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K Dornbusch

Publications and source records attributed to K Dornbusch.

At least 37 records · Page 2Linked to original sources

In vitro activity of cefepime, a new parenteral cephalosporin, against recent European blood isolates and in comparison with piperacillin/tazobactam.

Cefepime, a new parenteral cephalosporin with broad antibacterial spectrum and stability to the hydrolysis to many bacterial beta-lactamases, was tested against recent blood culture isolates (369 strains of gram-negative bacilli and 131 strains of staphylococci) collected in 29 European laboratories by the microdilution method in Mueller-Hinton broth. Cefepime was very active against the gram-negative bacilli (MIC50 less than or equal to 0.016-0.064 mg/l; MIC90 0.064-4 mg/l) and less active against Pseudomonas (MIC50 4 mg/l; MIC90 greater than 16 mg/l) or Acinetobacter (MIC50 and MIC90 greater than 16 mg/l). The staphylococci were also inhibited (MIC50 8 mg/l; MIC90 16 mg/l). Cefepime was very active against bacteria producing different plasmid-encoded beta-lactamases (MIC 0.016-0.5 mg/l). Piperacillin was not active against the latter strains (MIC from 2 to greater than 64 mg/l), but the presence of the beta-lactamase inhibitor tazobactam restored the activity of piperacillin. The bactericidal activity of cefepime and piperacillin/tazobactam against beta-lactamase-producing strains was confirmed by the killing curve technique.

Cefepime↗

Antibiotic susceptibility and beta-lactamase production in clinical isolates of Enterobacter spp.

The in vitro susceptibility of 237 clinical isolates of Enterobacter spp. (E. aerogenes, E. agglomerans and E. cloacae; 41, 64 and 132 respectively) to 16 different antibiotics is described. Four quinolones (ciprofloxacin, lomefloxacin, norfloxacin and ofloxacin), two new cephalosporins (cefpirome and cefepime) and imipenem, all showed high activity against the three Enterobacter species tested (MIC50 less than or equal to 0.125 mg/l, MIC90 less than or equal to 0.5 mg/l). Also the aminoglycosides gentamicin and tobramycin were highly active antibiotics (MIC50 less than or equal to 0.5 mg/l, MIC90 less than or equal to 1.0 mg/l). The susceptibility of beta-lactam-antibiotics to beta-lactamase produced by Enterobacter spp. was evaluated, and imipenem and cefepime were found to be most stable. Different methods for detection of inducible beta-lactamases were used, the agar dilution method being more sensitive than the double-disc diffusion test. Elevated beta-lactamase production was detected, via induction, in 83% of E. aerogenes strains and 70% of E. cloacae strains, with cefamandole used as the substrate and cefoxitin as the inducer. Constitutive, high level enzyme production was detected in 7 and 13% respectively of the E. aerogenes and the E. cloacae strains. In all the strains of E. agglomerans, 10% of E. aerogenes and 13% of E. cloacae, no beta-lactamases could be detected with the methods studied.

Aminoglycosides↗

In-vitro activity of the new penems FCE 22101 and FCE 24362 alone or in combination with aminoglycosides against streptococci isolated from patients with endocarditis.

Seven strains of viridans streptococci isolated from patients with endocarditis were inhibited in vitro by 0.06-2 mg/l and 0.016-0.5 mg/l of the penems FCE 22101 and FCE 24362 respectively. The MBCs were the same or two-fold higher than the respective MIC with three exceptions. One strain of Streptococcus faecalis was only inhibited (8 mg/ml respectively 0.5 mg/l; MBC greater than 32 mg/l) and one strain of Str. faecium was resistant (MIC greater than or equal to 16 mg/l). When combined with gentamicin or netilmicin a bactericidal and synergistic killing was observed within 1-8 h in all strains except Str. faecium. Synergy could also be confirmed in all cases by following bacterial growth kinetics after elimination of antibiotics, by calculating the difference between the times required for bacteria exposed to antibiotic and unexposed bacteria to increase in numbers (PAE).

Anti-Bacterial Agents↗

In-vitro activity of FCE 22101 against respiratory tract pathogens with reference to production of beta-lactamases.

