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T Bergan

Publications and source records attributed to T Bergan.

At least 19 recordsLinked to original sources

Multilocus enzyme electrophoresis of major O-antigen reference strains of Pseudomonas aeruginosa.

Multilocus enzyme electrophoresis was used to characterize 27 Pseudomonas aeruginosa serogroup reference strains used in the major O-antigen schemes according to which Pseudomonas aeruginosa has been typed. Sixteen enzyme loci were assayed, ten of which showed electrophoretic variation. Genetic diversity was expressed for each enzyme locus, and as the mean allelic diversity of loci. Ten electrophoretic types were identified among the strains. The genetic distance between pairs of electrophoretic types was expressed as the proportion of loci at which similar alleles occurred. More than 80% similarity was observed between any pair of electrophoretic types, reflecting the homogeneity of multilocus genotypes within this species. Similarity between electrophoretic types was represented in the form of a dendrogram and by multi-dimensional scaling. Three distinct clusters of electrophoretic types were revealed; within each the serogroups appeared to be randomly distributed.

Electrophoresis

Ciprofloxacin versus a tobramycin/cefuroxime combination in the treatment of serious systemic infections: a prospective, randomized and controlled study of efficacy and safety.

Sequential intravenous and oral ciprofloxacin (CF) was compared with a combination of tobramycin and cefuroxime (T/C) in the treatment of serious systemic infections. Altogether 310 patients were randomized, 160 receiving CF and 150 T/C, the 2 groups being reasonably well balanced. 29 patients without infection were excluded from the analysis. Complete clinical resolution was obtained in 75% (107/143) patients receiving CF and in 78% (107/138) receiving T/C; the difference was not statistically significant. The rate of bacterial eradication in septicaemia was 72% (95% confidence interval (95% c.i.): 58-86%) for patients treated with CF and 87% (95% c.i.: 77-96%) when T/C was given, while the eradication rates in urinary tract infection were 72% (95% c.i.: 54-90%) and 45% (95% c.i.: 23-67%) for CF and T/C, respectively. Significant differences in bacteriological response for other diagnoses were not detected. Also for lower respiratory tract infections (LTRI) the clinical and bacteriological responses were quite similar, although relatively more failures occurred in CF treated patients with LRTI caused by pneumococci. The frequencies of adverse reactions were comparable, but the reactions were less serious following CF treatment. Our results indicate that CF may be used for empirical treatment of serious infections. However, if pneumococcal etiology is likely, alternative antibiotics should be used, and if necessary, coverage against anaerobic bacteria should be added.

Adult

Azithromycin pharmacokinetics and penetration to lymph.

The study of pharmacokinetics of azithromycin and penetration to peripheral human lymph was carried out in 14 healthy male volunteers taking 1 g orally after overnight fasting. Samples were analyzed by microbiological assay. The mean peak concentrations were 0.82 +/- 0.23 mg/l after 1.7 +/- 0.5 h in serum and 0.22 +/- 0.07 mg/l after 3.1 h in lymph. Nine of the 14 subjects showed a second and lower serum peak indicating the existence of enterohepatic circulation. The total areas under the serum concentrations curves (AUCs) till infinity were 7.9 +/- 3.1 mg. h/l compared to 4.4 +/- 1.2 mg.h/l in lymph. The mean lymph AUC was 68.1 +/- 20.7% of the serum AUC indicating a penetration ratio of 0.68. However, the actual amounts penetrating the tissues were much higher than this ratio suggests. Thus, after 6 h 81% of the drug was within the tissue compartment and after 120 h, 63% of the azithromycin was still present in the tissue compartment. The urinary recovery of azithromycin was 14.7 +/- 7.7% during the first 48 h. The serum curves and lymph curves displayed a distinctly slower phase of elimination after 12 h. The mean serum half-life was 5.4 +/- 3.4 h during the first 12 h (after the peak), whereas the value was 44.2 +/- 10.1 h during the interval 12-120 h. The corresponding half-life values for the peripheral lymph were 5.4 +/- 2.2 h and 50.8 +/- 11.6 h. Azithromycin possesses key pharmacokinetic properties that are prerequisites for a convenient once-daily dosage schedule which may improve patient compliance.

Adult

Effect of meropenem on the intestinal microflora.

