Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody.

The monoclonal antibody, 19-F-12 (IgG2b), against human alpha-fetoprotein was conjugated to liposomes containing Adriamycin, and the therapeutic effects of the conjugate were experimentally studied using the alpha-fetoprotein-producing human hepatoma strain, Li-7, maintained in BALB/c nu/nu male mice. Three i.v. injections of liposomes containing Adriamycin (7.5 mg/kg) into tumor-bearing mice significantly inhibited the tumor growth, and the therapeutic effect of the antibody-conjugated liposomes was greater than that of unconjugated liposomes, as judged from the tumor weights and histological findings. Furthermore, the experiments were repeated with Adriamycin (4-5 mg/kg) in free form, since administration of Adriamycin (7.5 mg/kg) in free form was highly toxic for the mice. The results still indicated that the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was superior to that of free Adriamycin or Adriamycin in unconjugated liposomes. In contrast to the treatment for Li-7 in nude mice, the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was not much different from that of Adriamycin in normal mouse IgG (IgG2b fraction) conjugated liposomes against alpha-fetoprotein-negative human breast cancer strain MX1. Tissue distribution studies after i.v. injection of Adriamycin in various forms into mice revealed that preferential delivery of Adriamycin to tumors occurred to some extent with antibody-conjugated liposomes as compared to the unconjugated liposomes. In addition, reduction of the distribution of Adriamycin to the heart was achieved by administering the drug in the liposome-entrapped form, and this enabled the use of a higher dose (7.5 mg/kg) of Adriamycin without toxic side effect.

Interferon beta increases antitumor activity of 5-fluorouracil against human colon carcinoma cells in vitro and in vivo.

The modulating effect of human fibroblast-derived interferon beta (IFN-beta) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells in vitro and in vivo was investigated. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was carried out in vitro using the cultured human colon cancer cell line C-1. IFN-beta at concentrations of 50, 500, 5,000 and 50,000 IU/ml was added to the cultured tumor cells with or without 5-FU at concentrations of 10, 50 and 500 micrograms/ml. The antitumor activity of 5-FU with or without IFN-beta was assessed using Co-4, a human colon carcinoma xenograft in nude mice, with reference to thymidylate synthetase inhibition. IFN-beta was administered subcutaneously daily for 14 days at doses of 6,000, 60,000 and 600,000 IU/mouse. The combined antitumor effect with 5-FU was evaluated by simultaneous intraperitoneal administration of 5-FU at doses of 10 and 20 mg/kg daily for 10 days. The antitumor activity of IFN-beta alone increased in a dose-dependent manner against Co-4 in nude mice, whereas its antitumor activity in vitro against C-1 was limited. The synergistic effect of 5-FU and IFN-beta was observed both in vitro and in vivo, and the in vivo synergism was obtained without any enhancement of thymidylate synthetase inhibition or side effects in terms of death rate and body weight loss. These results suggest that the mechanism of the combined effect of 5-FU and IFN-beta is not related to enhancement of thymidylate synthetase inhibition or the host immune system, since human fibroblastoid IFN-beta is species-specific to humans. The clinical usefulness of this combination method for the treatment of advanced colorectal carcinoma is expected.

Similarity of serum-tumor pharmacokinetics of antitumor agents in man and nude mice.

A pharmacokinetic comparison was made between nude mice and human gastric cancer patients. This comparison is important in order to optimize the human tumor xenograft-nude mouse system as a screening panel for potential antitumor agents. In this report, mitomycin C (MMC), doxorubicin (DXR), 5-fluorouracil (5-FU) and cisplatin (DDP) were administered to nude mice bearing human tumor subcutaneous xenografts in maximum tolerated doses and to patients with gastric cancer at conventional doses. The concentrations of antitumor agents in serum and tumor were detected by bioassay for MMC and 5-FU, by high performance liquid chromatography for DXR, and by atomic absorption method for DDP. Peak drug concentrations in the serum (Cmax) the mice and humans correlated well with statistical significance (R = 0.999, P < 0.0001). When Cmax and drug concentrations in the tumor (T) the mice and human were compared with each other to evaluate the uptake of drugs into the tumor from the serum and calculated as T/Cmax, similar results were observed for the same agent with statistical significance (r = 0.990, p < 0.02). These results indicate that the human tumor xenograft-nude mouse system and humans are essentially similar pharmacodynamically, which further validates the uses of this system to evaluate potential antitumor agents.

