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Biomedical subjects

B Wiedemann

Publications and source records attributed to B Wiedemann.

At least 127 records · Page 7Linked to original sources

Induction of beta-lactamases: in vitro phenomena and clinical relevance.

An in vitro model was used to stimulate the plasma concentration-time curves for cefotaxime and cefoxitin as they would appear during treatment of patients with infections due to Enterobacter cloacae and Proteus vulgaris. The data showed that the induction of the chromosomally mediated beta-lactamase took place in both bacteria but that it had little or no effect on the bacterial kill. It is concluded that treatment failures in these settings were due to the selection of resistant mutants.

Cefotaxime↗

Resistance development to fluoroquinolones in Europe.

We did not observe an increase in quinolone-resistant strains in recent years despite a dramatic increase in drug usage. P. aeruginosa strains should be carefully monitored in the future since a trend to increased MICs seems obvious. Epidemiologic data on resistance have to be evaluated carefully, and special interest must be focused on the breakpoint in relation to the normal distribution of MICs. Conclusions can be drawn only if the increased numbers of strains are clearly separated from the normal distribution.

4-Quinolones↗

[In-vitro activity of enoxacin: a multicenter study].

The in vitro activity of enoxacin was tested in 14 German microbiological centers shortly after the introduction of the drug in Germany. 2748 unselected clinical isolates including 15 bacterial species were analysed using microtiter plates. The MIC90-values were as follows: Staphylococcus aureus 4 mg/l, Enterococcus faecalis 16 mg/l, Enterobacteriaceae 0.5 mg/l, Pseudomonas aeruginosa 8 mg/l. There is good correlation between these results and those of former investigations. It is known that quinolones are only moderately active against enterococci. 8.5% of S. aureus, and 1.4% of Enterobacteriaceae were found to be resistant (MIC greater than 4 mg/l). As to P. aeruginosa, the study revealed that despite a generally low rate of resistance in specific clinical settings, specific problems can arise: in one institution, the MIC90 of P. aeruginosa was 32 mg/l, with a resistance rate of 56.1% (n = 57). In the other centers the MIC90 was 2 mg/l and the resistance rate 5.0% (n = 302). In the first center, many of the isolates were from paraplegic patients or patients with cystic fibrosis pretreated with quinolones. This study will be repeated in two years' time in order to determine an eventual change in resistance.

Bacteria↗

Antibacterial properties of meropenem towards clinical isolates, beta-lactamase producers and laboratory mutants.

Clinical isolates (1017) obtained from a multicentre study were examined. The activity of meropenem was better than that of imipenem against Enterobacteriaceae and Pseudomonas aeruginosa. Meropenem was slightly less active against staphylococci than was imipenem. Meropenem had little activity against enterococci (MIC90, 16 mg/l). Mutants selected with imipenem or meropenem remained more sensitive to meropenem but MICs increased for both drugs. Other resistance mechanisms such as beta-lactamases or aminoglycoside modifying enzymes did not influence meropenem activity with the exception of beta-lactamase from Ps. cepacia.

Bacteria↗

The epidemiology of beta-lactamases.

Chromosomally mediated species-specific beta-lactamases, as well as plasmid-mediated beta-lactamases, contribute to bacterial resistance to beta-lactam antibiotics. Chromosomally mediated enzymes confer primary resistance to some drugs and secondary resistance, by mutation to over-production of the enzyme. By far the most prevalent and most important of the, more than thirty, described plasmid-mediated beta-lactamases are those of the TEM group. They can be found in nearly all Gram-negative bacterial species of clinical importance. Furthermore these enzymes have changed their specificity by mutation so that recently described TEM enzymes hydrolyse even third generation cephalosporins. Although there is no change in the quantity of these enzymes, as far as the percentage of producer strains in any species is concerned, there has been a change in quality. The enzymes are further distributed to new species and hydrolyse more so-called 'stable' beta-lactam compounds.

Bacterial Infections↗

[Risk factors in the susceptibility for infection in young children].

