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Biomedical subjects

K Dornbusch

Publications and source records attributed to K Dornbusch.

At least 55 records · Page 3Linked to original sources

Transferable trimethoprim resistance in urinary tract pathogens isolated in Finland and Sweden.

The incidence of trimethoprim resistance (MIC greater than 4 micrograms/ml) among urinary pathogens from inpatients was earlier shown to be 1.6-3.6% in Stockholm and 31-49% in Turku in 1977-1978. In strains from this study trimethoprim resistance could be transferred from 13/51 donor strains. Resistance to streptomycin was co-transferred in all matings but 2, and to tetracycline, ampicillin, carbenicillin and chloramphenicol in some cases. Sulphonamide resistance was co-transferred in 2 cases. In all matings but 1 at least 1 plasmid was transferred. A plasmid with similar molecular weight was transferred from 5 Turku and 4 Stockholm donor strains. Restriction enzyme digestion of this plasmid DNA showed many common bands after electrophoresis. In DNA-DNA duplex studies, using 3H-labelled Col E 1::Tn 7 as the probe, the presence of Tn 7 DNA sequences was confirmed in the 5 donor strains from Turku and 1 from Stockholm. Electrophoresis of plasmid DNA with and without digestion with restriction enzymes together with DNA-hybridization were thus useful methods to investigate the presence of genetic determinants for trimethoprim resistance in 2 areas. Other determinants than transposon Tn 7 were also present.

Anti-Bacterial Agents↗

Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method.

Combinations of gentamicin with cefotaxime, moxalactam, and ceftazidime were tested against 43 bacterial strains, most of them blood isolates. With an interaction index of less than or equal to 0.5 as borderline, synergism was demonstrated against 30 to 40% of the strains by the fractional inhibitory concentration index and against 50 to 70% by the fractional bactericidal concentration index. The reproducibility of the index was within +/- 0.2 for two-thirds of 40 repetitive assays and within +/- 0.4 to 0.5 for all of these assays. Similar results were obtained when netilmicin was substituted for gentamicin. The killing curve system for studying antibiotic synergism was standardized to give results comparable to those obtained with the interaction index. This was achieved when one-half of a previously determined minimum bactericidal concentration was used for single drugs and the amount of antibiotic was at least halved again when drugs were used in combination. An initial bacterial concentration of 10(5) to 10(6) colony-forming units per ml is recommended. Given these conditions, synergism could be defined as a 2-log 10 or more decrease in viable count given by both drugs together, as compared with the more active of the pair after 24 h. Prediction of killing curve results could then be obtained with the fractional bactericidal concentration index. When cephalosporins and gentamicin were combined from the start, the beta-lactam antibiotics were less susceptible to inactivation, as demonstrated in time-killing assays. If one of the antibiotics were added after 24 h, synergism was not demonstrable. The results indicate that the new cephalosporins may be advantageously combined with aminoglycosides.

Aminoglycosides↗

Levels of trimethoprim and sulfamethoxazole in human oviduct mucosa and plasma.

The oviductal and plasma levels of trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied in 9 women after oral and i.v. administration of a drug combination (Eusaprim R, Wellcome Foundation Ltd). The concentration of TMP in a healthy endosalpinx was found to be twice as high (4.7 microgram/g, range 2.8-8.3) as in plasma (2.6 microgram/ml, range 2.1-3.6). Conversely, the endosalpingeal level of SMZ (38 microgram/g, range 12-65) was about half that in plasma (77 microgram/ml, range 58-95). The agar well diffusion method was used for the concentration determinations. The specimens were collected during surgery for non-infectious genital diseases. The implication of treatment by the given drugs is discussed.

Drug Combinations↗

Comparison of direct and standardized antibiotic susceptibility testing in bacteriuria.

In clinical isolates of bacteria from urine, the antibiotic susceptibility was tested with a direct disc diffusion method in which the inoculum was not primarily standardized. The results were compared with those from parallel tests using standardized inoculum. Of a total 2,272 urine specimens, 700 were accepted for direct susceptibility testing, 189 were not accepted because of mixed culture or indistinct inhibition zones. The overall concordance between the direct and the standardized tests was 95.8% (2,800 observations with 118 discordant results). The direct diffusion method used in this way is time saving and economical and can reliably be used in a clinical microbiological laboratory serving mainly outpatients.