Mode of action of estra-1,3,5(10)-triene-3, 17 beta-diol, 3-benzoate, 17[4-[4-[bis(2-chloroethyl)amino]phenyl]-1-oxobutoxy] acetate] (KM2210) on MCF-7 human breast tumours transplanted into nude mice.

KM2210 is a benzoate of an estradiol-chlorambucil conjugate with three active metabolites, KM2202, estradiol (E2) and chlorambucil (CBL). The mode of action of this compound was assessed using MCF-7 human breast tumours transplanted into nude mice. The growth of MCF-7 in nude mice was inhibited by KM2210 and enhanced by E2, although the serum levels of E2 in nude mice treated with KM2210 and E2 were similar. The antitumour activity of CBL was completely blocked by extrinsic E2, while KM2210 suppressed the growth of MCF-7 in spite of the presence of E2 in the serum of tumour-bearing nude mice. KM2210 and KM2202 suppressed the expression of cytosol estrogen receptor (ER) of MCF-7 cells detected by the dextran-coated charcoal and fluorescent E2 staining method, although CBL did not affect the ER expression of MCF-7 cells. This inhibitory effect of KM2210 on ER was also corroborated by the fact that the pretreatment with KM2210 prevented the E2-stimulated growth of MCF-7 in nude mice. These results indicated that one of the effects induced by KM2210 is the blockage of ER expression in combination with the alkylating antitumour activity of CBL. KM2210 is thought to be a promising agent with unique modes of action for ER-positive breast carcinomas.

Early resection of primary orthotopically-growing human colon tumor in nude mouse prevents liver metastasis: further evidence for patient-like hematogenous metastatic route.

We have developed an orthotopic transplant model of human cancer to immunodeficient mice utilizing microsurgical techniques with intact tissue. The resulting transplanted human tumors grow locally and metastasize in a clinical-like pattern. However, there has been no definitive evidence in colon cancer that the human tumors metastasize via hematogenous route in nude mice. In the present study, in order to obtain definitive evidence of physiological spread of the human tumors, the primary tumors were resected 10 days after the initial orthotopic transplantation to the nude mice. The resection prevented metastases from forming, demonstrating that metastases of the human colon cancers occur after 10 days and by physiological and non-seeding mechanisms in the transplanted nude mice.

Immunochemotherapy prevents human colon cancer metastasis after orthotopic onplantation of histologically-intact tumor tissue in nude mice.

A metastatic model of human colon cancer has been previously established using orthotopic onplantation of histologically intact in tissue nude mice. In this study, effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) on Col-2-JCK, a human colon cancer xenograft, were evaluated using this model. When 5-FU and MMC were administered without OK-432, liver metastases were not reduced even at maximum tolerated doses of both drugs, although cecal tumor growth was significantly reduced. On the other hand, when combined with OK-432, both 5-FU and MMC reduced liver metastases with synergistic reduction of cecal tumor growth, demonstrating the potential of combining immunotherapy with chemotherapy against metastases.

Antitumor activity of (2''R)-4'-O-tetrahydropyranyl adriamycin on human gastric cancer cell lines in vitro and in vivo.

The antitumor activity of (2''R)-4'-O-tetrahydropyranyl adriamycin (pirarubicin; THP) was assessed using human gastric cancer cell lines in vitro and in vivo. The cytotoxicity of THP on MKN-28 and MKN-45 was superior to that of adriamycin (ADM) as detected by a growth assay with an MTT colorimetric endpoint. When the same doses of THP and ADM were administered intraperitoneally to nude mice bearing St-15, St-40 and SC-1-NU, the antitumor activity of THP was almost equivalent to ADM in terms of relative mean tumor weight. However, the adverse effects of THP were also significantly lower than those of ADM in terms of death rate, body weight loss and spleen weight loss. This was also confirmed in THP or ADM combination chemotherapy with mitomycin C and 5-fluorouracil on St-15 and MKN-45. These results indicated that THP is a candidate anthracycline to replace ADM for combination cancer chemotherapy in gastric carcinoma.

Combined effect of 5-fluorouracil and carboplatin against human gastric cancer cell lines in vitro and in vivo.

