Biomedical subjects

K Dornbusch

Publications and source records attributed to K Dornbusch.

At least 19 recordsLinked to original sources

PubMed1994

Production of a plasmid mediated AmpC-like beta-lactamase by a Klebsiella pneumoniae septicaemia isolate.

A septicaemia Klebsiella pneumoniae isolate from Greece (Ath1) was shown to be resistant to third generation cephalosporins, aztreonam and cefoxitin and this resistance was not decreased in the presence of clavulanic acid. The gene coding for the resistance phenotype, associated with a beta-lactamase showing cephalosporinase activity and a pI of 8.6, could be transferred into Escherichia coli K-12 by conjugation and transformation. DNA-hybridisation showed that this gene was located on two different plasmids, 7.8 and 80 kb respectively. The larger, conjugative plasmid also carried genes coding for another beta-lactamase (pI 6.6) and resistance to aminoglycosides, tetracycline, chloramphenicol and trimethoprim. Under highly stringent conditions the gene coding for the pI 8.6 beta-lactamase hybridised with chromosomal DNA from Citrobacter freundii OS60 but not from E. coli or Enterobacter cloacae. Furthermore, the restriction map of this beta-lactamase gene corresponded to that of ampC from C. freundii OS60. The regulatory ampR gene could not be detected in the plasmid DNA from the Ath1 K. pneumoniae by DNA hybridisation. The relationship between a plasmid-mediated extended spectrum beta-lactamase in a K. pneumoniae septicaemia isolate and chromosomal AmpC beta-lactamase from C. freundii was demonstrated.

Citrobacter freundii↗

PubMed1992

Extended spectrum beta-lactamase from Klebsiella oxytoca, not belonging to the TEM or SHV family.

In clinical isolates of Klebsiella oxytoca resistance to cefuroxime and aztreonam was mediated by a beta-lactamase, designated KH, (pI 5.25) which could be transferred into Escherichia coli by electroporation, but not by conjugation. The transformants produced two enzymes with pIs 5.25 and 8.4 respectively, and showed resistance to cefuroxime, aztreonam, cefotaxime and ceftazidime. Substrate and inhibition profiles indicated that KH beta-lactamase was different from TEM- or SHV-like enzymes, but similar to chromosomal K1 beta-lactamase. The enzyme profile with pI 8.4 was similar to the enzyme from the recipient and showed elevated activity in transformants. The plasmid profiles of the transformants were different from those of their donors. However, a plasmid fragment of the K. oxytoca isolate KH11 hybridized with a plasmid ranging in size from 4.8 to 7.8 kilobases in all the transformants and most of the donors. Gene probes encoding TEM-1 or SHV-1 did not hybridize with plasmid DNA from the K. oxytoca isolates. Furthermore, a probe of the ampC gene did not hybridize with the plasmid but to DNA fragments of the same size in whole cell DNA preparations from the E. coli XAC recipient and the TKH11 transformants. This indicates that no gross rearrangements in the chromosomal beta-lactamase gene region had occurred in the transformants which could explain the increased expression of the pI 8.4 beta-lactamase.

Aztreonam↗

PubMed1991

Characterization of Klebsiella oxytoca septicaemia isolates resistant to aztreonam and cefuroxime.

Eleven clinical isolates of Klebsiella oxytoca from Stockholm hospitals were found to be resistant to aztreonam and cefuroxime, but susceptible to cefotaxime, ceftazidime and imipenem. Resistance could be overcome by combining the beta-lactams with the inhibitor clavulanic acid. Crude beta-lactamase preparations from the isolates inactivated aztreonam and cefuroxime rapidly. By isoelectric focusing, a single common beta-lactamase of pI 5.25 was detected. The K. oxytoca isolates belonged to three subgroups, based on their plasmid profiles and Bg/II restriction endonuclease digestion of plasmid DNA. It was concluded that resistance to aztreonam and cefuroxime in these isolates was conferred by a beta-lactamase distinct from TEM-1, TEM-2 and SHV-1, but possibly derived from TEM-like enzymes.

Aztreonam↗

PubMed1991

Synergy and cumulated killing effect of the penems FCE 22101 and FCE 25199 in combination with gentamicin against bacteria isolated from septicaemia.

Blood isolates of Enterococcus faecalis, Streptococcus sanguis, Staphylococcus aureus, E. coli and Klebsiella oxytoca were tested for their synergistic and cumulated killing effect (CKE) with the new penems FCE 22101 or FCE 25199 in combination with gentamicin. The tissue cage model in rabbits was used to study the CKE in vivo after antibiotic treatment of the bacteria in vitro. Synergy was observed within two to seven h with all isolates in early logarithmic phase, except with S. aureus, which was rapidly killed by the penems alone. After one h treatment with the antibiotic combinations in vitro, a CKE was demonstrated for up to six h both in vitro and in vivo. The magnitude of the CKE differed between strains and in vitro vs. in vivo.

Animals↗

PubMed1991

Characterization of beta-lactam-resistant Klebsiella oxytoca isolated in a neonatal intensive care unit.

