Cefotaxime in serious infections--a clinical and pharmacokinetic study.
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Adolescent↗
Biomedical subjects
T Bergan
Publications and source records attributed to T Bergan.
Dose-related pharmacokinetics after oral administration of a new formulation of erythromycin base.
1 Erythromycin concentrations in serum and urine were determined in 24 healthy male, fasting subjects after oral administration of 250, 500, or 1000 mg of erythromycin base (250 mg capsules containing enteric-coated pellets). The subjects also received a film-coated erythromycin stearate tablet (equivalent to 500 mg base). 2 The mean +/- s.d. maximal serum erythromycin concentrations were 1.9 +/- 0.8, 3.8 +/- 1.4, 6.5 +/- 2.9 and 2.9 +/- 1.7 mg/l for 250, 500, or 1000 mg base and 500 mg stearate, respectively. The serum peaks usually occurred after 2 h irrespective of dosage form given. 3 The mean +/- s.d. areas under the serum concentration v time curves (AUC0-infinity) were 4.5 +/- 1.7, 11.2 +/- 4.3, 27.2 +/- 10.6 and 7.5 +/- 3.4 mg l -1 . h after 250, 500, or 1000 mg base, and 500 mg stearate, respectively. 4 The urinary recoveries were 5.0, 6.7, 8.6% of the base doses given and 4.4% of the stearate dose given. 5 Dose-dependent excretion of erythromycin occurred. The increase in AUC was larger than multiples of the lowest base dose.
Administration, Oral↗
Interaction between diphenolic laxatives and intestinal bacteria in vitro.
The ability of the laxative diphenols desacetylbisacodyl, oxyphenisatin, and phenolphthalein to inhibit growth and cause leakage of potassium ion from microbial cells in vitro was studied with 25 aerobic and 25 anaerobic bacterial strains. None of the aerobes, but some of the anaerobes showed growth inhibition. Potassium release assayed by flame photometry was observed in strains which showed growth inhibition, but also in other strains including anaerobes and aerobes. The highest antibacterial activity among the diphenols was observed with phenolphthalein and the least with desacetylbisacodyl; this relationship as noted for both growth inhibition and potassium release. Enzymatic hydrolysis of picosulphate to the free diphenol desacetylbisacodyl carried out by three strains of anaerobic bacteria was indicated by high pressure liquid chromatography.
Bacteria↗
Demonstration of extracellular proteolytic enzymes from Legionella species strains by using synthetic chromogenic peptide substrates.
Crude concentrates of extracellular proteases from strains belonging to species within the genus Legionella were examined for their effect upon synthetic chromogenic tri- and tetrapeptides. For the species L. pneumophila, similar and reproducible substrate degradation patterns were found. Strains from the other Legionella species produced proteases with dissimilar proteolytic patterns, which were all distinct from those of the L. pneumophila proteases.
Chromogenic Compounds↗
Pharmacokinetics of a new cephalosporin, cefotaxime (HR 756) in patients with different renal functions.
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Adolescent↗
Dose dependence of piperacillin pharmacokinetics.
Pharmacokinetics were evaluated for piperacillin given as doses of 15, 30 and 60 mg/kg body weight to 12 healthy volunteers subdivided into three groups which were each given different dosage levels. For the 15, 30 and 60 mg/kg doses, the serum half-lives were 0.8, 1.0 and 0.9 h, and the disposition phase distribution volume coefficients, delta d. beta, 0.31, 0.30, ad 0.25 l/kg. The total body clearances for the three doses normalized to 70 kg body weight were 18.53, 14.00 and 13.53 l/h for the 15, 30 and 60 mg/kg doses, respectively. The corresponding values for the total area under the curves per 1.0 g dose were 57.1, 75.0 and 79.6 micrograms/ml. The urinary elimination of the antibiotic corresponding to the antimicrobial activity of unchanged drug rose from 50.0 to 71.3% of the dose, for a dose increment of 15 to 60 mg/kg. These results document that piperacillin is subject to dose-dependent pharmacokinetics. Capacity-limited kinetics is a property shared by other ureidopenicillins.
Adult↗
Dose-dependent pharmacokinetics of azlocillin compared to mezlocillin.
The pharmacokinetics of azlocillin at intravenous doses of 1.0, 2.0 and 5.0 g and of 2.0 g mezlocillin were studied in a cross-over study on 10 healthy volunteers. The serum concentrations and total area under the serum curves for azlocillin increased more than expected from the multiples of the dose size. Likewise, the percentage of urinary excretion of an antibacterially active agent increased steadily with higher doses. The same applied to the serum half-life (t 1/2), whereas the total body clearance was reduced. All these characteristics are indicative of dose-dependent, i.e. capacity-limited pharmacokinetics. The t 1/2 was 0.89, 0.98, and 1.53 h for each dose. For 2.0 g mezlocillin, the serum values, urinary recovery, and t 1/2 were lower than the values after the same dose of azlocillin. The t 1/2 was 0.64 h. The total body clearance was 12,0, 9.2, and 6.4 liters/h for the three doses of azlocillin and 14.4 liters/h for 2. g mezlocillin. Dose dependence appears to be more pronounced with azlocillin than found previously with mezlocillin. Unchanged azlocillin and its biotransformation products are excreted more slowly than mezlocillin and its metabolites.
