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Biomedical subjects

T Bergan

Publications and source records attributed to T Bergan.

At least 181 records · Page 10Linked to original sources

Azlocillin in respiratory tract infections with Pseudomonas aeruginosa in children with cystic fibrosis.

In 5 children with cystic fibrosis, 13 courses of lower respiratory infections due to Pseudomonas aeruginosa were treated with azlocillin, 100--200 mg/kg body weight intravenously every 8 h for 10--15 days. The clinical course during azlocillin treatment was more favourable than had been the case previously in the same patients when treated with combinations of carbenicillin and aminoglycosides. No side effects ascribable to azlocillin were observed, although one allergic reaction occurred, but this was probably elicited by another allergen. Upon repeated courses of treatment, the minimum inhibitory concentration of the infecting organisms increased steadily against both azlocillin and carbenicillin. It is concluded that azlocillin represents an important alternative in the treatment of lower respiratory tract infections due to P. aeruginosa in patients with cystic fibrosis.

Adolescent↗

Piperacillin in the treatment of urinary tract infections.

The ureidopenicillin piperacillin was given to 20 patients with urinary tract infections. The infecting microbes all had a minimum inhibitory concentration below 0.6 microgram/ml. One strain of Staphylococcus aureus produced beta-lactamase. All patients were freed of their microbes at the end of 7 days therapy. 1--2 weeks after the end of therapy, 1 relapsed and 3 had superinfections. Among the 16 who were without bacteria or leucocyturia after 1--2 weeks, 2 exhibited a superinfection 4--6 weeks after the end of therapy.

Adult↗

Pharmacokinetics of a new cephalosporin, CGP 9000 (cefroxadine), in healthy volunteers.

Oral doses of 125, 250, and 500 mg of a new cephalosporin, CGP 9000 (7 beta-[D-2-amino-2-(1,4-cyclohexadienyl)-acetamido]-3-methoxy-ceph-3-em-4-carboxylic acid), given to healthy volunteers, were evaluated pharmacokinetically. The mean peak concentrations with the respective doses were 4.5 +/- 1.4, 7.7 +/- 2.7, and 12.3 +/- 4.2 microgram/ml. The maximum serum concentration occurred after 0.5-1.5 h. The amounts recovered unchanged in urine during 12 h were 96.4 +/- 5.1, 92.4 +/- 11.7 and 96.7 +/- 7.6% of the respective doses. There was straight linear kinetics with a doubling of area under the serum curve for each dose, rising from 6.1 with the lowest, through 12.1 with the middle dose to 23.6 microgram.h/ml with the highest dose. There was an apparent lag of 0.3-0.4 h before absorption. Absorption was relatively rapid, with mean absorption rate constants of 4.68-6.26 h-1. Serum half-life varied between 0.9 and 1.0 h with the different doses. The mean renal clearance values with the three doses ranged between 322 and 344 ml/min.

Administration, Oral↗

Pharmacokinetics of metronidazole in healthy adult volunteers after tablets and suppositories.

A cross-over study on metronidazole was carried out with 10 healthy adult volunteers who received tablets (250, 500 and 1,000 mg) and suppositories (500, 1,000 and 2,000 mg). The bioavailability of the suppositories was approximately 90% of the corresponding tablet dose as judged by area under the serum curves and amounts excreted in urine. The absorption was faster after the tablets. The mean curve peaks of unchanged metronidazole after the tablets occurred within 1 h and were 3.7 microgram/ml after 250 mg, 9.8 microgram/ml after 500 mg, and 11.8 microgram/ml after 1,000 mg. The suppositories rendered peaks of 5.5, 9,5 and 14.0 microgram/ml 4 h after doses of 500, 1,000 and 2,000 mg, respectively. In the dosage range 250-1,000 mg, the relationship between the dose and the total area under serum curves was similar for tablets and suppositories. Parts of the drug in serum and urine were antibacterially active metabolites. The mean recovery in urine within 36 h was 7-14% of the dose. The serum half-life of unchanged metronidazole (chemical assay) was 8.8-10.5 h. The terminal phase half-life of the total biologically active compound (microbiological assay) was 7.8-15.1 h.

