cefsulodin and Peritonitis

The kinetics of cefotiam and cefsulodin were studied in plasma and dialysate after intravenous and intraperitoneal administration of 1 g to patients undergoing continuous ambulatory peritoneal dialysis. Instillation of autologous hemoglobin as a marker permitted calculation of the cavity volume and, hence, the rate of transfer to and from the peritoneal cavity with time. The patients were divided into 4 groups. Groups 1 and 2 were intravenously given cefotiam (5 patients) and cefsulodin (4 patients), respectively. Groups 3 and 4 (5 patients each) were given cefsulodin intraperitoneally. Group 3 did not have peritonitis, while the patients in Group 4 were studied during peritonitis. Blood and dialysate samples were obtained at selected times during the 5-hour dwell and, for plasma, until 24 hours after drug administration. Pharmacokinetic analysis of the data showed that only 6.0 and 8.7% of the intravenous doses of cefotiam and cefsulodin, respectively, were recovered in the dialysate at the end of the dwell. The net amounts of cefsulodin lost from the dialysate after intraperitoneal administration were 81 and 84%, in Groups 3 and 4 respectively. The peritoneal transfer clearances (using a unidirectional clearance model), calculated after intravenous (17 +/- 10 ml/min, Group 2) and intraperitoneal (17 +/- 5 ml/min, Group 3) administrations were the same. Mass balance of cefsulodin in the body and in the dialysate after intraperitoneal administration indicated that a significant amount (40%, Group 3) of the dose is unaccounted for. One explanation for this imbalance is retention of the drug in the peritoneal lining. This hypothesis is supported by the retention being lower in the peritonitis patients (less than 20%, Group 4), for whom the linings are expected to be partially eroded.

Topics: Adult; Aged; Aged, 80 and over; Biological Transport; Cefotiam; Cefsulodin; Hemodialysis Solutions; Humans; Infusions, Parenteral; Injections, Intravenous; Middle Aged; Peritoneal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

Cefsulodin (CFS), a new antipseudomonal cephalosporin, shows a potent antibacterial activity against Pseudomonas aeruginosa and some Gram-positive bacteria, whereas it shows low activity against many Gram-negative rods. Against clinical isolates of P. aeruginosa, CFS was about 10 times more active than sulbenicillin and carbenicillin, and had a similar activity to gentamicin and dibekacin. The CFS was administered by an intravenous bolus injection at a dose of 1 g to each of 14 patients operated for acute peritonitis with drainage or radical mastectomy with drainage to treat breast cancer. These cases included 3 of localized peritonitis due to perforative appendicitis, 3 of diffuse peritonitis due to perforative duodenal ulcer, 2 of panperitonitis due to intestinal obstruction and perforative sigmoid colon cancer, 4 of subacute cholangitis, localized peritonitis T-tube choledochal drainage due to choledocholithiasis, and 2 of breast cancer. Materials from drain exudate were taken at intervals with sterilized paper discs and CFS concentrations were determined by the paper disc bioassay method with P. aeruginosa NCTC 10490 as the test organism. Serum concentrations of CFS just after injection reached 135.4 +/- 66.1 micrograms/ml, and they were 2.7 +/- 1.5 micrograms/ml at 6 hours after injection. Concentrations in purulent exudates of patients with acute peritonitis increased quickly after intravenous bolus injections, and reached maximum levels relatively early after injection in cases 2 to 3 days after operation. In cases 10 to 13 days after operation, CFS levels were comparatively low and reached to peak levels at 4 to 5 hours after injection. Levels of CFS in purulent exudate tended to increase in proportion to the severity of symptoms, as did CFS levels in appendix wall. Pseudomonas spp. were not isolated in this study, but MICs of CFS were mostly around 1.56 to 3.13 micrograms/ml when clinically isolated Pseudomonas spp. were present at 10(6) cells/ml. Levels of CFS in infected exudate were higher than the above MIC values against Pseudomonas spp. Therefore, CFS were a useful drug for the chemotherapy against pseudomonal infections.

Topics: Acute Disease; Adult; Aged; Cefsulodin; Drainage; Drug Resistance, Microbial; Exudates and Transudates; Female; Humans; Injections, Intravenous; Kinetics; Male; Middle Aged; Peritonitis; Pseudomonas aeruginosa