[Boutonneuse fever--an unusual disease with difficult diagnosis].
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Diagnosis, Differential↗
Biomedical subjects
I Nilsson-Ehle
Publications and source records attributed to I Nilsson-Ehle.
Amphotericin clearance in vitrectomized versus nonvitrectomized eyes.
Ocular clearance of amphotericin B after direct intravitreal injection was studied in a rabbit model. Unmodified phakic eyes, Candida-infected eyes, aphakic eyes, and aphakic vitrectomized eyes were employed. Using high pressure liquid chromatography to assess drug level, the half-lives of drug disappearance after single 10-microgram (microgram) intravitreal injections were 9.1, 8.6, 4.7, and 1.4 days, respectively. The disappearance slope for vitrectomized eyes was significantly different from all nonvitrectomized eyes with P less than 0.001. The rapid disappearance of amphotericin from vitrectomized eyes must be considered in clinical management of patients with fungal endophthalmitis.
Amphotericin B↗
Pharmacokinetics of clavulanic acid, given in combination with amoxycillin, in volunteers.
To study the absorption and disposition of clavulanic acid, ten healthy men received one intravenous and one oral dose of 125 mg clavulanic acid in combination with amoxycillin. Serum and urine concentrations were measured with high-performance liquid chromatography. The mean terminal half-lives in serum were 0.97 and 0.94 h, respectively. Total serum clearance was 248 +/- 55 ml/min X 1.73 m2. Renal clearance was 108 +/- 20 and 115 +/- 18 ml/min X 1.73 m2 after intravenous and peroral administration. Urinary recovery over 12 h was 49.4 +/- 8.7% of the intravenous and 35.7 +/- 13.0% of the oral dose. The bioavailability of the oral dose averaged 60.0 +/- 23.1% but varied considerably (range 31.4-98.8%), indicating very variable absorption from the gastrointestinal tract.
Administration, Oral↗
Ceftriaxone: pharmacokinetics and effect on the intestinal microflora in patients with acute bacterial infections.
12 patients with acute bacterial infections were treated with ceftriaxone, 1.5 g intravenously twice daily for 7-13 days. Pharmacokinetic variables were studied in 11 patients. In older subjects, serum half-lives were longer and serum clearances lower than in younger individuals. After the last dose, a larger increase in AUC compared to the first dose was observed in older patients and a biphasic elimination curve appeared in all patients but 2, with a terminal half-life of 15.6 h and 11.4 in old and young subjects, respectively. Estimated biliary clearances showed large individual variation, with a range of 0-16 ml/min X 1.73 m2. Changes in the colonic microflora were pronounced. Almost total disappearance of staphylococci, streptococci and enterobacteria was found, and there was a marked tendency to overgrowth of yeasts and enterococci. One patient with the highest estimated biliary clearance of ceftriaxone developed diarrhoea after 7 days of therapy. A toxin-producing Clostridium difficile was isolated from the stool.
Acute Disease↗
Metronidazole: pharmacokinetic observations in severely ill patients.
Single and multiple dose pharmacokinetics of metronidazole and its two major metabolites were studied in ten patients. Patients with hepatic insufficiency had longer average serum half-life of metronidazole (11.2 h) than individuals with normal liver and kidney function (5.9 h) or isolated moderate renal impairment (6.5 h). Patients with hepatic disorder presented larger areas under the serum concentration curve, lower serum clearances and a tendency to more rapidly rising trough values of metronidazole. In patients with renal insufficiency trough values of the hydroxy metabolite seemed to rise faster and serum half-life was prolonged. The acetic acid metabolite was detected in serum of all patients with renal dysfunction but only in half of those with normal renal function and then at lower levels. A reduced 24-h total urinary recovery of metronidazole among patients with renal disorder was explained by a decreased excretion of hydroxy metabolite. The kinetics of metronidazole itself seem not to be influenced by renal impairment while the elimination rate of metabolites is reduced. The decreased clearance of the drug in patients with hepatic dysfunction makes a dose reduction in this patient group advisable.
Adult↗
Cefuroxime in acute septic arthritis.
Cefuroxime was used in 17 patients with clinical, bacteriological and/or laboratory signs of acute septic arthritis in comparison with 10 patients given cloxacillin and ampicillin alone, or in combination. 14 patients in the study group had positive cultures (Staphylococcus aureus, 10, S. epidermidis, 1, Streptococcus pyogenes group G, 2 and Acinetobacter, 1). Three more patients with non-bacterial arthritis were included in an antibiotic penetration study. In 6 patients serum and joint fluid concentrations of cefuroxime were repeatedly determined by an assay using high pressure liquid chromatography. After 1.5 g intravenous cefuroxime the joint fluid concentrations were 16-80 and 5-40 mg/l at 2 and 8 h, respectively, exceeding the serum concentrations during that period of time. From the clinical and pharmacokinetic data a dosage of 1.5 g cefuroxime intravenously t.i.d. is recommended to the adult patient. This high dosage resulted in primary healing in 11 patients with one relapse one year later in a patient with a knee arthroplasty. Half the dosage intramuscularly in 6 patients failed in 2. No side effects were seen during cefuroxime therapy.