Adolescent↗

Comparison of metronidazole assay by microbiological and chemical methods.

Chemical (thin layer chromatography/fluorescence quenching in situ) and microbiological (agar well, diffusion technique with Clostridium perfringens as indicator strain) methods of assaying metronidazole have been compared. On dummy samples made with pure metronidazole in pooled human serum, both methods had a coefficient of variation ranging from 5.5 to 9.6 per cent of the mean. The microbiological method slightly underestimated the real amounts, and also had lower values than the chemical procedure. Comparison of serum and urine samples taken during the early, middle and late periods after medication to volunteers showed that biotransformation to antibacterially active metabolites contributes significantly to the antibacterial activity, particularly in urine. Biotransformation explains why microbiologically determined concentrations were higher than those determined chemically in samples taken at least 16-20 hours after intake of tablets or suppositories. It is important to be aware of the circumstance that the results of microbiological assay are sensu strictu limited to the particular indicator strain used, since other bacteria may exhibit other patterns of sensitivity to metronidazole and its metabolites.

Biological Assay↗

Pharmacokinetics of azidocillin in healthy adults.

Two cross-over studies with azidocillin-sodium were carried out on healthy volunteers. In the first, we gave single doses of 375 mg, 750 mg, 1500 mg as tablets, 750 mg as a suspensions, i.m. and i.v. injections of 799 mg, and a course of 750 mg tablets twice daily for 14 days. In the second study, two 750 mg tablet batches were compared with the same dose i.v. Mean peak concentrations after 750 mg as tablets were 6.5-8 microgram/ml, as suspension 12.4 microgram/ml, and i.m. 18.5 microgram/ml. The urinary recovery of active antibiotic was 37-40% of the dose after the tablets, and nearly 50% after i.v. dosage. Thus, urinary elimination after the tablets was 75-83% of the amount eliminated after i.v. dosage. Bioavailabilities stipulated on the basis of the area under serum concentration curves in comparison with i.v. dosage were 57-60% for the tablets and 64% for the suspension. The bioavailability of the i.m. dose was comparable to that of the i.v. injection. The relatively small difference between the tablets and the suspension indicates that the tablets had favourable biopharmaceutical properties. Serum half-life of azidocillin was 0.6-0.7 h after the i.v. doses. For the other dosage forms, the half-life values varied between 0.6 and 1.1 h. The distribution volume Vd,beta ws 27-34 l after i.v. administration.

Adult↗

Netilmicin in the treatment of neonates with moderate and severe infections.

Thirty neonates and infants have been treated for verified or suspected infections with a combination of netilmicin and ampicillin intravenously for 7 days. The infecting organisms were isolated in 18 patients, of whom 2 had osteomyelitis and 2 had pneumonia. In 3 cases of pneumonia and 9 cases of suspected septicaemia bacteriological cultures were negative. None of the children died, and in all but the 2 cases of osteomyelitis, therapy led to complete resolution of the signs of infection and recovery without sequelae. No adverse reactions to antibiotic therapy were recorded. Upon follow-up examinations at the age of 3 months there has been no sign of auditory impairment as assessed by Brain Stem Evoked Response. Netilmicin is thus tolerated well in neonates and infants, and when guided by serum concentrations considered to be a safe and reliable aminoglycoside.

Drug Evaluation↗

Prophylactic metronidazole in electrive colo-rectal surgery.

