The combination of pivampicillin and pivmecillinam versus pivampicillin alone in the treatment of acute pyelonephritis.

96 patients with clinical symptoms of acute pyelonephritis were randomized to 2 weeks treatment with either a fixed combination of pivampicillin and pivmecillinam or to pivampicillin alone. If needed, treatment was first started with the respective parenteral equivalents of the drugs. Acute pyelonephritis was bacteriologically verified in 57 patients, in whom Escherichia coli was isolated in 80% of the cases, Klebsiella in 7% and Proteus mirabilis in 5%. 22 of the 39 patients excluded did not have significant bacteriuria (less than 10(8) c.f.u./l). Combination treatment was superior to pivampicillin/ampicillin alone, in terms of clinical effect, with successful treatment being noted in 93% in the combination group and in 53% in the ampicillin group (p = 0.002). The combination was also more effective bacteriologically and it did not select resistant strains in the urinary tract. Ampicillin treatment alone, was, however, associated with a significant increase in urinary strains resistant to ampicillin and to mecillinam. Unsuccessful responders had a significantly higher mean age (p less than 0.01) than successful responders. No serious side-effects were noted.

Replacement therapy in terminal renal failure in Sweden 1975-1981. What resources will be needed in the future?

In 1975 the Swedish Society of Nephrology started annual reports on renal replacement therapy in Sweden. 1975-1981 the annual number of new patients rose from 35 to 52 per million, largely due to increasing numbers of older patients (60 years or more) and of diabetics. In three out of seven health care regions the annual incidence was higher, 41-80 patients per million, than in the other four regions (19-49 patients). These differences correlated with the proportions of older patients and of diabetics, suggesting varying selection criteria. During the same period the total number of patients on replacement therapy rose from 103 to 208 per million, in two regions from about 130 to 250, and in five regions from about 90 to 190 per million. The prevalence graphs for all regions run parallel due to higher mortality rates in the regions with high incidence of replacement therapy. About 50% of the patients had functioning grafts, a percentage which did not change throughout the years. It is suggested that at least 65-75 new patients, including 15-17 diabetics, per million population may be candidates for replacement therapy.

The pharmacokinetics of cimetidine and its sulphoxide metabolite in patients with normal and impaired renal function.

1 The pharmacokinetics of cimetidine and its sulphoxide metabolite was studied after a single intravenous dose of 200 mg cimetidine in nine patients with normal renal function and ten patients with severe renal failure on regular haemodialysis and during continuous oral cimetidine treatment in ten patients with normal renal function and 31 patients with different degrees of renal failure. 2 In normal renal function a mean of 47.3% of the single intravenous dose was excreted as unchanged drug and 12.8% as cimetidine sulphoxide. The mean plasma elimination half-life (T1/2) of cimetidine was 2.0 h and of cimetidine sulphoxide 1.7 h. 3 In severe renal failure a mean of 2.2% of the single intravenous dose was excreted as unchanged drug and 0.5% as cimetidine sulphoxide. The mean plasma T1/2 of cimetidine was 3.9 h. The plasma concentrations of the sulphoxide metabolite increased successively with time after dosing and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients with different degrees of renal failure given reduced doses of cimetidine the plasma concentrations of the sulphoxide metabolite were higher with decreasing renal function. The mean plasma T1/2 of cimetidine was 3.1 h in mild renal dysfunction (creatinine clearance 50-75 ml/min) and 4.5 h in severe renal failure (creatinine clearance 5-15 ml/min) and of cimetidine sulphoxide 5.3 and 14.4 h respectively. 5 Toxicity studies of cimetidine sulphoxide may be needed to assess if high plasma concentrations of the sulphoxide metabolite in severe renal failure are of clinical significance.

Pharmacokinetics of cimetidine and its sulphoxide metabolite during haemodialysis.

A single intravenous dose of cimetidine 200mg was administered to 6 patients with severe chronic renal failure one hour prior to haemodialysis. The plasma concentrations of cimetidine and its sulphoxide metabolite at the start of haemodialysis were 2.74 +/- 0.12 and 0.76 +/- 0.08 microgram/ml, and after dialysis for 4h 1.08 +/- 0.10 and 0.51 +/- 0.08 microgram/ml, respectively (mean +/- SE). The average haemodialysis clearance (ClHDa) of cimetidine during dialysis was 46-92 ml/min at a dialysate flow rate of 320 ml/min and blood flow rates in the 6 patients between 160-240 ml/min. The mean ClHDa of the sulphoxide metabolite was 44% higher than that of cimetidine, and ranged between 49-148 ml/min. During haemodialysis the mean plasma elimination half-life (t 1/2) of cimetidine was 3.24h (range 2.08-5.08) and of the sulphoxide metabolite 9.49h (range 4.70-14.39). There was a significant relationship between the elimination rate constant (beta) and ClHDa of the sulphoxide metabolite (p less than 0.01), but no such relationship was found between beta and ClHDa of cimetidine. The mean total amount of cimetidine eliminated during dialysis was 27.3mg (range 17.9-31.8), which was 9.0-15.9% of the given dose. Between 12.2-21.2mg (mean 15.3) of the sulphoxide metabolite was eliminated in the dialysate. Major adjustment of the dose of cimetidine on days of dialysis is not necessary.

Quinton-Scribner arteriovenous shunts for hemodialysis. A review of 6.5 years' experience.

Quinton-Scribner shunts have been used as a reliable access to the blood-stream in 56 patients treated with intermittent hemodialysis in the years 1965-71. The mean age of 29 men and 27 women was 39 years. Two hundred and thirty-two cannulae showed a mean survival time of 11.2 months for 103 arterial cannulae and 9.0 months for 129 venous cannulae. 700 shunt clotting episodes occurred during 1157 patient months, i.e. 0.6 clotting episode/month. In 350 episodes where saline flushing could not remove the clot, the effect of treatment with streptokinase was considered evident in 79.7%. Shunt cannula infection was a common complication while aseptic cutaneous necrosis and bleeding from the cannulated vessel were seen less frequently. Both severe and less harmful bleeding episodes were seen as a complication of dicumarol therapy. The number of complications to streptokinase treatments was low. The advantages and disadvantages of the Quinton-Scribner shunt for hemodialysis are discussed.