The effectiveness, safety and utility of DL-8280, a pyridonecarboxylic acid derivative, in the field ofsuppurative skin and soft tissue infections were compared with those of Cefaclor (CCL) by a double-blindmethod.
DL-8280 was orally administered in daily dose of 600 mg and CCL was orally administered in dailydose of 750 mg. Each group was treated for 14 days. The results were as follows:
1) Final global improvement rate of DL-8280 was evaluated in 121 patients and out of them “Cured” was marked in 67, “Remarkably improved” in 28, “Moderately improved” in 12, “Slightlyimproved” in 8, “Unchanged” in 2 and “Aggravated” in 4. The percentage of “Cured” and “Remarkably improved” was 78.5%, and increased to 88.4% when “Moderately improved” was included. “Aggravated” and “Remarkably aggravated” shared 3.3%.
For the global improvement rate of CCL, “Cured” was noted in 56, “Remarkably improved” in 27, “Moderately improved” in 23, “Slightly improved” in 5, “Unchanged” in 7, “Aggravated” in 1 and “Remarkably aggravated” in 1 out of 120 patients. The percentage of “Cured” and “Remarkably improved”was 69.2%, increased to 88.3% by addition of “Moderately improved”, whereas “Aggravated”and “Remarkably aggravated” rated 1.7%.
No significant difference was shown between two drug groups.
2) Side effect was noted in 2.3% of 129 patients treated with DL-8280 and 5.4% of 130 patientstreated with CCL, showing no statistically significant difference between two drug groups.
3) In regard to global utility rate of DL-8280, “Remarkably useful” was noted in 65 cases, “Useful” in 39, “Slightly useful” in 11, “Not useful” in 6 out of 121 patients. “Remarkably useful”shared 53.7% and the total of “Remarkably useful” and “Useful” shared 86.0%.In the CCL group, “Remarkably useful” was noted in 55, “Useful” in 41, “Slightly useful” in 14, “Not useful” in 11, “Harmful” in 1 out of 122 patients. “Remarkably useful” shared 45.1%, and thetotal of “Remarkably useful” and “Useful” shared 78.7%.
No significant difference was shown between two drug groups.
4) In regard to global improvement rate by evaluation day, DL-8280 group was significantlysuperior to CCL group on days 3, 10 and 14.
Especially in the group 1, DL-8280 group was significantly superior to CCL group throughout thestudy period.
Taking together, DL-8280 has tendency to superior to CCL in treatment of suppurative skin and softtissue infections. Because of the result obtained and that no resistant bacteria was observed so far, DL-8280 can be expected as useful drug for this field.

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Little is known about the clinical significance of isolating Citrobacter in the clinical laboratory. During a one-year period, Citrobacter isolates were obtained from 50 patients with suspected infectiousepisordes. The majority of the suspected infectious episorde involved respiratory tract (48%) or urinarytract (30%). Citrobacter freuindii was associated with 76% of the episorde and Citrobacter diversus with 24%. All of the infections were hospital aquired. Most C. freuindii isolates were not susceptible topenicillins, 1st and 2nd generation cephems, nor chloramphenicol, but were susceptible to 3rdgeneration cephems, aminoglycosides, tetracyclines, nalidixic acid and pipemidic acid.
Most patients with Citrobacter urinary tract infection had underlying diseases and factorspredisposing to infection. These data suggest that Citrobacter is a cause of significant opportunisticinfection and nosocomial infection in the hospital.

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Staphylococci were detected in 24 (11.5%) of tears obtained from lacrimal punctum of 207 healthyschool children. Among these, Staphylococcus aureus was found in 7 cases and coagulase negativestaphylococci were isolated from 17 cases. In S. aureus, the largest number of the organisms in per one ultear was 7.50×10² colony forming units (CFU). Three and 4 strains were encapsulated and unencapsulated, respectively. Apart from one strain, the capsular type was determined. All coagulasenegative staphylococci were identified except for two strains and Staphylococcus warneri was the mostfrequent in population followed by S. epidermidis.
In no case was more than 2.50×10³ CFU of these organisms found in per one μl of tears, suggestingthat these amounts of the organisms would not be related to the eye infections.

