Four-hundred and seventy-eight hepatitis B virus (HBV) carriers were followed for more than 5years. Thirty-six cases (7.5%) cleared hepatitis B surface antigen (HBsAg) from serum during the observation period. In these 36 cases, the investigation of HBV carriers in relation to the clinical course and HBV markers was performed.
1) Fourteen of them (Group I) developed anti-HBs and other 22 (Group II) remained anti-HBs free. The difference of the two groups was significantly related to the age. Group II suggested to have possibility to develop anti-HBs in the future.
2) The correlation between the clearance of HBsAg and other HBV markers (HBeAg, anti-HBe, anti-HBc) was not found.
3) Annual clearance rate of HBsAg was 1.27%. Annual clearance rates of various age groups exhibited significant rise in groups over 40 years old.

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Hepatitis B virus vaccine (HEPTAVAX-B^®) manufactured by Merck Sharp and Dohme in the U.S.A. was administered (three doses of 20 mcg) to seventy-five medical personnel.
The results were as follows:
1.The anti-HBs seroconversion rate after 2 or 3 vaccinations was 94.2%(65/69).
2.The third vaccination gave a very significant booster effect with a marked increase in antibody titer.
3.In terms of adverse reactions, local pain was observed in 25%(56/223 total doses), fatigue in 16%(36/223) and fever in 4%(8/223). But most of these adverse effects were mild and disappeared within 2 days after vaccination.
It was considered that HEPTAVAX-B is a safe and effective vaccine for the prevention of hepatitis B infection.

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We investigated the incidence of HAV and HBV infection to find the epidemiologic difference in persons under the various environments such as 188 persons lived at Chikugo district, 120 persons with alcohol or drug addict, 68 sailors, 93 weak minded children, 73 medical staffs and 75 foresters, in 1978. Furthermore, 302 persons lived at Chikugo district were examined for comparing anti-HAV positive rate in 1983 with those in 1978. Anti-HAY by RIA, HBsAg by R-PHA and anti-HBc by RIA were examined. In persons lived at Chikugo district (Chikugo general population), the prevalence of anti-HAV and HBsAg and/or anti-HBc were same level as in Japanese population.Age distribution of anti-HAV in 1978 showed low incidence below 25 years old and increasing incidence over 25 years old in Chikugo general population. The prevalence of anti-HAV in Chikugo general population was compared between 1978 and 1983 and the age distribution curve of anti-HAV in 1983 was different from 1978, i.e. lower prevalence of anti-HAV in persons at 30-39 years old in 1983 than in 1978. This phenomenon was considered as the consequence of improvement in sanitary condition.
Among alcohol or drug addicts, particularly in younger generation, the prevalence of anti-HAY (25.0% at 20-29 years old and 70.4% at 30-39 years old) and HBsAg and/or anti-HBc (70.0% at 20-29 years old and 80.0% at 30-39 years old) were significantly higher than those at the same age among Chikugo general population. Moreover, HBsAg was found in 8 out of 120 persons (6.7%) in this group. It was considered from the result of anti-HBc titre that 3 of these 8 persons were taken from cases of persistent HBs antigenemia and the remaining were those of transient HBs antigenemia. Thus, the cases with transient HBs antigenemia in addicts was found more frequently than in general population. Our data suggested that these addicts may require longer period to clear HBsAg than general population.

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In order to find out the carrier rate of thermophilic campylobacter in intestinal contents from 452 chickens in 11 poultry farms were examined. They were cultured on Skirrow's blood agar at 43°C for 2-3 days under microaerophilic condition. Thermophilic campylobacter was recovered from 4 weeksold chicken, broiler and end-of-lay hen, but not from two-days-old chicken. Recovery rates were 2.6% in 4-weeks-old chicken, 28.3% in broiler and 32.8% in end-of-lay hens. One hundred and nineteen out of 126, or 93.7% of the isolates were Campylobacter jejuni and other 7, or 6.3% were Campylobacter coli. The carrier rates of thermophilic campylobacter in chicken at 11 farms were quite different, and in some farms they were heigher than 40%.
The cloaca swabs were collected from 24 chickens in a farm at intervals during 9 months period, and they were examined for Campylobacter. Ten chickens were positive for Campylobacter 3 successive times or more during 3 months or more. One of them excreted the organism for 9 months. Other 4 chickens were positive for Campylobacter during 7 months or more intermittently.
The number of the organism in the intestinal contents ranged from 10³ to 10⁴ CFU/g.
C. jejuni was also isolated by direct culture from 12 out of 34 excreted feces which were collected at poultry farm B. At the same farm, C. jejuni was also recovered from 7 of 34 drinking water samples and from 3 of 27 house flies by enrichment culture using CEM medium.
Ninety five out of 115 strains or 83% were typable by means of serotyping system based on a slide agglutination technique using 32 specific antisera, which was developed in our laboratory. Serogroup TCK 4, 7, 12, 20, 21 and 24, which were frequently encountered among human isolates, were also common in these chicken isolates.