38 patients participated in a double blind study comparing the effect of a single dose of 2.0 g metronidazole given 15 hours prior to surgery with a placebo in reducing postoperative infections after elective colonic surgery. In 17 patients given metronidazole, only 2 had infections caused by aerobes, no anaerobe was recovered. Among 8 infected patients among a total of 21 in the placebo group, there were 5 anaerobic isolates (Bacteroides 3, peptococci 1, clostridia 1) and 8 aerobic bacteria. There was a significant difference between both total number of infections in the groups receiving metronidazole and placebo (p = 0.015). In addition, the clinical course of the 2 infections in the metronidazole group was moderate compared to that in the placebo group. Suppression of anaerobes appears to have enabled the body to better eliminate aerobes as well, since fewer aerobes were found in the metronidazole group. It is concluded that metronidazole given as short term prophylaxis produces suffiecent antibacterial levels in tissues and body fluids during and shortly after operation to significantly reduce the frequency of postoperative infections.

Aged↗

[Production and purification of thermolabile enterotoxin of Escherichia coli (author's transl)].

Heat labile enterotoxin (LT toxin) of Escherichia coli could be produced optimally and quantitatively in a trypticase soy broth with 0.2% yeast extract after 12 hours. Treatment of the cells with polymyxin B increased the yield of LT toxin. After concentration by ammonium sulphate precipitation, the LT toxin fraction was separated successfully from other proteins by Ultrogel AcA-34 gel exclusion chromatography. A 0.15 mol/l Tris-HCl buffer with gradually increasing pH was used as eluent. Purity was determined by gel electrophoresis. The presence of LT toxin in one isolated fraction ws demonstrated in vitro by assaying activity in the intestines of rats (by collection of liquid and quantification of cAMP in intestinal fluid). The reproducibility of the LT fraction was ascertained by a specific radioimmunoassay (RIA) and by an enzyme-linked immunosorbent assay (ELISA). The LT fraction had a molecular weight of 72,000 dalton. Two subunits of the toxin with molecular weights of 30,000 and 40,000 dalton respectively were found.

Bacterial Proteins↗

Pharmacokinetics of the new broad spectrum penicillin CP-33994-2.

1.0 g of the new broad spectrum penicillin CP-33994-2 ws given i.m. to volunteers with varying renal function levels. Peak values of 40-50 microgram/ml were commonly observed in serum. The serum half-life was 1.1-1.5 h in normal renal function and increased to 7.0-17.0 h in patients with inulin clearance values of 12-14 ml/min. There was an appreciable lag before apparent absorption. Absorption rates and protein binding were uninfluenced by renal function. The renal clearance of the penicillin was less than the glomerular filtration rate. This may be due to either chemical instability of the compound such that it is inactivated before assay, or a substantial portion is changed (instability, metabolism) before excretion. A minor adjustment in dosage schedule is necessary in reduced renal function. Even patients with an inulin clearance of 12-14 ml/min have urine concentrations which are of antibacterial interest, at least in acute urinary tract infections without anatomical or other particular problems.

Female↗

Radioimmunoassay of tobramycin compared to microbial methods.

A commercial radioimmunoassay (RIA) for tobramycin was compared with microbial methods by determining the concentrations of known standards prepared with pooled human serum. The correlation coefficients were r=0.94 for the RIA method and an agar diffusion procedure using commercial paper disk standard, and r=o.95 for a standard agar well diffusion procedure. The agar well method tended to overestimate the real concentrations.

Anti-Bacterial Agents↗

Short term chemotherapeutic prophylaxis in gastrointestinal operations.

In a prospective, randomized study on surgical prophylaxis in elective gastrointestinal operations, 145 adults were allocated to either one of three groups. Those in group 1 received one single preoperative dose of 200 milligrams of doxycycline and 2 grams of tinidazole. Those in group 2 were given three doses of 80 milligrams of gentamicin and 600 milligrams of clindamycin with eight hour intervals, beginning one hour preoperatively. Group 3 patients served as controls and obtained no antimicrobial agent. The prophylactic regimens significantly reduced the infectious complications, as evidenced by fewer infections, less total antibiotic dosage and shorter hospitalization. In the prophylactically treated groups, anaerobic infections were less frequent than in those in the control group.

Adult↗

[Metronidazole].

Explore the source record for details and available documents.

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↗