The antitumor activity of a sequential combination of 5-fluorouracil (5-FU) and carboplatin (JM-8) was evaluated using gastric cancer cell lines in vitro and in vivo. In the in vitro study, the sequence of 5-FU followed by JM-8 showed higher antitumor activity than that of the reverse sequence. The sequence of 5-FU at 5 micrograms/ml for 24 h followed by 5 micrograms/ml JM-8 for 24 h showed antitumor activity almost equivalent to that of 10 micrograms/ml 5-FU for 24 h and higher activity than that of 10 micrograms/ml JM-8 for 24 h on two cell lines. To evaluate the antitumor activity and toxicity of 5-FU and JM-8 in vivo, BALB/cA nu/nu mice bearing human gastric cancer xenografts St-15, St-40 and SC-1-NU were administered 5-FU and JM-8 intraperitoneally. The sequence of 5-FU prior to JM-8 showed higher antitumor activity than that of the reverse sequence on all the xenografts, and simultaneous administration of 5-FU and JM-8 showed the most potent antitumor activity on St-40 and SC-1-NU. On the other hand, the sequence of 5-FU before JM-8 showed the lowest toxicity in all the treated groups, in terms of death rate, body weight loss and spleen weight loss. This combination is thought to be a promising chemotherapy regimen, showing high antitumor activity without an increment of toxicity.

Usefulness of fecal alpha-1-antitrypsin for detection of gastrointestinal bleeding in patients with gastric cancer.

Hemoglobin (Hb), albumin (Alb), immunoglobulin G (IgG) and alpha-1-antitrypsin (AAT) were measured in 87 fecal samples from 29 normal volunteers and 68 fecal samples from 33 patients with gastric cancer before surgery to evaluate the usefulness of fecal AAT as an indicator of gastrointestinal bleeding in patients with gastric cancer. Mean values and standard deviation of fecal Hb, Alb, IgG and AAT in normal volunteers were 0.13 +/- 1.19 micrograms/g, 6.96 +/- 20.48 micrograms/g, 17.52 +/- 10.16 micrograms/g, and 0.483 +/- 0.315 mg/g, respectively. These parameters in the patients with gastric cancer were significantly higher than those in the normal volunteers. No statistically significant correlations were observed between these fecal parameters, except between fecal Alb and IgG. Data obtained from peripheral blood also showed no significant correlation with these fecal parameters. When the cut-off levels of fecal Hb, Alb, IgG and AAT were set at M + 2SD of the values obtained from the normal volunteers, sensitivity, specificity and accuracy were 80.0%, 86.2% and 84.1% for fecal AAT, and 66.7%, 96.6% and 86.4% for fecal Hb in the patients with advanced gastric cancer in a cohort consisting of patients with advanced gastric carcinoma and normal volunteers. Since fecal AAT showed higher sensitivity in patients with advanced gastric cancer with a low number of false negative cases, we concluded that measurement of fecal AAT could be a promising method for assessment of gastrointestinal bleeding in patients with advanced gastric carcinoma instead of immunological detection of fecal Hb.

Site-specific chemosensitivity of human small-cell lung carcinoma growing orthotopically compared to subcutaneously in SCID mice: the importance of orthotopic models to obtain relevant drug evaluation data.

We have developed a novel in vivo model of human small-cell lung carcinoma (SCLC) using orthotopic reconstitution by injecting human SCLC in the tail vein of severe combined immunodeficient (SCID) mice whereby the SCLC grows in the lung and other organs. Cisplatin (DDP) had significant antitumor effects on the SCLC growing orthotopically in the lung whereas mitomycin C (MMC) did not, thereby reflecting the clinical situation. However, the opposite effects were found when the SCLC was growing subcutaneously, where the tumors responded to MMC and not to DDP. This suggests that the tumors growing orthotopically reflect the clinical effects of drugs on human SCLC more closely than the tumors growing subcutaneously. Therefore, this orthotopic reconstitution model of human SCLC in SCID mice is thought to be useful for studies on the treatment of human SCLC and emphasizes the need for orthotopic models for relevant cancer drug evaluation.

Chemosensitivity testing of clinical gastrointestinal cancers using histoculture and the MTT end-point.

Three-dimensional histoculture with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end-point was utilized for chemosensitivity testing of 100 clinical gastrointestinal cancers and the results were compared with those obtained with cell-suspension culture with the MTT end-point. Of the 100 surgical specimens, 91 were evaluable using histoculture assay and 66 were evaluable using the cell-suspension assay. When the assay results were compared with historical frequency of clinical response to chemotherapy, the results of the histoculture assay showed a closer correlation than those of the cell-suspension assay. Therefore, the histoculture assay seems to have a higher evaluability rate and a closer correlation with clinical chemosensitivity of gastrointestinal cancers than the cell-suspension assay.

