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Biomedical subjects

T Bergan

Publications and source records attributed to T Bergan.

At least 109 records · Page 6Linked to original sources
PubMed1984

Microbial spectrum and antimicrobial susceptibility in infections after gastrointestinal surgery.

Operations on the gastrointestinal tract is associated with a high frequency of postoperative infections. This is due to contamination of the operating area with bacteria from the normal microflora of the intestines. The bacterial spectrum in infections occurring after colorectal surgery, appendicectomy and cholecystectomia are presented. Escherichia coli is the single most frequent species in all these instances. The anaerobic bacteria dominating in the normal bowel flora also cause a high number of infections. Prophylactic regimens in colorectal surgery have consisted of metronidazole combined with either ampicillin or doxycycline. The level of resistance to tetracyclines is higher than against ampicillin and it appears that tetracyclines select for development of resistance to a larger extent than ampicillin.

Ampicillin↗
PubMed1984

Penetration of antibiotics to tissues and infected foci.

There is proportionality between the area under the curve of concentrations in serum and the area under the curve in tissues and other extravascular foci of the body. A high peak area under the serum curve - PAUC - establishes high extravascular concentration levels in tissues, operation areas and infected sites. Most antibiotics are able to produce satisfactory antibacterial levels in interstitial tissue fluid regardless of serum protein binding. Binding to components of interstitial space, like alpha 1-globulin, inhibits the establishment of the concentrations. Administration of a prophylactic agent by infusion 1 h before an operation suffices to produce anti-bacterial levels in wound tissues to inhibit growth of susceptible bacteria contaminating it during the operation.

Anti-Bacterial Agents↗
PubMed1984

Prophylactic regimens in colorectal surgery. Comparison between metronidazole used alone or in combination with either ampicillin or doxycycline.

Sixteen hospitals are participating in this study, that started in October 1982 and will be concluded when 456 patients have been admitted. The study includes patients eligible for elective colorectal surgery. Inclusion criteria, surgical techniques, definition of recognizable infection, sampling of specimens for bacteriological investigations, bacteriologic techniques, and evaluation criteria were standardized. Patients were divided into 2 main groups. Patients in Group 1 received either a single intravenous dose of 1500 mg metronidazole or this dose was combined with a single, intravenous dose of 6 g ampicillin. Patients in group 2 received either a single intravenous dose of 1500 mg metronidazole or this dose combined with a single intravenous dose of 400 mg doxycycline. Dosage regimens were allocated randomly. The current results concern 136 patients. Postoperative infections were seen in 6.7% of the patients receiving metronidazole alone, and 2.9% of the patients receiving metronidazole + ampicillin (Group 1). In Group 2, postoperative infection occurred in 17.1% of the patients receiving metronidazole alone, and in 2.7% of those receiving metronidazole + doxycycline.

Adult↗
PubMed1984

The pharmacokinetics of one single preoperative dose of metronidazole or tinidazole.

Eight patients who were subjected to colorectal surgery received 1500 mg metronidazole and another 8 patients 1600 mg tinidazole. The two groups of patients were comparable in respect to age, body size, diagnoses, types of operations, premedication, and anaesthesia. Concentrations of the parent compounds and hydroxy-metronidazole were determined by high pressure liquid chromatography in serum and tissues (subcutaneous fat, rectus abdominal muscle, peritoneum, greater omentum, distal ileum, colon, appendix). The serum and tissue concentrations of metronidazole and tinidazole were within overlapping ranges. Hydroxy-metronidazole but not hydroxy-tinidazole was detected. The total area under the serum curves was 505 (SD: +/- 181) mg . h/l for metronidazole, 137 (+/- 38) mg . h/l for hydroxy-metronidazole, and 810 (+/- 286) mg . h/l for tinidazole. The serum half-life values in the same order were 8.5, 11.2, and 14.2 hours. The distribution volume (Vd,area) were 30.1 liter for metronidazole and 38.8 liter for tinidazole. The range of tissue concentrations were completely overlapping. The two regimens can, consequently, be assessed as pharmacokinetically similar.

Aged↗
PubMed1984

Comparative pharmacokinetics of metronidazole and tinidazole used as single dose prophylactic agents.