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The clinical efficacy and safety of ofloxacin (OFLX; DL-8280) and cefaclor (CCL) were compared bya double-blind study using 250 patients with bacterial bronchitis. Patients were orally administered witheither 200 mg of OFLX or 250 mg of CCL three times a day for 14 days, and the following results wereobtained.
1) Clinical efficacy judged by committee:
The efficacy rate of acute bronchitis was 86.7% in OFLX group and 85.7% in CCL group. On theother hand, 78.4% of the patients in OFLX group and 50.0% of those in CCL group were effective inchronic bronchitis group. Statistically significant difference was observed between OFLX group andCCL group in chronic bronchitis group (p°0.001).
2) Clinical efficacy judged by the doctors in charge:
The results of the clinical efficacy judged by the doctors in charge was similar to the efficacy judgedby committee.
3) Bacteriological efficacy judged by committee:
Eradication rate of OFLX group was 90.2%(55 of 61 strains) and that of CCL group was 50%(35 of70 strains) (p°0.001). Furthermore, H influenzae and K pneumoniae were eliminated in a higher rate inOFLX group than in CCL group (p°0.001, p°0.05, respectively).
4) Side effects and abnormal laboratory findings:
Side effects were observed in 10 cases (8.1%) in OFLX group and in 10 cases (8.4%) in CCL group.Both OFLX and CCL did not show serious side effects or abnormal laboratory findings. There was nosignificant difference bwtween the two drug groups in the incidence of side effects and abnormallaboratory findings.
5) Clinical utility:
When the clinical utility was expressed by the satisfaction rate (very satisfied and satisfied), it was75.7% in OFLX group (107 patients) and 52.7% in CCL group (110 patients) (judged by committee).When the utility was judged by doctors in charge, it was 68.9% in OFLX group and 43.0% in CCL group.Both results revealed that OFLX was significantly superior to CCL (p°0.001).From these results, it was confirmed that OFLX was a more useful drug than CCL for the treatmentof bacterial bronchitis.

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The clinical efficacy, safety and usefulness of Ceftazidime (CAZ) in complicated urinary tract infectionswere evaluated in comparison with Cefoperazone (CPZ) in double blind manner, and thefollowing results were obtained.
CAZ 1g/day, CAZ 2g/day or CPZ 2g/day was administered by intravenous drip infusion twice dailyfor 5 days.
In the overall clinical efficacy evaluation according to the criteria proposed by UTI committee in Japan, the efficacy rates were 63% in 125 cases in the CAZ 1g/day group, 68% in 119 cases in the CAZ 2g/day group and 52% in 119 cases in the CPZ 2g/day group, with no significant difference among thethree groups (H-test). When 2 groups were compared (X²-test), however, the CAZ 2g/day was shown tobe superior over CPZ .2 g/day with statistically significant difference. As to the clinical efficacy classifiedby the type of infections, CAZ (both 1g/day and 2g/day) was more effective than CPZ (2g/day) withstatistically significant difference in polymicrobial infections. It was noteworthy that in the G-5 group, CAZ 1g/day was significantly better than CPZ 2g/day.
The elimination rates in bacteriuria were 53%, 52% and 45%, in CAZ 1g/day, CAZ 2g/day and CPZ 2g/day, and the clearance rates in pyuria were 35%, 33% and 23%, respectively, with no significantdifference among the three groups. In the clearance + decrease rates, however, the CAZ 1g/day and CAZ 2g/day groups showed better results than CPZ 2g/day group with statistically significantdifference.In the bacteriological response, CAZ 1g/day and 2g/day showed statistically higher eradicationrates than CPZ 2g/day in the total number of organisms and gram negative bacteria, but in gram positivebacteria, CPZ 2g/day showed higher eradication rates than CAZ 1g/day with statistically significantdifference. When reviewed for each organism, CAZ 1g/day and 2g/day showed higher eradication ratesthan CPZ 2g/day in S. marcescens with statistically significant difference; however, there was nosignificant difference among the three groups in the other organisms. Number of organisms whichemerged after treatment was large with S. faecalis and Yeast-like organisms in all the three groups. No severe adverse reaction or abnormal laboratory finding was observed in any group; therefore, there was no significant difference among the three groups. From the above results, CAZ was judged to be an antibiotic with clinical usefulness equal to, or evenhigher than that of CPZ.

