The newly developed cephalosporin antibiotic agent, DQ-2556, was evaluated in vitro and in vivo. The results were as follows;
1. Antimicrobial activity: Minimal inhibitory concentrations (MICs) against 480 clinical isolates including 15 different species were determined and compared with those of cefotiam, ceftizoxime, ceftazidime and cefzonam. DQ-2556 showed excellent antimicrobial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus and gram-negative bacteria. The MICs of DQ-2556 were almost equal to those of the other cephalosporins or were lower.
2. DQ-2556 concentrations in serum and sputum: A patient with diffuse panbronchiolitis was given 1 g of DQ-2556 intravenously and its concentrations in serum and sputum were measured at intervals by HPLC. A peak concentration in serum was observed immediately after the infusion, and reached 69.7 μg/ml. A peak sputum level of 1.8μg/ml was observed 3-4 hours after the infusion. This suggests that DQ-2556 has rapid and good penetration into the lung.
3. Clinical efficacy and adverse reactions: Fourteen patients with respiratory tract infections were treated with DQ-2556. An overall efficacy rate was 78.6%(excellent in 1 case, good in 10, fair in 2, poor in 1). Fever and rash were observed in 1 case as an adverse reaction. With regards to abnormal laboratory findings, neutrocytophilia and elevation of LDH in 1 case, and elevation of GOT and GPT in another case were observed. All of these were mild and improved rapidly after completion of DQ-2556, indicating that DQ-2556 is a safe agent.

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A clinical study of Y-26611, a newly-developed quinolone derivative, was carried out to evaluate its efficacy and safety in patients with infections in the fields of internal medicine and urology. An animal investigation of the photoallergenicity of Y-26611 was also conducted. The following results were obtained.
1) As a rule Y-26611 was orally administered in doses of 200 mg or 300 mg b. i. d. to patients with pneumonia, chronic respiratory tract infections and complicated urinary tract infections, and in doses of 100 mg or 200 mg b. i. d. to patients with acute uncomplicated cystitis for 3 to 14 days.
2) The total number of patients enrolled was 191, 90 internal medicine patients (87 evaluated for clinical efficacy), 101 urology patients (73 evaluated on the basis of the criteria proposed by the Japanese UTI Committee).
3) The overall clinical efficacy rate was 84.3% (88.2% in respiratory tract infections and 82.7% in urinary tract infections).
4) The bacterial eradication rate was 73.3% in internal medicine infection and 92.3% in urology infections. Y-26611 showed good bacteriological efficacy not only against gram-positive bacteria but also gram-negative bacteria.
5) The clinical adverse effect rate was 17.9% (23.6% in patients with infections in the field of internal medicine and 12.9% in the field of urology). Allergic symptoms were observed in 13.2% of the patients.
6) Phototoxicity testing of Y-26611 was performed by oral administration to mice and guinea pigs. No phototoxic reactions were noted in mice at doses up to 300 mg/kg. In guinea pigs, phototoxic reactions were observed at a dose of 100 mg/kg, but they were milder than those observed after lomefloxacin (LFLX) administration.
In a contact photoallergenicity study, a slight photoallergenic respones was observed in guinea. pigs treated with both Y-26611 and LFLX. Furthermore, Y-26611 caused erythema without ultraviolet-ray irradiation, suggesting contact allergenicity. Penetration of Y-26611 into skin was remarkably higher in pigmented rats than in albino rats, while its elimination rate was markedly slower in pigmented rats than in albino rats. These findings showed that Y-26611 was very effective in both respiratory tract infections and urinary tract infections. However, a high rate of clinical adverse effects was observed allergic symptoms in particular, indicating problems in terms of the safety of Y-26611.

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Fundamental and clinical studies of cefditoren pivoxil (CDTR-PI), a newly developed oral cephem antibiotic, were carried out in the field of surgical infections, and the following results were obtained. The transport of cefditoren (CDTR) into bile reached its maximum, 95.4 μg/ml, at 3 hours after oral administration. The transport of CDTR into gallbladder tissue reached its maximum, 0.72μg/g, at 3 hours after oral administration. The transport of CDTR into mammary glands reached its maximum, 0.72μg/g, at 2 hours after oral administration. When CDTR-PI was administered to 52 patients with surgical infections, clinical response was excellent in 12 patients, good in 32 patients, fair in 6 patients, and poor in 2 patients. The overall rate of effectiveness was 84.6%. In the bacteriological study, 50 strains were isolated and 37 strains were eradicated. The rate of bacterial eradication was 74.0%. Side effects, either subjective or objective, were not observed. As an abnormal laboratory test, elevation of GOT was observed in one patient but had no serious clinical implications.

