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Biomedical subjects

B Wiedemann

Publications and source records attributed to B Wiedemann.

At least 73 records · Page 4Linked to original sources
PubMed1999

An in-vitro study of the antimicrobial susceptibilities of Yersinia enterocolitica and the definition of a database.

The antibiotic susceptibilities of 151 Yersinia enterocolitica strains isolated from humans, animals and the environment, and belonging to biovars 1A (n = 22), 1B (n = 13), 2 (n = 12), 3 (n = 31), 4 (n = 63) and 5 (n = 10) to 71 antibiotics were examined. Biovars could be characterized phenotypically by their similar antibiograms. For the majority of biovars only minor differences in susceptibilities were detected. Ninety-nine percent of all Yersinia strains were resistant to amoxycillin, but biovar-related differences in MICs were demonstrated. Significant differences, characteristic of specific biovars, were detected for fosfomycin, some beta-lactams (in particular amoxycillin/clavulanate, and ticarcillin). Strains of biovar 1A were resistant or of intermediate susceptibility to ticarcillin and had fosfomycin MICs of 16-64 mg/L and amoxycillin/clavulanate MICs of 4-32 mg/L. Most strains of biovar 1B (n = 11) were sensitive to amoxycillin/clavulanate (MIC = 0.5-2 mg/L). Most strains of biovar 2 (n = 10) showed an antibiotic phenotype resembling that of strains of biovar 1A, but they were more susceptible to fosfomycin (MIC = 4-16 mg/L). Twenty-seven strains of biovar 3 had amoxycillin/clavulanate MICs of 4-32 mg/L; 19 of them were sensitive to ticarcillin and fosfomycin. Biovar 4 strains were uniformly sensitive or of intermediate susceptibility to amoxycillin/clavulanate (MIC = 0.5-4 mg/L), sensitive to fosfomycin (MIC = 1-4 mg/L) but resistant to ticarcillin. The prevailing antibiotic phenotype of biovar 5 (n = 7) was similiar to the phenotype of biovar 4, although these biovar 5 strains were slightly more susceptible to amoxycillin/clavulanate and showed a heterogeneous pattern of susceptibility to fosfomycin (MIC = 1-32 mg/L). The results of this study show that unambiguous statements cannot be made about the natural antibiotic susceptibility to certain beta-lactams and fosfomycin of Y. enterocolitica. The data indicate a complex regulation of beta-lactamases in Y. enterocolitica. Some beta-lactamases are found more frequently or will be expressed predominantly in specific biovars.

Anti-Bacterial Agents↗
PubMed1999

The effect of moxifloxacin on its target topoisomerases from Escherichia coli and Staphylococcus aureus.

The effect of moxifloxacin on its target enzymes was evaluated by three different approaches: (i) the MICs of moxifloxacin and nine other fluoroquinolones were determined for mutants of Escherichia coli (n = 13) and Staphylococcus aureus (n = 5) carrying different combinations of resistance mutations; (ii) the activity of moxifloxacin on isolated targets was determined as IC50 values for wild-type and mutant type II topoisomerases from E. coli; and (iii) the mutation frequencies were determined for two single-step mutants (MI with a Ser83-->Leu mutation in gyrA and WT-4 with a Ser80-->Ile mutation in parC) and their parent strain (WT). Of the quinolones tested, moxifloxacin was the only one showing an equivalent high activity against both targets. This is reflected by a comparable high susceptibility of the test strains of E. coli and S. aureus and by the IC50 values of moxifloxacin which were 50-90% lower than those of ciprofloxacin, norfloxacin and sparfloxacin for the wild-type and single mutant enzymes of gyrase and topoisomerase IV. However, double mutant GyrA was significantly more sensitive to moxifloxacin than to the other fluoroquinolones tested, while wild-type topoisomerase IV was two-fold more refractory. Mutation rates of WT, MI and WT-4 for ciprofloxacin and moxifloxacin were 5 x 10(-8) vs 4 x 10(-10); <6 x 10(-11) vs <6 x 10(-11); and 2 x 10(-6) vs 5 x 10(-7), respectively. These data indicate an equivalent high inhibitory activity of moxifloxacin on DNA gyrase and topoisomerase IV of E. coli.

