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DiscussionCarbenicillin is an established antibiotic for infections due to two difficult groups of organisms-Ps. aeruginosa and the indolepositive Proteus spp.4 Non-,3-lactamase-producing E. coli are very susceptible to carbenicillin and Str. faecalis moderately so. Though carbenicillin is particularly useful against Ps. aeruginosa high parenteral doses (up to 30 g/day) may be needed to treat systemic infections with this organism. High urinary concentrations of carbenicillin have been reported,5 with intramuscular doses of 500 mg giving concentrations greater than 500 mg/l. Such levels will eradicate sensitive Ps. aeruginosa (M.I.C.< 100 mg/l) but the injections are often painful and the patient usually needs to be in hospital.Serum levels in volunteers and patients after oral carfecillin were found to be insufficient to treat systemic infection with Ps. aeruginosa, even when renal function was impaired, but urinary levels were sufficient to suggest that urinary infections might be eradicated.In severe renal failure the mean serum half life of carbenicillin is only 10-20 hours,2 which is short compared with that of gentamicin particularly as our dose was lower and given for seven days instead of 14. Our patients also had a high prevalence of urinary tract abnormalities. The overall cure rate with indanyl carbenicillin in the series of Ries et al. 9 was 50% as compared with 60% in our series, though no pseudomonas infections were treated with indanyl carbenicillin in the former series as compared with 12 in ours. Ps. aeruginosa rarely causes primary, uncomplicated urinary tract infection but it may cause infection secondary to other urinary tract conditions or operations where catheterization may have been necessary."' The only antibiotic therapy available to such patients is by the parenteral route, which usually means a stay in hospital. The availability of a well-tolerated oral agent for such cases represents a therapeutic advance. Further studies with carfecillin are necessary, and possibly a longer course of treatment should be given in difficult cases, but this drug promises to be a useful oral treatment of urinary infections when the choice of effective antibiotics is limited.The formulation of carfecillin to be marketed in the United Kingdom will differ slightly from that used in our studies reported here, the main change being improved oral absorption.3 Its performance in curing infection will probably be at least as good as that of the previous formulation, but side effects and tolerability will need to be reassessed.

Although hyperlipidemia is a well recognized complication of the nephrotic syndrome, the precise disturbances of lipoprotein metabolism which cause the elevated plasma lipid and lipoprotein concentrations have not been clearly defined in humans. This study examines the metabolism of apolipoprotein B-containing lipoproteins in patients with nephrotic-range proteinuria and in healthy controls. Two radioiodinated tracers of very low density lipoproteins (VLDL1, Sf60 to 400, and VLDL2, Sf20 to 60), were used to trace the metabolism of apolipoprotein B through the delipidation cascade from very low density lipoproteins (VLDL) to low density lipoproteins (LDL). The data from the apoB specific radioactivity curves and the pool sizes of apoB in four subfractions were analyzed by a multicompartmental modeling procedure using the SAAM 30 program. The main findings in the nephrotic group were: 1.) a consistent decrease in the fractional rate of apoB transfer from VLDL1----VLDL2 (median values-nephrotic 0.92 pools/day vs. controls 3.66, P less than 0.02) and from VLDL2----IDL (1.49 vs. 2.74, P less than 0.05); 2.) increased secretion of apoB into VLDL2 (14.5 mg/kg/day vs. 4.2, P less than 0.02); 3.) a trend towards decreased removal of IDL and LDL attributable to a defect in LDL receptor-mediated removal as previously shown (Metabolism 39:187-192, 1990). These findings suggest that catabolic defects of the apo B-containing lipoproteins are as important as increased hepatic synthesis in the pathogenesis of nephrotic hyperlipidemia in humans.