FCE 22101 is a new penem with broad antibacterial spectrum, excluding the pseudomonads, and has stability to many beta-lactamases. FCE 22101 and imipenem were very potent against the bacteria studied, including beta-lactamase producing strains, which can be isolated from patients with respiratory tract infections (MIC less than or equal to 8 mg/l). No strains were found to be resistant to FCE 22101. FCE 22101 was rapidly bactericidal and more stable to inactivation by beta-lactamases from Branhamella catarrhalis, Haemophilus influenzae, Enterobacter cloacae and Klebsiella pneumoniae than imipenem and ceftibuten. The other antibiotics tested varied in their activities against the respiratory tract pathogens.

Anti-Bacterial Agents↗

Comparative in-vitro activity of the penem FCE 22101 against recent European blood culture isolates.

Recent blood culture isolates (462 strains of Gram-negative bacilli and 288 strains of staphylococci) collected in 30 European laboratories were tested for susceptibility to five beta-lactam antibiotics by a microdilution method in Mueller-Hinton broth. The penem FCE 22101 and imipenem were very active against the Gram-negative bacilli, except the pseudomonads, FCE 22101 being four- to 16-fold less active (MIC50 2 mg/l; MIC90 8 mg/l) than imipenem MIC50 0.5 mg/l; MIC90 2 mg/l). Ceftibuten and ceftazidime were also active (MIC50 0.25 mg/l; MIC90 greater than 16 mg/l). The MIC of piperacillin (MIC50 8 mg/l; MIC90 greater than 64 mg/l) were two- to 16-fold reduced in the presence of the beta-lactamase inhibitor YTR-830 against these bacteria. Only imipenem and piperacillin inhibited the pseudomonads (MIC50 4 and 8 mg/l respectively; MIC90 16 mg/l and greater than 64 mg/l), with two-fold reduction in MIC50 of piperacillin in the presence of YTR-830. The staphylococci were very susceptible to FCE 22101 and imipenem (MIC50 less than or equal to 0.25 mg/l) except some cefazolin-resistant strains. In Staphylococcus aureus penem resistance was better expressed after bacterial growth at 30 degrees C. Some strains of Staph. epidermidis were susceptible to FCE 22101 but resistant to imipenem. The cephalosporins were not active against the staphylococci, and the presence of YTR-830 caused a four- to 16-fold reduction in MIC of piperacillin.

Anti-Bacterial Agents↗

Evaluation of a disk approximation test of inducible beta-lactamases in Enterobacteriacae and Pseudomonas aeruginosa.

A modified disk approximation test of inducible beta-lactamases in Enterobacteriacae and Pseudomonas aeruginosa was evaluated. The amount of inducer was adapted to produce the smallest possible zone of inhibition and the distance between the centre of the disks was standardized. Among several beta-lactam antibiotic disks tested, imipenem (0.06 microgram per disk) or cefoxitin (10 micrograms per disk) placed at a distance of 14-16 mm from a cefotaxime disk (30 micrograms) most efficiently revealed inducible beta-lactamases. A positive induction test (primarily expected with Enterobacter spp, Citrobacter freundii, Serratia spp, Pseudomonas aeruginosa and indole positive Proteus spp) may serve as a warning of the risk of selecting mutants with beta-lactamase mediated cross-resistance during systemic treatment with ureidopenicillins, later generations of cephalosporins or monobactams. Such resistance was exemplified by characterization of some laboratory mutants with hyperproduction of beta-lactamases. However, evaluation of the specificity and sensitivity of the disk approximation test (and other indirect induction tests) still remains to be done.

Enterobacteriaceae↗

Distribution and resistance patterns of Haemophilus influenzae: a European cooperative study.

The first European survey of the prevalence of antibiotic resistance in Haemophilus influenzae was conducted between February and October 1986. Eighty laboratories in nine countries participated (Austria, Belgium, France, FRG, The Netherlands, Spain, Sweden, Switzerland and the UK). A total of 1,961 clinical isolates was examined for type b encapsulation, beta-lactamase production and susceptibility to ampicillin, chloramphenicol, cefaclor, erythromycin and tetracycline, using a unique microdilution method. The proportion of isolates resistant to these antibiotics varied considerably between individual countries. The highest prevalence of ampicillin resistance was found in Spain (30.6%), and the lowest in the FRG (1.6%), with a mean value of 10% for all countries. Chloramphenicol resistance was highest in Spain (24.9%) and Belgium (10.9%) and lowest in The Netherlands (0.6%) and Austria (0.5%), with a mean value of 4.7%. Resistance to erythromycin ranged from 27% of the isolates in The Netherlands to 1.1% in Austria. For tetracycline, values ranged from 1.5% in the UK to 17.8% in Belgium and 25.4% in Spain. The lowest mean prevalence of resistance was observed for cefaclor (breakpoint 8 mg/l): 5% or less in all countries. These inter-country differences could only partially be explained by variations in the proportion of type b strains, the source of the isolates and the mode of collection.

