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The patients or carriers with infectious enteritis admitted to the Hospitals for infectious diseases in the last 5 years (1996-2000) were studied. The total number of cases admitted in each year were 969, 1,113, 981, 637 and 573 respectively. A total of 1,527 Shigella spp. strains including 1,078 strains from overseas travelers' cases were isolated. The isolates of Salmonella spp. excluding S. Typhi and S. Paratyphi A were 562 in number. A total of 61 Vibrio cholerae O1 strains including 44 strains from overseas travelers was isolated. These V. cholerae O1 strains were all of El Tor type. Entamoeba histolytica, Giardia lamblia, Cryptosporidium parvum and Isospora belli were detected in 225, 46, 3 and 3 cases respectively. Abdominal pain, nausea and vomiting were frequently observed in the cases caused by Vibrio parahaemolyticus. The highest body temperature and the highest frequency of bowel movements were revealed in the cases caused by Salmonella spp. Bloody stool was observed in 55.3% of the cases due to Escherichia coli, in 40.5% of the cases due to Campylobacter spp. and in 24.1% of cases due to Shigella spp. As for shigellosis and salmonellosis, the clinical symptoms were more serious in the domestic cases than those in travelers. OFLX-resistant strains accounted for 1.7% of Shigella spp. isolates. No strains of Salmonella spp. were resistant to OFLX. The incidence of drug-resistant isolates of Campylobacter jejuni were 26.0% for OFLX and 2.5% for EM.

During the thirty one-year period between 1969 and 1999, a total of 6,876 strains of group A streptococci isolated in Sapporo City General Hospital were classified by T-agglutination method. This research consisted of 5,866 strains of scarlet fever-patients (scarlet fever-strains), 450 of child-patients (child-strains), 141 of adult-patients (adult-strains) and 409 strains of the indistinct. The results were summarized as follows: 1. Total of 6,866 strains were classified to sixteen kinds of T-types such as T12 (44.1%), T4 (21.7%), T1 (9.2%), T6 (4.4%), T3 (2.8%), T22 (2.1%), T18 (1.9%), T28 (1.6%) & others. This pattern of type distribution, three prevailing types of T12/T4/T1, have been reported in other areas generally. But original increase of isolation rates of strains of some T-types as T6, for example, also appeared in Sapporo. 2. Long-term observations demonstrated that the isolation rates of individual T-type, especially T4 or T1, had been forming a small epidemic-wave having a 4 to 8 year-interval and these of type T3 or type T6 on the other hand were repeating sudden prevalence every several years. 3. The isolation rates of type T12 or type T4 in scarlet fever-strains, were significantly higher than in child-strains or adult-strains. It was shown that Type T1 was distributed widely irrespective of patient-group and age-group. It was also characteristic to be distributed to many T-types in adult-strains.

Prulifloxacin (PUFX), a new quinolone antimicrobial agent, was administered to a total of 122 patients and carriers to investigate its clinical efficacy, safety and usefulness in infectious enteritis (bacillary dysentery, enteritis caused by Salmonella spp. and enteropathogenic E. coli, cholera and so on). In addition, the minimum inhibitory concentration (MIC) of UFX (active compound) was determined against each clinical isolate, and compared with that of ciprofloxacin (CPFX), ofloxacin (OFLX), tosufloxacin (TFLX) and nalidixic acid (NA). The correlation between the concentration of UFX in feces and the change of the fecal microflora were also investigated when PUFX was administered to the patients with acute infectious enteritis. A daily dose of 400 mg of PUFX was administered orally in two divided doses (morning and evening) for 5 days, with the exception of 7 days administration against salmonella enteritis and 3 days administration against cholera. 84 cases were adapted for evaluating the usefulness. The clinical efficacy was 100% in all the enteritis except salmonella enteritis, in which it was 88.9% (8/9 cases). On the bacteriological efficacy, the elimination rate was 100% in all isolates except Salmonella spp., in which it was 75.0% (12/16 cases). As for the adverse effect, uriticaria in moderate degree was observed in 1 (0.9%) of 109 cases. Abnormal changes in laboratory findings were seen in 3 (3.0%) of 100 cases, consisting of 1 with eosinophilia and 2 with elevated S-GPT, although they were all slight in degree. The usefulness rate was 65.5% (55/84 cases) for "very useful" and 95.2% (80/84 cases) for "very useful" and "useful". MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae, was 0.025, 0.05, 0.025 and 0.05 microgram/ml, respectively. These values were the same as those of CPFX and TFLX, and superior to OFLX and NA. UFX concentrations in feces followed by administration of PUFX in 3 cases with acute infectious enteritis were higher than that of MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae. The changes of the fecal microflora, which influence the efficacy and safety of PUFX, were not observed.

