1984 Volume 32 Issue Supplement2 Pages 440-451
A new semisynthesized penicillin TA-058 for parenteral use, with broad spectrum for gram positive and negative bacteria, was administered to 21 hospitalized patients with infection of abdominal organs: 12 with acute appendicitis, 5 with cholecystitis and cholangitis, 3 with acute panperitonitis and intestinal obstruction due to abdominal cancer and one with duodenal ulcer. TA-058 at a dose of 1 g was given by intravenous bolus injection before or during operation. Tissue specimens of different sites were taken from the surgically removed organs. Samples of purulent ascites and the biles were subsequently taken at intervals.
TA-058 concentration was determined according to a plate agar well bioassay method with M. luteus ATCC 9341 or E. coli ATCC 27166 as the test organisms.
The levels of TA-058 in the common duct bile increased quickly after injection and reached to the peak about at 1 hr. and then declined very slowly. That of the peak level was 520.0μg/ml and the mean level was 256.74±131.79μg/ml (5 cases, n=12) at 28 to 166 min. after the administration. In cases of obstructed cystic duct, TA-058 was observed in the gall bladder bile through the gall bladder wall, the peak level was 29.4μg/ml and the mean level was 11.67±17.29μg/ml (2 cases, n=4) at 13 to 197 min. after injection. In cases of opened cystic duct, which reached 285.0μg/ml, that was higher than in the common duct bile, and the mean was 172.0±80.19μg/ml (2 cases, n=4) at 125 to 178 min. after injection. TA-058 peak level in gall bladder wall was 32.7μg/g and the mean level was 16.3±9.44μg/g (5 cases, n=7) after i. v. TA-058 level in the infected appendix wall was directly proportional to degree of severity of inflammation, that the mean level was 9.22±14.61μg/g (12 cases) at 15 to 103 min. after i. v. TA-058 observed quickly in purulent ascites and stayed high levels for a long time. In purulent ascites of panperitonitis, TA-058 levels were trace, 0.83, 8.3, 48.0, 44.0 and 43.3μg/ml at 0, 1, 2, 53, 63, 70 min. after injection, respectively. The mean level of purulent ascites was 26.42±17.44μg/ml (4 cases, n=15) at 0 to 70 min. after i. v. In cases of empyemic appendicitis, TA-058 level in the pus in appendix wall was higher than which in appendix wall itself. The mean level was 11.23±7.79μg/ml (3 cases) after i. v.
These results were suggested, TA-058 gives prolonged high concentrations in the bile, purulent ascites and the infected tissues satisfactory for relatively long time, that were higher than the MICs against pathogenic bacteria, particularly E. coli and K. Pneumoniae.
For this reason, TA-058 is one of the preferred drugs for treatment of abdominal infections.
