Basic and clinical studies on cefamandole

Abstract

Cefamandole sodium (CMD), a newly synthesized cephalosporin antibiotics, was examined on its in vitro activity against bacteria isolated from human infection foci, serum levels and urinary excretion rates in human, tissue concentrations in rats, serum and bile levels and biliary excretion rates in rabbits as well as its effectiveness in clinical cases. The results obtained were as follows: 1) Antibacterial activity: CMD was found to be more active against most of E. coli and P. mirabilis strains than cephalothin (CET), cefazolin (CEZ), cephaloridine (CER) and cefoxitin (CFX). Against S. aureus, CMD was found to be similarly active to CEZ, more active than CFX, and less active than CET and CER, although most of P. vulgaris and P. rettgeri strains were highly resistant to CMD. 2) Serum level and urinary excretion (human): The peak serum level of CMD in a patient with liver cirrhosis was found to be 86 μg/ml at 15 min. after single intravenous injection of 1 g and the serum levels descended thereafter as follows; 30 min. 68 μg/ml; 60 min. 49 μg/ml; 120 min. 28.6 μg/ml; 240 min. 3.2 μg/ml; 360 min. 0.8 μg/ml. The urinary excretion rate was 52% in 6 hours after administration. 3) Organ distribution (rats): The highest tissue concentrations of CMD after intramuscular administration of 100 mg/kg were found in kidneys, followed by liver, serum, lungs, muscles, spleen and brain. This distribution pattern was similar to that of CEZ and CFX. The peak levels of CMD in kidney, liver, serum and lungs were higher than those of CEZ and lower than those of CFX. The descent of CMD tissue concentrations was more gradual than that of CFX and steeper than that of CEZ. No remarkable inactivation of CMD mixed with rat organ homogenates was observed after overnight storage in a icebox. 4) Biliary excretion (rabbits): Concentrations of CMD in the bile of rabbits collected through choledochus canula was estimated at 10 min. intervals after an intravenous injection of 50 mg/kg. Markedly higher (4–5 times) concentrations were found in the bile than in the sera throughout the 3 hr. course of the experiment. The total biliary recovery of CMD in 3 hrs. reached up to 1.2–1.4% of the dose. Comparing these findings with those formerly obtained about CEZ and CER, the biliary excretion of CMD was similar to that of CEZ, while that of CER was much lower than them. 5) Clinical trials: Eight clinical cases (pneumonia 2, biliary tract infection 2, U. T. I. 2, sinusitis 1, peritonitis 1) were treated with CMD 1–2 g/day by intravenous injection or drip infusion. Excepting two drop out cases (one pneumonia case died of heart failure, another sinusitis case discharging P. aeruginosa) four out of six cases favorably responded to the treatment. No side effects were observed, although one case showed temporary eosinophilia (11%). © 1979, Japanese Society of Chemotherapy. All rights reserved.