Cephacetrile, a new cephalosporin: in vitro, pharmacological and clinical evaluation.

Cephacetrile, a parenteral cephalosporin, was evaluated for in vitro antibacterial activity, clinical pharmacology and effectiveness in the treatment of severe infections. The antibacterial activity against 187 isolates was determined by an agar-dilution technique. The MICs were 0.06 to 0.5 mug/ml for Group A Streptococcus, D. pneumoniae, and Staph. aureus, 4-6 mug/ml for E. coli and Klebsiella-Enterobacter 8-32 mug/ml for Pr. mirabilis and more than 500 mug/ml for Ps. aeruginosa. A few strains of Klebsiella and E. coli had MICs of more than 125 mcg/ml. Serum levels after 0.5 and 1 g of i.m. cephacetrile were respectively 14.6 and 18.6 mug/ml after 1 hr, and 1.5 and 2.5 mug/ml after 6 hr. Serum levels after i.v. infusion of 0.5 and 1 g were respectively 16 and 25 mug/ml after 1 hr., and 1 and 2 mug/ml after 6 hr. Urine levels after 0.5 and 1 g i.m. cephacetrile were respectively 500 and 650 mug/ml in the 0-3 hr period, and 250 and 300 mug/ml in the 3-6 hr period. Renal clearance was 166 +/- 5 ml/min/1.73 m2; renal excretion was about 20% of the dose 6 hr after i.m. injection. Cephacetrile was well tolerated when administered i.m. with lidocaine. Mild phlebitis occurred sometimes after i.v. infusions. The clinical response, evaluated in 36 patients with severe systemic, respiratory and urinary infections, was good in all but two cases.