Abstract
Fundamental and clinical studies of imipenem (MK-0787), a new type of carbapenem antibiotic, and MK-0787 combined with cilastatin sodium (MK-0791), a renal dipeptidase inhibitor, were carried out.
The results obtained were as follows
1. MK-0787 500 mg alone or MK-0787 500 mg with MK-0791 500 mg was administered by intravenous drip infusion over 30 minutes. Plasma levels of the drug were similar either following the administration of 500 mg of MK-0787 alone or 500 mg of MK-0787 with 500 mg of MK-0791. When MK-0787 was administered with MK-0791, MK-0787 and MK-0791 levels at 2 hours after the end of infusion in uterine arterial plasma were 6.8μg/ml and 3.2μg/ml, respectively, and in venous plasma were 8.4μg/ml and 4.7μg/ml, respectively. MK-0787 tissue levels ranged from 0.8μg/g to 3.8 peg at 205 minutes after the end of infusion. Based on these results, the plasma and tissue levels of MK-0787 and MK-0791 with b.i.d. dosage exceeded the MICs of the drug against clinical isolates in the field of obstetrics and gynecology such as E. faecalis, E. colt Klebsiella sp., Peptococcus sp., Peptostreptococcus sp. and B. fragilis immediately after the administration. However, it seemed that the b. i. d. dosage was insufficient to maintain the in vivo concentration of these agents high enough to inhibit the growth of the above bacteria.
2. Eighteen patients with obstetric and gynecologic infection (12 with intrauterine infections, 2 with pelvic dead space inflammation, 2 with pelvic peritonitis, 1 with a vaginal cuff abscess and 1 with a vulvar abscess) and 1 patient with other infection (abdominal wall abscess) were evaluated, but 1 patient with pelvic peritonitis was later excluded from the efficacy evaluation because of a serious illness. MK-0787/MK-0791 was administered twice daily in a 30-minute intravenous drip infusion. Clinical results were excellent in 1 patient, good in 16 and poor in 1, for an efficacy ratio of 94.4%.
3. No side effects were observed. Only abnormal laboratory findings observed were elevation of S-GOT and S-GPT in 1 patient which normalized 2 weeks after the treatment was discontinued. These results suggest that MK-0787/MK-0791 will be useful for the treatment of obstetric and gynecologic infections.