A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.

Vivax malaria is the most frequent among imported malaria in Japan, comprising about 60% of the total cases. Usually, after the acute phase therapy, e.g. with chloroquine, patients with vivax malaria are treated with the standard course of primaquine, i.e. 15 mg base/day for 14 days, as curative therapy. Recently, however, cases of relapse of vivax malaria after this standard primaquine therapy were reported from various countries and were also encountered in Japan. This report showed that the relapse after the standard primaquine therapy occurred most frequently in the cases acquired in Papua New Guinea, followed by Indonesia and Thailand. In contrast, the relapse rate of the cases acquired in India was low. Most of the relapsed cases were successfully treated with either of the regimens 1) 30 mg/ day for 7 days, 2) 2 courses of the standard primaquine therapy given 1 month apart or 3) 15 mg/ day for 21 days, without noticeable side effects. It is imperative to establish the most appropriate regimen with primaquine for the curative treatment of vivax malaria contracted in the areas mentioned above.

The efficacy, safety and usefulness of balofloxacin (BLFX) for patients with acute infectious enteritis and the carriers mainly shigellosis, were investigated. The drug was administered at a daily dose of 200 mg twice a day for 3 days to patients with cholera, 7 days to patients with Salmonella enteritis and 5 days to patients with other conditions of infectious enteritis including shigellosis; 1. The efficacy was analyzed in 89 of the 135 patients who received the administration (43 patients with shigellosis, 14 with Salmonella enteritis, 8 with enteropathogenic/ enterotoxigenic Escherichia coli enteritis, 3 with cholera, 7 with enteritis with other pathogenic bacteria, 6 with polymicrobial infectious enteritis and 8 with acute enteritis that was pathogen-negative). 2. In patients bearing symptoms and who thus could be analyzed for drug efficacy, the drug was markedly effective or effective 50/52 (96.2%). 3. Bacteriologically, the drug was effective for Shigella spp. in 41 (100%) of 41, Salmonella spp. in 12 (85.7%) of 14, and enteropathogenic/enterotoxigenic Escherichia coli in 8 of 8 cases. 4. Adverse effects were seen in 5/133 patients (3.8%) receiving the drug, including two cases of skin eruption, one of the numbness of the hands, one of oral aphtha, and one of nausea. In patients for whom laboratory findings were available, 20/115 (17.4%) showed abnormalities, mainly elevations of GOT and/or GPT, but these were slight. 5. In terms of subjective reports of usefulness, 51/82 (62.2%) were markedly satisfied, and 73/82 (89.0%) were either satisfied or markedly satisfied. 6. The influence of administration of BLFX on fecal concentration and intestinal microbial flora was investigated in 2 patients with acute infectious enteritis. Results approximately equivalent to such flora levels in healthy subjects were obtained. These results suggest that BLFX is highly useful for infectious enteritis such as that caused by shigellosis.