Modulation by l-leucovorin of 1-hexylcarbamoyl-5-fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice.

Experimental biochemical modulation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) with l-leucovorin (LV) was carried out using human gastric (H-111) and colon (Co-4) carcinoma xenografts serially transplanted into nude mice. Thirty-five or 70 mg/kg HCFU dissolved in 0.2 ml of 1% hydroxymethyl cellulose was administered po daily for 3 weeks except Sundays, and 50, 100, 200 or 300 mg/kg LV dissolved in 0.2 ml physiological saline was administered po 30 min before administration of HCFU. The biochemically modulated antitumor activity was evaluated in terms of actual tumor weight, the relative mean tumor weight and the degree of inhibition of thymidylate synthetase (TS) in the tumors at the end of the experiments, assayed according to the method of Spears et al. Although 35 mg/kg HCFU was ineffective against gastric carcinoma H-111, combination with 200 or 300 mg/kg LV resulted in a positive antitumor effect of HCFU on this strain without any increase of side effects in terms of body weight loss and mouse mortality. The colon carcinoma strain Co-4 showed marginal sensitivity to HCFU (35 mg/kg) alone, but 50 or 100 mg/kg LV modulated the antitumor activity of HCFU on Co-4 to produce a significant positive effect without any increase in toxicity, and HCFU administered with 100 mg/kg LV was more effective than the maximum tolerated dose of HCFU (70 mg/kg) alone. The TS inhibition rate was closely related to the biochemical modulation of HCFU antitumor activity by LV, suggesting that the modulation involves an increase of the ternary complex of TS, 5,10-methylene tetrahydrofolate from LV and 5-fluorodeoxyuridine 5'-monophosphate (FdUMP). Combination of HCFU and LV is therefore thought to be useful in increasing the antitumor activity of HCFU on gastrointestinal carcinomas without enhancing its toxicity.

Experimental and clinical studies on aclarubicin in the treatment of solid tumors.

Experimental and clinical studies were performed on aclarubicin in the treatment of solid tumors. In experimental cancer chemotherapy using human tumor xenografts transplanted to nude mice, aclarubicin showed a moderate antitumor effect (retardation of tumor growth) and nearly the same spectrum of activity in vivo as Adriamycin (doxorubicin). In in vitro sensitivity tests using 3H-thymidine uptake inhibition of a single cell suspension prepared from xenografts, aclarubicin showed a stronger inhibition than that of Adriamycin, mitomycin C and cyclophosphamide. In phase II clinical studies in patients with solid tumors, 3 intravenous dose schedules [schedule A: 20 mg (equal to 14 mg/m2) daily every other week, schedule B: 40 to 60 mg (28 to 42 mg/m2) twice a week, and schedule C: 60 to 100 mg (42 to 70 mg/m2) once a week] were investigated. Aclarubicin produced a 15 to 20% response rate for carcinomas of the stomach, lung, breast and ovary by schedules A and B. Dose-schedule limiting factors were digestive and hematologic toxicity.

Pyloric stenosis in a patient with progressive systemic sclerosis.

A 64-year-old Japanese woman with progressive systemic sclerosis (PSS) who developed severe pyloric stenosis is described. The conservative treatments brought only the temporary symptomatic relief, and pyloroplasty became necessary. No ulcerative lesions or tumors were found in the resected stomach or duodenum specimens implicated for stenosis. The histological examinations revealed edema and replacement fibrosis in the pyloric ring. The possible mechanisms of pyloric stenosis are discussed.

[Factor XIII in the treatment of postoperative refractory wound-healing disorders. Results of a controlled study]. / Faktor XIII in der Behandlung postoperativer therapierefraktärer Wundheilungsstörungen. Ergebnisse einer kontrollierten Studie.

