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35 males and 23 females with skin and soft tissue infection, lower respiratory tract infection, urinary tract infection or septicemia with known etiology were treated with cefamandole nafate. The patients were to a large extent (30%) alcoholics and/or drug abusers. Cefamandole was given intravenously as 4 daily doses of 1 g in 52 cases and of 2 g in 6 cases for 8 to 16 (mean 10) days. The effect was considered to be good in 40 patients (70%). Adverse reactions, mostly slight and transient, were seen in 22 patients (38%). Peak serum levels varied from 26 to 82 (mean 50) micrograms/ml after 1 g doses and from 68 to 100 micrograms/ml after 2 g. Previous statements of a better in vitro activity of cefamandole than of older cephalosporins against some gram-negative bacilli were corroborated.

Cefamandole levels were measured in peripheral blood, and in skeletal muscle and subcutaneous fat samples taken from 20 patients during amputation of the leg for severe ischemia. Tissue samples were taken from both proximal and distal levels in the amputated limb. Cefamandole was administered as either a 2 g intravenous bolus given with induction of anaesthesia, or a combination of 1 g intramuscularly with the premedication plus 1 g intravenously with anaesthetic induction. Levels of cefamandole in serum and proximal muscle and fat samples were well above the minimum inhibitory concentrations required for most Gram-positive and Gram-negative organisms. Cefamandole levels in more distal samples were somewhat lower but still achieved therapeutic levels in most cases. Higher tissue levels of cefamandole were achieved when 2 g were given intravenously as a bolus.

Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creatinine clearance decreased; i.e., with normal renal function the half-life was 1.49 +&- 0.10 h, and in anephrics the half-life was 11.48 +/- 1.9 h. The greatest increase in half-life occurred when the creatinine clearance was less than 20 ml/min. At these levels of renal impairment, there was significant variance in calculated half-life among patients. The maximum urine concentration and rate of cefamandole urinary excretion decreased as renal function declined. Evidence suggesting renal and nonrenal methods of drug elimination is presented. Hemodialysis resulted in increased cefamandole elimination.