Anti-Infective Agents↗
PubMed1999

Impact of gyrA and parC mutations on quinolone resistance, doubling time, and supercoiling degree of Escherichia coli.

Isogenic mutants derived from quinolone-susceptible isolate WT by introducing gyrA (S83L, D87G) and parC (S80I, E84K) mutations associated with quinolone resistance were characterized with respect to quinolone resistance, growth rate, and degree of global supercoiling. The latter was determined by use of a pair of reporter plasmids carrying supercoiling-dependent promoters pgyrA and ptopA, respectively, transcriptionally fused to the reporter gene bla coding for TEM-1 beta-lactamase. The quotient (Qsc) of the beta-lactamase specific activity determined for a mutant carrying either plasmid was taken as a measure of the degree of global supercoiling. These Qsc data were comparable to results obtained from the separation of topoisomers of plasmid pBR322 on chloroquine-containing agarose gels and indicate a reduced degree of negative supercoiling in resistant mutants relative to the parent, WT. The S83L mutation in gyrA had the strongest influence on quinolone resistance while leaving other parameters nearly unaffected. The gyrA double mutation (S83L plus D87G) had an effect on quinolone resistance similar to that of a single mutation. Phenotypic expression of the parC mutation (S80I) was dependent on the presence of at least one gyrA mutation. Expression of high-level fluoroquinolone resistance (ciprofloxacin MIC, > 4 micrograms/ml) required a combination of the gyrA double mutation and one parC mutation (S80I or E84K). Such mutants showed considerable alterations of growth rate, global supercoiling, or both. Introduction of a parC mutation affected neither the doubling time nor the degree of supercoiling, while the presence of the gyrA D87G mutation was associated with a significant reduction in the degree of DNA supercoiling.

4-Quinolones↗
PubMed1998

Identification and natural antibiotic susceptibility of Morganella morganii.

Our data should elucidate whether or not natural antibiotic susceptibility can be used as an aid for subspecies or biovar discrimination of Morganella morganii (II). Furthermore, our goal was to create a database of the natural susceptibility of M. morganii (III) and we were interested in the relative frequency of the recently described subspecific taxa (I). On the basis of trehalose fermentation (TRE), ornithine decarboxylase (ODC), and lysine decarboxylase (LDC) activities, we determined the biovar for 90 clinical isolates of M. morganii. Within these strains we examined the natural antibiotic susceptibility of 53 morganellae to 70 antibiotics by determination of the MICs with a microdilution procedure. (I): 80 strains (89%) of all morganellae belonged to M. morganii ssp. morganii (TRE-), with biovar A (LDC-, ODC+) predominating (67 strains). The remaining strains of this subspecies were identified as biovar B (LDC+, ODC+; 12 strains) and biovar C (LDC-, ODC-, one strain). Ten strains of M. morganii ssp. sibonii (TRE+) were found: four strains belonged to biovar F (LDC variable, ODC-) and six strains to biovar G (LDC-, ODC). (II): With one exception we found no significant differences in antibiotic susceptibility between different biovars. M. morganii ssp. morganii strains are more susceptible to tetracycline than strains of M. morganii ssp. sibonii, but there is no evidence that this parameter could be useful to differentiate biovars within a subspecies. It could be shown that 8 of 30 strains of biovar A and 2 of 12 strains of biovar B were tetracycline resistant. However, one M. morganii ssp. sibonii strain was clinically susceptible to tetracycline according to French and American standards. (III): The natural population of M. morganii is primarily (naturally) resistant to certain penicillins like benzylpenicillin, oxacillin, and amoxicillin, first and second generation cephalosporins (excluding cefoxitin), cefpodoxime, all antibiotics of the ML group (macrolides and lincosamides), sulfamethoxazole, glycopeptides, fosfomycin, and fusidic acid, naturally sensitive to aminoglycosides, piperacillin, mezlocillin, ticarcillin, third and fourth generation cephalosporins, carbapenems, aztreonam, quinolones, trimethoprim, cotrimoxazole, and chloramphenicol. M. morganii is naturally resistant to a wide range of antibiotics. The natural resistance pattern is useful for validation of sensitivity tests. Susceptibility to antibiotics is an unsuitable parameter for the discrimination of the described subspecific taxa of M. morganii. M. morganii strains that do not belong to biovar A are rare.

