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T Bergan

Publications and source records attributed to T Bergan.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Degree of absorption, pharmacokinetics of fosfomycin trometamol and duration of urinary antibacterial activity.

The pharmacokinetics and in particular bioavailability of fosfomycin trometamol was studied and compared to the earlier emerging calcium salt formulation by administration of 50 mg/kg body weight orally of the two and an identical dose intravenously to all of eight healthy male volunteers. The serum and urine samples collected over 12 and 48 hours, respectively, were assayed microbiologically. The serum peak concentrations were 26.2 mg/l after trometamol and 6.5 mg/l after the calcium salt. Based on total area under the serum curves, the bioavailability of fosfomycin from the trometamol formulation was 42.3% compared to a mere 12% of the calcium salt. Urinary recovery was nearly completed within 12 hours, and the amounts eliminated in percentage of the doses were 87, 43, and 18% after the intravenous, the oral dose of trometamol and oral calcium salt, respectively. The serum half-life was 3.4 hours after intravenous administration, which demonstrates the inherent rate of elimination of fosfomycin. In comparison the half-life values were 3.6 hours after the trometamol dose, and 5.6 hours after the calcium salt. The longer elimination of the latter is explainable by the less complete absorption and consequent delayed absorption of fosfomycin from the calcium salt formulation. The antibacterial activity in urine upon administration of 50 mg/kg was prolonged to 48 hours in nearly all cases of trometamol orally and more than after the calcium salt orally or the sodium salt intravenously. A dose of 3 g for adults - or 50 mg/kg - is consistent with the findings in this study.

Administration, Oral↗
PubMed1990

Requirements for the documentation of pharmacokinetic properties of antimicrobial agents.

Proper documentation of new antimicrobial drugs for governmental registration authorities includes extensive pharmacokinetic studies. Pharmacokinetics represents the bridge between the in vitro and in vivo phases of drug development. Both healthy human volunteers and patients must be studied, the former during the initial stages of the pharmacokinetic studies. The documentation should give information on the following: absorption from the gastrointestinal tract, bioavailability, pharmacokinetic model, impact of increasing doses (oral and intravenous), metabolism, routes and degree of elimination, interaction with food and other drugs, impact of the steady state, and serum protein binding. Basic pharmacokinetic parameters used are the serum half-life, clearance, distribution volume and dose dependence. The bioavailability of oral doses must be determined using the same dose sizes and subjects. Data on extravascular penetration should also be included in complete documentation. Key diseases in which the pharmacokinetics should be studied are reduced renal and liver function, heart failure, pregnancy, cystic fibrosis and intestinal diseases. The consequences of low age (e.g. newborns) and old age also require some attention.

Animals↗
PubMed1990

Bacteriuria in the puerperium. Risk factors, screening procedures, and treatment programs.

Screening for bacteriuria by culture of voided midstream urine was done in 6803 puerperal women; significant growth was found in 8.1%. The urine was recollected by suprapubic aspiration and bacteriuria was confirmed in 52%, corresponding to an incidence of bladder bacteriuria of 3.7%. A history of past urinary tract infection, bacteriuria in pregnancy, operative delivery, epidural anesthesia, and bladder catheterization increased the risk of postpartum urinary tract infection. Only 21% of the women complained of dysuria; this symptom occurred significantly more often after operative delivery and in patients with previous urinary tract infection. Two hundred fifty-one women with bladder bacteriuria were subjected to different treatments by randomized allocation: 153 patients with amoxicillin-susceptible bacterias were selected for amoxicillin treatment of 1, 3, and 10 days' duration. The cure rates were 84%, 94%, and 98%, respectively; the single-dose therapy was significantly less effective than 10 days' treatment (p less than 0.05). Forty-six women with amoxicillin-resistant bacterial infections received cephalexin or nitrofurantoin therapy of 7 days' duration; the cure rate was 91%. Fifty-two women served as control subjects and received no treatment. Ten weeks later 27% still had persistent bacteriuria in their suprapubic aspiration control specimens. All therapeutic regimens except the single-dose method showed a cure rate that was significantly higher than the spontaneous cure rate (p less than 0.05). Multiparity seemed to be a predisposing factor for persistence of bacteriuria. The study indicates that puerperal patients with positive midstream urine specimens should not be automatically treated, but more thoroughly examined. In cases of confirmed bladder bacteriuria, treatment should be recommended; 3 days' therapy appears to be sufficient.