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The most clinical laboratories employ the single-disk method forthe determination of drug sensitivity of clinical isolates. Since the agar dilution techniqueis a method that is recommended by the Japan Society of Chemotherapy as a standard assay method for thedetermination of drug sensitivity, a study that compares these two methods for the measurement of MIChas been made. This report describes such a study using the disks obtained from Showa Pharmaceutical Co., Ltd. and the agar dilution method.
Bacterial strains used were Escherichia coli ATCC25922 as the standard strain and 154 strains of clinical isolates identified in our laboratory including 26 strains of E. coli, 26 of Klebsiella pneumoniae, 24 of Enterobacter cloacae, 27 of Serratia spp., 25 of Proteus mirabilis and 26 of Pseudomonas aeruginosa. Antibiotics used were ampicillin, piperacillin, carbenicillin, cephalothin, cefsulodin, cefmetazole, cefotaxime, latamoxef (moxalactam), kanamycin, gentamicin, amikacin, chloramphenicol, tetracycline, minocycline, colistin, polymyxin, and nalidixic acid.
The MIC values obtained from the disk method were plotted against that from the agar dilution mehtod and found that the MIC values obtained from these two methods relate very well showing the percent agreement of about 95±5 for most drugs and most bacterial species. Exceptions were that the percent agreement of MIC for chloramphenicol appeared to be 76, and a little scatterings observed in the plots are nalidixic acid (72% agreement) in E. coli, piperacillin (55%) and cefsulodin (68%) in P. aeruginosa, kanamycin (75%), gentamicin (50%) and amikacin (78%) in Serratia spp. and cephalothin (38%) in P. mirabilis. Though the reason for these discrepanciesis not clear at the moment, a plausible explanation may be that a single standard curve for the calculation of MIC in a single drug cannot be applied to all species or genera of bacteria. Therefore, the improvement to be made is to draw a single standard curve for a species of bacteria and for a drug. Then itwill become possible to determine the MIC value accurately using the single disk method, in stead of doing the time consuming agar dilution test.

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The increasing incidence of ampicillin (ABPC)-resistant H. influenzae was observed from 383 strains isolated from children at Chiba University Hospital, Chiba City; 5/48 strains (10.4%) in 1979, 13/113 strains (11.5%) in 1980, 19/113 strains (16.8%) in 1981, and 19/109 strains (17.4%) in 1982.
2. A study of ABPC-resistant H influenzae strains was performed in infants and children at Asahi General Hospital, Asahi City, Chiba, from June, 1981 to February, 1982. They were diagnosed as respiratory tract infection and otitis media. Out of 197 patients found H influenzae in nasopharyngeal swabs. 7/197 strains (3.6%) were proved to be ABPC-resistant. Of29 strains of H influenzae from middle ear fluid, only one strain was ABPC-resistant.
3. In order to elucidate sensitivity of ABPC-resistant H influenzae against other antimicrobial agents, minimal inhibitory concentrations (MICs) were determinedby agar dilution method. The inoculum size was approximately 10⁶ cfu/ml. Fifty clinical isolates confirmed to be ABPC-resistant, because of β-lactamase positive, showed ABPC-MIC of 1.56, μg/m1 or more. However, they showed similar susceptibility to amoxicillin, cefatrizine, cefaclor anderythromycin. No strains were resistant to augmentin (BRL25000). Fourteen percent of the strains (7/50) were proved resistant to chloramphenicol. The newer cephalosporins, especially cefotaxime and latamoxef, showed high activity against all ABPCresistant
4. Twenty-three strains of ABPC-resistant H influenzae isolated from Chiba, Tokyo, and Hiroshima, were demonstrated to have type I penicillinase (classification by S. Mitsuhashi), corresponding to TEM-typed β-lactamase known to be transferred among other gram negative bacilli. strains.
5. Fifty strains of ABPC-resistant H. influenzae clinically isolated were examined for R-factor. H. influenzae CH-82 was used as the recipient. Conjugal transfer was examined by mixed incubation on membrane filter. The R-facters were demonstrated at 60% of theseABPC-resistant strains. The isolation frequency was similar to that of some enterobacteriaceae, but transfer frequency was lower. Judging from these observations, it can be explained that ABPC-resistant H. influenzae strains has been gradually increasing in Japan.