The pharmacokinetic properties of metronidazole (M) and tinidazole (T) were studied in patients undergoing colorectal surgery after a single preoperative dose of 1500 mg infused during 50 minutes. High-pressure liquid chromatography was used to determine serum concentrations, which for M and T were almost identical during the first 12 hours. After 24 hours, the concentration of T were slightly higher. Both drugs were detected in serum at 72 hours. The serum half-life (t1/2) was 9.4 hours for M and 17.6 hours for T, whereas the hydroxymetabolite of M had a t1/2 of 17.6 hours. There was considerable interindividual variation in both T and M concentrations. The prophylactic use of a single preoperative dose of 1500 mg of either M or T in elective colorectal surgery is supported by favourable pharmacokinetic properties of both drugs.

Adult↗
PubMed1984

Pharmacokinetics of metronidazole and its major metabolite after a high intravenous dose.

The pharmacokinetics of metronidazole (M) and hydroxy-metronidazole (OH-M) were determined in 8 healthy volunteers after a single dose of 1.5 g metronidazole given as an intravenous infusion during 50 min. High-pressure liquid chromatography was used for the assays. The serum concentration determined 1 h after the start of infusion was 40.21 +/- 6.54 mg/1. The peak concentrations of the metabolite were observed after 8-12 h. The serum concentrations of M and OH-M were detectable throughout the 48 h monitored. The serum half-life of M was 7.6 h and of OH-M 13.3 h. The terminal phase distribution volume was 43.2 lit and the total body clearance 4.0 lit./h. The prophylactic use of 1.5 g of metronidazole given as a single intravenous dose 1 h prior to surgery is supported by the pharmacokinetic assessments in this study.

Drug Evaluation↗
PubMed1984

Pharmacokinetics and bioavailability of metronidazole after tablets, suppositories and intravenous administration.

The pharmacokinetics of metronidazole were determined in cross-over study on 11 healthy volunteers after 400 mg tablets from two producers. 1000 mg suppositories and 800 mg intravenously (IV). High-pressure liquid chromatography was used to assay both unchanged metronidazole (M) and the hydroxy metronidazole metabolite (OH-M). The peak concentrations were observed 1.2 - 1.3 hrs after the administration of tablets and 4.9 hrs after the suppositories. After the IV dose, the OH-M peak appeared only after 8 hours. The serum half-life was 6.5 hrs after the IV dose, 6.1 - 6.8 hrs after the tablets and 6.8 hrs after the suppositories. After IV dosage, the terminal phase distribution volume was 38.1 lit and the total body clearance 4.09 lit/hr. The bioavailability of the tablets was 80.4 and 84.1 per cent and after the suppositories 53.8 per cent. The rate of elimination OH-M was faster after suppositories than after IV dosage where it was intermediate after the tablets. Accordingly, the serum-half-life was 9.7 hrs after suppositories, 19.2 hrs after IV infusion, and 10.6 and 11.8 hrs. after the tablets. The rates of apparent metabolization was graded in the same relative order, with a faster rate after the suppositories, 0.168 hrs-1 compared to 0.368 hrs-1 after the IV route of administration. The differences pertaining to OH-M is considered probably to be caused by interaction with the metabolic activity of the bacterial flora of the colon.

Absorption↗
PubMed1984

Pharmacokinetics of beta-lactam antibiotics.

Beta-lactam antibiotics represent the oldest class of antibiotics used in the treatment of infections. Consequently, a large number of agents have been developed. Penicillins and cephalosporins are generally available for parenteral application. Some are absorbed from the gastrointestinal tract. The serum half-life (t1/2) of most beta-lactams is 1-2 hours. Ceftazidime and temocillin are more long-lasting with a t1/2 of 4-6 hours and ceftriaxone of 8-10 h. These values relate to patients with normal renal function. The elimination is only moderately prolonged for beta-lactams and of little consequences for the dosage regimens, partly because of the high tolerance of this group of antibiotics. Penicillins and cephalosporins are eliminated by glomerular filtration and varying degrees of active transport across the epithelial cells of the renal tubuli and hepatobiliary system. Active transport mechanisms also explain the low concentrations of beta-lactam antibiotics in cerebrospinal fluid. Otherwise, penetration of these agents to unspecialized tissues is good. Substances with a low serum protein binding, such as ampicillin and amoxicillin, reach concentrations in peripheral human lymph which as assessed by the ratios of areas under the concentration curves are 50-80% of the serum levels. The serum protein binding appears to act mainly by inhibiting the rate with which the antibiotic passes into extravascular foci. For instance, temocillin with a serum albumin binding around 85% establishes levels in peripheral lymph which are 50-60% of those in serum. This may be explained by the fact that a higher protein binding is accompanied by more lipid solubility, which are two factors acting in opposite directions as concerns passage by diffusion across body barriers.