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We determined the efficacy and safety of combination therapy with imipenem/cilastatin sodium (IPM/CS) (mainly 1-2g/day) and amikacin sulfate (AMK) (mainly 200-400 mg/day) in patients with severe infections accompanying hematological malignancies. Of 168 patients treated, 135 were evaluated. Acute leukemia was the diagnosis in 63.7% of the evaluated cases and malignant lymphoma in 17.7%. The overall clinical efficacy was 61.5% and the following results were obtained for different categories: sepsis, 84.6%; suspected sepsis, 62.3%; and pneumonia, 50.0%. Although the patients were severely neutropenic (neutrophil count of less than 500/μl), they showed good responses with an efficacy rate of 59.4%. In particular, when IPM/CS and AMK were concomitantly used as first-choice therapy, the response rate was 80.0%. Adverse effects, which were observed in only 8 patients (4.8%), were mild and transient. Combination therapy with IPM/CS and AMK can be recommended as one of the best choices for empiric therapy of various infections accompanying neutropenia in hematological malignancies.

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1) There were 18 (17.6%) postoperative infections in 102 gastric cancer patients given cefmetazole (CMZ) (CMZ) prophylaxis.
2) There were significant differences in age and albumin values between the infection and noninfection groups.
3) There were no differences in infection rates among the various surgical methods (total vs subtotal gastrectomy) or CMZ administration protocols (500 ml, 60 min., d.i.vs 100 ml, 30 min., d. i.).
4) There was a high infection rate in patients with severe surgical stress, especially those over 80 years old, after total gastrectomy.
5) There was an increase in infections among patients with albumin levels≤4g/dl and/or total protein levels ≤7g/dl.
6) The postoperative infections were peritonitis in 8 cases, pneumonia in 6 cases, wound infection in 5 cases, and cholecystitis and sepsis in one case each. There were no relationships between the type of infection and either the method of surgery or the drug administration protocol.
7) The organisms isolated from the infectious sites were chiefly Staphylococcus epidermidis, Erterococcus faecalis and Enterobacter cloacae. Two strains of Staphylococcus aureus were isolated but they were not MRSA.
8) CMZ is useful for prophylaxis in gastric cancer surgery.

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We performed a multicenter double-blind clinical trial to compare cefditoren pivoxil (CDTR-PI), a new oral cephem antibiotic, with cefaclor (CCL) in the treatment of skin and skin structure infections (furuncle, furunculosis, carbuncle, cellulitis, erysipelas, lymphangitis and lymphadenitis). CDTR-PI was given orally in a dose of 200 mg three times a day, and CCL in a dose of 250 mg three times a day. One hundred fifty-nine patients were randomly assigned to receive either CDTR-PI (83 patients) or CCL (76 patients). One hundred fourty-five of these patients (CDTRPI, 73; CCL, 72) were evaluated in terms of efficacy, 150 (CDTR-PI, 77; CCL, 73) in terms of overall safety, and 147 (CDTR-PI, 75; CCL, 72) in terms of clinical usefulness.
1. No significant differences were detected in the efficacy rates between the two drug groups. The overall efficacy rate was 97.3% (71/73) for the CDTR-PI group and 90.3% (65/72) for the CCL group.
2. The global improvement rate after 5 days of treatment was 92.4% (61/66) for the CDTR-PI group and 84.8% (56/66) for the CCL group, with no significant difference between the two drug groups.
3. The safety rate was 87.0% (67/77) for the CDTR-PI group and 93.2% (68/73) for the CCL group, with no significant difference between the two drug groups.
4. The clinical usefulness rate was 90.7% (68/75) for the CDTR-PI group and 88.9% (64/72) for the CCL group, with no significant difference between the two drug groups.
5. The bacteriological response rate was 90.0% (36/40) for the CDTR-PI group and 91.2% (31/34) for the CCL group, with no significant difference between the two drug groups.
6. The side effect incidence was 11.7% (9/77) for the CDTR-PI group and 2.7% (2/73) for the CCL group, with no significant difference between the two drug groups. Abnormal laboratory values were noted in 2 patients in the CDTR-PI group and in 4 patients in the CCL group, with no significant difference between the two drug groups.
We conclude that CDTR-PI is as effective, safe and useful as CCL in the treatment of skin and skin structure infections.

