Treatment of life-threatening multiresistant staphylococcal and enterococcal infections in patients with end-stage renal failure with quinupristin/dalfopristin: preliminary report.

Background: Life-threatening infections with multiresistant gram-positive bacteria are increasing. Treatment with quinupristin/dalfopristin (Q-D) has turned out to be effective against such resistant pathogens.

Patients And Methods: We report on treatment of six patients on dialysis (four with additional liver injury) and of one renal graft recipient with normal renal function who had severe infections caused by multiresistant Staphylococus epidermidis (1/7), methicillin-resistant Staphylococcus aureus (4/7) and vancomycin-resistant Enterococcus faecium (2/7).

Cefodizime once daily in the treatment of lower respiratory tract infections.

Cefodizime (CAS 69739-16-8, HR 221) is a new third-generation cephalosporin with pharmacokinetic properties that make it suitable for once-daily administration in the treatment of lower respiratory tract infections (LRTI). Ninety-nine adult hospitalized patients (66 males, 33 females, median age 57.5 years) received a once-daily injection of 2 g cefodizime for LRTI.

Doppler echocardiographic study of three different mechanical valves in the aortic position: the use of external nominal diameter indexed to body surface area.

Background And Aims Of The Study: Previous studies have demonstrated the benefit of indexing body surface area (BSA) with ventriculo-arterial orifice diameters (or calculated effective surface dynamics) and with nominal external diameters of valves in order to study hemodynamic profiles in vivo or determine the clinical influence of this parameter. This study analyzes the relationship between BSA and nominal external diameter of mechanical valves implanted in the aortic position. It also evaluates the potential interest of using these diameters indexed to BSA in an echo-Doppler study of valves.

Cefodizime given in single or divided doses for the treatment of lower respiratory tract infection.

The safety and efficacy of two dose regimens of cefodizime (CAS 69739-16-8, HR 221) in hospitalized patients with lower respiratory tract infections were assessed in two consecutive studies. Sputum bacteriology, chest X-ray and a safety laboratory check were performed at baseline and after therapy. In order to compensate for the lack of a double-blind design the evaluation was conducted as a clinical intention-to-treat analysis.

Antibiotics and production of granulocyte-macrophage colony-stimulating factor by human bronchial epithelial cells in vitro. A comparison of cefodizime and ceftriaxone.

Cultured human bronchial epithelial cells (HBEC) produce both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 8 (IL-8). The influence of cefodizime (CAS 69739-16-8), a new broad spectrum cephalosporin with immunostimulatory effects, and ceftriaxone on the production of GM-CSF and IL-8 in HBEC primary cultures was investigated. HBEC were isolated from biopsy specimens obtained during fibreoptic bronchoscopy in 12 patients (most frequent diagnosis: chronic bronchitis).

Concentrations of cefodizime in bronchial secretions after single intravenous administration.

Unlabelled: The concentrations of cefodizime (HR 221, CAS 69739-16-8) in bronchial secretions were measured after administration of a single intravenous bolus of 2 g in 19 patients requiring fibreoptic bronchoscopy for diagnostic purposes or as therapeutic follow-up. These concentrations, which were obtained in absence of inflammation of the mucosa, were compared to serum concentrations obtained simultaneously. The penetration into bronchial secretions was rapid, maximum levels of between 1 and 5 mg/kg being already observed 1 h after injection.

Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole.

Twenty-three stabilized chronic uremic patients with no active or recent infection were treated for 10 days with either cefodizime (5 x 2 g intravenously, n = 10) or cotrimoxazole (960 mg orally b.i.d.

Effect of cefodizime on parameters of cell-mediated immunity in vitro.

A positive effect of cefodizime (CAS 69739-16-8), a new aminothiazolyl cephalosporin, on a number of immunological variables, and in particular phagocytosis, was demonstrated in several test systems. The aim of the present investigation was to establish whether clinically relevant concentrations of cefodizime affect cell-mediated immune variables. Peripheral lymphocytes from healthy subjects were isolated and incubated with cefodizime in increasing concentrations from 0 to 200 mg/l.

Treatment of acute gonococcal infections in Bangkok with a dose range of the new cephalosporin, cefodizime.

In this randomized dose range study conducted in Bangkok, 326 patients with presumed acute uncomplicated gonorrhoea were treated with a single intramuscular dose of either 0.25 g, 0.5 g, or 1.

Pharmacokinetic profile of cefodizime.

The pharmacokinetics of cefodizime (CDZ) were determined after i.v. and i.

Cefodizime: a new cephalosporin with apparent immune-stimulating properties in chronic renal failure.

In vitro experiments suggest that cefodizime, a new cephalosporin, causes an increase in phagocytic capacity. We therefore evaluated the effect of cefodizime on the phagocytic system in haemodialysis patients by an estimation of the 14CO2 production during glucose metabolisation by phagocytic cells, in the resting state, and after zymosan and latex. The production of 14CO2 after latex increased in five of six patients (mean +/- SD: from 17,932 +/- 11,859 before to 21,183 +/- 7849 d.

Dose linearity and other pharmacokinetics of cefodizime after single-dose intravenous administration.

Pharmacokinetics of cefodizime, a broad-spectrum cephalosporin antibiotic, were determined after intravenous (IV) administration of single doses of 1.0, 1.5, and 2.