Studies on beta-hemolytic streptococci have been carried out in 2 institutions for handicapped preschool children during the last nine-year period from 1985 to 1993. These studies were based on continuous throat cultures, 4 to 12 times a year, from 244 children including Down's syndrome and mentally retarded children in K-institution (K), and from 134 including cerebral palsy and other cerebrospinal disorders in H-institution (H). A significant difference (p < 0.05) was demonstrated in the isolation rates between K (11.1%) and H (6.4%). In K, isolation rates of beta-hemolytic streptococci ranged from 0 to 43.5%, showing a higher rate in winter (16.5%) than in summer (6.6%), and elevated-isolation rates of homologous types were demonstrate four times during the study period; i.e., type T12 in '87, type T28 in '88, type T1 in '90 and '92. In H, on the other hand, no higher rates (as to group A) were observed in winter or summer. In relation to disorders of children, the rates were 12.6% in Down's syndrome (mean age 2.7y), 10.0% in mentally retarded children (3.9y) and 6.4% in cerebral palsy or others with cerebrospinal disorders (3.3y). Down's syndrome, the youngest group, revealed the highest isolation rate of beta-hemolytic streptococci. In only two cases isolated hemologous types detected were over two times continuously.

A clinical study was conducted on fleroxacin (FLRX) in 143 patients and carriers with infectious enteritis (shigellosis, Salmonella enteritis, Campylobacter enteritis, pathogenic Escherichia coli enteritis, Vibrio parahaemolyticus enteritis, cholera, multiple bacterial infections, pathogen-negative enteritis). Furthermore, its antibacterial activity against clinical isolates, fecal concentration and effect on fecal microflora were conducted. FLRX was administered orally in doses of 200 mg once a day (200 mg group) or 300 mg once a day (300 mg group) for 3 days to cholera, for 7 days to Salmonella enteritis and for 5 days to the other infectious enteritis. The clinical efficacy rates were 100% in both the 200 mg and 300 mg groups. The bacteriological efficacy rates were 100% against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and V. cholerae O1, and 63.6% against Campylobacter spp. in the 200 mg group. The rates of the 300 mg group were 93.3% against Shigella spp., and 100% against Campylobacter spp. and pathogenic E. coli. As adverse effects, skin rash was observed in 1 case each in both groups (1.1%, 2.1%). Abnormal laboratory findings consisted of 1 case of increased eosinophils and 1 case of elevated GOT and GPT levels in the 200 mg group (2.8%), and 1 case of elevated GPT in the 300 mg group (2.9%). The clinical usefulness rates were 92.9% and 93.3% in the 200 mg and 300 mg groups, respectively. Antibacterial activity was somewhat inferior to that fo ciprofloxacin and equal to or better than that of norfloxacin, demonstrating MIC90 values against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and Campylobacter spp. of 0.1, 0.2, 0.1, 0.2 and 0.78 micrograms/ml, respectively. Peak fecal concentrations of the drug were 49.0 micrograms/g and 274.4 micrograms/g in the 200 mg group, and 43.3 micrograms/g and below the detection limit (5.0 micrograms/g) in the 300 mg group. With respect to fecal microflora (4 cases), a decrease in Enterobacteriaceae was observed in 3 cases during dosing. But this change showed a tendency to recover after completion of dosing. No effects were observed on anaerobic bacteria.