Anti-Bacterial Agents↗
PubMed1990

Transintestinal elimination of ciprofloxacin.

This study elucidates the routes of elimination of ciprofloxacin and its metabolites in two groups of 5 subjects each, one of healthy volunteers, the other of patients with severe renal failure having a creatinine clearance of 12 ml/min (range 8-16 ml/min). Each subject received one dose of 200 mg ciprofloxacin infused intravenously over 30 min. In an effort to recover the total dose administered, all urine and faeces were collected for the 7 days following dosing. Blood was collected at set intervals after dosing. Serum, urine, and faeces were assayed by high-pressure liquid chromatography for ciprofloxacin and metabolites. The ciprofloxacin serum half-life in healthy volunteers was 3.9 +/- 0.4 h and in patients with marked renal failure 11.2 +/- 2.5 h. The total amount of ciprofloxacin recovered in urine fell by a multiple of 3.4 from 65.3 +/- 10.7% in healthy subjects to 19.0 +/- 15.9% in patients with renal failure, and the metabolites from 12.2 +/- 2.3% in the former group to 5.8 +/- 5.1% in the latter. In contrast, the amount of ciprofloxacin eliminated in faeces increased, by a similar factor, from 11.4 +/- 2.6% in healthy subjects to 37.2 +/- 12.5% in patients with renal failure. The amount of metabolites in faeces increased analogously from 7.3 +/- 1.6 to 26.2 +/- 6.5%. Since ciprofloxacin was administered intravenously and biliary elimination of the drug and its metabolites is negligible, we propose that elimination by faeces is due primarily to transintestinal elimination. This study demonstrates that transintestinal elimination of ciprofloxacin serves as an extrarenal safety factor compensating for reduced elimination by the renal route.

Adult↗
PubMed1990

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↗
PubMed1990

Pharmacokinetic parameters and characteristics relevant to antimicrobial surgical prophylaxis.

The penetration of antimicrobial agents to tissues above the minimum inhibitory concentrations of potentially infecting microorganisms is the key to successful prophylaxis after surgery. The levels reach relevant inhibitory concentrations within 10-15 min after therapeutic doses have been administered. This applies even to compounds with a high serum protein binding like flucloxacillin (96% binding). Rapid appearance of extravascular levels is also observed for antibiotics with particularly large molecular size, such as the macrolides. Peak concentrations in extravascular fluid are lower than those in serum. Tissues like the kidneys and liver are exceptions to this general rule because of the special extraction and concentration powers of these key excretory organs. Once the levels in serum and extravascular fluids have equilibrated, extravascular levels tend to be similar to the remainder of the dosage intervals in the case of substances with serum half-life values (t1/2) of 8-12 hours or more (e.g. sulphadiazine, trimethoprim). Compounds with a short t1/2 in the order of ca. 1-2 hours exhibit extravascular concentrations after equilibrium which tend to be above those in serum (e.g. ampicillin, mecillinam). The mechanism of passage from blood to extravascular fluids is by passive diffusion following Fick's law of diffusion. The question remaining is what pharmacokinetic determinants may be relevant to the establishment of extravascular concentrations of antimicrobial agents. The major such variable is the serum concentrations of the agent. A direct linear relationship has thus been observed for a number of substances between the total areas under the concentration versus time curves (AUC) in serum and in peripheral fluids like lymph or tissue chamber fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents↗
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↗