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:
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 6.8 micrograms/ml and 3.2 micrograms/ml, respectively, and in venous plasma were 8.4 micrograms/ml and 4.7 micrograms/ml, respectively.
MK-0787 tissue levels ranged from 0.8 microgram/g to 3.8 micrograms/g 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. coli 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. 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%. 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.