Anti-Bacterial Agents↗
PubMed1998

beta-Lactamase induction and cell wall recycling in gram-negative bacteria.

beta-Lactams with the ability to induce beta-lactamase in gram-negative bacteria bind to essential penicillin-binding proteins (PBPs) after entering the periplasmic space. This leads to inactivation of transpeptidase activities and thereby a decrease in the number of peptide cross-links, allowing further degradation of murein by soluble lytic transglycosylases. If all DD-carboxypeptidases (PBP 4, 5, 6a and 6b) are inhibited as well, the degradation product aD-pentapeptide (N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic-acid-D-alanyl-D- alanine) accumulates, which is the case with inducing beta-lactams such as imipenem. These molecules in addition to tri- and tetrapeptides (N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic-acid-[D-alanine]) which are the usual degradation products of peptidoglycan, are released into the cytoplasm and displace the UDP-pentapeptide (UDP-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic-acid-D-alanyl-D-alanine) from the DNA-binding protein AmpR, converting it into an activator of AmpC beta-lactamase expression.

Journal Article↗
PubMed1998

New acetylenes isolated from the bark of Heisteria acuminata.

Five new linear acetylenic compounds, namely, pentadeca-6,8,10-triynoic acid (1), octadeca-8,10,12-triynoic acid (2), trans-pentadec-10-en-6,8-diynoic acid (3), cis-hexadec-11-en-7,9-diynoic acid (4), and cis-octadec-12-en-7,9-diynoic acid (5), were isolated from the bark of Heisteria acuminata by bioassay-guided fractionation, using cyclooxygenase (COX) and 5-lipoxygenase (5-LO) assays as models for antiinflammatory activity. The structures of compounds 1-5 were established by NMR, MS, IR, and Raman spectroscopy. These isolated compounds were found to be potent inhibitors of COX. Compounds 4 and 5 were the most potent inhibitors of 5-LO, whereas the other compounds only showed a weak inhibition at the same concentration.

Acetylene↗
PubMed1998

Induction of beta-lactamase in Enterobacter cloacae.

beta-lactamase induction in Enterobacter cloacae, which is linked to peptidoglycan recycling, was investigated with use of high-performance liquid chromatography of cell wall fragments in genetically defined cells of Escherichia coli. After treatment of cells with beta-lactams, we detected in the periplasm an increase of D-tripeptide (N-acetylglucosaminyl-1,6 anhydro N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid), D-tetrapeptide (N-acetylglucosaminyl-1, 6 anhydro N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid -D-alanine), and a yet-unknown anhydromuropeptide. We identified this anhydromuramylpeptide by fast atom bombardment-mass spectrometry as anhydromuramyl-pentapeptide. The amount of these molecules did not alter after treatment with cell wall-active non beta-lactams. The transmembrane protein AmpG transports not only D-tripeptide but also D-pentapeptide into the cell. In the cytoplasm these molecules are degraded into the corresponding monosaccharide peptides M-tripeptide (N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid) and M-pentapeptide (N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid-alanine-D-alanine). These findings indicate that besides M-tripeptide and D-tripeptide, probably M-tetrapeptide, D-tetrapeptide, M-pentapeptide, and D-pentapeptide are also signal muropeptides for beta-lactamase induction.

Bacterial Proteins↗
PubMed1998

Natural antibiotic susceptibility of Providencia stuartii, P. rettgeri, P. alcalifaciens and P. rustigianii strains.