Acinetobacter Infections↗
Pharmacokinetics of ceftazidime in elderly patients and young volunteers.
When given 2 g ceftazidime intravenously a group of 13 acutely ill but renally healthy, elderly patients demonstrated prolonged terminal half-life, increased area under the curve and reduced total and renal clearance compared to 9 young, healthy, male volunteers. The volume of distribution was enlarged in elderly males. Ceftazidime elimination correlated to renal function. Dosage twice daily for one week did not result in any clinically significant accumulation.
Adult↗
Single versus multiple dose doxycycline prophylaxis in elective colorectal surgery.
One hundred and two patients undergoing elective colorectal surgery were randomized in a prospective but "non-blind" way into two groups. The first group received 0.4 g of doxycycline preoperatively and the second group 0.2 g of doxycycline preoperatively and 0.1 g of doxycycline on the first, second and third postoperative day. All doxycycline was administered by intravenous infusion. The infection rate was 10% in the "one-dose" treatment group and 10% in the "four-dose" treatment group. It is thus concluded that 0.4 g of doxycycline preoperatively results in an acceptable rate of postoperative infections, which may be explained by the satisfactory concentration of doxycycline up till three days after administration. The advantage of "one-dose" treatment compared to "four-dose" treatment from practical and economical standpoints are obvious.
Clinical Trials as Topic↗
Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate.
We developed a rapid and precise method for the chemical determination of a new contrast agent, iohexol (N,N'-bis(2,3-dihydroxypropyl)-5-N-(2,3-dihydroxypropyl)-acetamido-2,4, 6-triiodoisophtalamide). Its sensitivity allows the monitoring of plasma concentrations for at least 6 hours after the injection of a single small dose. The elimination rate of iohexol was constant after approximately 90 minutes; plasma clearance in healthy volunteers averaged 127 ml/min. The injected dose was quantitatively recovered in urine. Determination of plasma clearance on two different occasions demonstrated a total variation of 11% (coefficient of variation); the methodologic imprecision was minor compared with the biologic variation. In 42 patients with normal to moderately impaired renal function, a comparison of iohexol and 51Cr-ethylenediaminetetraacetic acid clearances demonstrated an excellent correlation (correlation coefficient 0.98). The simplicity and rapidity of the new method makes it an attractive alternative to current methods for the assessment of glomerular filtration rate.
Adult↗
Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects.
We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase high-pressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected.
Chromatography, High Pressure Liquid↗
Pharmacokinetics of cephalothin: accumulation of its deacetylated metabolite in uremic patients.
The pharmacokinetics of cephalothin and its deacetyl metabolite were studied with use of a chemical assay involving high-pressure liquid chromatography. In seven patients with normal renal function, the half-life of cephalothin was about 28 min and concentrations of deacetylcephalothin in serum were low. In five patients with uremia, the half-life of cephalothin averaged 221 min and there was a continuous accumulation of the deacetyl metabolite in serum during treatment. Recovery of the drug in urine was quantitative when renal function was normal, whereas the amount of drug excreted was very low in cases of uremia. The results offer some explanation of the complex pharmacokinetics of cephalothin seen with microbiological tests and illustrate the usefulness of specific chemical assays, especially in the monitoring of serum concentrations of mixtures of antibiotic compounds that differ in antibacterial activity.
Cephalothin↗
Chemical assay, involving liquid chromatography, for aminoglycoside antibiotics in serum.
We describe a chemical assay involving "high-pressure" liquid chromatography for the quantitative determination of three aminoglycosides: netilmicin, tobramycin, and gentamicin. The drugs are separated from serum by means of precipitation of the serum proteins with acetonitrile after dilution with a buffer. The aminoglycosides are quantitatively extracted into the supernate, which is further purified by a two-step partition procedure involving derivatization of the drugs with o-phthalaldehyde. The drug derivatives are separated by reversed-phase chromatography and detected by on-line fluorometry. Sensitivity is 1 mg/L for tobramycin and 0.5 mg/L for netilmicin and gentamicin. Intra- and interassay variation was below 8%. Analytical recovery of each of the three drugs was 92 to 100%. Correlation with microbiological and radioimmunological assay methods was good. The assay is rapid (about 30 min), precise, and specific, and seems suitable for use in a routine clinical laboratory.
Anti-Bacterial Agents↗
Determination of chloramphenicol in serum and cerebrospinal fluid with high-pressure liquid chromatography.