The occurrence of Klebsiella oxytoca resistant to ampicillin, piperacillin, aztreonam and cefuroxime in a neonatal intensive care unit, including two cases of septicemia, was shown to consist of a spread on three consecutive occasions caused by three different biochemical Klebsiella oxytoca phenotypes. All isolates, except six surface isolates from one infant belonging to phenotype 1, were sensitive to cefotaxime (MIC 0.5-4 mg/l) and ceftazidime (MIC 0.25-1 mg/l). Isolates of phenotypes 1 and 2 produced a beta-lactamase with an isoelectric point of 5.5 and isolates of phenotype 3, a beta-lactamase with an isoelectric point of 7.9. The beta-lactamases of all three phenotypes hydrolysed benzylpenicillin and more slowly cephalothin. All phenotype 1 isolates carried a 2.9 Md plasmid and most isolates also a 36 Md plasmid. All phenotype 2 isolates carried a 4.8 Md plasmid and one isolate also a 30 Md plasmid. The phenotype 3 isolates carried only one 85 Md plasmid.

Animals↗

PubMed1990

Pharmacokinetics in healthy subjects of FCE 22101 and its acetoxymethyl ester, FCE 22891: effect of co-administration of imipenem/cilastatin on the renal metabolism of FCE 22101.

The pharmacokinetics of FCE 22101 were studied in eight healthy male subjects who received FCE 22101 intravenously alone or together with imipenem/cilastatin which was given to inhibit dehydropeptidase-I, a renal enzyme metabolizing penem and carbapenem antibiotics. The kinetics of FCE 22101 were also studied following oral administration of its acetoxymethyl ester, FCE 22891. For comparative purposes, the kinetics of imipenem and cilastatin, given alone or together with FCE 22101, were calculated. Intravenously administered FCE 22101 at a dose of 250 mg gave peak plasma concentrations of about 12 mg/l and the plasma half-life was about 60 min. Co-administration of FCE 22101 with imipenem/cilastatin did not affect the plasma kinetics of FCE 22101, nor did FCE 22101 influence the kinetics of imipenem or cilastatin. Cilastatin increased the urinary recovery of FCE 22101 from 17.5% to 53.0% with FCE 22101 alone to 73.2% to 91.8% when it was given with cilastatin. There was a high correlation between the urinary recovery of FCE 22101 in this study and that of imipenem given alone to the same subjects in previous studies; subjects who were high metabolizers of imipenem were also high metabolizers of FCE 22101. When FCE 22891 was given orally at a dose of 500 mg (corresponding to 400 mg of FCE 22101 free acid), peak concentrations of 2.2 to 6.1 mg/l were found. The absorption was rapid with peak concentrations achieved 20 to 80 min after administration. In comparison with imipenem, FCE 22101 seems to undergo less non-renal metabolism.

Adult↗

PubMed1990

Resistance to aminoglycoside antibiotics in gram-negative bacilli and staphylococci isolated from blood. Report from a European collaborative study. The ESGAR Study Group (European Study Group on Antibiotic Resistance).

The incidence of resistance to gentamicin, tobramycin, amikacin and netilmicin was determined by the microdilution method in Mueller-Hinton broth among blood culture isolates consecutively collected in 37 laboratories in 14 European countries. The distribution of bacteria was similar in each laboratory, Escherichia coli and staphylococci predominating. Resistance levels varied between laboratories but they were higher to all four antibiotics in Southern Europe than in Central and Northern Europe. Aminoglycoside resistance was usually associated with production of aminoglycoside-modifying enzymes, ANT(2"), AAC (3)-V, AAC (6')-I predominating in Gram-negative bacilli and APH (2") + AAC (6') and ANT (4')-I in staphylococci.

Aminoglycosides↗

PubMed1990

Resistance to beta-lactam antibiotics and ciprofloxacin in gram-negative bacilli and staphylococci isolated from blood: a European collaborative study. European Study Group on Antibiotic Resistance.

In 1987 and 1988 members of the European Study Group on Antibiotic Resistance collected 3440 consecutive isolates of Gram-negative bacilli (63%) and staphylococci (37%) from blood cultures and performed susceptibility testing by the microdilution method. The MICs of ampicillin and cefazolin for susceptible Gram-negative bacteria were 1-8 mg/l, of piperacillin less than or equal to 0.5-4 mg/l, of aztreonam, imipenem, cefotaxime and ceftazidime less than or equal to 0.125-1 mg/l and of ciprofloxacin less than or equal to 0.125-0.5 mg/l. For susceptible staphylococci the MICs of cefazolin were less than or equal to 0.5-8 mg/l, of cefotaxime 1-4 mg/l, of ceftazidime 4-16 mg/l, of imipenem and ciprofloxacin less than or equal to 0.125-1 mg/l. The antibiotic resistance rates varied between laboratories, being generally lower in northern Europe, except for imipenem, which showed uniform, low resistance rates. In Escherichia coli resistance to ampicillin, piperacillin and cefazolin could be seen to have increased since a previous survey.

Ampicillin Resistance↗

PubMed1990

Postantibiotic effect of the penem FCE 22101 against selected gram-positive and gram-negative bacteria in vitro and in vivo by the use of a tissue cage model in rabbits.

Isolates of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae were tested for their bactericidal activity and postantibiotic effect (PAE) with the new penem FCE 22101. The tissue cage model in rabbits was used to study PAE in vivo. The bactericidal activity against all four species was shown to be in the range of 0.05-4.0 mg/l. A 99.9% killing effect at MBC concentrations was reached within 2 hours with S. pneumoniae and K. pneumoniae and within 6-8 hours with S. aureus and H. influenzae. After in vitro exposure by FCE 22101 a PAE in vitro and in vivo was obtained against S. aureus, S. pneumoniae and H. influenzae strains but no PAE could be demonstrated against K. pneumoniae. FCE 22101 showed a good bactericidal activity and PAE against the strains investigated, except for K. pneumoniae.

Animals↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