Absorption↗
PubMed1984

In vitro interactions between metronidazole or tinidazole and ampicillin, doxycycline and co-trimoxazole on the effect against anaerobic bacteria.

The mutual interaction on the antibacterial activity of metronidazole and tinidazole with ampicillin, doxycycline and co-trimoxazole was studied by two-fold agar dilution series and chess-board determinations with 24 anaerobic bacterial strains which were recent clinical isolates. The nitroimidazoles had similar activity, and partial or complete synergy was observed in 83 - 88% of the strains when they were combined with ampicillin and doxycycline and 83 - 100% when combined with co-trimoxazole, which was moderately less active on a weight basis. A combination between ampicillin and a nitroimidazole would be preferable due to high level of synergy, high activity against anaerobes, and a more consistent supplementary activity against enterococci.

Ampicillin↗
PubMed1983

Severe toxic reaction to tinidazole.

A physician aged 44 years participated as a volunteer in pharmacokinetic studies with tinidazole (FASIGYN, Pfizer). He received 1600 mg of the drug as an intravenous infusion over 80 min. Shortly afterwards, he fainted and was unconscious for about 10 s. The attack was followed by low blood pressure, nausea and tiredness for several h. The serum concentration of tinidazole was 35.4 mg/l when the attack started. Blood tests showed a normal immunoglobulin E level, and a transient fall in the concentration of complement factor C3 after the infusion. It is concluded that tinidazole caused an acute toxic reaction with subsequent activation of complement factors.

Adult↗
PubMed1983

Penetration of metronidazole to tissues.

One dose of 500 mg metronidazole (M) was given to 21 patients before appendectomy and the concentrations of the parent compound and the major metabolite hydroxymetronidazole (OH-M), assayed in serum and tissue homogenates of appendix and subcutaneous tissues by high pressure liquid chromatography. Based on determinations in one specimen per patient during the initial 1.25-4 h after end of the 50 min infusion, the levels of M in relation to serum were 60.8% (+/- S.D. 19.8) for the appendix and 29.0% +/- 8.7 for subcutaneous tissue. The corresponding values for OH-M were 103.9 +/- 28.2 and 57.0% +/- 16.8. The slope of the log-linear regression curves of M corresponded to elimination half-life (T 1/2) values of 5.2 h in serum, 2.7 h in appendix and 2.6 h in subcutis tissue, but the differences were not statistically significant. The values of OH-M were similar for serum and appendix. OH-M had T 1/2 of 7.9 and 6.1 h for serum and subcutaneous tissue and 21.3 h in the appendix, but the values were not significantly different.

Adolescent↗
PubMed1983

Review of the pharmacokinetics and dose dependency of azlocillin in normal subjects and patients with renal insufficiency.

Cross-over studies on volunteers with several doses of azlocillin ranging from 1.0 to 5.0 g have shown that azlocillin is subject to dose dependent pharmacokinetics, the area under the serum curve becoming larger than expected as doses increase. There was also a tendency towards longer serum half-life values and excretion of more unchanged compound as the doses increase. The serum half-life varied between 0.9 h after 1.0 g increasing to 1.5 h after intravenous doses of 5.0 g given to adults. In neonates, values around 2.6 h have been observed, and they were slightly longer in premature babies at approximately twice the value in adults receiving similar doses per kg body weight. In normal adults protein binding lies between 35 and 40% for therapeutic concentrations. Approximately 60-75% of the dose appears as unchanged azlocillin in the urine, increasing with higher doses. Reduced renal function lowers urinary excretion, but concentrations are always above the break point for sensitivity of 32 mg/l in patients with creatinine clearances above 10 ml/min. In anephric subjects T1/2 of 2.5-6 h is observed. Dosage modifications only to one-third of normal are needed for a renal clearance of 10-25 ml/min. The concentrations of active compound are high in the bile in subjects with normal liver function.

Azlocillin↗
PubMed1983

Temocillin in peripheral lymph.

One gram of temocillin was given intravenously to five healthy volunteers to study the concentrations in serum and peripheral lymph obtained by cannulation of the lower leg. The 1 h serum level was 58.1 mg/l and the lymph level 14.3 mg/l. The mean peak lymph concentration was 30.6 mg/l and occurred between 1.5 and 2 h; the simultaneous serum level was 47.8 mg/l. The antibiotic levels in lymph were always below those in serum. The urinary recovery over 12 h was nearly 60%. The mean ratio between the areas under the concentration curves of lymph and serum was 0.558. The serum half-life was 4.9 h, the apparent beta-phase distribution volume 18.41. In comparison, the lymph half-life was 4.4 h. Protein binding appears to be of little consequence to the ability of temocillin to penetrate well into extravascular foci.