Adult↗
Pharmacokinetics of a new, microencapsulated erythromycin base after repeated oral doses.
Pharmacokinetics of a new preparation of microencapsulated erythromycin base was studied in 16 healthy subjects. They received 250 mg base 6-hourly or 500 mg 12-hourly for 7 days. The mean maximal serum peaks (+/- SD) after morning doses on days 1, 2, 3, and 7 were 1.4 +/- 0.9, 3.2 +/- 1.1, 3.6 +/- 0.6, 3.5 +/- 1.2 mg/l after the 250-mg dose and 3.2 +/- 1.5, 3.7 +/- 2.1, 3.6 +/- 1.8, and 3.0 +/- 2.0 mg/l after the 500-mg dose. The mean 24-hour urine recoveries were 1.8 and 1.2%, the serum half-lives were (days 1-7) 1.4-2.1 h and 1.9-2.8 h for the 250-mg and 500-mg doses. The mean areas under the serum concentration curves (+/- SD) were 5.8 +/- 2.2, 11.9 +/- 2.2, and 15.3 +/- 5.1 mg . h . 1(-1) after 250 mg and 14.2 +/- 4.9, 16.4 +/- 7.6, and 14.3 +/- 9.0 mg . h . 1(-1) after 500 mg on days 1, 2, and 7. The inter- and intrasubject variability was larger after the 500-mg dose. The pharmacokinetic results indicate that both dosage alternatives are suitable and result in similar steady-state peak levels, but the initial dose should be 500 mg.
Administration, Oral↗
Pharmacokinetics of phenoxymethylpenicillin in volunteers.
Pharmacokinetics of phenoxymethylpenicillin was studied in 12 healthy volunteers. They received four different single oral dose sizes. At all dose levels (0.4, 1, 2 and 3 g) phenoxymethylpenicillin was rapidly absorbed, usually with serum peaks within 0.75 h. The mean maximal serum peaks (+/- SD) were 6.1 +/- 2.0, 15.0 +/- 4.3, 26.3 +/- 10.0 and 35.5 +/- 10.8 mg/l after 0.4, 1, 2 and 3 g, respectively. The relationship between the mean peak serum concentrations and the doses was nonlinear (p less than 0.001). The mean areas under the serum concentrations vs. time curve (AUC) increased almost linearly with increasing doses, and the deviation from linearity was not significant (p less than 0.05). Very low penicillin concentrations were obtained in saliva. The urinary excretion during 10 h was 37--43% of the doses given. The pharmacokinetic results indicated that phenoxymethyl penicillin in the present formulation is rapidly and well absorbed up to as high doses as 3 g. The tablet formulations used were better absorbed than previous ones. The percent of absorption was relatively lower with the highest doses, but this probably has only minor therapeutic consequences.
Absorption↗
Chloramphenicol and thiamphenicol.
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Animals↗
Antibiotic levels in plasma and peritoneal fluid after amoxycillin, ampicillin, and bacampicillin treatment for pelvic inflammatory disease.
Fifteen patients with pelvic inflammatory disease had a thin polyethylene catheter inserted through the abdominal wall into the pouch of Douglas for sampling of peritoneal fluid. At hourly intervals peritoneal fluid and capillary blood were collected. Five patients each received a single oral dose of either 0.5 g of ampicillin or amoxycillin, or 0.8 g of bacampicillin (approximately equimolar doses). This highest median peak plasma level was observed after bacampicillin. Bacampicillin also showed less variation in individual plasma concentration. The area below the plasma curve was similar for amoxycillin and bacampicillin, whereas that of ampicillin was significantly smaller (p less than 0.01). The rate of penetration into peritoneal fluid was slower for amoxycillin than for bacampicillin, even though the area below the peritoneal fluid curve was similar for the two drugs. Therapeutic levels were maintained for 5--8 hours, longer after amoxycillin than after bacampicillin.
Administration, Oral↗
Polymyxin antibiotics: chemical and pharmacokinetic properties.
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Animals↗
Pelvic inflammatory disease: etiologic studies with emphasis on chlamydial infection.
Chlamydia trachomatis is one of the main etiologic agents in pelvic inflammatory disease (PID) in Oslo. Up to two thirds of the 65 PID cases studied were associated with a chlamydial infection. The incidence of cervical gonorrhea was low (7.7%). Anaerobic bacteria were not isolated from the fallopian tubes or peritoneal fluid of any of the patients. Chlamydia-associated PID is characterized by a protracted course and vague symptoms. The laparoscopic findings indicate more severe inflammatory changes of the tubes than in patients in whom these agents were not found. The highest incidence of chlamydia-associated PID occurred in younger subjects, among whom the intrauterine contraceptive device was more frequently used. Perihepatitis was diagnosed in PID patients with and without chlamydial infection of the genital tract.
Adolescent↗
Biology of Chlamydia.