Anti-Bacterial Agents↗

Effect of trimethoprim or trimethoprim/sulphamethoxazole usage on the emergence of trimethoprim resistance in urinary tract pathogens.

The frequency of trimethoprim (TMP)-resistant bacteria isolated from urine was studied in hospitals, in Stockholm, Sweden, and Turku, Finland. TMP has been in clinical use in Finland since 1973, whereas in Sweden TMP was available only in combination with sulphamethoxazole (SMZ) at the time for this study. All samples were collected solely from in-patients at 4 different occasions during a 20-month period 1977-78. The frequency of TMP-resistant strains (MIC greater than or equal to 8 micrograms/ml) in Turku increased from 31 to 49%, whereas it remained at a low level (1.6-3.6%) in Stockholm during the whole period. Also the frequency of TMP/SMZ-resistant strains (MIC greater than or equal to 64 micrograms/ml) increased in Turku from 24 to 45% but remained at the same level, 0-4% in Stockholm. In Turku there was also an increased frequency of resistance to SMZ (MIC greater than or equal to 512 micrograms/ml), ampicillin (MIC greater than or equal to 32 micrograms/ml) and nitrofurantoin (MIC greater than or equal to 64 micrograms/ml), while these frequencies remained at their initial levels in Stockholm. The distribution of bacteria was different in the two areas. In Turku there was also a change towards more nosocomial strains during the observation period. Since antibacterial agents are used more frequently in Turku than in Stockholm, this might be one explanation to the increase of resistance in Turku.

Ampicillin↗

Studies on beta-lactamase in Bacteroides fragilis.

Fifteen strains of Bacteroides fragilis, five highly resistant, five moderately resistant and five sensitive to benzylpenicillin and cephaloridine, were tested for beta-lactamase production. In the highly resistant and the moderately resistant groups of strains, a correlation between formation of beta-lactamase and MIC-values was found. Culture under controlled conditions in stirred fermentors gave higher yields of beta-lactamase than static cultures in bottles. The enzyme had its maximum activity at pH 5.0 and was stable between pH 5.5-8.5. Isoelectric focusing in polyacrylamide gels gave an isoelectric point of 4.9 +/- 0.2 for the enzyme. In the presence of the beta-lactamase inhibitors clavulanic acid and CP-45.899 at concentrations of 1 microgram/ml, the susceptibility to cephaloridine increased fourfold or more in the beta-lactamase-producing strains. Crypticity measurements (beta-lactamase activity broken/intact cells) with cephaloridine as substrate could indicate a diffusion barrier in the cell wall.

Anti-Bacterial Agents↗

Secretion of metronidazole into the human semen.

The concentration of metronidazole has been studied in blood and in seminal plasma from apparently healthy volunteers and men with subclinical prostatitis. The volunteers took one dose of 500 mg orally and the patients 250 mg twice daily for two to three days. Therapeutic concentrations of metronidazole were found in blood and semen two to three h after intake. In patients the mean concentration was 8.7 micrograms/ml in blood plasma and 7.0 micrograms/ml in seminal plasma. Split ejaculates were collected in four to six fractions and the concentrations of metronidazole in the different fractions were related to those for zinc and fructose. The results indicated that the drug was excreted from prostate, seminal vesicles, and the ampulla ductus deferens.

Adult↗

Characterization of three different beta-lactamases from the Bacteroides fragilis group.

beta-Lactamases from five strains of Bacteroides fragilis and two strains of Bacteroides uniformis, all resistant to beta-lactam antibiotics, were compared by means of isoelectric focusing and enzyme kinetic measurements. beta-Lactamases from the five B. fragilis strains were identical, whereas those from the two B. uniformis strains were distinguished from each other and also from the B. fragilis enzymes. The two B. uniformis strains were relatively resistant to cefoxitin (minimal inhibitory concentration, 32 micrograms/ml), but only one of the strains, B. uniformis 2986, was found to rapidly inactivate cefoxitin. This apparently enzymatic inactivation of cefoxitin seemed to be of minor importance, and the main factor for cefoxitin resistance was considered to be a decreased permeability of the drug. Transfer of resistance to beta-lactam antibiotics from these beta-lactamase-producing strains of B. fragilis and B. uniformis to a non-beta-lactamase-producing strain of Bacteroides distasonis was attempted, but with these isolates no transfer of resistance to beta-lactam antibiotics was demonstrated.

Bacteroides fragilis↗

Susceptibility testing to trimethoprim alone and combined with sulphonamides.

