Biomedical subjects

T Bergan

Publications and source records attributed to T Bergan.

At least 55 records · Page 3Linked to original sources

PubMed1989

Pharmacokinetics of ciprofloxacin with reference to other fluorinated quinolones.

The third generation quinolones, ciprofloxacin, enoxacin, fleroxacin, norfloxacin, ofloxacin and pefloxacin are all quickly and quantitatively well (75-95% of an oral dose) absorbed upon oral administration. The maximum serum concentrations appear after 1-2 hours. The serum and urine concentrations after oral or intravenous ciprofloxacin are directly proportional with the doses and follow normal, dose-independent pharmacokinetics. Ciprofloxacin and norfloxacin reach the same serum levels after the same doses. Steady-state levels are indifferent from those after the first dose. In contrast, enoxacin, oflaxacin and pefloxacin do reach somewhat higher levels after chronic administration. Ciprofloxacin is eliminated by the kidneys (active tubular secretion which is blocked by probenecid) (60% after an intravenous administration), by metabolism and by the transintestinal route. Metabolism is minimal (ca. 15-20% for ciprofloxacin and norfloxacin). Transintestinal elimination implies that the drug is eliminated by transport across the intestinal wall without significant biliary elimination (which is less than 1%). Penetration into tissues occurs readily. Concentrations in prostate secretion are high for ciprofloxacin and norfloxacin. Ciprofloxacin reaches high intracellular concentrations; within human neutrophils the levels reach 6 times the concentrations in the surrounding fluid. Concentrations in bile and tissues are in general comparable to those in serum. Cerebrospinal fluid (CSF) concentrations are low when meningi are normal, but 40-90% of the serum levels when the meninges are inflamed. Because the transintestinal route of elimination compensates for loss of renal elimination, the serum half-life of ciprofloxacvin is raised only to 5-10 hours even in total renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Ciprofloxacin↗

PubMed1989

Impact of ticarcillin/clavulanate on the intestinal microflora.

Ten healthy volunteers were given 5.2 g Timentin (5 g ticarcillin plus 0.2 g clavulanate by intravenous bolus three times daily for seven days. Stool specimens were collected before and 2, 3, 5, 7, 14 and 21 days after the start of treatment to study the effect on the normal intestinal microflora. The concentrations of ticarcillin and clavulanate in serum, urine and faeces were determined by a microbiological method and the pharmacokinetics were studied on days 1, 3 and 7. There were no significant differences in the serum concentrations of ticarcillin and clavulanate during the three days. The total 8-h recovery in urine of ticarcillin was 62% of the dose and of clavulanate 19%. The mean serum half-life of ticarcillin was 1.0 h and of clavulanic acid 0.91 h. There were no measurable concentrations of ticarcillin or clavulanate in the faecal specimens. The number of enterobacteria slightly decreased, while there was a minor increase in the number of enterococci and streptococci during the administration of ticarcillin/clavulanate. The anaerobic microflora was also slightly affected. There was a minor decrease in the number of anaerobic cocci, bifidobacteria, eubacteria, lactobacilli and clostridia, but the number of bacteroides was not influenced by the treatment. After treatment the aerobic and anaerobic microflora returned to normal in all volunteers. The present microbiological findings indicate that ticarcillin/clavulanate has a minor ecological impact on the human intestinal microflora.

Adult↗

PubMed1989

Elimination of ciprofloxacin and three major metabolites and consequences of reduced renal function.

The pharmacokinetics and elimination of ciprofloxacin and its three major metabolites desethylene ciprofloxacin (M1), sulfonylciprofloxacin (M2), and oxociprofloxacin (M3) were determined in 18 volunteers with normal and varying degrees of reduced renal functions. One dose of 500 mg ciprofloxacin was given orally. Samples were assayed by high-pressure liquid chromatography. Serum concentrations of both ciprofloxacin and its metabolites were only slightly influenced by the renal function. The serum concentrations of the metabolites were less than 10% of the ciprofloxacin levels, even in reduced renal function, and were overlapping within groups of patients arranged according to renal function. Dialysis reduced the serum concentration of the parent compound and its metabolites. The serum half-life of ciprofloxacin in normal renal function was 5.8 +/- 1.2 h; this rose to 10.8 +/- 2.3 h in the group with clearances of 10-30 ml/min. Compared to the latter group, the t1/2 was lower (7.0 +/- 2.9 h) in the patients with terminal renal failure. The period of monitoring has a distinct consequence for the t1/2 of ciprofloxacin. The shorter t1/2 values emanate if monitoring had stopped after 10 or 12 h. A slower gamma-phase of elimination was observed and this was particularly distinct in subjects with renal functions within the normal range. The total renal elimination of the parent compound and its metabolites was approximately 60% over the 48-hour collection period in normal renal function and was reduced by about 20% in the group with clearances within the range of 10-30 ml/min. In renal impairment, there was a shift towards a higher proportion of the dose being eliminated as M2. M1 contributed only up to 2% of the dose in urine. Irrespective of the renal capacity, the amount of M3 recovered in urine was 3-4%.