The natural antibiotic susceptibility of 38 Providencia rettgeri, 35 P. stuartii, 23 P. alcalifaciens and 20 P. rustigianii strains was examined. MIC values were determined by a microdilution procedure and evaluated by a table calculation programme. P. stuartii was the least susceptible Providencia sp. and was naturally resistant to tetracyclines, some penicillins, older cephalosporins, sulphamethoxazole and fosfomycin and to antibiotics to which other species of Enterobacteriaceae are also resistant. It was naturally sensitive to modern penicillins and cephalosporins, carbapenems and aztreonam, but its susceptibility to aminoglycosides and quinolones was difficult to assess. P. alcalifaciens and P. rustigianii strains were the most susceptible Providencia spp. They were naturally sensitive or intermediate to tetracyclines and sensitive to aminoglycosides and quinolones. Susceptibility to sparfloxacin, biapenem and sulphamethoxazole permitted the discrimination of P. alcalifaciens and P. rustigianii strains. The natural antibiotic susceptibility of P. rettgeri strains was between that of P. stuartii and that of the other providenciae. P. rettgeri was resistant to tetracyclines and fosfomycin, but more susceptible to aminoglycosides, quinolones, fosfomycin and numerous beta-lactam antibiotics than P. stuartii. A database is described of the natural antibiotic susceptibilities of Providencia spp. It can be used for the validation of antibiotic susceptibility test results of these micro-organisms.

Anti-Bacterial Agents↗
PubMed1998

[Therapy of tumor pain].

The incidence of cancer pain is about 90%. The first step in the treatment strategy is a causal therapy, including tumor mass reduction. An adequate pain management should start sometimes before the onset of a causal treatment. A good pain relief in cancer patients is mostly possible by the consequent application of the World Health Organisation 3 step analgesic ladder for the treatment of cancer. Pain management has become more comfortable since the development of new ways of applications e.g. transdermal fentanyl, water soluble morphine granulate and retarded drugs. With those new preparations, we got new possibilities and a bigger variety in the practical use of the WHO analgesic ladder. Basics for a good social integration of the patient are treatment of side effects, periodic consultations and a professional psychological support.

Analgesics↗
PubMed1998

[Mucoviscidosis quality assurance. Problems, success and prospects 1995-1998].

The German project "quality assurance in cystic fibrosis" collects data from 97 CF centres with 4,306 patients. Project goals are improvement of quality of life and life expectancy catching up with international standards. Collection of data and evaluation are done anonymously. In Germany, most patients including adults are under care of paediatric institutions. Nutrition and lung function data with decisive prognostic significance (weight for height, one-second-capacity) exhibited less favourable results for patients treated by very small institutions (less than 20 patients). Between 1995 and 1997 some parameters could be improved particularly in pupils children and young adults. In Germany, mean cumulative survival was 29.3 years for 1997. This figure is comparable to other European countries. However, further improvement with respect to quality of structure has to be made.

Adolescent↗
PubMed1997

[Ketamine for treatment of chronic pain: meta-analysis].

The idea of using Ketamine to treat chronic pain is mainly based on the central antinoceptive effect of the substance acting as a noncompetitive antagonist at the NMDA-receptor. In the present meta analysis over a period from 1/1981 up to 6/1996 twelve publications (1994-1996), which have dealt the use of Ketamine for patients with chronic pain, are evaluated and discussed. The entire positive evaluation of the drug is based on the results of the studies under consideration. The studies investigating 88 cases are classified, i.e. seven studies are assigned to level 3, two studies to level 4, and three studies to level 5. A significant reduction of pain has been proven for patients with neuropathic pain by four cross-over-studies comparing the drug with placebo. However, observations have been restricted to a few hours after the administration of the drug. A positive effect of Ketamine as compared with opioids has been demonstrated by three studies, one of them with statistical significance. Positive long term results have been observed by two studies considering the subcutaneous and intravenous application of Ketamine (72-480 mg, daily) to 14 cancer pain patients, to whom opioids have been administered with insufficient effects before. A successful five-week-application (oral) of Ketamine has been described convincingly in a case report of a patient with postherpetic neuralgia. Two studies interpret the additional intrathecal administration of Ketamine to cancer patients as a possibility of either impeding the development of tolerance of the local anesthetic or reducing morphine requirements. Only one paper has dealt with the known side effects of Ketamine. Here, the therapy had to break off in two cases. In nine cases the side effects could be suppressed by Droperidol. For the future, research with more study power is necessary to establish Ketamine in the therapy of chronic pain.

