LABORATORY AND CLINICAL STUDIES ON AC-1370

Abstract

AC-1370, a new cephem invented by AJINOMOTO Co. and developed by MOCHIDA Pharmaceutical Co., was examined on its antibacterial activity in vitro as well as on its clinical effectiveness. The results obtained were as follows:
1) Antibacterial activity in vitro: Bacterial strains isolated from human infection foci were examined on their sensitivities against AC-1370 in comparison with those against cefoperazone (CPZ), cefotaxime (CTX), and cefazolin (CEZ).
Strains of each species showed sensitivities against those antibiotics in the orders as follows:
S. aureus: CEZ>CTX>CPZ>AC-1370 E. coll. CTX>CPZ>CEZ AC-1370 Klebsiella: CTX>CPZ>CEZ>AC-1370 Serratia: CTX>CPZ AC-1370 CEZ E. cloacae: CTX>CPZ>AC-1370 CEZ P. aeruginosa: CPZ t AC-1370>CTX P. mirabilis: CTX CPZ AC-1370>CEZ Indole (+) Proteus: CTX>CPZ>AC-1370 I, : CEZ
2) Blood levels and urinary excretion: A 38y old male suffering from bronchial asthma with normal renal function was administered with i.v. drip infusion of 1 g AC-1370 for one hour. The blood level of the drug rose up to the peak of 92 μg/ml at the end of the infusion, gradually descending down to 1.1 gg/ml six hours thereafter. 88.3% of the dose was recovered from his urine in seven hours.
Taking this opportunity, the lengths of the inhibitory zones produced by AC-1370 on agar plates (“Band Culture Method” OKUBO) were compared among the drug solutions diluted with fresh human serum, inactivated human serum, “monitrol” serum, and phosphate buffer: The inhibitory zone was longest when the solution was made of fresh human serum.
3) Clinical trials: Eighteen patients (RTI 12, UTI 3, BTI 2, and subcutaneous phlegmon 1) were treated with AC-1370 0.5-2.0 g twice daily by d.i. Two of the RTI cases were dropped out during the administration as they were diagnosed as pulmonary tuberculosis. Eleven of the remaining 16 cases (68.8%) well responded to the therapy, and two fairly. Neither clinical untoward reactions nor abnormal laboratory findings attributable to the drug administration were observed except for GOT and GPT elevation in two of the patients.
Considering the reported evidence that AC-1370 shows significant in vivo activity against experimental infections despite its relatively weak antibacterial activity in vitro, the drug should become one of the useful chemotherapeutics in the clinic.