The clinical efficacy, safety and usefulness of Rokitamycin (RKM), a new macrolide antibiotic, were compared with those of Ofloxacin (OFLX) for the treatment of Campylobacter enteritis by a double blind method. The daily dose level of RKM or OFLX was 600 mg. They were orally administered in three divided doses for 5 days. Of 223 cases studied, 106 cases were diagnosed as Campylobacter enteritis. Ninety cases (RKM group: 50, OFLX group: 40) except for 16 excluded or drop-out cases were analysed. There was no significant difference between the two groups in any background factors. The effectiveness and usefulness was evaluated in 88 cases (RKM group: 48, OFLX group: 40). The results obtained were as follows: 1. In a total of 82 strains of Campylobacter jejuni/coli (RKM group: 42, OFLX group: 40), the bacteriological efficacy rate of RKM (95.2%) was superior to that of OFLX (70.0%) with a significant difference (p = 0.006). 2. In 76 symptomatic patients (RKM group: 42, OFLX group: 34) on the day of the beginning of drug administration, the clinical efficacy rate was 97.6% in the RKM group and 85.3% in the OFLX group with no significant difference between the two groups. 3. In 88 evaluable patients, the global clinical efficacy rate of RKM (95.8%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.001). 4. Side effect was observed in 1 (1.9%) of the 54 patients in the RKM group and none of the 44 patients in the OFLX group. Slightly abnormal laboratory findings were seen in 4 (10.8%) of the 37 patients treated with RKM and 3 (9.7%) of the 31 patients treated with OFLX, but there was no significant difference between the two groups. 5. In 88 evaluable patients, the clinical usefulness of RKM (91.7%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.01). From these results, RKM is considered to be a very useful agent for the treatment of Campylobacter enteritis.

11,119 patients with scarlet fever admitted in the last sixteen years, from 1973 to 1988, to Sapporo City General Hospital, were studied statistically on symptoms and laboratory findings. The results were summarized as follows: 1. Annual number of patients have reduced suddenly since 1981, and become zero in 1989. The patients increased in number during the winter season. Eighty two percent of the cases were between 3 and 8 years of age, and the average age was 5.8 year-old. 2. Cases of above-38 degrees C temperature were seen in about 81.4%, and from 2 to 5 days-duration of temperature were seen in 86.6% of the patients in the year 1976. Cases of above-moderate rash were observed in 68.2%, sever redness of throat in 29.9%, strawberry tongue in 86.3% and angular stomatitis in 37.7% of the patients. In recent statistical analysis (1982-1988), we found, however, a tendency that patients having stronger symptoms were being introduced to our hospital. 3. The higher rates of cases showing elevated ASD titer were seen in the elder patients and in the winter. C-reactive protein (CRP) titers were mostly in the range of (-) to (greater than or equal to 6+), having 2.4 + on an average. 4. Patients who developed into overt nephritis were not seen. Cases of microscopic hematuria (greater than or equal to 3 red cells/f in urine sediments), however, were observed in 1.1% (125/11,119). Sever complications were hardly seen. 5. Reappearance of beta-hemolytic streptococci (on a week after discharge) were found in 3.1% (241/7,877). 6. Reinfection or relapse cases of scarlet fever were found in 6.7% (642/9,585).(ABSTRACT TRUNCATED AT 250 WORDS)

For the purpose of evaluation of clinical efficacy, safety and usefulness on acute infectious enteritis (bacillary dysentery, and enteritis caused by Salmonella spp., Campylobacter spp., enteropathogenic E. coli, and so on), T-3262, a newly developed pyridone-carboxylic acid derivative, was administered to a total of 136 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). The daily dose of 450 mg of T-3262 was administered orally three times after meals for 5 days, with the exception of 7 day administration against Salmonella enteritis. A total of 89 cases were evaluated; 23 with Shigella spp., 30 with Salmonella spp., 15 with Campylobacter spp., 6 with enteropathogenic E. coli, and 15 cases with the other pathogens or pathogen-negative. The efficacy on clinical symptoms judging from duration of fever, and duration of diarrhea and abnormal stool character was 100% in all the enteritis except enteropathogenic E. coli enteritis, in which it was 50% (n = 2). Concerning bacteriological response, elimination of the causative organisms from the feces was 100% in Shigella spp. (n = 19), Salmonella spp. (n = 30), and enteropathogenic E. coli (n = 6), although 64.3% in Campylobacter spp. (n = 14). As an adverse effect, epigastric discomfort was observed in one (0.8%) of 130 cases. Deteriorations in laboratory findings were seen in five (6.2%) of 81 cases, consisting of two with elevated GOT and GPT, two with elevated GPT, and one with increased eosinophils count, although they were all slight in degree. MICs of T-3262 which inhibited 90% of the isolates of Shigella spp, Salmonella spp., and Campylobacter spp., were 0.025, 0.05, and 0.78 microgram/ml, respectively. These values were lowest among the quinolone derivatives tested, except that the MIC90 against Campylobacter spp. was the same as that of ofloxacin.

