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Biomedical subjects

B Wiedemann

Publications and source records attributed to B Wiedemann.

At least 19 recordsLinked to original sources
PubMed1992

Tn21-specific structures in gram-negative bacteria from clinical isolates.

A total of 807 gram-negative clinical isolates were treated with five different probes: intragenic segments for the transposase gene tnpA; the resolvase gene tnpR; the modulator of the resolvase, tnpM; the integraselike factor gene tnpI; and a 20-mer oligonucleotide for the recombinational site of action for the integrase. A total of 8% of the isolates hybridized with all five Tn21-related probes, and another 11% represented transposons in which one or more of the tested genes were missing. This 11% included groups whose descriptions have been published as well as groups that have not yet been described. The not-yet-described groups include various deletion products and some precursor structures, as is predicted for the evolution of Tn21-like transposons. The integration system appears to be coupled with Tn21-like structures and yet independent from these structures, implying an independent evolution of this system from Tn21-like transposons. The structures were found with similar incidence levels in all species tested except Pseudomonas aeruginosa, for which a novel separate family of class II transposons has been described before.

Base Sequence↗
PubMed1991

[Evaluation of the development of resistance as a factor for the limitation of therapeutic possibilities].

From the microbiological point of view a variety of highly active compounds has contributed to improved efficacy of antibacterial chemotherapy during the last few decades. In some cases, however, resistance has increased due to different molecular mechanisms. Resistance to the new generation of broad-spectrum beta-lactams is in the cases of TEM and SHV enzymes based upon the stepwise acquisition of point mutations within the structural gene. Multiresistance to aminoglycosides is caused by a combination of different genes coding for aminoglycoside modifying enzymes on transferable plasmids. Resistance to glycopeptides has recently been detected in enterococci and is due to a new mechanism of resistance. These substances have so far had unlimited activity against methicillin-resistant Staphylococcus aureus and have been widely used for treatment of pseudomembranous colitis. While all the three mechanisms of resistance mentioned above are transferable among different strains, no evidence exists so far for transferable resistance to 4-quinolones. However, for S. aureus and Pseudomonas aeruginosa an increase of resistance has been reported. The underlying mechanisms seem to be unchanged. The detection of global changes in the development of resistance and the discrimination of these changes from local events requires recording of statistically significant data obtained with approved methods and evaluation of the data with standardized international breakpoints. Consequently, the use of new agents should be controlled efficiently.

Anti-Bacterial Agents↗
PubMed1991

Use of a broad-host-range gyrA plasmid for genetic characterization of fluoroquinolone-resistant gram-negative bacteria.

The gyrA genotypes of ciprofloxacin-resistant clinical isolates of Escherichia coli (n = 3), Klebsiella pneumoniae (n = 4), Providencia stuartii (n = 2), Pseudomonas aeruginosa (n = 1), and Acinetobacter calcoaceticus (n = 1) were analyzed in a dominance test. This test is based on the dominance of a wild-type gyrA gene (gyrA+) over the quinolone resistance allele (gyrA) in a heterodiploid strain. Plasmid pBP515, developed to carry the gyrA+ gene of E. coli K-12 on a broad-host-range vector derived from pRSF1010, was used to obtain heterodiploid strains. Plasmid pBP515 encodes kanamycin and gentamicin resistance and is transferable via mobilization by a pRP1-derived helper plasmid (pRP1H) to strains of several gram-negative species. After the introduction of pBP515, single-cell MICs (as measured by reduction of the viable cell count) of ciprofloxacin and nalidixic acid decreased by 4- to greater than 8,000-fold for all strains tested, and 8 of the 11 strains regained ciprofloxacin susceptibilities similar to those of the respective wild types. The results indicate that (i) high-level fluoroquinolone resistance in clinical isolates of E. coli, K. pneumoniae, P. aeruginosa, and A. calcoaceticus can result from mutational alteration of the gyrA gene, and (ii) gyrA mutations are involved in high levels of fluoroquinolone resistance in P. stuartii. Additional mutations outside the gyrA locus may contribute to resistance in K. pneumoniae and P. stuartii.

Acinetobacter↗
PubMed1991

Microbiological evaluation of cefpodoxime proxetil.

Cefpodoxime, the active de-esterified molecule of the orally absorbable cephalosporin cefpodoxime proxetil, inhibits streptococci, Neisseria spp., and most Enterobacteriaceae, with MIC50 and/or MIC90 values of less than or equal to 2 mg/L; with regard to the latter family of bacteria, the MIC50 and/or MIC90 values of cefpodoxime are consistently greater than or equal to 4 mg/L for only Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Morganella morganii. The MIC50 of cedpodoxime for coagulase-negative staphylococci is greater than 2 mg/L, while the MIC for Staphylococcus aureus strains is 4 mg/L. In comparison with other orally absorbable cephalosporins, cefpodoxime is slightly less active than cefixime, cefetamet, and cefotiam against Gram-negative bacteria, but more active than cefuroxime, cefaclor, and cefalexin. Against staphylococci, the activity of cefpodoxime is comparable to that of cefotiam and cefuroxime, and superior to that of cefaclor, while cefixime and cefetamet have insufficient activity against these species. In common with other cephalosporins, cefpodoxime has no activity against enterococci. In vitro models simulating human serum cefpodoxime concentrations demonstrate that a dosage regimen of 200mg is probably sufficient to treat most infections. However, further study is needed to clarify whether infections due to bacteria such as S. aureus, with higher cefpodoxime MICs, can be treated with this dose regimen.

