Hemodialysis-Associated Infections: Treatment with Cephapirin

Abstract

Large doses of cephapirin (50 mg/kg) administered during the first and last half hours of routine hemodialysis produced effective antimicrobial serum concentrations for 48 h. Repetitive administration during five successive hemodialysis sessions did not result in accumulation or accelerated metabolism of cephapirin. Ten infectious episodes in nine patients were treated in this manner with good clinical results and no toxicity.Much of the morbidity of chronic renal failure has not been relieved by hemodialysis (HD). Infections remain among the most common causes of hospitalization and death (6). Contributing to a lengthy hospitalization may be the administration of parenteral drugs by recommended schedules (3)(4)(5). If infections can be treated by administering antibiotics only at the time of HD, the benefits will include cost reduction, the length of hospital stay, and the achievement of a full course of therapy.Cephapirin, a semisynthetic cephalosporin for parenteral use, has been chosen to test this proposal. It is a derivative of 7-aminocephalosporanic acid and is metabolized to desacetylcephapirin, which also appears to be microbiologically active (7). The half-life of 1.0 g of cephapirin during HD is 107 min (5). There are no data regarding the dose of cephapirin that must be administered during HD to maintain sufficient antibacterial activity for the interdialysis period, usually a minimum of 42 h. We have performed single-and multiple-dose pharmacokinetic studies to establish dosage schedules and treated 10 infectious episodes to determine the feasibility of this approach. MATERIALS AND METHODSSingle-dose pharmacokinetics. Nine patients with end-stage renal disease and no other active clinical illness whose creatinine clearances were <5 ml/min were studied on either a Travenol, Lifemed, or Milton Roy recirculating single-pass HD machine using extracorporeal EX-23 coils. A 40-mg/kg amount of cephapirin was administered by intravenous infusion over 30 min, starting 1 h before HD; arterial and venous samples were drawn at the initiation of HD, at 1, 2, and 4 h, and at the completion of HD. Multiple-dose pharmacokinetics. Five patients received 50 mg of cephapirin per kg in 75 ml of normal saline during the first 30 min of a routine HD (predialysis dose) and then received a duplicate amount of the drug during the last 30 min of HD (postdialysis dose). Cephapirin was administered through the arterial line of the dialyzer and was drawn in by the negative pressure of the machine. Venous blood samples were obtained at the conclusion of each HD period (peak) and just before the initiation of the next session (trough). HD was conducted for 5.5 h on a schedule of three times a week; the patients were studied for five consecutive HD periods. After administration of the last dose of cephapirin, serum concentrations were assayed at 24, 48, and 72 h.Plasma assay cephapirin. Arterial and venous blood samples were drawn in 5-ml sodium heparin vacuum tubes. Blood samples were placed immediately in an ice bath, and the pla...

Pharmacokinetics of ceforanide in patients with end stage renal disease on hemodialysis

“…Antibiotic-free human plasma was the diluent for all specimens except for the dialysate assay, in which antibiotic-free dialysate was used. These methods have been previously described (2,3,6).…”