[Epidemiological and therapeutic study on gonorrheal infection--study on NY-198 (lomefloxacin) single administration therapy. Sapporo Clinical Research Group for STD].

The efficacy of single administration of NY-198 in the treatment of gonococcal infections was studied employing male patients with gonorrheal urethritis and female patients with gonorrheal cervicitis. The clinical efficacy was evaluated on the basis of the efficacy rates which was estimated on each observation day for each patient. In the male patients, NY-198 was administered in a dose of 200 mg in 25 cases and a dose of 400 mg in 65 cases. The rate of eradication of N. gonorrhoeae (i.e. efficacy) on the 3rd day of administration was 96% in the 200 mg administration group and 100% in the 400 mg administration group. On the 7th day after administration, the eradication rate was 100% in both the 200 mg and 400 mg administration groups. When the eradication rate on the 7th day was statistically estimated for patients who returned to the hospital only on the 3rd day, it was 97.9% in the 200 mg administration group. In the female patients, NY-198 was administered in a dose of 200 mg to 4 cases and a dose of 400 mg to 5 cases. The eradication rate on each observation day was 100% in both dosage groups. In conclusion, single administration of NY-198 in a dose of 200 mg or 400 mg was highly effective, and considered to be a therapeutic method highly useful clinically.

[Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of cefetamet pivoxil].

We studied the epidemiology of 109 cases of gonococcal infections (105 males with urethritis and 4 females with cervicitis), together with the basic and clinical effects of cefetamet pivoxil in the cases. The peak of age distribution of the male patients was in the younger half of their twenties, and all of the 4 female cases were between 20 and 39 years old. The major source of infections in the males younger than 25 years old was their girl friends or so-called pick-up friends, and that of the males older than 25 years old workers serving at an amusement center, for example, bars and so-called special massage parlor, which accounted for about three fourths of the male cases between 35 and 44 years old. The distribution of the MIC (inoculum size; 10(6) CFU/ml) of Cefetamet against beta-lactamase non penicillinase producing Neisseria gonorrhoeae (non-PPNG) ranged from 0.025 to 0.1 microgram/ml and that against beta-lactamase producing Neisseria gonorrhoeae ranged from 0.025 to 0.05 microgram/ml. The isolation rate of PPNG was 10.2% (9/88). In male patients with gonococcal urethritis, the efficacy rate was 100% on days 3 and 7 for 1,000 mg single dose and 7-day treatment and 500 mg single dose treatment. One of the cases treated with 250 mg single dose therapy was unchanged at 3, but the efficacy rate of the remaining cases was 100% at day 7. Complicated urethritis with C. trachomatis was noticed in 25.7% (5/105) of the male urethritis and in 25.0% (1/4) of the female cervicitis cases. The only side effect was diarrhea observed in 1 of the 124 case (0.8%).

[The therapeutic effect of norfloxacin on chronic prostatitis].

The clinical efficacy of norfloxacin (NFLX) was evaluated in 74 patients having chronic prostatitis with the subjective symptoms suggesting the inflammations of prostate and more than five white bloodcells (WBCs)/hpf in their prostatic secretions (EPS). Of these, gram negative rods with greater than or equal to 10(3)CFU/ml (GNR group) were isolated from the EPS in 10 patients (13.6%) and gram positive cocci with greater than or equal to 10(3) CFU/ml (GPC group) were obtained in 46 patients (62.2%). E. coli (70.0%) was the most frequent strain isolated among GNR group and S. epidermidis (40.4%), S. aureus (19.1%), E. faecalis (17.0%) and S. haemolyticus (14.9%) were frequently isolated among the GPC group. The overall clinical efficacy of NFLX was determined at the second and fourth week by the three factors, (1) the effect on bacteria, (2) WBCs in the EPS and (3) the subjective symptoms in the patients with bacteria of greater than or equal to 10(3) CFU/ml being isolated. The overall clinical effectiveness rate was 71.4% and 100%, respectively, in the GNR group. In the GPC group, its rate was 79.3% and 88.0%, respectively. The patients with no bacteria or less than 10(3) CFU/ml isolated from the EPS had an overall clinical effectiveness rate of 89.8% at the second week and 90.0% at the fourth, when it was evaluated by the effect on WBCs and subjective symptoms. In the effect of NFLX on bacteria in the EPS, it eliminated them in 75.0% and 83.9% at the second and fourth week, respectively, of all patients with GNR or GPC of greater than or equal to 10(3) CFU/ml isolated from the EPS. The minimum inhibitory concentrations (MIC) of NFLX against E. coli isolated from the EPS was distributed from 0.025 microgram/ml to 3.13 micrograms/ml with most below 0.1 microgram/ml. Those against all other GNR were below 0.78 microgram/ml. NFLX showed good antimicrobial activities against GPC with most of MIC being distributed from 0.78 microgram/ml to 1.56 micrograms/ml. NFLX produced the highest eradication rate in bacteriological response not only against GNR such as 100% at the first, the second and fourth week but GPC as 89.2%, 93.8% and 96.0%, respectively. In the effect of NFLX on WBCs in EPS, 40-50% of patients got free from the inflammation of prostate by NFLX treatment. This became prominent in the GNR group as the treatment was continued although not in the GPC group. The subjective symptoms were improved by NFLX treatment in most of the patients.