The efficacy of factor-XIII concentrate in the improvement of postoperative wound healing disorders (suture dehiscences, fistulae) was examined in 61 patients. In an open, randomised, and controlled trial the results (decrease of wound area, signs of inflammation, wound secretion, drainage volume, contrast x-ray films, and colour photos) were evaluated twice: open judgement by the clinicians themselves and blind judgement by an independent evaluation committee. The blind evaluation of the clinical data showed relevant general improvement in the patient groups treated with factor-XIII concentrate: 61.9% (dosage: 750 IU factor XIII for 3 days) and 76.2% (dosage: 1500 IU factor XIII for 3 days) as compared to 10.5% in the control group without factor XIII substitution. The differences were significant (Mann-Whitney-U-Test, p less than or equal to 0.001). These results would suggest substituting factor XIII activity in plasma above 70% of normal value in case of wound healing disorders.

[Investigation of adsorption, metabolism and excretion of cefuroxime axetil in volunteers of gastrectomized patients].

Adsorption, metabolism and excretion (ADME) of cefuroxime axetil (CXM-AX) 500 mg given orally at 30 minutes after meals to male volunteers who had undergone gastrectomy was compared with that of healthy volunteers. 1. The transition of the drug's serum concentrations was observed as follows: Tmax was somewhat shorter and T 1/2 longer in the gastrectomized volunteer group than in the healthy volunteer group. 2. Total urinary recovery rates of cefuroxime (CXM) were not significantly different between the 2 groups, averaging 53.6% for the gastrectomized volunteer group and averaging 54.5% for the healthy volunteer group. 3. Total urinary recovery rates of CXM-delta 2 were not significantly different between the 2 groups either, averaging 1.7% for the gastrectomized volunteer group and 1.3% for the healthy volunteer group. 4. The above results suggest that ADME of CXM-AX in the gastrectomized volunteers is not fundamentally different from that of the healthy volunteers. The absorption, however, may be reduced when peristalsis of the intestinal tract is accelerated as a result of gastrectomy.

[Bacteria isolated from intraabdominal infection and their susceptibilities to antimicrobial agents].

Bacteria isolated from intraabdominal infections during the period from July 1982 to June 1993 were investigated with regard to their classifications according to a joint research by 9 university hospitals in Japan. The following results were obtained. 1. A total of 971 strains were isolated from 684 out of 597 patients with peritonitis, and 287 strains out of 971 were isolated from postoperative peritonitis. 2. The most predominant organism isolated from patients with acute peritonitis was Escherichia coli (28%), followed by Bacteroides fragilis group (17%), Gram-positive anaerobic cocci (16%), Enterococcus spp. (9%) and Klebsiella spp. (8%). 3. Against E. coli, cefmenoxime, cefuzonam, cefozopran, aztreonam and carumonam showed MIC50 less than 0.05 micrograms/ml. Against B. fragilis group, erthromycin, clindamycin, imipenem, lincomycin and latamoxef showed MIC50 less than 0.78 micrograms/ml. 4. The most predominant organism isolated from patients with postoperative peritonitis was Enterococcus spp. (20%) and followed by Pseudomonas spp. (14%), and Staphylococcus spp. (13%), E. coli (9%), Enterobacter spp. (8%) and Klebsiella spp. (8%). We suggest that cefazolin, cefmetazole, flomoxef, cefmenoxime, cefuzonam, and latamoxef are the first choice agents in empiric therapy for the treatment of acute peritonitis.

[Year to year changes in isolation frequencies of different bacteria from postoperative infections].

Bacterial species isolated from postoperative infections during the period from July 1982 to June 1993 were studied regarding isolation frequencies of different species in different years in a joint research project involving nine (9) university hospitals in Japan. The obtained results are summarized as follows. (1) Altogether, 1,453 strains were isolated with 153 strains obtained during the most recent one year from July of 1992 through June of 1993. The most numerous source of isolation was postoperative intra-abdominal sepsis. (2) Gram-positive cocci were the most often isolated, among them methicillin-resistant Staphylococcus aureus was isolated in increasing frequencies until June, 1992. (3) In the last one year, Enterococcus spp. was isolated the most from postoperative infections followed by Staphylococcus spp. and Pseudomonas spp. Rates of isolation of anaerobic bacteria were relatively low with annual isolation frequencies ranging 8 to 15 per cent.

[Antibiotic susceptibility of bacteria isolated from surgical infection (second report)].