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A total of 2549 strains of Salmonella sp. serovar Typhimurium isolated from various sources in Japan were studied to evaluate the usefulness of biotyping by the system of Duguid et al. and phage-typing by Gershman's system as epidemiological tool.
1. Prior to the studies, each test for biotyping was standardized and modified if necessary. For the sugar fermentation tests, semi-synthetic broth with 3% of sugar was used instead of peptone water containing 1% of the substrate. Tartrate utilization was tested in Kauffmann-Petersen's broth in place of the photometric or plate inhibition method.
2. Although the strains studied were divided into 17 biovars by the primary biochemical tests, approximately 80% of the strains accumulated in biovars 1, 25 and 26. Biovar 1 was mostly consisted of strains isolated from man, beef, pork, and abattoir environmental samples, whereas the majority of strains from chicken distributed in biovar 26. No geographical difference of biovar distribution was not observed.
3. There was no relationship between biovars and phagovars. Also, no difference was recognized in biovars between antigenic forms, 05 + and 05-(Copenhagen variety).
4. When strains originated in 6 cluster outbreaks of gastroenteritis were studied, it was demonstrated a single biovar by the primary and secondary biochemical tests or a single phagovar was involved in each of incidents. In one of the 6 outbreaks in which a causative food was fortunately ferreted, strains from the food also revealed the same biovar as that of human strains.
5. From the results obtained here, usefulness of biotyping by the system of Duguid et al. and phage-typing by the Gershman's system were confirmed. However, it was very timeconsuming to accomplish the whole tests. It is reasonable that routine epidemiological investigation is confined to the primary biotyping, and that the secondary biotyping and phage-typing are performed as occasion demands.

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A vitamin K deficiency- associated bleeding tendency during antibiotic therapy has recently become a serious problem, especially with the use of the new cephems. Broad spectrum antibiotics such as the cephems of the 2nd and 3rd generation may cause a marked change in the intestinal bacterial flora, leading to vitamin K deficiency in some patients. The changes of the intestinal bacterial flora and blood coagulation system including protein induced by vitamin K absence or antagonist (PIVKA II), an abnormal prothrombin which is demonstrated in patients with vitamin K deficiency, were investigated in children during antibiotic therapy. The influences of oral food intake and diarrhea, and the differences classified by antibiotics and age were also investigated.
Among the 160 patients, 37 patients (23%) showed the existence of PIVKA II and 24 patiens (15%) showed an abnormal prothrombin time (PT), activated partial thromboplastin time (APTT), hepaplastin test (HPT), and thrombotest (TT). Bleeding tendencies were noted in 11 patients (7%). PIVKA II became positive within 7 days after the initiation of antibiotics in 71% of the 37 patients, and returned negative with vitamin K administration.
PIVKA II was infrequently demonstrated in infants and frequently demonstrated in patients with sepsis, intrauterine infection, and central nervous system infection. None of patients with urinary tract infection were positive for PIVKA II. As for the relationship between the detection rate of PIVKA II and the antibiotics used, PIVKA II was frequently demonstrated in patients treated with latamoxef (LMOX), cefmetazole (CMZ), and cefoperazone (CPZ). None of the patients treated with cefotaxime (CTX), ceftazidime (CAZ), and ampicillin (ABPC) were positive for PIVKA II. LMOX, CMZ and CPZ have a 1-methyl-1-H-tetrazole-5-yl-thiomethyl group at position 3 of dihydrothiazine nucleus, and further investigation about the influences of this group to the vitamin K assosiated blood coagulation system is necessary.
The change of the intestinal bacterial flora was investigated for 124 of the 160 patients, and 83 of those (67%) showed a decrease of the intestinal bacterial flora. Twenty-three of the 83 patients (28%) were positive for PIVKA II. In 23 patients who had both a decrease of the intestinal bacterial flora and a decrease of oral food intake with or without diarrhea, 15 patients showed positive PIVKA II, a detection rate of 65%. This suggests that insufficient oral intake of vitamin K and the decrease of the intestinal bacterial flora play important roles in the etiology of the vitamin K deficiency during antibiotic therapy. A careful monitoring of the blood coagulation system, including PIVKA II, is necessary for patients receiving antibiotic therapy with broad spectrum agents such at the new cephems, and prophylactic use of vitamin K is indicated in newborn infants and patients with poor oral intake.