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The clinical efficacy and safety of Cefminox (CMNX, MT-141), a new cephamycin, was objectively compared with that of cefotaxime (CTX) in patients with chronic respiratory tract infections, bacterial pneumonia or lung abscess in a well controlled study. Patients over 15 years old with apparent clinical signs and symptoms were administered CMNX or CTX intravenously b.i.d. for 14 days at a daily dose of two grams. The parameters assessed were clinical efficacy, rate of improvement of clinical signs and symptoms, bacteriological response, appearance of side effects, abnormal laboratory findings and clinical usefulness.
Clinical efficacy was analyzed statistically in 218 patients (108 administered CMNX, 110 administered CTX) and 42 patients out of a total 260 patients were excluded. Side effects were analyzed in 243 patients (CMNX: 121, CTX: 122) and laboratory abnormalities were also analyzed in 232 patients (CMNX: 116, CTX: 116) in whom judgement was possible.
The following results were obtained.
1. On the basis of committee judgement the overall clinical efficacy rate was 76.6% for CMNX group and 67.0% for CTX group for total cases. The corresponding figures for patients with pneumonia and lung abscess and those with respiratory tract infections other than pneumonia and lung abscess were 78.9% for CMNX group and 63.2% for CTX group, and 74.0% for CMNX group and 73.2% for CTX group, respectively.
2. As to improvement rate of clinical signs and symptoms, significantly higher rate was obtainedwith CMNX in CRP at day 3 in patients with pneumonia and lung abscess, and ESR on day 14 in patients with respiratory tract infections other than pneumonia and lung abscess.
3. The bacteriological elimination rate of causative organisms was 91.5% out or 47 pateints treated with CMNX and 80.8% out of 52 patients treated with CTX. No significant difference was observd between the two drug groups.
4. Some side effects were observed in 6 patients out of 121 in the CMNX group and 9 out of 122 in the CTX group, with no significant intergroup difference in incidence of these side effects.
5. Some abnormal laboratory findings were observed in 26 (22.4%) out of 116 patients in theCMNX group and 42 (36.2%) out of 116 in the CTX group, the difference between these two groups being significant. The observed laboratory abnormalities included eosinophilia in 6 (5.2%) for CMNX group and 16 (13.8%) for CTX group. There was significant difference in incidence of eosinophilia.
6. It was found that the clinical usefulness was rated as very useful for 61 patients (55.0%) and useful for 20 patients (18.0%) out of 111 patients in the CMNX group, while in the CTX group the clinical usefulness was rated as very useful for 43 patients (39.1%) and useful for 27 (24.5%) out of 110 patients for total cases. For patients with pneumonia and lung abscess the clinical usefulness was rated as very useful for 34 patients (56.7%) and as useful for 11 (18.3%) out of 60 in the CMNX group and as very useful for 25 patients (36.8%) and useful for 16 (23.5%) out of 68 in the CTX group. In these cases significant difference was observed between the two drug groups (p<0.05), while no significant difference was observed for patients with respiratory tract infections other than pneumonia and lung abscess.
From the above results it was concluded that CMNX is a more useful antibiotic than CTX for the treatment of respiratory tract infections.