The genus Chlamydia consists of two species, Chlamydia trachomatis and C. psittaci. The former includes (a) the trachoma/inclusion conjunctivitis (TRIC) agents, subdivided into the serotypes A-K; (b) the lymphogranuloma venereum (LGV) agents, subdivided into the serogroups (L 1-3); and (c) the mouse penumonitis agent. The major characteristics differentiating the two species are sulfonamide susceptibility and the formation of distinct inclusion granula in host cells, in the case of C. trachomatis, whereas C. psittaci is resistant to sulfonamides and forms less dense inclusions. Chlamydiae are characterized by a special growth cycle. The infective form of Chlamydia is the elementary body (EB), which stimulates its own phagocytosis by the host cell, an event followed by the EB's transformation into the reticulate body (RB). The RB forms small buds which subdivide by simple fission to produce several RB within the host cell cytoplasm. The growth cycle is completed by transformation of the RB into the infective EB from before liberation of the latter from the host cell. The chlamydiae are deficient in independent energy metabolism. Thus, their supply of ATP and essential building blocks must be obtained from the host cell cytoplasm. The TRIC agents have neuraminidase localized to the surface structures. Receptors of the microbe are temperature-sensitive, whereas the host cell is trypsin-sensitive.
Anti-Bacterial Agents↗
Inhibitory activity and bactericidal kinetics of mecillinam/ampicillin combinations against Enterobacteriaceae, Pseudomonas and Acinetobacter.
Mecillinam, ampicillin and combinations of the two were tested against Enterobacteriaceae by traditional agar dilution and under in vitro conditions simulating in vivo pharmacokinetics. Synergy was demonstrated by agar dilution in 30% of the strains. At simulated in vivo conditions, synergy between ampicillin and mecillinam was detected in a high osmolality medium, but not when the osmolality of the medium was low. The bactericidal effect was detected with mecillinam after one hour, while that of ampicillin or the combination was detected after 15 min. Changed bacterial morphology was observed by electron microscopy. Mecillinam produced ovoid spherical cell structures whereas combinations of the two drugs produced larger bacterial spheres.
Acinetobacter↗
Contamination of chlorhexidine cream used to prevent ascending urinary tract infections.
Chlorhexidine-containing cream is often used as an antimicrobial barrier to ascending urinary tract infection in patients with indwelling urethral catheters. The cream is dispensed in small tubes for personal use but repeated use of a tube still entails a potential infection hazard. The extent of cream contamination was analysed by emulsifying it in 1% peptone broth with 1% Tween-80 added as a wetting agent, and culturing quantitatively for bacteria and fungi by membrane filtration. Twenty-three per cent of cream samples and 35% of swabs taken from outside the tube beneath the screw cap demonstrated microbial contamination. Isolates included potential pathogens such as enterococci, staphylococci, Proteus mirabilis, Pseudomonas aeruginosa, opportunists like Moraxella spp. and diphtheroids, and contaminants such as Bacillus spp., micrococci, and a mould of the genus Cladosporium. Contamination of cream with a particular bacterial strain was found to precede urinary tract infection with the same microbe. We recommend that chlorhexidine cream for this use be dispensed in single dose units to ensure sterility.
Bacteria↗
Legionnaires' disease combined with erythema multiforme in a 3-year-old boy.
A case of Legionnaires' disease (LD) is described in a 3-year-old boy. He had fulminant disease with typical signs like bilateral pneumonia, gastrointestinal symptoms, and somnolence indicating involvement of the central nervous system. There was no premorbidity. An outstanding development was erythema multiforme, which has never previously been described in LD. The basic disease was caused by Legionella pneumophila. This is evidenced by specific serum IgM at admission and a subsequent significant rise in titers against L. pneumophila. At an early stage respiratory syncytial virus (RSV) was isolated from the patient's throat, although there was no antiviral serological response at the outset of erythema multiforme or 3 weeks after onset of disease; anti-RSV appeared later. The prolonged course of the disease can be explained by the successive occurrence of two infections. The possibility that the virus could have contributed to the development of erythema multiforme cannot be ruled out. The role of concomitant medication cannot be separated out, but on the basis of general knowledge of their immunogenicity and the fact that immunosuppressive cortisone was given at the time it is less likely that the antibiotics contributed significantly.
Child, Preschool↗
Pharmacokinetics of netilmicin in children with and without cystic fibrosis.
The pharmacokinetics of intravenous netilmicin was studied in cystic fibrosis (CF) and non-CF patients who were closely matched according to age. The serum concentrations showed a moderately higher variance within the CF group. The serum half-life in CF patients was 1.37 h compared with 2.29 h in the non-CF subjects (P less than 0.05). The apparent distribution coefficients were 0.306 and 0.356 liters/kg in the CF and non-CF groups, respectively. The mean body clearance was 6.6 liters/h per 1.73 m2 in the CF group compared with 5.3 liters/h per m2 in the non-CF controls, but the difference was not significant. The mean renal clearance in CF patients was 4.7 liters/h per 1.73 m2. From a pharmacokinetic point of view, the dosage of netilmicin required may be the same in CF as in non-CF patients.
Child↗