Ceftizoxime↗
PubMed1991

[The effect of combination epidural anesthesia techniques in upper abdominal surgery on the stress reaction, pain control and respiratory mechanics].

Twenty-eight patients undergoing upper abdominal operations (mainly selective proximal vagotomy [SPV]) were referred for assessment of the hormonal metabolic reaction (adrenocorticotropic hormone [ACTH], arginine vasopressin [AVP], cortisol, and glucose), the postoperative pain reaction, and respiration according to the method of anesthesia (group 1: neuroleptanesthesia [NLA], group 2: NLA in combination with epidural opiate analgesia, group 3: NLA in combination with local anesthesia). To alleviate postoperative pain piritramide was systematically administered in group 1, whereas in groups 2 and 3 a thoracic epidural catheter was injected with morphine or bupivacaine. Postoperative analgesia was better in patients with epidural administration than in those with systemic application. On the 1st and 2nd postoperative days the vital capacity was statistically significantly higher by 10%-15% in groups 2 and 3 than in group 1. As expected, the neurohormonal and metabolic stress response was highest in all patients in the intraoperative and immediate postoperative phases: ACTH, AVP, and glucose levels were in most cases significantly higher compared with the initial values. However, cortisol levels decreased intraoperatively, probably as a result of the generally used induction agent etomidate. Comparison of the three methods of anesthesia revealed that all mean hormone levels analyzed in group 2 patients were lower both intraoperatively and 2 h postoperatively, which implies that epidurally administered morphine reduces the stress reaction, probably indirectly through additional selective alleviation of pain at the spinal cord level. The various differences in hormonal reactions of patients in groups 1 and 3 gave no clear evidence, however, of possible mitigation of the stress reaction by epidural local anesthetics in upper abdominal operations.

Adult↗
PubMed1990

Antibacterial activity of cefpodoxime proxetil in a pharmacokinetic in-vitro model.

The antibacterial activity of cefpodoxime proxetil was studied in an in-vitro model simulating doses of 100, 200 and 400 mg. Strains of Klebsiella spp. Proteus mirabilis, Escherichia coli, Streptococcus pyogenes, and Haemophilus influenzae were effectively reduced by a dose of 200 mg. While for Esch. coli no dose-activity relationship was observed--the maximal effect was achieved with a simulated dose of 100 mg--Staphylococcus aureus could be reduced effectively only by a simulated dose of 400 mg. The lower doses showed stepwise lower activities. Apart from broad spectrum beta-lactamases like SHV 2 or TEM 5 the presence of plasmid coded beta-lactamases in Esch. coli and H. influenzae did not affect the antibacterial activity of cefpodoxime proxetil. The results show that cefpodoxime was more active against Gram-negative bacteria than amoxycillin, and comparable activity to intramuscular cefotiam in the in-vitro model.

Amoxicillin↗
PubMed1990

Antibacterial activity of lomefloxacin in a pharmacokinetic in vitro model.

An in vitro model simulating two-compartment pharmacokinetics was used to study the antibacterial activity of lomefloxacin after single oral doses of 200 and 400 mg. Lomefloxacin produced reliable bactericidal activity against gram-negative aerobic bacteria and staphylococci. Bacterial strains for which MICs were less than 0.5 microgram/ml were inhibited with both dosing schedules. Doubling the dose from 200 to 400 mg increased the bactericidal activity only against Pseudomonas aeruginosa. Against Enterococcus faecalis lomefloxacin showed no effect. Selection of resistant variants during the simulation of treatment was observed with Staphylococcus aureus and P. aeruginosa.

4-Quinolones↗
PubMed1990

Resistance to aminoglycosides: the situation in the Federal Republic of Germany.

The susceptibility of important pathogens to aminoglycosides was analysed using data from five studies encompassing different patient groups. Enterobacteria were generally sensitive to all modern aminoglycosides without marked differences. The frequency of resistance of Pseudomonas aeruginosa and other non-fermenters to gentamicin was 5-15% and to amikacin was 0-3%, and similar values applied for staphylococci. A higher rate of resistance was observed in pathogens isolated from urological patients: for non-fermenters resistance to gentamicin, tobramycin and netilmicin was 24-28%, whereas resistance to amikacin was 12%; and for staphylococci resistance was 33% for gentamicin, 48% for tobramycin and 9% for netilmicin. It is concluded that resistance to aminoglycosides is not an important problem in the Federal Republic of Germany, probably because aminoglycosides are used in combination with beta-lactam antibiotics, except in the case of urinary tract infections. Aminoglycosides are still important antibiotics, thus their rational use and constant surveillance are necessary to preserve their efficacy.

Acetyltransferases↗
PubMed1990

[Risk factors of fitness for child day care in 2 independent studies].

The condition of the acute respiratory disease (ARD), conditions of exposure and disposition were found out with 245 and 83 children from 8 crèches of a large town and from two crèches of a little town. The children were from 6 to 36 months old. The prospective studies were performed independently of each other within a period of one year. Your problem circles were identical to a large extent. These are load factors in the perinatal period, time of stay in the crèche, shift work of the parents, kind of the adaptation phase during the first admission in the crèche. The employment of the linear function of discrimination found permits the general paediatrician to elaborate an additional information for the judgement of the possibility of attendance into the crèche in general and for the time of convalescence after ARD.

Child Day Care Centers↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

[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↗
PubMed1989

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↗
PubMed1989

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↗