Influence of experimental rhinitis on the gonadotropin response to intranasal administration of buserelin.

The influence of experimental rhinitis on the absorption of buserelin, measured as the serum luteinizing hormone (LH) response, has been investigated. A single dose of 200 micrograms buserelin was given to 24 healthy male volunteers after induction of experimental rhinitis with histamine and after use of a saline spray (placebo control). Except on one occasion, when the pump-spray apparently was incorrectly operated, serum LH concentration rose after buserelin.

Multiple-dose pharmacokinetics of ofloxacin, a new broad-spectrum antimicrobial agent.

Twelve healthy male volunteers received 14 oral doses of ofloxacin (300 mg each), and the concentrations of the unchanged drug were measured at various times in serum and urine over a period of 15 days. Serum and urine ofloxacin concentrations were determined in specific assays using high-pressure liquid chromatography (HPLC); urine levels were also determined by means of a microbiological assay. A washout period of 72 hours followed the first and 14th doses, allowing comparison of serum pharmacokinetics at the beginning and end of the multiple-dose regimen.

The effect of food on the pharmacokinetics of ofloxacin.

After oral administration of a single dose of ofloxacin (300 mg), with and without a standard breakfast, to 12 healthy male volunteers in an open, randomized crossover study, concentrations of the unchanged drug were estimated at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a wash-out period of 1 week. Ofloxacin concentrations were determined using high pressure liquid chromatography (HPLC): parallel determinations using a microbiological assay were in close agreement.

[Clinical pharmacology of ofloxacin: a new chemotherapeutic agent belonging to the gyrase inhibitor group].

Ofloxacin (HOE 280, DL 8280, OFX) is a new broad-spectrum chemotherapeutic agent belonging to the group of the gyrase inhibitors. The tolerability and pharmacokinetics have been investigated for the dose range from 100 mg to 2 X 600 mg. The substance has proved to be well tolerated; investigation of the effects on renal enzymes after multiple dosing with 300 mg b.

Dose linearity and other pharmacokinetics of ofloxacin: a new, broad-spectrum antimicrobial agent.

After oral administration of a single dose of ofloxacin (100, 300 or 600 mg) to 13 healthy male volunteers in an open, randomized crossover study, concentrations of the unchanged drug were estimated at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a wash-out period of 1 week. Ofloxacin concentrations were determined using both high pressure liquid chromatography (HPLC) and a microbiological assay.

Renal tolerance of ofloxacin, a new gyrase inhibitor.

An open study was carried out in 12 male, healthy volunteers to investigate the renal tolerance of ofloxacin, a new, broad-spectrum oral antibacterial agent. Subjects received single doses of 300 mg and then repeated doses of 300 mg ofloxacin twice daily for 7 days. Urine was collected in several fractions during the study and the excretion of creatinine, alanine-aminopeptidase (AAP), gamma-glutamyl transferase (GGT) and n-acetyl-beta-glucose aminidase (NAG) was calculated in 12-hour fractions.

A radioimmunoassay to measure piretanide in human serum and urine.

This paper describes a specific radioimmunological method for determining the diuretic agent piretanide (4 phenoxy-3-(1-pyrrolidinyl)-5-sulfamoyl benzoic acid) in human serum, plasma and urine. The antiserum was raised in rabbits against an immunogen of piretanide coupled to bovine serum albumin. The iodinated hydroxy derivative of piretanide was used as tracer.

Thin-layer chromatographic determination of imipramine and desipramine in human plasma and urine at single-dose levels.

Thin-layer chromatographic methods were up-dated for pharmacokinetic studies of imipramine in plasma and urine. The free parent compound and its free desmethyl metabolite desipramine are determined in plasma. Conjugates of both compounds in urine are cleaved on treatment with glucuronidase/arylsulfatase.

Kinetics of UV-erythema in normal subjects.

In the expanding field of clinical dermatopharmacology we standardized an erythema model for testing drugs with effects on UV-induced inflammation in normal male Caucasian subjects. Using a light source with fibre-optic transmission and precise radiation characteristics, some of the shortcomings of conventional UV-application could be overcome. The radiation geometry during the various experiments was kept constant by a tube, permitting a defined area of exposure.

Pharmacodynamics and urine pharmacokinetics of three doses of piretanide.

Three doses (3 mg, 6 mg and 12 mg) of piretanide, a new high ceiling diuretic, and placebo were given to 8 volunteers to investigate the relationship between the pharmacodynamic parameters, the dose and its urinary excretion. Intake of food and fluid were standardized from 48 h before until 24 h after drug administration. Urinary output, excretion of unchanged drug, and the excretion and clearance of Na+ and K+ were measured hourly for 7 h after treatment.

[Adequate and inadequate trials in "clinical" pharmacology].

Our definition, based on 14 years of practical experience, is as follows: In clinical pharmacology, a procedure is adequate if it can be used in normal subjects in a non-invasive way and if it generates relevant information concerning pharmacotherapy in patients. Six examples are discussed in detail; the variable body weight may cause wide variations, for example, in absorption characteristics; unhomogeneous groups of subjects are likely to lead to poorly reproducible results. Body position and food intake (individual eating habits) may disguise drug effects by creating additional "noise".