Ten healthy volunteers were given 500 mg of meropenem by intravenous infusion over 30 min three times daily for seven days. Stool specimens were collected before, during and after meropenem administration. The numbers of enterobacteria and streptococci decreased during the administration period, while the numbers of enterococci increased. There was a decrease in the numbers of clostridia, bacteroides and gram-negative cocci, while the numbers of gram-positive cocci and rods were not changed by the administration of meropenem. The intestinal flora returned to normal in all volunteers within two weeks after the termination of meropenem administration.

Adult

Efficacy of cefcanel on staphylocci.

The minimum inhibitory concentration (MIC) of cefcanel, a new oral cephalosporin, has been tested against 153 staphylococci subdivided into the species Staphylococcus aureus. S. epidermidis sensu lato and S. saprophyticus, with and without beta-lactamase production. The concentration inhibiting 50% of the strains was 0.5 mg/l for all three species while the corresponding values for 90% of the strains were 1, 2 and 1 mg/l, respectively. These values apply to all the strains. The MICs of the non-beta-lactamase-producing strains were identical to the MICs of the beta-lactamase-producing strains for S. aureus, three twofold steps lower for S. epidermidis and one step higher for S. saprophyticus. Consequently, beta-lactamase production had no consistent consequences for the activity of cefcanel against S. aureus and S. saprophyticus. In contrast, the beta-lactamase production of S. epidermidis did influence the activity of cefcanel. Among the tested cephalosporins, cefcanel had the highest antistaphylococcal activity, and no strain was resistant to this new cephalosporin.

Cefazolin

Penetration of ciprofloxacin and metabolites into human lung, bronchial and pleural tissue after 250 and 500 mg oral ciprofloxacin.

Ciprofloxacin (CIP) and metabolite concentrations in lung tissue, parietal pleura and bronchial tissue were assessed in 43 adult patients who underwent lung surgery. A single oral dose of CIP was given for prophylaxis of bacterial infections. Two to 6 h prior to tissues sampling, 23 patients received 250 mg and 20 subjects 500 mg of the substance. Blood plasma samples were obtained at the same time as the lung tissue samples. CIP and its metabolites were assayed chemically by high-pressure liquid chromatography (HPLC). After 250 mg CIP, the individual lung tissue CIP concentrations during the 2- to 6-hour post-dose period ranged from 0.5 to 4.8 mg/kg. In 20 of the 23 lung samples, the CIP concentrations were above 1 mg/kg. After 500 mg CIP, the corresponding lung CIP concentrations ranged from 1.6 to 6.0 mg/kg. The CIP lung concentrations were, irrespective of the dose size, between 2 and 7 times higher than the simultaneous blood plasma concentrations. This indicates an excellent penetration of CIP and its metabolites into lung tissue. Bronchial tissue was obtained in 9 cases. Penetration into bronchial mucosa tissue was good as well, as indicated by tissue/plasma ratio values between 1.5 and 4.4. Individual CIP concentrations in the patients given 250 mg CIP, ranged from 1.0 to 1.6 mg/kg. In the patients who received 500 mg, the range was from 1.7 to 3.4 mg/kg. Tissue/plasma ratio values between 0.8 and 2.1 indicated that penetration to pleural tissues was good as well. Metabolite concentrations in all of the tissues assayed (lung, bronchial mucosa, pleural tissue) were low when compared to the concentrations of CIP. The concentrations in lung, pleural and bronchial tissue will probably permit low doses in the treatment of most respiratory tract infections. The broad spectrum of antibacterial activity, the good tissue penetration, chemical stability and the good safety record of the substance means that the drug is potentially a useful agent for perioperative antibiotic prophylaxis.

Administration, Oral

Comparative antibacterial activity of the penem ALP 201.

The minimum inhibitory concentration (MIC) of the new penem ALP 201 was tested against 243 recent clinical isolates of which 95 were from the family Enterobacteriaceae, 50 were from the genus Streptococcus, 50 were Staphylococcus aureus and 48 were Staphylococcus epidermidis. An agar dilution technique was used to determine the MIC50 and MIC90 of ALP 201 in comparison with cefotaxime, cefuroxime, clindamycin, imipenem, piperacillin, tobramycin and vancomycin. Overnight cultures were suspended to produce inocula of 10(5) colonies from a replicator. ALP 201 was shown to have an activity similar to imipenem against most species; ALP 201 was less active than imipenem against Serratia spp. and was more active against S. epidermidis. beta-Lactamase production did not affect the activity of ALP 201. All the other compounds tested were less active than ALP 201 and imipenem.