Isolated bacteria from infections in general surgery in 1984 and 1985 have been investigated to find bacterial composition and their susceptibilities to antibiotics in a joint research in which 6 university hospitals in Japan participated. A summary of findings from the investigation is as follows. 1. One hundred and seventy-two (1984) and 211 (1985) cases were included in the study. Cases in which bacteria were detected were 147 and 174 in the respective years. The detection rate was higher than 80% in either year. 2. Total numbers of strains isolated in 1984 and 1985 were 267 and 293, respectively; major sources of these strains were intraperitoneal infection exudates in either year. 3. The most frequent isolate from primary infection cases in both years was Escherichia coli (15-21%), followed by Bacteroides spp. and Staphylococcus spp., in that order. The most frequently isolated from postoperative infection cases were Enterococcus spp. (16-22%), followed by Pseudomonas spp. The diversity of isolated species, as well as the similarity of incidences of different species were noted in cases of postoperative infections. It is suspected that a certain species, even if its pathogenicity is essentially low, may become to be a causative organism once its number increases due to its survival through a perioperative prophylactic use of antibiotics, and also due to the decreased host resistance to infections caused by underlying diseases or surgical stress. 4. Staphylococcus spp. was the most frequent isolate from postoperative infections occurring after clean operations, while Enterococcus spp. and Pseudomonas aeruginosa were major isolates from infections after clean-contaminated operations. Isolates from infections occurring after contaminated operations included Enterococcus spp. greater than E. coli greater than Klebsiella pneumoniae, P. aeruginosa, Bacteroides spp. (1985). 5. In cases without the presence of clinical factors cause by depressed host defense, E. coli and Bacteroides spp. were major isolates, while in cases with the factors, a wide variety of bacterial population tended to be found. 6. Before an administration of antibiotics in primary infections, E. coli, Staphylococcus spp. Bacteroides spp. and Klebsiella spp. were most commonly isolated, while after a chemotherapy, Enterococcus spp. were the most frequent isolates, followed by P. aeruginosa during 1985. These findings reflected the antibacterial spectrum of cephems usually used in surgical field.(ABSTRACT TRUNCATED AT 400 WORDS)

[Antibiotic susceptibility of bacteria isolated from surgical infections (first report)].

In vitro activities of several antimicrobial agents against bacterial pathogens isolated from patients with primary and postoperative infections were investigated in 1982 and 1983. Antimicrobial agents examined were as follows: sulbenicillin (SBPC), piperacillin (PIPC), cephalothin (CET), cefazolin (CEZ), cefmetazole (CMZ), cefotiam (CTM), cefoperazone (CPZ), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), lincomycin (LCM), gentamicin (GM) and amikacin (AMK). Specimens for bacterial isolation included plus, fluid drawn by centesis, or bile. Blood samples of septicemia were excluded. The antimicrobial activities of these drugs were determined by the agar plate dilution method of the Japanese Society of Chemotherapy. There were 123 strains obtained in the 1982 survey and 252 strains in the 1983 survey. Little or no differences were seen in frequencies of isolation between the isolates of principal species in 1982 and those in 1983. Isolation frequencies of pathogens in primary infections were, in an order of decreasing frequency, E. coli (25.6%), anaerobes (21.1%), Streptococcus sp. (14.3%), Staphylococcus sp. (11.3%); in postoperative infections, Streptococcus sp. was most frequent (28.6%), followed by Pseudomonas sp. (17.6%), anaerobes (12.6%), E. coli (10.9%), Staphylococcus (10.1%). Against S. aureus, CEZ, CTM, LCM and GM had similar degree of activity with CET being somewhat more active. CMX was the most active drug among the third generation cephems tested against S. aureus. No strain was CTM, CEZ, and LCM-resistant at the same time. Over 90% of E. coli, were sensitive to CTX, CZX and CMX, inhibited by 0.10 microgram/ml, while E. coli were slightly less susceptible to CPZ and LMOX. Penicillins were not very active against K. pneumoniae, and only 60% of K. pneumoniae were inhibited by PIPC at concentrations of 12.5 micrograms/ml. Third generation cephems, CTX, CMX and CZX, proved highly active against K. pneumoniae; over 90% of K. pneumoniae was inhibited by CTX, CMX and CZX at a concentration of 0.10 microgram/ml. About 60% of P. aeruginosa was inhibited by 3.13 micrograms/ml of PIPC and GM but was resistant to SBPC. This survey should be very useful for the selection of an appropriate drug for prophylaxis if the frequencies of incidences of pathogens in postoperative infections are taken into account in selecting the most active antibiotic agent(s) against the most frequent genus, genera and species of pathogens.