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Biological Assay↗
Quantitation of antibiotics by high-pressure liquid chromatography: cephalothin.
A technique for quantitative determination of cephalothin and desacetylcephalothin in serum using a method based on high-pressure liquid chromatography is described. Both compounds were quantitatively extracted from serum by using dimethylformamide. After separation of the drugs by reverse-phase chromatography and detection by ultraviolet light absorption at 254 nm, serum concentrations of cephalothin and desacetylcephalothin as low as 1.0 mug/ml were measured. No interfering absorption was found in extracts of serum samples from normal humans or patients receiving a variety of other drugs, including other antimicrobial agents. Serum specimens obtained after an intravenous infusion of cephalothin to two human subjects and three dogs were assayed by the chemical and microbiological assays. When values, as determined by the chemical method and the microbiological assay in samples from human subjects, were compared, the correlation coefficient (r) was 0.96, whereas, in the dogs, the r value was 0.79. The chemical procedure described in this report for determination of cephalothin and desacetylcephalothin permits future pharmacokinetic investigations of these compounds. This assay is sensitive, specific, accurate, and rapid (approximately 30 min), and appears suitable for routine clinical use.
Animals↗
Liquid chromatographic assay of cerfuroxime in serum.
We describe a procedure for determining cefuroxime concentrations in serum by using high-performance liquid chromatography. The drug is extracted from serum with dimethylformamide and separated from other substances in the extract by reversed-phase chromatography. The ultraviolet (280-nm) absorption of the effluent was monitored and quantitated based on the height of the cefuroxime peak. Intra-and inter-assay imprecision (cv) was less than 3.1 and 4.3%, respectively. Serum concentrations as low as 1.0 mg/liter could be accurately measured. No interference from various other drugs and antibiotics was found. A biological half-life of 52 min in serum was observed after intravenous injection of the drug into a human volunteer.
Cephalosporins↗
Quantitation of amphotericin B with use of high-pressure liquid chromatography.
A chemical method for determination of concentrations of amphotericin B in serum and cerebrospinal fluid (CSF) is described. After extraction with methanol, the antibiotic was separated by reverse-phase, high-pressure liquid chromatography and quantitated by absorption at 405 nm. The lower limit of detection of this assay was 0.02 microng/ml. Relative standard deviations of less than 3.6% were noted for multiple determinations of sera containing 0.20 and 1.00 microng of amphotericin B/ml. No interfering peaks were found in extracts of serum or CSF from normal humans or in extracts of serum from patients treated with other drugs and antimicrobial agents, including 5-fluorocytosine. Comparison of the method with microbiological assays showed correlation coefficients of 0.90 and 0.83 for serum and CSF determinations, respectively. This chemical assay is very rapid (less than 30 min), sensitive, accurate, and specific and appears to be suitable for routine clinical use.
Amphotericin B↗
High-pressure liquid chromatography as a tool for determination of antibiotics in biological fluids.
The toxicity of some antibiotics used today necessitates rapid, specific and accurate determinations of antibiotic concentrations in biological fluids. Microbiological assays do not fulfill these needs and new procedures have recently been developed, for instance, fluorimetric assays, radioimmunoassays and radioenzymatic assays. However, these techniques have not been generally applicable to various antimicrobial agents. - The technique for high-pressure liquid chromatography (HPLC) has recently been applied to determination of antibiotics in biological fluids. The methods involve extraction of drug from the biological samples, separation by HPLC and detection by ultraviolet spectrophotometry of fluorimetry. Results obtained with tetracycline, amphotericin B, and cephalothin show that this procedure meets the demands for rapid, specific and accurate monitoring of antibiotic concentrations in body fluids. Because of its versatility, the HPLC technique seems to be applicable to the determination of a variety of antibiotics and other drugs in clinical and experimental medicine.
Anti-Bacterial Agents↗
Serum gentamicin assay by high-performance liquid chromatography.
We describe a high-performance liquid chromatographic method for the quantitative determination of gentamicin in serum. The antibiotic was separated from serum by passage through a silicic acid column, derivatized with o-phthalaldehyde, and eluted with ethanol. The derivatized gentamicin was then separated into all three of its major components by reversed-phase chromatography and quantified by fluorometry. Concentrations in serum as low as 0.5 mg of gentamicin per liter could be accurately determined. A standard curve showed a linear response for serum containing gentamicin at concentrations ranging from 0 to 20 mg/liter. Tobramycin, amikacin, ampicillin, penicillin G, methicillin, carbenicillin, chloramphenicol, clindamycin, and cephalothin did not interfere with the gentamicin assay. Comparison with an accepted microbiological assay yielded a correlation coefficient of 0.99. This chemical assay is rapid (less than 30 min), sensitive, accurate, specific, and appears to be applicable to other aminoglycosides.
Bacillus subtilis↗