Deferoxamine does not increase the risk for bacteremia in hemodialysis patients.
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Biomedical subjects
Publications and source records attributed to J Boelaert.
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The pharmacokinetics of nisoldipine have been studied after oral administration of one 10 mg tablet to 3 groups of patients: Group A (n = 8) with a mean creatinine of 90 ml/min, Group B (n = 8) with a mean creatinine clearance of 12 ml/min and Group C of 12 patients on maintenance haemodialysis. All of them were studied off-dialysis and 7 were also studied on a dialysis day. No significant differences were observed between Groups A, B and C (on an interdialysis day) in AUC (0-7h), tmax, Cmax and plasma protein binding. Unchanged nisoldipine could not be recovered from the urine in any patient. Haemodialysis did not significantly affect AUC, tmax and Cmax, and nisoldipine could not be detected in the dialysate. The results indicate that the dose of nisoldipine need not be changed in patients with renal dysfunction, and that a supplementary dose is not required after haemodialysis. Blood pressure in the uraemics fell more than in the patients with good renal function.
The single-dose pharmacokinetics of 200 mg of oral itraconazole were studied in seven uremic patients, seven patients treated by hemodialysis, and five patients treated by continuous ambulatory peritoneal dialysis. Plasma concentration-versus-time profiles showed wide intersubject variation. This study could not demonstrate any significant effect of renal dysfunction and hemodialysis or continuous ambulatory peritoneal dialysis treatment upon the pharmacokinetics of itraconazole, and firm conclusions concerning dosing in such patients should await confirmation of our data in a larger patient population.
Increased risk that patients with iron overload who are undergoing dialysis will have bacteremia caused by Yersinia enterocolitica has previously been shown. Iron overload is known to increase the virulence of Y. enterocolitica. Whether alterations of the phagocyte defense against this organism are also involved has not yet been determined. We compared neutrophil defense against a serum-resistant strain of Y. enterocolitica in three groups of individuals: nine patients receiving hemodialysis who had iron overload (group 1), nine patients receiving hemodialysis who did not have iron overload (group 2), and 10 healthy controls (group 3). Y. enterocolitica phagocytosis and killing were studied in the presence of autologous or pooled normal human serum. Phagocytosis was significantly decreased in group 1 compared with that in the other two groups. The use of normal serum for opsonization did not improve the phagocytosis function. Killing was moderately decreased in the group 1, but only in the presence of autologous serum. We conclude that in patients with iron overload who are undergoing dialysis, the high frequency of Yersinia bacteremia is attributable not only to increased virulence of this microorganism but also to disturbances of the mechanisms specifically involved in the neutrophil defense against Yersinia invasion.
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Once daily 60 min iv infusions of acyclovir at 2.5 mg/kg were administered to six uraemic patients (three male, three female of mean age 52 years and body weight 60 kg) treated by continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were taken for analysis of acyclovir by radio-immunoassay. A three-compartment pharmacokinetic model was found necessary to explain the profiles obtained. Steady-state was reached by the third day, with little change in mean peak or trough plasma levels between day one (25 and 3 microM) and day five (29 and 4 microM). Mean total plasma clearance was 46 ml/h/kg, of which 12% was due to peritoneal dialysis. The model parameters predicted efficient transfer of acyclovir from the peritoneum to plasma, such that hypothetical peritoneal dosing might give 91% bioavailability. In patients treated by CAPD, iv acyclovir should be administered at 2.5 mg/kg/day.