The frequency and the duration of acute respiratory disease (ARD) have been registered in 245 children aged from 6 to 36 months staying in 8 crèches of a large town during a period of one year. The exterior conditions of life were comprehended. From this material 10 risk factors were determined. By elaborating a score for prognosis it was possible to discriminate 2 groups of children. One part was susceptible, the other resistant to infections. This publication should be a contribution for answering the question for crèche fitness after getting over an ARD.

Child, Preschool↗

[Fitness for child nurseries and exposure].

For one year in 245 children, aged from 6 to 36 months staying in 8 crêches of a large town, frequency and duration of acute respiratory disease (ARD) were registered. The exterior conditions of life were comprehended. From this material 10 risk factors were determined. By elaborating a score for prognosis it was possible to discriminate 2 classes of children. One part was susceptible, the other resistent to infections. This publication shall be a contribution for answering the question for crêche fitness after getting over an ARD.

Analysis of Variance↗

Development of resistance to nalidixic acid and the fluoroquinolones after the introduction of norfloxacin and ofloxacin.

Since 1975, the group Resistenz of the Paul-Ehrlich-Gesellschaft für Chemotherapie has monitored the development of resistance in isolates of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis in the Federal Republic of Germany, West Berlin, Austria, and Switzerland. Despite a marked increase in the use of 4-quinolones, there was no increase in the percentages of nalidixic acid-resistant strains of Enterobacteriaceae between 1975 and 1986. However, different bacterial species showed considerable variation, and there were also considerable differences in the percentages of nalidixic acid-resistant strains of Enterobacteriaceae from different centers. The frequency of resistance to fluoroquinolones was unchanged from 1983 to 1986 and was less than 4% in all species except P. aeruginosa. In this species, there was an increase from about 3 to 10% from 1983 to 1986 for strains for which the MIC was fourfold above the mode MIC of ciprofloxacin, enoxacin, and ofloxacin.

Anti-Infective Agents↗

[Resistance pattern of clinical bacterial isolates. Results of a super-regional multicenter study of the Resistance Study Committee of the Paul Ehrlich Society of Chemotherapy].

In a multicentre study conducted by the Paul-Ehrlich-Gesellschaft we tested about 3,584 clinical isolates from 25 laboratories towards different chemotherapeutics. Using a microdilution test Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis strains regarded as causative pathogens were studied. The data were evaluated for the number, frequency and qualitative characteristics of multiple resistance patterns. None of the strains under test was resistant to all antibiotics tested. Amikacin showed the lowest prevalence of resistance. The significance of such data in the epidemiological control of resistance to chemotherapeutics is discussed.

Anti-Bacterial Agents↗

Inhibition of R-plasmid transfer in Escherichia coli by 4-quinolones.

Inhibition of transfer of four conjugative R plasmids by ciprofloxacin, enoxacin, norfloxacin, ofloxacin, and pipemidic acid was investigated in an Escherichia coli mating system. The absolute concentrations needed for inhibition of conjugation varied from 0.12 microgram/ml for ciprofloxacin to 16 micrograms/ml for pipemidic acid, but the relationship to the MICs for the parent strains was identical for all substrates. Concentrations for a 90% reduction of transconjugants were in the range of one to six times the MIC for the parent strains, which also had lethal effects on donors and recipients. A similar effect on conjugation was found with chloramphenicol. These observations question the specificity of transfer inhibition by quinolones and cast doubt on the clinical importance of such an effect.

Conjugation, Genetic↗

Flow cytometric analysis of nephroblastomas and related neoplasms.

A total of 59 cases of nephroblastoma and related neoplasms were studied by flow cytometry of paraffin-embedded tissue. According to clinical prognosis, cases were subdivided into three groups: Group 1 (low risk) consisted of congenital mesoblastic nephroma (n = 13) and cystic, partially differentiated nephroblastoma (n = 2). Group 2 (intermediate risk) comprised the various subtypes of "typical" nephroblastoma (n = 24) including cases of fetal rhabdomyomatous nephroblastoma (n = 4). In group 3 (high risk) there were cases of anaplastic nephroblastoma (n = 3), clear cell sarcoma of the kidney or "bone metastasizing renal tumor of childhood" (n = 7), and malignant rhabdoid tumor of the kidney (n = 6). The three clinically different groups of tumors also varied in the proportion of cases with aneuploid tumor DNA stemlines, in S-phase fractions, and in proliferation indices (PI = S + G2 + M). Group 1 was generally characterized by a small number of cases with aneuploid tumor DNA stemlines and low values for S-phase fractions and PI, whereas Group 3 showed the largest number of cases with aneuploid tumor DNA stemlines and high values for S-phase fractions and PI. Group 2 was in between. It is concluded that flow cytometry on paraffin-embedded tissue from pediatric tumors may be a useful adjunct in determining prognosis, and that the subdivision of nephroblastomas and related neoplasms into three prognostically different groups is warranted.