Carbapenems

Pharmacokinetic comparison between fosfomycin and other phosphonic acid derivatives.

The pharmacokinetic comparison of phosphonic acid derivatives is based upon a survey of available literature on the whole group of compounds and on our own studies on fosfomycin. All three clinically used compounds, fosfomycin, fosmidomycin, and alafosfalin, are available for both oral and parenteral administration. The highest bioavailability is observed for the trometamol derivative of fosfomycin (37-44%); the calcium salt of fosfomycin is 2-2.5 times less absorbed and fosmidomycin has a bioavailability of 20-30%. The peak serum concentration of fosfomycin when given as the trometamol salt is about 2 times higher than the one reached with fosfomycin calcium or fosmidomycin. Urine recovery of unchanged drug is comparable after intravenous doses of fosfomycin and fosmidomycin, 80-95%, whereas the figure is only 10-20% for alafosfalin because it is extensively metabolized. After oral administration, urine recovery is highest for fosfomycin trometamol, 35-60%, compared to approximately 25% (range 18-29%) for fosfomycin calcium, 26% for fosmidomycin, and 6-17% for alafosfalin. The serum half-life of fosfomycin is 2-4 h (higher, up to 5.5 h, for some formulations of the calcium salt), 1.5-2.0 h for fosmidomycin, and about 1 h for alafosfalin. Thus, among available phosphonic acid derivatives and formulations, the trometamol derivative of fosfomycin has the most favourable characteristics. This applies to both bioavailability and urinary recovery, while at the same time the medium long half-life renders moderate fluctuation of concentrations whereby longer dosage intervals are possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

[Metronidazole].

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Humans

Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part I: Comparison of the antibacterial effect of sulphonamides alone and in combination with trimethoprim.

Plasma half life and in vitro activity were major criteria for selection of sulphonamides which are likely to give a strong synergistic action with trimethoprim in vivo. On the basis of literature data six sulphonamides, sulphadiazine, sulphachloropyridazine, sulphamethoxazole, sulphaisodimidine, sulphamerazine and sulphamethomidine appeared particularly suitable for combination with trimethoprim. An investigation of the activity in vitro of these compounds and their combinations with the latter against clinically isolated, sulphonamide-sensitive Klebsiella-Enterobacter and Escherichia coli strains showed optimal synergy at trimethoprim-sulphonamide ratios between 1:10 and 1:40, but that appreciable mutual potentiation occurred within a rather broad range of concentration ratios. Limited experiments indicated that synergy occurs less frequently and is less pronounced against sulphonamide resistant bacteria. The different sulphonamides behaved rather similarly in their combinations with trimethoprim, and in order to find the best sulphonamide, detailed comparisons of the pharmacokinetic properties of the different combinations are necessary.

Bacteria

Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part 2: Comparative pharmacokinetics of five sulphonamides.

The pharmacokinetics and renal excretion of the sulphonamides sulphachloropyridazine, sulphadiazine, sulphaisodimidine, sulphamerazine, and sulphamethoxazole were investigated in a cross-over study with doses of 800 mg each. The serum half-life, urine levels, distribution volume, protein binding and potential antibacterial activity in the urine renders sulphadiazine the preferred component in a combination tablet together with trimethoprim for the treatment of urinary tract infections.

Adult

Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part 3: Pharmacokinetic characterization of sulphadiazine and sulphamethoxazole given with trimethoprim.