Adult↗

PubMed1989

Tolerance of intravenous ciprofloxacin.

Available information about the safety of intravenous (i.v.) administration of ciprofloxacin is reviewed. No increased incidence of systemic toxicity is apparent over the oral route. CNS side effects occur, but at a low rate and they are mild. Caution is indicated in patients with tendency for seizures. Laboratory changes are minimal, mainly mild elevations of liver enzymes. No increased risk of crystalluria has been seen. Local side effects in the form of erythema and burning are relatively common in some volunteer studies and are also seen in clinical studies, infusion phlebitis also occurs. It is recommended that i.v. ciprofloxacin is administered in slow infusion through a large or preferably central vein.

Ciprofloxacin↗

PubMed1989

Susceptibility of clinical isolates to dactimicin and gentamicin.

Dactimicin is a new aminoglycoside and its in vitro activity has been compared with that of gentamicin against 100 recent clinical isolates. The minimum inhibitory concentrations were determined by agar dilution. Dactimicin was generally one two-fold dilution step less active or as equally active as gentamicin against enterobacteria and pseudomonas. Dactimicin was several times more active than gentamicin against Acinetobacter and staphylococci. Both compounds share poor activity against enterococci and have a variable effect on other streptococci. They are highly active against serogroup A streptococci and pneumococci.

Aminoglycosides↗

PubMed1988

Pharmacokinetics of ciprofloxacin.

The fluorination of piperazinyl substituted quinolones has led to an interesting development of a series of new broad spectrum antibacterial agents that may be administered orally as well as parenterally and are well tolerated. Norfloxacin was an early compound, later followed by ciprofloxacin, enoxacin, ofloxacin and pefloxacin. In this overview the emphasis will be on the most extensively studied compound including comparisons, where data are available, with norfloxacin and ofloxacin. Enoxacin and pefloxacin will be omitted due to their pattern of side effects, which at present curtail their therapeutic use. More recent substances such as fleroxacin and defloxacin have not been sufficiently investigated to be considered in this context.

Anti-Infective Agents↗

PubMed1988

Imipenem/cilastatin, an alternative treatment of pseudomonas infection in cystic fibrosis.

Imipenem, a new N-formimidoyl thienamycin was given together with cilastatin to 20 patients with cystic fibrosis and pulmonary infection due to Pseudomonas aeruginosa. The antibiotic was given in short-term infusions for 9-14 days (mean 11.5) in a dose of 45-60 mg/kg body weight/day. Good clinical results were obtained in all patients with significant improvement of clinical score, pulse rate, vital capacity and FEV1.0 (P less than 0.001). Blood PO2 increased and WBC decreased significantly. A slight increase in the minimum inhibitory concentration was noted during treatment but all strains examined were fully susceptible at follow-up one month later. The peak serum concentration was significantly increased in patients receiving the high dose of imipenem, but the sputum concentration was low in all patients and there was no difference in clinical or bacteriological outcome. The plasma and urinary clearance increased with body weight and was inversely correlated to clinical score. Imipenem/cilastatin appears a good alternative for the treatment of pulmonary infections caused by P. aeruginosa in cystic fibrosis.

Adolescent↗

PubMed1988

Plasmid profiles compared with serotyping and pyocin typing for epidemiological surveillance of Pseudomonas aeruginosa.

