Ampicillin↗
PubMed1981

Bacterial elimination and therapeutic effectiveness under different schedules of amoxicillin administration.

Bacterial elimination kinetics under different simulated administration schedules of amoxicillin was followed in vitro by using a simple model for simulation of pharmacokinetic parameters. The results were compared to those obtained in lethally infected mice by determining the viable bacterial count in the blood at various times post-infection and under different schedules of amoxicillin administration. A satisfactory correlation could be established between the in vitro and in vivo results. Multiple administration of amoxicillin was found to induce a beta-lactamase in vitro as well as in vivo in the Escherichia coli strain used. No difference was however found between the various administration schedules of amoxicillin in terms of surviving animals. Taking into account the lasting elimination of viable bacteria from the blood, the best treatment of E. coli-infected mice was found to be a twice daily administration of the higher amoxicillin dose.

Amoxicillin↗
PubMed1981

[Aminoglycoside modifying enzymes (author's transl)].

Bacterial resistance to aminoglycoside antibiotics can occur by a variety of mechanisms (including alteration of the drug target site, interference with drug transport into the cell, or enzymatic detoxification of the antibiotics) due to chromosomal mutations or the inheritance of new genetic information mediated by resistance plasmids. Studies with 475 gram-negative bacteria isolated at the university hospital Bonn revealed that about 10% of the strains were resistant to gentamicin. 44 of 46 strains produced aminoglycoside modifying enzymes; the remaining two strains do not produce detectable enzymatic activity. Among those aminoglycoside transferases causing multiresistance to modern aminoglycosides, the nucleotidyltransferase ANT-(2") occurs most frequently and accounts for 88% of the gentamicin resistant klebsiella strains. The gentamicin acetylating enzymes AAC-(2'), AAC-(6'), and AAC-(3) are detected less frequently. All aminoglycoside transferases, except one acetyltransferase AAC-(2') from Proteus vulgaris, were found to be plasmid encoded.

Aminoglycosides↗
PubMed1980

Microbiological basis of antibiotic therapy.

The parameter used most frequently as a basis for chemotherapy is the minimal inhibitory concentration (MIC). The results of this test are widely influenced by the method applied. A test under in vivo-like conditions is most likely to serve as a basis for rational therapy. The MIC values, measured in different body fluids under varying conditions, also vary, however. Therefore it is unlikely that any measured MIC corresponds with the actual MIC at the site of the infection. The consequence is that a standard test has to be applied which always gives reproducible results. The measured values can thus only to be regarded as relative data in comparison with the concentration of the drug at the site of the infection. Pathogen elimination in vivo during therapy and population-kinetics under the influence of varying concentrations of a drug in vitro are discussed with to the evaluation of the efficacy of different dosages of an antibiotic.

Anti-Bacterial Agents↗