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We carried out a well-controlled trial to evaluate the efficacy, safety, and usefulness of cefclidin (CFCL) in bacterial pneumonia, using ceftazime (CAZ) as the reference drug. Either drug was given intravenously in a dose of 1 g twice a day for 14 days. The following results were obtained:
1) The overall clinical efficacy rate determined by attending physicians was 86.9% (53/61) for CFCL and 90.3% (56/62) for CAZ. The efficacy rates judged by the Efficacy Assessment Committee (Study Committee) were 85.7% (54/63) for CFCL and 89.1% (57/64) for CAZ. There was no statistically significant difference in efficacy between the two drugs.
2) As for bacteriological responses, the eradication rate was 100% (28/28) in patients receiving CFCL and 96.7% (27/28) in patients receiving CAZ, with no statistically significant difference between them.
3) Adverse reactions were observed by attending physicians in 10/77 (13.0%) patients treated with CFCL and in 2/75 (2.7%) patients receiving CAZ (χ²-test, p<0.05). The incidence of adverse reactions was significantly higher for CFCL than for CAZ. The incidence of abnormal laboratory findings assessed by attending physicians was 16.4% (12/73) for CFCL and 21.1% (15/71) for CAZ. The Study Committee judged that adverse reactions occurred in 9/77 (11.7%) patients receiving CFCL and 2/75 (2.7%) patients receiving CAZ, with no statistically significant difference between the two drugs. In addition, the Study Committee judged that the incidence of abnormal laboratory findings was 27.4% (20/73) for CFCL and 31.0% (22/71) for CAZ, with no statistically significant difference between them. None of the symptoms or abnormal changes were severe.
4) The usefulness rate judged by attending physicians was 83.9% (52/62) for CFCL and 86.2% (56/65) for CAZ. The usefulness rate according to the Study Committee was 76.6% (49/64) for CFCL and 89.1% (57/64) for CAZ, with no significant difference between the two drugs.
On the basis of these results, CFCL was concluded to be useful in the treatment of bacterial pneumonia, providing a high clinical and bacteriological response without severe adverse reactions.

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We carried out a well-controlled study to evaluate the efficacy, safety, and usefulness of cefclidin (CFCL) in respiratory tract infections, using ceftazidime (CAZ) as the reference drug. Either CFCL or CAZ was given intravenously in a dose of 2g daily (1g b. i. d.) for 14 days as a rule. The following results were obtained:
1) The overall clinical efficacy rate assessed by attending physicians was 89.9% (62/69) for CFCL and 85.7% (72/84) for CAZ, and there was no statistically significant difference between the two agents. For moderate infections the efficacy rate and “excellent” response rate was significantly higher for CFCL than for CAZ (U-test, p<0.05). In the judgment by the Efficacy Assessment Committee (Study Committee), the rates were 83.3% (60/70) for CFCL and 80.0% (68/85) for CAZ, with no statistically significant difference between the two agents.
2) With regard to bacteriological response, the eradication rate in monomicrobial infections was 91.2% (31/34) for CFCL and 69.2% (27/39) for CAZ (χ²-test, p<0.05). The overall eradication rate was higher for CFCL than for CAZ, 90.5% (38/42) vs 72.5% (37/51). In particular, the eradication rate forPseudomonas aeruginosawas 73.3% (11/15) for CFCL and 53.8% (14/26) for CAZ.
3) Adverse drug reactions were observed in 4.5% (4/89) in the CFCL group and 3.1% (3/96) in the CAZ group. The incidence of abnormal laboratory findings was judged by attending physicians to be 21.2% (18/85) in the CFCL group and 20.9% (19/91) in the CAZ group. The Study Committee rates were 23.5% (20/85) for CFCL and 26.4% (24/91) for CAZ. No severe symptoms or abnormal findings were observed, and there was no significant difference between the two drugs.
4) The usefulness rates judged by attending physicians were 88.4% (61/69) for CFCL and 82.1% (69/84) for CAZ (U-test, p<0.05). The usefulness rates according to the Study Committee were 80.6% (58/72) for CFCL and 77.9% (67/86) for CAZ, with no significant difference.
Based on the above results, it was concluded that CFCL is useful from the viewpoint of efficacy and safety in the treatment of respiratory tract infections. Since CFCL exhibits a potent in vitro activity and a high eradication rate againstP. aeruginosa, it appears that this drug is likely to be useful in the treatment of refractoryPseudomonasrespiratory infections.

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