The plasmid profiles of 112 clinical isolates of Pseudomonas aeruginosa were determined by two reproducible, rapid, plasmid screening methods. Plasmid DNA was present in 15% of isolates examined. Plasmids varied in size from 1.2 X 10(6) to 60.2 X 10(6) mol. wt. The dominant serotypes encountered were O:11 and O:4, which comprised 38% and 12% of strains, respectively. Four pyocin types (1, 10, 3 and 5) dominated (respective frequencies: 56, 15, 12 and 6%). Reproducibility of pyocin typing was distinctly inferior to both plasmid profiling and serotyping. Strains of identical serotypes could be further differentiated by dissimilar plasmid profiles. Serologically untypable or polyagglutinable strains were successfully characterised by plasmid profile patterns. Thus, plasmid profiling was shown to be a useful adjunct to serotyping for the epidemiological typing of P. aeruginosa.

Anti-Bacterial Agents↗

PubMed1988

Tolerance of intravenously administered ciprofloxacin.

Twelve healthy volunteers received single doses of 200, 300, and 400 mg ciprofloxacin intravenously (30-min infusion). Crystals appeared in the urine of only 1 subject after the 400 mg dose. The crystals appeared in the 0-2 h urine specimen only and were observed immediately upon voiding while the urine was maintained at 37 degrees C. The pH of the urine was 7.3. The event was without untoward consequences to the person as evidenced by urinalysis and blood chemistry. Local skin reactions occurred on the arm of the infusion (cutaneous erythema, itching and burning sensation). The reactions were less after the lowest dose. The reactions started within minutes after the beginning of the infusion and disappeared either during the infusions or immediately after the end of administration. These local reactions were of moderate degree and did not necessitate termination of the infusion.

Adolescent↗

PubMed1988

HPNS effects among 18 divers during compression to 360 msw on heliox.

Heliox compression deeper than 16 ATA can lead to EEG changes associated with confusion and somnolence. In man the symptoms termed the high pressure neurologic syndrome (HPNS) can also include increased tremor, memory problems, dizziness, nausea, and vomiting. In a series of 3 dives at NUTEC, a compression profile developed for operational use down to 360 msw was evaluated. In each dive 6 different divers were compressed to 360 msw on heliox. Neuropsychologic and neurophysiologic testing were performed repeatedly. The HPNS testing revealed only mild effects of the compression. Only 3 divers had impairments of more than 2 SD in peripheral motor function compared to their predive average. Memory was impaired periodically in 2 divers. The same was found for perceptual speed and reasoning. Fifty percent of the divers had an increase of more than 2 SD in postural tremor, but that had minimal effect on their motor performance. Six of the 18 divers had an EEG power spectrum with both alpha band inhibition and theta increase. While the performance impairment was most marked around 240 msw, the EEG changes occurred mainly deeper than 300 msw. In only 1 of the 18 divers marked EEG changes, marked tremor increase, and marked cognitive performance impairment were observed at the same time. Although mild HPNS was observed, the divers were little impaired during the compression to 360 msw. The results confirm that using a compression profile with rates decreasing progressively with increasing depth, and with several intermediate stops, provides fit divers at depth. By using standard batteries of HPNS testing we were able to obtain evidence for the acceptability of this compression profile.

Central Nervous System Diseases↗

PubMed1988

Consequences of diarrhoeal disease on the pharmacokinetics of norfloxacin.

The pharmacokinetics of 400 mg norfloxacin administered orally were studied in 19 patients both during the acute phase of bacterial gastroenteritis and during convalescence, after normalization of bowel movements. The peak serum concentrations, total area under the serum concentration curve, rate of elimination and serum half-life in the beta-phase were all similar during the acute phase of the disease as well as after normalization of the intestinal function. The only difference was that the time to peak concentrations was longer (p less than 0.01) during the acute phase of the disease. That finding suggests that the faster intraintestinal transport of the drug during the acute stage of the disease leads to a reduced efficiency of early absorption. However, since the bioavailability was not affected, norfloxacin is obviously absorbed at a lower intestinal level and no dose adjustment should be necessary in patients with diarrhoea.

Adolescent↗

PubMed1988

Effect of recent antibacterial agents against bacteria causing diarrhoea.