The clinical efficacy, safety and usefulness of lomefloxacin (LFLX, NY-198), a new quinolone antimicrobial agent, were compared with those of pipemidic acid (PPA) in the treatment of infectious enteritis (bacillary dysentery, enteropathogenic Escherichia coli enteritis and Campylobacter enteritis) by a double blind method. Daily dosage of LFLX and PPA was 600 mg and 2000 mg, respectively administered orally divided into 4 doses. The duration of the treatment was 5 days. Of 290 cases studied, 100 cases were excluded and 21 cases were dropped from analysis of effectiveness and usefulness. The effectiveness and usefulness was evaluated in 169 cases (LFLX group: 83, PPA group: 86). There was no significance difference between the two groups in any background characteristics. The results obtained were as follows: 1. In 73 symptomatic patients (LFLX group: 35, PPA group: 38) on the day of the beginning of administration, the clinical effect was 91.4% in the LFLX group and 84.2% in the PPA group with no significant difference between the two groups. 2. In a total of 184 strains (LFLX group: 90, PPA group: 94), the bacteriological effects of LFLX (93.3%) was superior to that of PPA (80.9%) with significant difference (p = 0.0153). 3. In 169 evaluable patients, the global clinical effects of LFLX (92.8%) was superior to that of PPA (79.1%) with a significant difference (P = 0.0144). 4. Side effects were observed in 1 (0.7%) of the 141 patients in the LFLX group and none of the 143 patients in the PPA group. Abnormal laboratory test values were noted in 10 (7.6%) of the 132 patients treated with FLLX and 7 (5.1%) of the 136 patients treated with PPA, but they as no significant difference between the two groups. 5. In 169 evaluable patients, the clinical usefulness of LFLX (91.6%) was superior to that of PPA (76.7%) with a significant difference (P = 0.0111). From these results, LFLX is considered to be a clinically useful medicine in the treatment of infectious enteritis including bacillary dysentery.

For the purpose of evaluation of clinical efficacy, safety and usefulness on Salmonella enteritis, T-3262 (Tosufloxacin tosilate), a newly developed pyridone-carboxylic acid derivative, was administered to a total of 103 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). And when T-3262 was administered to the patients of acute infectious enteritis, fecal drug concentration and their correlation to the changes in the fecal microflora were investigated. The daily dose of 450 mg T-3262 was administered orally three times after meal for 7 days. A total of 63 cases were evaluated (one case of mixed infection caused by Shigella flexneri and Salmonella sp. was included). The clinical efficacy was good in all the enteritis (N = 6). As the bacteriological effect, 60 out of 61 were eradicated, and eradication rate was 98.4%. Adverse effects were observed in four of 102 cases (3.9%), consisting of one with skin rash, one with nausea, headache and stomatitis and two with soft stools. Deteriorations in laboratory findings were seen in 5 of 23 cases (17.4%), consisting of one with elevated GOT, two with elevated GOT and GPT, one with elevated BUN and one with increased eosinophiles count, although they were all slight in degree. MICs of T-3262 which inhibited 90% of the isolates of Salmonella spp. was 0.05 microgram/ml, which was the lowest among the quinolone derivatives tested. The values of the fecal drug concentration of 7 cases of acute infectious enteritis, to which T-3262 administered, were higher than that of MIC90 and recovery rates of T-3262 were distributed from 2.85 to 46.3%. The degrees of changes of the drug concentrations were dependent on individual cases, and did not show the same trend. In addition, changes in the fecal microflora with in 24 hrs after T-3262 administration did not show the same trend.