Adult↗
PubMed1983

Distribution to human peripheral lymph of amoxycillin and of ampicillin from the oral prodrug bacampicillin.

Equivalent doses of 1600 mumol each of amoxycillin (582 mg) and ampicillin from bacampicillin (800 mg) were studied in five fasting healthy volunteers in a cross-over study. Peripheral lymph was collected from the legs by cannulation of subcutaneous lymph vessels. Antibiotic concentrations were determined by bioassay. Passage to the lymph was rapid; for both agents lymph peaks occurred between 1-2 h after serum maxima. The compounds showed similar ranges of serum and of lymph concentrations; the mean individual peak concentration, area under the concentration curves, and elimination half-life in serum were 9.6 mg/l, 24.8 mg.h/l, and 0.80 h respectively for amoxycillin and 11.0 mg/l, 21.4 mg.h/l, and 0.93 h for ampicillin from bacampicillin. In lymph, the corresponding values were 5.5 mg/l, 21.9 mg.h/l, and 1.1 h for amoxycillin and 4.7 mg/l, 16.1 mg/l, and 1.0 h for ampicillin. The ratios between concentrations in lymph and serum were similar. The ratios between the total areas under the concentration curves was 0.88 +/- 0.19 for amoxycillin compared to 0.80 +/- 0.10 for ampicillin from bacampicillin. The areas under the lymph concentration vs. time curves ranged from 69-107% of the serum curve values of amoxycillin and 71-97% for ampicillin. Both drugs persisted longer in lymph than in serum. This pattern was somewhat more pronounced for amoxycillin, probably because of its more sustained serum concentrations due to delayed absorption. Thus the two antibiotics were similar in respect to passage into peripheral lymph.

Adult↗
PubMed1983

Antibiotic resistance in staphylococci from a hospital environment.

The antibiotic resistance of Staphylococcus aureus and coagulase-negative staphylococci has been followed over 4 years (1977-1980). 90% of the strains produced beta-lactamase. Coagulase-negative staphylococci were more resistant than S. aureus, although beta-lactamase production occurred more rarely. Strains from the sputum of children with cystic fibrosis (CF) were more multiresistant than isolates from other sources. The strains from hospitalized patients (HP) were more resistant than isolates from out-patients. A higher frequency of beta-lactamase production occurred among strains from CF and HP patients compared to out-patients. This occurred in samples from pus and wounds in 66% of the strains derived from non-hospitalized patients compared with 93% from surgical patients.

Anti-Bacterial Agents↗
PubMed1983

In vitro activity of antifungal agents against yeast species.

The antimicrobial activity of 8 antifungal agents have been compared in vitro against 151 strains of yeast fungi and 2 of Geotrichum candidum. The drugs were the classical nystatin and amphotericin-B, 5-flucytosine, and 5 imidazoles, clotrimazole, econazole, ketoconazole, miconazole, and tioconazole. An agar dilution technique with incubation at 37 degrees C was used. By this procedure, econazole was the most active agent per weight basis among those suitable for topical therapy. Tioconazole had a wide spectrum and high activity. Ketoconazole had an antimicrobial activity which makes it an interesting agent considering its applicability in systemic therapy. The activity of 5-flucytosine surpasses that of other systemically applicable agents.

Antifungal Agents↗
PubMed1983

Relationship between pharmacokinetics and bioavailability of cefroxadine (CGP 9000) and renal function.

The pharmacokinetics and bioavailability of cefroxadine were studied in 15 patients with different renal functions after administration of 0.5 g as oral capsules and as intravenous infusions. Microbiological assays by agar diffusion and high-pressure liquid chromatography may both be used for this agent since no metabolite can be found. The bioavailability is near 100% of the oral dose regardless of renal function. Urinary recovery varied from about 50% in renal glomerular filtration rates (GFR) of less than 7 ml/min to nearly 100% in normal renal function. The serum concentrations, serum elimination half-life and total body clearance were significantly influenced by reduced renal function. Nonrenal elimination occurred in reduced renal function; the maximum serum elimination half-life was 24.6 h. Dose modifications according to renal function are suggested with from three doses/24 in normal renal function to one dose/24 h in patients with GFR of 10 ml/min. The relative distribution volume corresponded to approximately 30% of the body weight. Tubular secretion of cefroxadine took place. The concentrations in urine remained above 32 mg/l for 12 h in all subjects regardless of renal function.

Adult↗