The susceptibility of 424 bacterial isolates causing diarrhoea were tested by agar dilution technique on Mueller-Hinton Agar against amoxicillin, ampicillin, ceftriaxone, chloramphenicol, co-trimoxazole, ciprofloxacin, doxycycline, norfloxacin and ofloxacin. The bacterial species included were Aeromonas hydrophila, Edwardsiella tarda, Pleisomonas shigelloides, Salmonella spp., Shigella spp., Vibrio cholerae and Vibrio parahaemolyticus. The most active compounds were the fluorinated 4-quinolones studied, that is, ciprofloxacin, norfloxacin and ofloxacin, and ceftriaxone. The other antibacterial agents were considerably less active; a substantial portion of tested isolates were resistant to them.

4-Quinolones↗

PubMed1987

Pharmacokinetics of ciprofloxacin: intravenous and increasing oral doses.

The pharmacokinetics of ciprofloxacin, after administration of single oral doses of 100, 250, 500, and 1,000 mg, and an intravenous dose of 100 mg, were determined in 12 healthy volunteers (six women and six men). Serum concentrations were determined by high-pressure liquid chromatography, and urine samples were assayed microbiologically. The peak serum concentrations and the total areas under the serum concentration curves increased in proportion to the size of the oral dose. The pharmacokinetics of ciprofloxacin were described by a dose-independent linear relationship. The apparent oral bioavailability was 85 percent, based on comparison of the total areas under the serum concentration curves of the 100-mg dose. The serum concentrations during steady state were not significantly higher than after the first dose. The serum half-life ranged from 3.0 to 3.4 hours after the oral doses, and was 2.9 hours after the intravenous dose. The elimination-phase apparent distribution volume coefficient, delta d,area, was 2.76 liters/kg, and the total body clearance was 42.0 liters/hour. The 24-hour urinary excretion was 42.2 +/- 15.6 percent after the 100-mg intravenous dose and 42.5 +/- 17.6 percent after the 500-mg twice-daily oral dose during steady state.

Administration, Oral↗

PubMed1987

Production and characterization of monoclonal antibodies to toxic shock syndrome toxin 1 and use of a monoclonal antibody in a rapid, one-step enzyme-linked immunosorbent assay for detection of picogram quantities of toxic shock syndrome toxin 1.

Twenty-six hybridoma cell lines that produced monoclonal antibodies to toxic shock syndrome toxin 1 (TSST-1) were generated by immunizing mice with a highly purified preparation of TSST-1 and fusing their splenic lymphocytes with SP2/0-Ag-14 cells. One monoclonal antibody of the immunoglobulin G1 isotype, designated as PEC-1 10-2SCH, was selected for extensive study. The specificity of this antibody was determined by testing spent culture fluid filtrates of TSST-1- and non-TSST-1-producing strains of Staphylococcus aureus by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and enzyme-linked immunoelectrotransfer blot techniques. Monoclonal antibody PEC-1-10-2SCH was specific for TSST-1-producing strains of S. aureus, reacting with TSST-1 and two other proteins which appear to be unique to S. aureus strains that produce TSST-1. Monoclonal antibody PEC-1-10-2SCH was used in conjunction with polyclonal rabbit antibodies to TSST-1 in a rapid, one-step, sensitive, specific, and quantitative enzyme-linked immunosorbent assay. This assay was shown to be more sensitive, faster, and simpler to perform than previously described isoelectric focusing, immunodiffusion, and solid-phase radioimmunoassays for TSST-1. Monoclonal antibody PEC-1-10-2SCH was not reactive with Staphylococcus protein A under the conditions of the test.

Antibodies, Monoclonal↗

PubMed1987

Tolerance of ciprofloxacin at injection site, systemic safety and effect on electroencephalogram.

The safety of ciprofloxacin, given via 30- and 60-min intravenous infusions at a dose of 300 mg every 12 h for 4 days, was studied in 12 healthy subjects (6 females, 6 males). Local effects of the drug were assessed by frequent examination at the infusion site while systemic safety was determined by haematological and biochemical tests and by careful microscopic examination of the urine for drug crystals and by electroencephalographic studies performed in all subjects before and after dosing. At the site of infusion erythema, itching and a burning sensation developed 10-15 min after onset of infusion in some subjects. These symptoms were slight and did not necessitate termination of the infusions. The rash disappeared in some instances during the infusion and in others within minutes after the end of infusion. The changes usually disappeared, even during the infusion. The incidence of the adverse reactions was not related to the duration of the infusion (30 or 60 min), but was less (frequency and extent) when the anticubital vein was used for infusion rather than when smaller more peripheral veins were employed. Thrombophlebitis occurred after 1 of 96 administrations, and was followed by a return to normal. The electroencephalograms remained normal in all instances. One subject experienced mild nausea of a few hours duration. Only 1 volunteer showed crystalluria; the two such specimens from this subject had the most alkaline pH of all urine samples collected in this study. The probability of crystalluria upon intravenous administration appears not to be higher than after oral administration of ciprofloxacin.