Plasma levels and renal excretion of sulphonamide and trimethoprim following oral administration of co-trimazine (140 mg sulphadiazine + 90 mg trimethoprim) and co-trimoxazole (800 mg sulphamethoxazole + 180 mg trimethoprim) were monitored in healthy volunteers after a single dose and in the steady state after 12-hourly dosage. The plasma levels of free, non-protein bound components after co-trimazine were approximately half those after co-trimoxazole and thus correlated with the doses given. Urine recovery of trimethoprim was better after co-trimazine (70%) than after co-trimoxazole (58%). Sixty-six percent of the sulphadiazine was recovered as unchanged, active sulphonamide in the urine compared with only 13% of the sulphamethoxazole. Consequently, the sulphonamide levels of sulphadiazine were 2.5 times those of sulphamethoxazole. With respect to plasma half-life after the first dose, sulphadiazine with 8.0 hours was closer to trimethoprim with a half-life of 8.8 hours after cotrimazine and 9.6 hours after co-trimoxazole than to the half-life of sulphamethoxazole which was 7.7 hours. The distribution volume of sulphadiazine was closer to that of trimethoprim than was that of sulphamethoxazole. On the basis of these characteristics, it has been concluded that sulphadiazine is more suitable for a fixed combination tablet with trimethoprim than sulphamethoxazole, particularly for the treatment of urinary tract infections. Some renal tubular reabsorption occurs with both unchanged sulphonamides but is more pronounced with sulphamethoxazole. The solubilities of the sulphonamides and their acetylated metabolites at acid urinary pH indicate that therapy with co-trimazine is at least as safe as with co-trimoxazole. With the former drug, the result of scrutiny for crystals after dosage until the steady state was negative, whereas crystals of acetylated sulphamethoxazole were detected and verified chemically in two of eight subjects.

Drug Combinations

Pharmacokinetics of sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function.

The pharmacokinetics of tablets containing combinations of sulphadiazine (SDZ) and trimethoprim (TMP) (cotrimazine) and tablets with sulphamethoxazole (SMZ) and TMP (co-trimoxazole) were compared in patients with different renal functions. In normal renal function, SMZ is more similar to TMP than in renal impairment. In renal impairment although the serum half-life (t1/2) of both active and total SDZ remains similar to that of TMP, the t1/2 of total SMZ becomes several times higher than the t1/2 of TMP. The unchanged SMZ maintains approximately the same elimination velocity in reduced as in normal renal function. Consequently, for co-trimoxazole there is a buildup of SMZ metabolites which can only contribute to toxicity for co-trimoxazole, whereas the co-trimazine components have t1/2 values of the same order, also in renal dysfunction. The distribution volumes of SDZ, SMZ or TMP are the same regardless of renal function. However, the distribution volume of SDZ is closer to that of TMP, i.e. higher than the SMZ values. More active SDZ is excreted in the urine than SMZ both in normal and in reduced renal function. Thus co-trimazine, in addition to having some advantages in the normal individual, is in many respects distinctly more suitable in patients with renal functional impairment. On the basis of the patients with renal functional impairment. On the basis of the pharmacokinetic properties, dosage schedules are suggested that will give approximately the same plasma levels regardless of renal function.

Drug Combinations

Double-blind comparison of sulphonamide-trimethoprim combinations in acute uncomplicated urinary tract infections.

The effects of a twice daily dosage of a combination of 410 mg sulphadiazine + 90 mg trimethoprim (SD + TMP) and 800 mg sulphamethoxazole + 160 mg trimethoprim (SMZ + TMP) were compared in uncomplicated urinary tract infections. All but one patient in each treatment group, i.e. 36 SD + TMP treated and 42 SMZ + TMP treated patients respectively, were cured. The percentage of side-effects related to therapy in the patients receiving the combination with sulphadiazine was 15.1% and in those with sulphamethoxazole 23.7%. Due to the small number tested, however, differences were not statistically different. It is noteworthy that only one of the SD + TMP patients had to stop therapy because of a rash, whereas therapy was stopped for this reason in three of the SMZ + TMP patients. SD + TMP represents a good alternative to SMZ + TMP in the treatment of urinary tract infections.

Adolescent

Comparison of sulfamethoxazole alone and combined with trimethoprim in urinary tract infections.

In a double blind, randomized study, sulfamethoxazole was compared alone and in combination with trimethoprim as commonly used in therapeutic regimes for the treatment of uncomplicated acute urinary tract infections in out-patients. The cure of sulfamethoxazole alone was 92.2%, and for sulfamethoxazole plus trimethoprim 97.6%. The rate of side-effects for the former was 5%, for the latter 21.8%. If the failure rate plus the rate of occurrence of rash, which necessitated discontinuing the drug, are combined, it appears that 8.8% of the patients were at a disadvantage receiving sulfamethoxazole compared to 9.7% for the combination of sulfamethoxazole plus trimethoprim. When considering the cure rate and rate of side-effects together, therefore, the position of sulfamethoxazole alone as a suitable drug in this type of infection is defended.

Adult