In routine sensitivity testing by the disc diffusion methods, one member for each group of related antibiotics is chosen to represent the group. Each new antibacterial drug is evaluated with respect to its previous antibiotic class disc. In this study, trimethoprim combined with sulphadiazine in the ratio 1:4 was compared when combined with sulphamethoxazole in the ratio 1:20. Trimethoprim inhibited 86% of the bacterial strains tested at smaller than or equal to microgram/ml and the sulphonamides 50% of the strains at smaller than or equal to 64 microgram/ml. Regression line analysis showed that in sensitivity testing to trimethoprim alone discs with 5 micrograms can be used. Trimethoprim combined with sulphamethoxazole or sulphadiazine inhibited 84% respectively 91% of the strains at 0.5-8 microgram/ml. Trimethoprim combined with either sulphonamide produced superimposable regression lines. Therefore, sensitivity testing to trimethoprim/sulphadiazine can be performed by using discs with trimethoprim/sulphamethoxazole and the inhibition zone greater than or equal to 15 mm denotes susceptibility in the treatment of lower urinary tract infections.

Bacteria↗

Antibacterial activity of cefuroxime in human bone.

Bone samples were taken at orthopaedic surgery from 12 patients, who had been treated with 2 doses of 750 mg cefuroxime by intravenous infusion. After grinding, extraction and assay by the agar diffusion method the levels of cefuroxime ranged between 0.4--1.9 micrograms/g bone. Using an electrophoretic method followed by microbiological assay, higher levels of cefuroxime were measured, possibly because of a diminution in the binding capacity of the bone.

Bacterial Infections↗

Cefuroxime in soft tissue infections and septicaemia.

Data are presented on the absorption, antibacterial activity, clinical efficacy and side effects of cefuroxime in 33 cases with proven bacterial infection in soft tissues and in patients with septicaemia. The drug was administered mainly intramuscularly (i.m.) but also intravenously (i.v.). Peak serum concentrations 1 h after an injection of 750 mg cefuroxime i.m. were between 16-25 mug/ml. After 8 h the levels were mostly < 4 mug/ml in patients with normal renal function. I.v. injection gave only slightly higher maximum serum level obtained was approximately 40 mug/ml. No accumulation of the drug occurred in patients with normal renal function. Cefuroxime was active against all the gram-positive bacteria isolated from our patients as well as most of the gram-negatives. The clinical effect was satisfactory in 96%. The drug was well tolerated. Side effects were slight and relatively few.

Adolescent↗

Gentamicin resistance in gram-negative bacilli: occurrence of modifying enzymes and their influence on susceptibility testing.

Among 272 gram-negative bacilli, regarded as strains with reduced susceptibility to gentamicin by the disc test, 156 strains were resistant (greater than or equal to f microgram/ml) by the agar dilution method. Altogether 76% of the 156 strains were cross-resistant to tobramycin, kanamycin, streptomycin and amikacin. Amikacin showed the highest antibacterial activity in vitro. 32 of the resistant strains produced acetylating or adenylylating enzymes, which caused resistance. The production of enzymes was not limited to any genera. Complete cross-resistance to aminoglycoside antibiotics was recorded in 45%, 98% and 22% respectively, of Pseudomonas aeruginosa, Ps. maltophilia and other gram-negative rods. Enzyme-producing strains were not cross-resistant to all aminoglycosides. Changes in MICs and inhibition zones with different inocula among enzyme-producing strains emphasize the importance of standardized inocula in susceptibility testing.

Aminoglycosides↗

Influence of medium composition on bacterial susceptibility testing to gentamicin and netilmicin.

The composition of the growth medium, especially the presence of divalent cations Mg2+ and Ca2+, affects the susceptibility of bacteria to aminoglycoside antibiotics. Regression lines were calculated for gentamicin and netilmicin with 146 fresh clinical isolates and by the use of the standardized disc diffusion and agar dilution methods on PDM-agar or Mueller-Hinton agar. At the break-point less than or equal to 4 micrograms/ml, denoting susceptibility different zones of inhibition were obtained on the different agar media. When performing regression line analysis from tests with 56 isolates by the disc diffusion method on Mueller-Hinton agar versus MIC's in Mueller-Hinton broth, the resulting lines were different from those when performing the MIC's in agar. Furthermore, the bacteria were twofold or more susceptible in unsupplemented Mueller-Hinton broth than on Mueller-Hinton agar.

Bacteria↗