English Abstract↗
PubMed1997

Antibacterial activity of grepafloxacin.

Grepafloxacin has an extremely broad spectrum of activity. Its activity against Gram-positive bacteria exceeds that of currently available quinolones. Grepafloxacin-resistant mutants seem to occur less frequently than ciprofloxacin- or ofloxacin-resistant mutants, and the increase in MIC against the former mutants is less than that of the latter. This applies only to the relative differences (in dilution steps); the absolute values are similar. Grepafloxacin kills Gram-positive bacteria at concentrations little above the MIC. Its pharmacodynamic profile against pneumococci is promising, favouring use of this drug for respiratory tract infections.

Anti-Infective Agents↗
PubMed1997

The signal molecule for beta-lactamase induction in Enterobacter cloacae is the anhydromuramyl-pentapeptide.

Beta-lactamase induction in Enterobacter cloacae, which is linked to peptidoglycan recycling, was investigated by high-performance liquid chromatographic analysis of cell wall fragments in genetically defined cells of Escherichia coli. After treatment of cells with beta-lactams, we detected an increase in a D-tripeptide (disaccharide-tripeptide, N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-mes o-diaminopimelic acid), aD-tetrapeptide (disaccharide-tetrapeptide, N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-mes o-diaminopimelic acid-D-alanine), and aD-pentapeptide (disaccharide-pentapeptide, N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-mes o-diaminopimelic acid-D-alanyl-D-alanine)levels in the periplasms of bacterial cells. Furthermore, only the accumulation of aD-pentapeptide correlates with the beta-lactamase-inducing capacity of the beta-lactam antibiotic. The transmembrane protein AmpG transports all three aD-peptides into the cytoplasm, where they are degraded into the corresponding monosaccharide peptides. In the absence of AmpD the constitutive overproduction of beta-lactamase is accompanied by an accumulation of aM-tripeptide (monosaccharide-tripeptide, anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid) and aM-pentapeptide (L1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid-D-alanyl-D-alanine), but not aM-tetrapeptide (anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid-D-alanine), in the cytoplasm. Only the amount of aM-pentapeptide is increased upon treatment with imipenem. These findings indicate that aD-pentapeptide is the main periplasmic muropeptide, which is converted into the cytoplasmic signal molecule for beta-lactamase induction, the aM-pentapeptide.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

Antimicrobial effects of continuous versus intermittent administration of carbapenem antibiotics in an in vitro dynamic model.

In an in vitro dynamic model we compared the antimicrobial effects of two carbapenems, imipenem (MIC, 1 microg/ml) and meropenem (MIC, 0.25 microg/ml) on Pseudomonas aeruginosa. The antibiotics were administered either as short-time infusions once or three times a day or as continuous infusions with steady-state levels ranging from 0.5 to 20 microg/ml. From the resulting kill curves the period of time until the onset of bacterial death (dt), the rate constant of bacterial death (ka), the maximal reduction of CFU (mr), and the period of time until bacterial regrowth occurred (tr) were determined. Additionally, the occurrence of bacterial resistance during the simulations (rq) and the postantibiotic effect (PAE) were recorded. For both investigated carbapenems no significant difference in dt, ka, mr, and PAE values between the short-time infusions and continuous infusions with steady-state levels above 2 microg/ml could be detected. The tr was longest with continuous infusions of over approximately 24 h, corresponding to steady-state levels of 3 microg/ml for imipenem and 2.5 microg/ml for meropenem. An increase in MIC was observed only during continuous infusions with steady-state levels below 2 microg/ml. Independent of the chosen method of application and despite the lower MIC of meropenem, imipenem was slightly more effective than meropenem.

Bacteremia↗
PubMed1997

[Not Available].

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Book Imprints↗