Cephalexin: human studies of absorption and excretion of a new cephalosporin antibiotic.

1. Serum levels, half-lives and urine concentrations of cephalexin, an oral cephalosporin antibiotic which is unique in its absorption and excretion, are reported in human volunteers, fasting, non-fasting and non-fasting plus probenecid. Accumulation does not seem to occur.2. Cephalexin clearance was 376 ml./min and the ratio of cephalexin/creatinine clearances was 2.6 in one volunteer.3. Cephalexin had no effect on the urinary excretion of leucocytes, red cells or protein.4. The very high rate of absorption giving high serum levels and urine concentrations suggest cephalexin will be a useful antibiotic in susceptible bacterial infections in man.

Urinary and faecal Escherichia coli O-sero-groups in symptomatic urinary-tract infection and asymptomatic bacteriuria.

The degree of correspondence between urinary and faecal Escherichia coli O-groups has been assessed in non-pregnant women with symptomatic urinary-tract infection or asymptomatic bacteriuria. In 20 of 26 patients with symptomatic urinary tract infection E. coli of the same O-groups as that of the urinary infecting strain was also present in the patient's faecal flora of only five of 25 patients with asymptomatic bacteriuria. This finding indicates that the majority of episodes of symptomatic urinary tract infection in non-pregnant women are not preceded by a significant period of asymptomatic bacteriuria. E. coli O6 showed correspondence between urinary and faecal isolates more frequently than did other O-groups, but it had a relatively low prevalence in the faecal flora of patients with urinary-tract infection caused by E. coli of other O-groups. This finding lends support to previous suggestions that E. coli O6 may be especially pathogenic for the urinary tract.

Serum amyloid P component in chronic renal failure and dialysis.

A normal reference interval for serum amyloid P component (SAP) concentration in the serum was established in 500 healthy adult individuals (274 women, 226 men), by electroimmunoassay calibrated with standards of highly purified, isolated SAP. The mass of SAP in these was determined from the extinction coefficient of SAP at 280 nm measured here precisely for the first time by spectrophotometry and cryogenic drying. The mean (SD, range) SAP concentration was significantly lower in women: 24 mg/l (8, 8-55), compared to 32 mg/l (7, 12-50) in men (P less than 0.001). In renal insufficiency patients, 38 with chronic renal failure, 79 on hemodialysis and 66 on continuous ambulatory peritoneal dialysis, the mean values for SAP concentration were all significantly higher than normal (range of means, 39-59 mg/l in men and 35-42 mg/l in women), but did not correlate with serum creatinine, duration of dialysis or the presence of an acute phase response. The metabolism of SAP is thus altered in renal failure and is not normalized by dialysis, but it is not clear whether this is relevant to the pathogenesis of dialysis related arthropathy and amyloidosis.

Joint problems in patients on maintenance hemodialysis.

A questionnaire about joint symptoms was sent to 130 maintenance hemodialysis patients. All patients had a skeletal survey to assess the degree of hyperparathyroidism. 40 patients had no joint symptoms, 31 had mild joint symptoms, and 59 had severe joint symptoms. A higher proportion of these patients had radiological evidence of hyperparathyroidism, vascular or soft tissue calcification. Several different patterns of joint symptoms evolved including calcification problems, carpal tunnel syndrome, avascular necrosis, ruptured tendon and infection. We also describe a new syndrome of recurrent hemarthroses progressing to chronic capsulitis occurring in patients who have been on dialysis for more than 10 years.

Heparin inactivation, acidosis and copper poisoning due to presumed acid contamination of water in a hemodialysis unit.

An accident in a hemodialysis unit involving 13 patients is reported. Circumstantial evidence suggests that acid contamination of the water supply to the unit resulted in inactivation of heparin with widespread extracorporeal clotting and secondary copper intoxication which proved fatal in one patient. Serum copper concentrations were raised in 6 of the 11 patients and whole blood copper concentrations were raised in 4 patients. Results of serum ceruloplasmin, whole blood lead and zinc analyses are reported together with tissue analyses for copper in the fatal case. The majority of the patients showed evidence of a metabolic acidosis.

