118 patients with complicated intra-abdominal infections participated in an open randomized comparative multicenter trial in order to compare the clinical and microbiological efficacy and safety of biapenem with imipenem/cilastatin (Tienam). 31 men and 27 women (mean age 52.3 years) were enrolled in the biapenem group, and 43 men and 17 women (mean age 52.3 years) in the imipenem/cilastatin group. The patients received either biapenem 500 mg every 8 h or imipenem/cilastatin 500 mg/500 mg every 6 h by intravenous infusion for up to 13 days (mean 6.5 days). 28/43 evaluable patients (65.1%) receiving biapenem and 27/40 evaluable patients (67.5%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 28/43 evaluable patients (65.1%) receiving biapenem and in 27/40 evaluable patients (67.5%) receiving imipenem/cilastatin. No significant differences in clinical or microbiological efficacy between the two treatment groups were found. The present study shows that biapenem may be useful in the treatment of intra-abdominal infections.

In order to compare the clinical and microbiological efficacy and safety of meropenem with imipenem/cilastatin, 249 patients with intra-abdominal infections participated in an open randomised comparative multicentre trial. Seventy-five men and 57 women (mean age 51 years) were enrolled in the meropenem group and 67 men and 50 women (mean age 52 years) in the imipenem/cilastatin group. The patients received either meropenem, 500 mg q 8h, or imipenem/cilastatin, 500 mg/500 mg q 8h by intravenous infusion for up to 17 days (mean 5 days). Ninety-seven of 99 patients (98%) receiving meropenem were clinically cured while 86 of 90 patients (96%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 89 of 94 evaluable patients (95%) receiving meropenem and in 78 of 81 evaluable patients (96%) receiving imipenem/cilastatin. There was no significant difference in clinical and microbiological efficacy between the two treatment groups. Adverse reactions were noted in 26 patients receiving meropenem and in 36 patients receiving imipenem/cilastatin. The present study shows that meropenem is effective and well tolerated in the treatment of intra-abdominal infections.

The immune responses against isolated microorganisms in patients with intraabdominal infections treated with meropenem or imipenem/cilastatin were investigated. Fifty-nine patients received meropenem 500 mg t.i.d. intravenously for 3-21 days (mean 5.4 days) and 50 patients imipenem/cilastatin 500 mg/500 mg t.i.d. intravenously for 3-17 days (mean 5.1 days). Three serum samples were taken from each patient, the first sample at admission, the second sample between three and seven days after start of antibiotic treatment, and the third sample between 14 and 28 days later. Ninety-eight per cent of the patients in the meropenem group and 95% of the patients in the imipenem/cilastatin group were cured. There was no difference in the clinical outcome between the two treatment groups. Escherichia coli, Bacteroides fragilis group, anaerobic cocci, Staphylococcus epidermidis, and Klebsiella spp. predominated among the isolated microorganisms. Thirty-nine patients in the meropenem group had significant immune responses against one or more of the isolated microorganisms while 31 patients in the imipenem/group had significant responses. E. coli and B. fragilis gave rise in antibody titres in most patients indicating that these species are the most important pathogens in intraabdominal infections.

The efficacy and safety of piperacillin plus tazobactam and of imipenem plus cilastatin were compared in an open randomized multicentre study. In the piperacillin/tazobactam group, 40 men and 29 women (mean age 53 years, range 18-92) received 4 g piperacillin with 500 mg tazobactam every 8 h; in the imipenem/cilastatin group 40 men and 25 women (mean age 54 years, range 16-91) received 500 mg imipenem with 500 mg cilastatin, also every 8 h. Antibiotics were administered intravenously for at least three days and for not more than 14 days. Infections were verified by culture of material obtained at laparotomy or by puncture of an abscess before the start of therapy. Fifty of 55 evaluable patients in the piperacillin/tazobactam group (91%) and 40 of 58 evaluable patients in the imipenem/cilastatin group (69%) were clinically cured. Four relapses or failures were recorded in the piperacillin/tazobactam group and 18 in the imipenem/cilastatin group (P < 0.005). Eradication of the microorganisms isolated were similar in both groups. Adverse reactions in both groups were mild and dominated by nausea and diarrhoea. At the dosage used piperacillin/tazobactam was as safe as, and statistically more effective than, imipenem/cilastatin in the treatment of intra-abdominal infections caused by sensitive organisms.

THE study of transplantation antigens in humans depends to a large extent on the existence of suitable immunological techniques in vitro. In animal experiments a cytotoxic technique was found to have wide application for the study of transplantation antigens. It has been clearly shown that iso-antisera directed against histocompatibility antigens can lyse various nucleated target cells in vitro in the presence of complement, usually derived from guinea-pig serum1.