Ampicillin Resistance↗

Laboratory- and species-specific interpretive breakpoints for disk diffusion tests of chloramphenicol susceptibility of Haemophilus influenzae.

A total of 601 clinical isolates of Haemophilus influenzae isolated in six different regions of Sweden were tested for chloramphenicol susceptibility by using agar dilution MIC determinations and disk diffusion tests. For seven strains MICs were 4 micrograms/ml or higher, and for one strain the MIC was 2 micrograms/ml. All eight strains produced chloramphenicol acetyltransferase. For the remaining 593 strains, MICs were less than or equal to 1 microgram/ml, and the MICs for 50% and 90% of the strains were both 0.5 microgram/ml. Disk diffusion tests carried out by using revised interpretive criteria introduced in 1984 by the Swedish Reference Group for Antibiotics correctly identified the 593 strains as susceptible and the 8 strains as resistant. Quality assessments were performed in 29 clinical microbiology laboratories. The revised criteria for chloramphenicol disk diffusion testing gave rise to false resistance results in some laboratories. The interpretive accuracy improved when the interlaboratory variation was compensated for by using adjusted breakpoints. Such revision was possible through peak correction, single-strain regression analysis, and standard curve regression analysis. Peak-corrected breakpoints improved the accuracy from an overall incidence of false-resistant isolates of 4.4% to 2.3%. Single-strain regression analysis and standard curve regression analysis provided laboratory- and species-specific breakpoints which reduced false resistance rates of 0.14% and 0%, respectively.

Chloramphenicol↗

Susceptibility to beta-lactam antibiotics and gentamicin of gram-negative bacilli isolated from hospitalized patients: a Swedish multicenter study.

A total of 952 blood and 1543 urine isolates of gram-negative bacilli from hospitalized patients in 1986-1987 were consecutively collected by 10 Swedish laboratories and tested for susceptibility to 8 beta-lactam antibiotics and to gentamicin. The isolates were mostly Escherichia coli (58% and 44%, respectively) and Klebsiella sp. (17% and 18%). Resistance to ampicillin in blood and urine isolates was found in 35% and 45%, respectively, to piperacillin in 5% and 6%, to cephalothin in 26% and 34%, to cefuroxime in 12% and 22%, to cefotaxime in 3% and 5%, to ceftazidime in 1% and 1%, to imipenem in 0.5% and 0.1%, to aztreonam in 3% and 2%, and to gentamicin in 0.8% and 0%. Resistance of clinically important gram-negative bacilli to new beta-lactam antibiotics and to gentamicin is infrequent in Sweden.

Ampicillin↗

In vitro susceptibility to tetracycline and doxycycline in clinical isolates of Haemophilus influenzae.

The most common indication for the use of tetracyclines in Sweden is respiratory tract infections. Among the tetracyclines, doxycycline dominates with about 75% of the consumption. It is therefore used for routine susceptibility testing, while tetracycline is the test drug in most other countries. Six hundred strains of Haemophilus influenzae isolated from different parts of Sweden were tested for susceptibility to doxycycline and tetracycline. The results were compared with those from earlier reports on resistance rates in Sweden and other countries. The MIC50's of the strains were slightly lower for tetracycline than for doxycycline, but some strains with reduced susceptibility to tetracycline were fully susceptible to doxycycline. The level of resistance to doxycycline in H. influenzae was very low (less than 1%) and has not changed significantly over the past ten years, making doxycycline a suitable antibiotic for instance in the treatment of chronic bronchitis when H. influenzae is involved.

Adolescent↗

The role of biotransformation in the genotoxicity of allylic compounds.

Allylic compounds exert direct genotoxic activities which depend on the chemical nature of the leaving group and on further substituents. Besides the direct genotoxic effects, metabolic activation mechanisms are also conceivable. Epoxidation seems to play a minor role in bioactivation, whereas the metabolic formation of strongly mutagenic alpha, beta-unsaturated carbonyl compounds is obviously of great importance for the indirect genotoxicity of allylic compounds. Only in the case of 2,3-dichloro-1-propene is an epoxide formed which is extremely unstable and immediately rearranges to the strong mutagen, 1,3-dichloroacetone.