Adult↗

PubMed1987

Pharmacokinetic properties of the cephalosporins.

Most cephalosporins can only be administered parenterally. Among agents that are absorbed from the gastrointestinal tract, those with bioavailabilities of 85 to 90% include cefroxadine, cefadroxil, cefsumide, cephalexin, cephradine, cephacetrile, and cefazaflur. Most cephalosporins are eliminated rapidly, with serum half-lives (t1/2s) of 1 to 2 hours. Exceptions are cefonicid with a t1/2 of 4.4 hours, cefpiramide with a t1/2 of 5.0 hours, and cefotetan with a t1/2 of 3.5 hours. The longest half-life is shown by ceftriaxone with a t1/2 of 8.5 hours. Cephalosporins are eliminated mostly by the kidneys, some with a substantial contribution from active tubular secretion, which is blocked by probenecid. The degree of metabolism varies. Only a few cephalosporins have a high biliary elimination. For example, with intravenously administered cefoperazone, about 70% appears in bile. High biliary elimination is also observed with cefmenoxime, ceftriaxone, cefbuperazone, and latamoxef (moxalactam). Because these are not appreciably absorbed from the gastrointestinal tract, the consequence is high intraintestinal concentrations of the drugs and a marked ensuing depression of the normal microflora with simultaneous emergence of resistant bacteria. The untoward ecological impact may even lead to Clostridium difficile-associated enterocolitis.

Animals↗

PubMed1987

Effect of norfloxacin on human oropharyngeal and colonic microflora and multiple-dose pharmacokinetics.

10 healthy volunteers received 200 mg norfloxacin orally every 12 h for 7 days. Saliva, throat and faecal specimens were collected days 0, 3, 5, 7, 14 and 21 to study the effect of norfloxacin on the normal microflora. The concentrations of norfloxacin in serum, urine, saliva and faeces were determined by a microbiological method and all samples except faeces were also assayed by high-pressure liquid chromatography (HPLC). The pharmacokinetics of norfloxacin were studied on day 3. The mean peak serum concentration (+/- SD) attained after 0.75-1.0 h was 0.75 +/- 0.15 mg/l measured by HPLC, and the mean terminal serum half-life was 4.2 +/- 0.6 h. The mean cumulative urinary elimination was 29% during 12 h after dosing. There was no significant difference between values obtained by microbiological assay and by HPLC. The saliva concentration was approximately 30% of the serum levels 1.0-1.5 h after administration. No accumulation in faeces was found during the administration period, and mean concentrations were 940 mg/kg. The changes in the oropharyngeal flora were minor and only branhamella were affected. In the colonic flora, the number of enterobacteria was strongly depressed while the anaerobic microflora was only slightly affected. Two weeks after the administration period, both the oropharyngeal and colonic microflora had returned to normal.

Adult↗

PubMed1987

Ceftazidime treatment of chronic Pseudomonas infection in patients with cystic fibrosis.

Twenty-one patients with cystic fibrosis (CF), aged 1-18 years, with chronic lower respiratory tract infection caused by Pseudomonas aeruginosa, received 38 treatment courses of ceftazidime of 10-14 days duration. A favorable clinical response was observed in 28 of the 38 treatment courses. The minimal inhibitory concentration values of ceftazidime for the Pseudomonas isolates were concentrated around 0.5-1.0 mg/l, although a wide range of sensitivities was found (less than 0.03-32 mg/l). P. aeruginosa was eliminated after five treatment courses, but recurred after 1 month in four of these patients. The organism was permanently eradicated in one patient until his death 8 months later. Ceftazidime was well tolerated. The doses used in this study (50 mg/kg body weight i.v. twice daily) should probably be increased in order to achieve better microbiological response.

Adolescent↗