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The concentration of DL-8280, a new oral antibacterial agent, in prostatic fluid and tissue was determined, and based on this result, DL-8280 was administered to the patients with acute prostatitis.
For the determination of prostatic fluid levels of DL-8280, 300mg of DL-8280 was administered orally to 6 male healthy volunteers, three were the twenties and three were the fifties. Prostatic fluid was obtained by prostate massage at 1, 2 and 3 hours after dosing in the twenties and at 2 hours after dosing in the fifties. The prostatic fluid levels of DL-8280 in the twenties occurred a little later comparing with serum levels and the average level at 3 hours after administration was 1.82μg/ml. The prostatic fluid level of DL-8280 in the fifties was 2.78μg/ml at 2 hours after dosing and that of the twenties was 1.50μg/ml.
The concentration of DL-8280 in prostatic tissue was determined with the sample obtained by transurethral resection prostatectomy (TUR-P) from the patients with benign prostatic hyperplasia who were given 300g of DL-8280 orally before the operation. The prostatic tissue levels of 2-3μg/g was obtained correlatively with serum levels at 1, 2 and 3 hours after dosing.
Since these results showed a possible efficacy of DL-8280 on bacterial prostatitis, 9 patients of acute prostatitis were administered DL-8280 orally. The efficacy rate was 80%, 100% and 100% at Evaluation on Day 3 (5 patients), on Day 7 (9 patients) and on Day 14 (7 patients), respectively.
Transient rash was observed in one patient as a side effect.

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The new delivertive of pyridonecarboxylic uoid, ofloxacin showed excellent clinical and bacteriological effect in a typhoid patient.
The drug was administered with the daily doses of 800mg for four days and of 1200mg for following 10 days. As the side effect, the patient felt slight nausea on the last day of medication, but the symptom disappeared in the next day. Any abnormality of laboratory data was not observed with the medication.

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A 44-year-old female addmitted to Sasebo Kyosai Hospital for high fever, cough and sputum. A chest roentgenograph showed right lower lobe infiltrates and pleural effusion. She was treated by β-lactam antibiotics at first, but after diagnosed as Legionnaires' disease with positive culture of L. pneumophila from pleural effusion, the antibiotics were changed to minocycline (200 mg, daily) and erythromycin (1.6 g, daily). The patient became afebrile by 24 hours after erythromycin administration. The laboratory findings and chest roentgenogram findings were gradually changed to normal.
About one month later, the cervical and axillary lymphadenopathy was revealed and she was diagnosed histologically as reticulim cell sarcoma. The combination therapy of antineoplastica (adriamycin, vincristin and cyclophosphamide) and predonisolone was started for the disease. The days after the treatment, severe neutropenia due to the antineoplastica occurred and she had high fever again.
Her chest X-ray showed infiltrative shadow on the middle of the left lung field. By the detection of intraneutrophile gram negative cocci in her sputum and positive culture of Branhamella catarrhalis, the patient was diagnosed as Branhamella catarrhalis pneumonia.
Although many antibiotics such as minocycline, mezlocillin, cefmetazole, piperacillin and cephoperazon were administered, the patient was getting to severe respiratory failure and died.
Indirect immunofluorescent antibody (IFA) titer of her serum to L. pneumophila, serogroup 1 was always within 1: 32 with no significant elevation.

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Meningitis, septicemia, and granulomatosis infantiseptica are common clinical manifestations of listeriosis. In Japan, 283 cases of listeriosis have been reported from 1958 to 1980. Although more than half of the reported cases are infants, adult cases are recently increasing as one of the opportunistic infections.
Here reported a case of listeria meningitis occured during remission of acute lymphocytic leukemia.
The clinical course of the case: A 28 years old male had been treated in our clinic as an in- or outpatient due to acute lymphocytic leukemia (ALL) of FAB-type L-2. In February 1982, he was again admitted to our hospital to receive DVP (Daunorubicin + Vincristin + Prednisolone) therapy as well as intrathecal Methotrexate administration, resulting in a complete remission.
In May, during his short at-home stay, the patient took raw cow liver. Soon thereafter, he began to complain fever (39°C), headache and diarrhea, followed by unconsciousness in seven days.
In spite of chemotherapy (ampicillin, minocycline) and y-globulin administration, the patient took a fatal course. Culture of CSF yielded a strain of Listeria monocytogenes of type 4B.
It should be needless to say that the immunodefficiency of the patient due to ALL, although in its remission stage, had induced the listeria infection. The raw liver ingested during his at-home stay might have been the source of the pathogen, although no confirmatory evidence could be found.

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