Allyl Compounds↗

In vitro aminoglycoside resistance of gram-negative bacilli and staphylococci isolated from blood in Sweden 1980-1984.

The in vitro susceptibility to gentamicin, tobramycin, amikacin and netilmicin in septicaemia isolates was followed during 1980-1984 in 6-8 Swedish laboratories. The bacterial distribution was similar over the years and was dominated by Escherichia coli and staphylococci. Resistance to gentamicin was found in 2.3-3.6%, to tobramycin in 1.4-3.4%, to amikacin and netilmicin in 0.5-0.9%. Production of aminoglycoside modifying enzymes was observed among resistant strains.

Amikacin↗

In-vitro activity of Sch 34343 against Gram-negative bacteria producing characterized beta-lactamases.

The activity of Sch 34343 against 13 strains producing large amounts of characterized beta-lactamases was compared with that of imipenem, latamoxef (moxalactam), aztreonam and other third-generation cephalosporins. Sch 34343, like imipenem, was active against all strains, including many resistant to all other beta-lactams. MICs of Sch 34343 determined for 16 different inocula were rarely increased even at very high inocula. Sch 34343 was rapidly bactericidal against Escherichia coli TEM-2, Enterobacter agglomerans (with an induced beta-lactamase) and two strains of Bacteroides fragilis with highly active cephalosporinases. Like cefoxitin, Sch 34343 was only slowly inactivated by concentrated crude penicillinases which inactivated cefotaxime within 1 h. Sch 34343 was even more stable to cephalosporinases than was cefoxitin. Stability of the antibiotics to the different beta-lactamases was also determined by pre-incubating them with dilutions of the beta-lactamases before determination of MICs against E. coli 25922. Very large amounts of all enzymes were required to increase the MICs significantly for Sch 34343 and imipenem. These results indicate the good stability of Sch 34343 to beta-lactamases.

Anti-Bacterial Agents↗

Scandinavian quality surveys of gentamicin assays 1978-1983.

During 1978-1983 44 Scandinavian laboratories participated in 7 quality surveys of gentamicin serum assays. In each survey 2 test solutions of gentamicin were distributed. In the first 4 surveys very few non-microbiological assays were used while in the 7th survey almost half the laboratories had access to enzyme immunoassay (EMIT). The gentamicin survey mean (SM) concentrations, which did not differ significantly from the intended concentrations, were used as target values. In survey 1, 65% of the results of either of the 2 test solutions were outside the SM +/- 25% and 16% were outside SM +/- 50% ("highly misleading"). In surveys 5 and 7 the corresponding figures were 27 and 5% and 18 and 0%, respectively. The EMIT performed excellently in all surveys. Agar well diffusion assays using Diagnostic Sensitivity Test agar (Oxoid) performed better than other plate diffusion assays. Laboratories participating regularly performed better than others. It is concluded that the survey program, which continues, provides an external facility for unbiased control of commercially available as well as non-commercial assay techniques and that it has been instrumental in the improvement of gentamicin assay standard. It is stressed that the surveys cannot replace internal quality control, best performed by daily measurement and regular statistical evaluation of samples of known potency.

Biological Assay↗

Comparative study of netilmicin/tinidazole versus netilmicin/clindamycin in the treatment of severe abdominal infections.

The efficacy of netilmicin combined with tinidazole (N + T) or clindamycin (N + C) in the treatment of severe abdominal infections was evaluated in a prospective randomized study with 20 patients in the N + T group and 21 patients in the N + C group. Normally the maintaining dose for netilmicin was 2.25 mg/kg every 12 h, for tinidazole 400 mg every 12 h and for clindamycin 300-600 mg every 6-8 h. The mean duration time of treatment was 8 days in the N + T group and 10 days in the N + C group respectively. In the N + T group 18 patients were cured and in the N + C group 17 patients. Among aerobic bacteria Escherichia coli was most frequently isolated and among anaerobes Bacteroides sp. All aerobic bacteria with 2 exceptions were susceptible to netilmicin and all anaerobic bacteria but 2 to tinidazole or clindamycin. Adequate serum levels were obtained for each antibiotic during therapy. In this study with a small number of patients the combination of netilmicin and tinidazole was as effective as netilmicin and clindamycin.

Adolescent↗