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The clinical efficacy and safety of Aspoxicillin (ASPC), a new semisynthetic penicillin, were compared with those of piperacillin (PIPC) in 276 patients with respiratory tract infections in a multi-center double-blind trial.The patients were randomized to be treated either with 2g of ASPC or PIPC intravenous drip infusion twice a day for 14 days.
The results were as follows:
1.Out of 276 patients included in this trial, 242 patients (122 received ASPC and 120PIPC) were applied to the evaluation of the clinical efficacy by the committee members, while 245 patients (121 received ASPC and 124PIPC) were adopted by the doctors in charge for the statistical analysis of the clinical efficacy evaluated by doctors in charge.
2.The clinical efficacy rates in all cases adopted by committee members were 76.2% in ASPCgroup and 78.3% in PIPC group, respectively.In the cases of bacterial pneumonia, the efficacy rates were 77.3% in ASPC group and 84.6% in PIPC group, and in cases of chronic respiratory tract infections, 85.1% in ASPC group and 67.9% in PIPC group, respectively.There was no significantdifference in the clinical efficacy evaluated by the committee members between the two groups.
3.The clinical efficacy rates by doctors in charge were 83.2% in ASPC group and 79.8% in PIPC group in all cases.In the cases of bacterial pneumonia, the efficacy rates were 71.4% in ASPC group and 80.0% in PIPC group and in the cases of chronic respiratory tract infections, 85.1% in ASPC group and 67.9% in PIPC group, respectively.There was statistically significant difference in the efficacy rate for chronic respiratory tract infections between the two groups (P<0.05), but in other cases there was no significant difference between the two groups.
4.Bacteriological efficacy was evaluated based on the rate of eradication of causative organism from the sputum.There was no significant difference in the eradication rate between the two groups. The degrees of improvement in several symptoms associated with infection, such as body temperature, cough, volume and properties of sputum, dyspnea, rales, chest pain, cyanosis and chest X-ray were also compared between the two groups, but no significant differences were noted.
5.Adverse reactions were noted in 5.3% of ASPC group, and in 4.7% of PIPC group.Abnormal laboratory findings were observed in 25.2% of ASPC group and in 22.4% of PIPC group.Most frequently reported findings were elevations in transaminases and increase in eosinophils.There was no significant difference in the incidences of adverse reactions and abnormal laboratory findings between the two groups.
6.The global clinical utility rates evaluated by the committee members were 73.4% in ASPC group and 74.2% in PIPC group, and those by doctors in charge were 78.9% in ASPC group and 74.2% in PIPC group.There was no significant difference between the two groups.
From these results it may be summarized that ASPC is as useful as PIPC in the treatment of respiratory tract infections.

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The clinical effectiveness and side effects of TMS-19-Q (TMS) in the patients with respiratory tract infections, mainly mild bacterial pneumonia, mycoplasmal pneumonia and PAP, were compared with those of midecamycin (MDM) by means of double-blind controled stiudy. TMS or MDM was orally administered 600 or 1200mg per day respectively. Total 185 cases (94 in TMS and 91 in MDM) were analyzed and the results obtained were as follows:
Overall clinical efficacy ratings of TMS and MDM groups were 84.4% and 90.6% in pneumonia, and 85.7% and 78.9% in airway tract infections. Bacteria isolated and defined as the pathogen were 28 strains mainly consisting of Streptococcus pneumoniae and Haemophilus influenzae.
The side effects were observed 1.1% in TMS group and 4.6% in MDM group, and abnormal changes of laboratory findings were noted 15.2% in TMS and 13.2% in MDM.In respect to clinical effectiveness and side effects, statistical analysis showed that the data on both drugs were not significantly different.
From these results, daily 600mg dosage of TMS was as useful as daily 1200mg dosage of MDM in the treatment for mild and moderate respiratory tract infections.

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Pseudomembranous colitis (PMC) induced by antibiotics, especially clinidamycin or lincomycin, has been well known by clinicians as a common side effect among the patients who were on the drugs. The isolation of Clostridium difficile from faeces and the detection of cytopathic toxin of C. difficile have been the prevailing methods in determining the etiological mechanism of antibiotics-associated PMC.
The first case of PMC induced by rifampicin (RFP) was reported in 1980. Only seven cases were described afterwards in the western hemisphere. On the other hand, no case of PMC definitely associated with RFP has been reported, as far as we know, in Japan.
An eighty two year old woman developed colitis 13th day after commencing antituberculous agents, RFP (0.45g/day), ethanbutol (1.0g/day) and isoniazide (0.4g/day).
Colonoscopy showed the presence of pseudomembrane-like mucosal change, although it was not confirmed by histopathology. C. difficile resistant to RFP (1.8×10⁹ colony forming units 1g wet weight faeces) was isolated from faeces and cytopathic toxin was detected in the supernatant of the faeces. After being diagnosed asC.difficile colitis, withdrawal of antituberculous agents and administration of metronidazole (0.75g/day) led to rapid recovery.

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