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The susceptibility patterns of gram-negative aerobic organisms to aminoglycosides differ widely from one European health care center to another and depend upon local antibiotic prescribing policies. Reports of the susceptibility of Pseudomonas aeruginosa to gentamicin and tobramycin have ranged from as low as 49.8 percent and 77.7 percent, respectively, in Greece, to as high as 96.6 percent and 99.2 percent, respectively, in the United Kingdom. The susceptibility of P. aeruginosa to gentamicin, tobramycin, and amikacin decreased in our hospital from 73.1 percent, 94.8 percent, and 95.6 percent, respectively, in 1982, to 43.1 percent, 70.6 percent, and 74.3 percent, respectively, in 1984. A prospective surveillance study of the susceptibility of gram-negative aerobic bacilli to four aminoglycosides (gentamicin, tobramycin, amikacin, and netilmicin) was performed over a period of 17 months. Gentamicin and tobramycin were freely used, while the use of amikacin was restricted throughout the hospital during a four-month baseline period (May through August 1984). Gentamicin and tobramycin accounted for 94 percent of the aminoglycoside use. During the following 13 months (September 1984 through September 1985), amikacin was used as the first-line aminoglycoside and accounted for more than 97 percent of the aminoglycoside usage. A total of 1,866 organisms were analyzed during the baseline period; 5,429 were analyzed during the amikacin-usage period. The overall susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increased from 86.9 percent, 90.4 percent, 94.2 percent, and 88.3 percent, respectively, to 92.3 percent, 94.0 percent, 97.3 percent, and 92.3 percent, respectively. P. aeruginosa isolates had the most striking changes, with the susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increasing from 43.1 percent, 70.6 percent, 74.3 percent, and 50.6 percent, respectively, during the baseline period, to 64.5 percent, 81.6 percent, 90.8 percent, and 65.1 percent, respectively, during the amikacin-usage period. The use of amikacin as a first-line aminoglycoside, while use of the other aminoglycosides was restricted, seemed to have a favorable influence on the susceptibility pattern of gram-negative aerobic isolates in our hospital.
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Seventy-five aztreonam treatment courses in 74 patients with gram-negative septicemia resulted in 56 clinical cures (75%), 12 partial clinical cures (16%), and 7 clinical failures (9%). Eradication of the original pathogen from the blood was obtained in all patients but two, who had relapses 1 and 4 days, respectively, after treatment. In nine patients (12%) a superinfection was reported. Significant adverse reactions were limited to one transient urticarial rash. Aztreonam may prove to be an effective alternative for the treatment of gram-negative septicemia, but superinfections should be carefully monitored.
Compared with four beta-lactam antibiotics and amikacin, BRL 36650 and BMY-28142 were the most active against 509 Enterobacteriaceae, including cefotaxime-resistant isolates and resistant laboratory mutants. BRL 36650 was more active than aztreonam, ceftazidime, and BMY-28142 against Acinetobacter spp., Pseudomonas aeruginosa, and other Pseudomonas spp.; all strains were inhibited by 2 micrograms/ml or less.
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Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.
Pharmacokinetics of ciprofloxacin after single oral administration of 250 mg were studied in patients with and without renal failure. Ciprofloxacin concentrations were measured by HPLC. The elimination half-life was 8.7 +/- 0.9 h (mean +/- S.E.M.) in six renal failure patients not on haemodialysis, as compared to 4.4 +/- 0.2 h in six patients with normal renal function. The urinary recovery of unchanged ciprofloxacin was 5.3 +/- 1.7% of dose over 24 h in the renal failure patients, as compared to 37.0 +/- 3.7% in the patients with normal renal function. In haemodialysis patients, the half-life was 5.8 +/- 0.9 h on an interdialysis day, and 3.2 +/- 0.4 h during haemodialysis.
The minimum inhibitory concentrations of temocillin against more than 1000 clinical isolates were determined by an agar dilution method. Temocillin showed excellent activity against Haemophilus influenzae, pathogenic Neisseria species and Branhamella catarrhalis, including beta-lactamase producing strains, but showed very low activity or was inactive against Gram-positive cocci and Campylobacter, Bacteroides, Acinetobacter and Pseudomonas species. Good activity was obtained against 702 Enterobacteriaceae, including isolates resistant to the other penicillins and first- and second-generation cephalosporins, with 92% of all the strains inhibited at a concentration of 8 mg/L. However, the most striking property of temocillin was its high beta-lactamase stability which resulted in both a very narrow range of MICs within which all the isolates were inhibited, and a small influence of inoculum size on the MICs.
Temocillin pharmacokinetics in renal impairment were investigated following an intravenous bolus injection of 15 mg/kg. The 28 patients were divided into 5 groups of varying renal function, from normal to uraemic [including a group being treated with haemodialysis and a group on continuous ambulatory peritoneal dialysis (CAPD)]. The distribution of temocillin into the tissues was not affected by renal dysfunction. Uraemia as compared to normal renal function resulted in a 4.3-fold decrease in temocillin clearance and a 3.1-fold decrease in urinary recovery over 24 hours, as well as a 5- and 3.7-fold increase in the beta half-life and the area under the curve (AUC), respectively. Haemodialysis doubled the serum clearance and halved the beta half-life of temocillin in the uraemic subject, but CAPD over 24 hours eliminated only 8% of the temocillin dose, resulting in a minimal change in pharmacokinetics. Temocillin dosage adjustments in renal failure are proposed.