Reticulosarcoma occurring during long-term hemodialysis.

Reticulosarcoma occuring during long-term hemodialysis. A case of chronic renal failure due to polycystic disease of the kidneys with development of a reticulosarcoma with cerebral involvement during maintenance hemodialysis is described. Immunosuppression from uremia could have played an important part in tumor induction in this case and might also be a significant factor in the high incidence of de-novo malignancies in renal transplant recipients.

Rhabdomyolysis and acute renal failure in chronic alcoholics with myopathy, unrelated to acute alcohol ingestion.

Rhabdomyolysis leading to acute renal failure necessitating hemodialysis is described in three chronic alcoholics. In each case an acute medical or surgical event, but not alcoholic intoxication, was implicated. Renal biopsies demonstrated acute tubular necrosis with intraluminal deposits consisting of Tamm-Horsfall protein and myoglobin. After recovery all three patients were demonstrated to have proximal muscle weakness with similar electromyographic abnormalities but nerve-conduction was impaired in only two. Muscle biopsies showed mixed, but predominantly type II fiber atrophy and reduced muscle phosphorylase levels. In the one patient tested the lactate response to forearm muscle ischemia was abnormal. It is postulated that chronic alcoholics may be predisposed to rhabdomyolysis and acute renal failure following acute medical and surgical stress as well as acute alcohol abuse. The muscle damage in these patients may be due to impaired intra cellular glycogen metabolism.

The serum half-life and urine concentrations of cephazolin sodium in patients with terminal renal failure: effect of haemodialysis.

The serum and plasma half-life of cephazolin has been determined in 5 maintenance haemodialysis patients during a non-dialysis period and then again in the same patients during haemodialysis with a Meltec Maxi-Multipont dialyser using cuprophance membranes. The mean half-life during the non-dialysis period was 28.3 hours and fell to a mean of 4.97 hours during haemodialysis. Percentage recovery of cephazolin in the urine was markedly reduced in 4 maintenance dialysis patients although adequate urine concentrations of cephazolin were achieved for many sensitive organisms. A dosage schedule for patients with creatinine clearances of less than 5 ml. per minute and for maintenance haemodialysis patients is suggested.

A prospective study of patients with radiological pyelonephritis, papillary necrosis and obstructive atrophy.

Twenty-six patients with radiological unilateral chronic pyelonephritis, 36 patients with bilateral chronic pyelonephritis, 14 patients with papillary necrosis and nine patients with obstructive atrophy have been followed from five to 135 months for a total of 374 patient years. Serial changes in renal function and pyelographic appearances have been correlated with bacteriuria, analgesic ingestion, blood pressure and reflux. The calculated survival rate at five years was 95 per cent for patients with bilateral pyelonephritis and 92 per cent for patients with papillary necrosis. The ten-year survival rate was 86 per cent and 56 per cent respectively. The survival rate for patients with unilateral pyelonephritis and obstructive atrophy was 100 per cent at five and ten years. Bacteriuria was not associated with deteriorating renal function determined by serial plasma creatinine estimations. Although all patients in whom there was some radiographic change had bacteriuria on later review, other factors, including excess analgesic intake, reflux and stones were recognized in most. There was a high incidence of analgesic ingestion among patients whose renal function declined and in whom there was some change in serial radiographs. The prevalence of hypertension among patients with normal renal function was 12 and 28 per cent for patients with unilateral pyelonephritis and bilateral pyelonephritis respectively. There was a significant increase in both blood urea and plasma creatinine in all patients with hypertension (diastolic pressure greater than 90 mm Hg) and a much higher prevalence of hypertension in patients whose plasma creatinine exceeded 1.3 mg/100 ml. Thrity per cent of patients with unilateral pyelonephritis and 50 per cent with bilateral pyelonephritis had vesicoureteric reflux of varying degrees. There was no evidence to suggest that major degrees of reflux (grade 3) was associated with further renal damage. These observations indicate the benign course of the majority of patients with radiological pyelonephritis. Control of blood pressure, and analgesic intake will help to preserve renal function whilst prevention of symptomatic urinary infection by long term low dose therapy will reduce morbidity.

