Fundamental and clinical studies were performed on a newly developed
carbapenem antibiotic,
imipenem/cilastatin sodium (
MK-0787/
MK-0791), and results were summarized as follows. The antibacterial activity of
MK-0787 at an inoculum of 10(6) cells/ml against strains of S. aureus which were sensitive or resistant to
cefazolin (CEZ), E. coli, P. mirabilis, K. pneumoniae, S. marcescens and P. aeruginosa were determined and compared with activities of
ceftazidime (CAZ), CEZ,
cefmetazole (CMZ),
ceftizoxime (CZX),
latamoxef (LMOX),
cefamandole (CMD),
cefoperazone (CPZ),
cefsulodin (CFS) and
piperacillin (PIPC). The peak MIC of
MK-0787 was less than or equal to 0.024 micrograms/ml against S. aureus, which were sensitive or resistant to CEZ, 0.10 micrograms/ml against E. coli, P. mirabilis, or K. pneumoniae, 0.39 micrograms/ml against S. marcescens and 1.56 micrograms/ml against P. aeruginosa. The antibacterial activity of
MK-0787 against these bacteria was, on the whole, superior to that of CAZ, CEZ, CMZ, CZX, LMOX, CMD, CPZ, CFS or PIPC. The pharmacokinetics of
MK-0787/
MK-0791 was studied in 10 children at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg by a 30-minute
intravenous drip infusion. Maximum serum levels of
MK-0787, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg were 41.6 micrograms/ml and 72.9 micrograms/ml, respectively, at the end of infusion and 0.1 micrograms/ml at 6 hours, respectively, after
drip infusion. The half-life of both dose levels was 0.9 hour. Mean peak serum levels of MK-0791, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 49.7 micrograms/ml and 87.0 micrograms/ml, respectively, with half-life of 1.1 and 0.6 hour, respectively. Urinary recovery rates of
MK-0787 for 6 hours at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 47.8-82.7% and 25.5-78.0%, respectively, and of MK-0791 for 6 hours were 51.7-93.4% and 40.3-94.4%, respectively. Twenty-four patients, including 1 with purulent
meningitis, 1 with
septicemia, 1 with
pyothorax, 10 with
bronchopneumonia, 7 with
pyelonephritis and 4 with
infections of cutaneous soft tissue were treated with
MK-0787/
MK-0791 at dose levels of over 100 mg/100 mg/kg/day with purulent
meningitis and
septicemia and 28.8 mg/28.8 mg-72.8 mg/72.8 mg/kg/day with other
infections. The clinical response in all patients was excellent or good.(ABSTRACT TRUNCATED AT 400 WORDS)