Aneuploidy↗

[Inhibition of gyrase by 4-quinolones: effect on the structure of DNA].

DNA gyrase is an essential enzyme in bacterial metabolism. Its function is the introduction of negative supercoils into DNA. These favour the unwinding of certain parts of DNA und thus are likely to facilitate processes like replication and transcription. Inhibition of DNA gyrase by quinolones and possible effects on the structure of DNA are reviewed.

Anti-Infective Agents↗

Elimination of plasmids by enoxacin and ofloxacin at near inhibitory concentrations.

The abilities of the 4-quinolones enoxacin and ofloxacin, inhibitors of DNA gyrase subunit A, to eliminate plasmids from Escherichia coli have been studied in a narrow concentration range just below the MIC. These compounds cured most efficiently at the highest concentration which still allows cell growth and produced 20% to 100% plasmid-free cells, depending upon the plasmid tested. Higher concentrations were required to eliminate plasmids from a gyrANalr strain, consistent with their higher MICs, but maximal curing frequencies were similar to those obtained with the Nals strain. Kinetics of plasmid elimination indicated that plasmid loss occurred by inhibition of plasmid replication, which seems to be somewhat more sensitive to the action of 4-quinolones than chromosome replication. Low or high curing frequencies with a given curing agent seem to be a property of the plasmid tested.

Enoxacin↗

Genetic and biochemical basis of resistance of Enterobacteriaceae to beta-lactam antibiotics.

Resistance to beta-lactam drugs is usually determined by genes mediating the production of beta-lactamases. These genes can be located on resistance plasmids or on the chromosome. Resistance to drugs which have been available for many years is mostly transposable. Although the origin of these genes is not known, it is possible to draw a hypothetical flow diagram of the evolution of resistance genes in general. The mechanism of resistance although mediated in Gram-negative bacteria mostly by beta-lactamases cannot be simply described as the hydrolytic function of the enzyme. It is a complex interaction involving the affinity of the drug for the target and the lactamase, the amount of drug in the periplasmic space, the amount of enzyme and the number of lethal target sites. Usually one of these factors is predominant.

Anti-Bacterial Agents↗

Beta-lactam antibiotics and selection of resistance: speculation on the evolution of R-plasmids.

In this paper we describe two genetic mechanisms which are responsible for the development of resistance to third-generation cephalosporins. One is a plasmid-mediated mechanism involving a mutation in the SHV-1-gene towards the production of the beta-lactamase SHV-2 which has increased affinity for these antibiotics. The other is chromosomally mediated and occurs at high frequency by mutation of inducible beta-lactamase-genes, leading to derepressed production of the enzyme. Together with other examples of resistance genes these two mechanisms lead us to a hypothesis about the evolution of beta-lactamase producing bacteria.

Anti-Bacterial Agents↗

Development of resistance in the past decade in central Europe.

In a multicentre study conducted by the Paul-Ehrlich-Gesellschaft we tested about 35,000 bacterial isolates from different hospitals in the Federal Republic of Germany, Berlin (West), Austria and Switzerland between 1975 and 1984. None of the bacterial species under test showed an increase in the number of resistant strains. A slight decrease in the percentage of resistant strains to some antibiotics was observed with Staphylococcus aureus; Klebsiella spp. showed a significant decrease in this respect. Because of this phenomenon and the introduction of new drugs, chemotherapy today is usually safer than ten years ago. However, in some places the amount of resistant strains was significantly different from the overall resistance. In comparison of these data with those from the U.S.A. (Atkinson & Lorian, 1984) no difference in an antibiotic-species pair exceeded 13%.

Bacterial Infections↗