Dialysis arthropathy, beta 2-microglobulin and the effect of dialyser membrane.

Patients with dialysis arthropathy had the greatest mean serum beta 2-microglobulin (59.5 mg/l) but there was no threshold concentration of beta 2-microglobulin above which all patients developed dialysis arthropathy. Haemodialysis patients without dialysis arthropathy and patients on continuous ambulatory peritoneal dialysis (CAPD) also had grossly elevated values of beta 2-microglobulin (47.9 mg/l and 30.7 mg/l respectively). There was a significant positive correlation between duration of treatment and serum beta 2-microglobulin for the patients treated by haemodialysis, but this was not the case for patients on CAPD. There was a significant negative correlation between residual urinary volume and serum beta 2-microglobulin for the patients on haemodialysis without dialysis arthropathy, and also for the patients on CAPD. This was not true for the patients with dialysis arthropathy. Both duration of treatment and residual urine volume correlated with serum beta 2-microglobulin, and therefore an analysis of covariance was used to take account of this in comparing the groups. This showed that there was no difference between serum beta 2-microglobulin in haemodialysis patients with and without dialysis arthropathy. However, CAPD patients had a significantly lower corrected mean serum beta 2-microglobulin. Haemodialysis with cuprophane membranes was associated with an increase in beta 2-microglobulin of 11.5%, whereas haemodialysis with polycarbonate was associated with a decrease of 6.8% at 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Some administrative problems in adaptation of houses for home dialysis.

A study of the rate of adaptation, cost, and method of payment for converting the house for home dialysis in 35 patients from Fulham Hospital has shown considerable differences among local authorities in assessing and demanding contributions from patients in various areas. It is shown that delay in adapting houses has resulted in the dialysis unit being unable to take on at least 19 new patients during the years 1967-70. A more uniform approach, together with some central financial arrangements, might avoid undue hardship and delay.

The pharmacokinetics of cefuroxime after intravenous injection.

Cefuroxime, a new cephalosporin antibiotic which is stable to most beta-lactamases produced by gram-negative bacteria, was given by bolus intravenous injection to six volunteers in doses of 500 mg and 750 mg. The concentrations of cefuroxime in serum and urine were measured at pre-determined times after injection and the data analysed by a two-compartment open system model. A serum concentration of 8 microgram/ml was exceeded for 100.3 min (+/- 18.3) after a 500 mg dose and for 144.5 min (+/- 19.8) after 750 mg. The ultimate serum half-life was 1.1 h. Excretion of cefuroxime in the urine was almost complete in 24 h, the clearance being 150 ml/min/1.73m2. About 45% was excreted through the renal tubules. The injections were well tolerated and no changes in haematological or biochemical values were seen. The resulting data are compared with those published for some other cephalosporins. It is concluded that the favourable pharmacokinetics, especially the high concentrations of unbound cefuroxime in the serum, are likely to aid effective therapy of human infection caused by sensitive bacteria.

Comparative double-blind study of cephalexin and co-trimoxazole in urinary tract infections.

Treatment with cephalexin 1 g twiec daily and cotrimoxazole 2 tablets twice daily was compared in a double-blind, randomised study of 100 women with urinary tract infections. CO-trimoxazole gave a significantly higher cure rate compared with cephalexin two and six weeks after the one-week course of treatment. The higher failure rate with cephalexin was not related to the age of the patient, presentation, pyelographic appearances, or type of organism in the initial infection. Among the failures all but one of the organisms were sensitive to cephalexin. With the dosage regimen and duration of treatment used in this study cotrimoxazole appears to be superior to cephalexin in the management of acute urinary infections.