[Epidemiological and therapeutic studies on gonococcal infections--one shot therapy by spectinomycin--[Sapporo Clinical Research Group for STD]].

From January through March of 1985, the Sapporo Clinical Research Group for STD treated 69 cases of gonococcal infections (61 cases of male gonococcal urethritis and 8 cases of female gonococcal cervicitis) at its facilities in Sapporo City. The therapeutic efficacy of one shot therapy of Spectinomycin (SPCM) was investigated, and an epidemiological study on the cases and bacteriological studies on the isolated strains of Neisseria gonorrhoeae were made. The male patients were between 19 and 55 years old, with a peak age distribution in the younger half of the twenties. The female patients were between 18 and 40 years old. The major source of infections was a so-called special massage parlor which accounted for 36.1% of male cases. The isolation rate of PPNG were 16.7% (11/66). The MIC (inoculum size; 10(6) CFU/ml) of SPCM ranged from 3.13 to 25 micrograms/ml regardless of beta-lactamase production. In male patients, the eradication rate (efficacy rate) of N. gonorrhoeae by SPCM was 94.7% on the first day, 93.6% on the third day and 100% on the seventh day after 2 g one shot therapy. In female patients, the rate was 100% on the third and seventh day after 2 g one shot therapy, and 75% on the first day, 66.7% on third day and 100% on seventh day after 4 g one shot therapy. We considered that one shot therapy of SPCM was effective for gonococcal infection also in the present time. Especially SPCM was effective for infections by PPNG, since it was not resolved by beta-lactamase of N. gonorrhoeae. Positive rate of Chlamydia trachomatis was 16.3% in male gonococcal urethritis, and the serous discharge tended to remain longer in the positive patients than in the negative patients. There was only one side effect (1.4%), therefore SPCM was recognized to be a safely administrated antimicrobial agent.

[Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of norfloxacin].

We studied the basic and clinical effects of norfloxacin (NFLX) in 120 patients with gonococcal infections (110 men with urethritis and 10 women with cervicitis)--all residents at Sapporo City; and epidemiologically analyzed the sources of their infections. The male patients were between 16 and 67 years old and the female patients were between 20 and 61 years old, with a peak in the early 20s both for sexes. 70.6% of the male patients in their 10s were infected from their girl friends or so-called pick-up friends and 50% of the female patients from their husbands. The other half of the female were workers serving at so-called special massage parlors. The minimum inhibitory concentration (MIC) of NFLX against N. gonorrhoeae distributed was 0.0125 approximately 3.13 micrograms/ml, with a peak at 0.025 micrograms/ml. NFLX inhibited 93.3% of the clinical strains of this species at less than 0.1 microgram/ml and 96.2% at less than 1 microgram/ml, where the inoculation was 10(6) CFU/ml. Twenty one (20.2%) of the 104 N. gonorrhoeae strains were penicillinase-producing one (PPNG). NFLX inhibited 18 of these PPNG (85.7%) at less than 0.1 microgram/ml and the other 3 strains at 1.56 approximately 3.13 micrograms/ml. Oral administration of 200 mg NFLX showed the average peak serum level of 0.72 micrograms/microliter in 2 hours and the average peak level in the urethral secretions of 0.5 micrograms/ml in one hour. These two concentrations of NFLX covered 95.2% of the MIC distribution against N. gonorrhoeae. The clinical efficacy of 600 mg NFLX (peros) was 97.4 and 93.1% for a 3-and 7-day treatment for male urethritis; and 100% for both 3-and 7-day treatment for female cervicitis. Complicated urethritis with C. trachomatis was noticed in 32.7% of the male urethritis and in 20% of the female cervicitis cases. Urethral secretions among about half of these patients were observed even after treatment with NFLX. As a subsequent treatment, another effective chemotherapeutic is required against C. trachomatis. No adverse reactions were detected with NFLX. All the above results demonstrate that NFLX is a highly effective and safe chemotherapeutic agent for treatment of gonorrhoea.

[Epidemiologic and therapeutic studies on gonorrheal infections--use of AT-2266--Sapporo Clinical Research Group for STD].

From August of 1982 through February of 1983, the Sapporo Clinical Research Group for STD treated 131 cases of male gonorrheal urethritis at its affiliated clinical facilities in Sapporo City. The therapeutic efficacy of AT-2266 was investigated, together with an epidemiological study on the cases and bacteriological studies on the isolated strains of gonococcus. In addition, a few cases of female gonorrheal cervicitis were treated, and the therapeutic results for 3 of these cases evaluated. AT-2266 was administered at a daily dosage of 600 mg in one dose to 14 patients, 2 doses to 10 patients and 3 doses to 98 patients. At the end of 3 days of this therapy, the gonococci had been eliminated in all of the cases, but there was variation in the status of disappearance of the secretion. The "excellent" efficacy rates for these three regimens were thus 7.7%, 50% and 57%, respectively. These results showed that administration of the total dosage in two or more divided doses maintained higher minimum concentrations of the antibiotic in the blood and the urine, and were thus more clinically beneficial than when the dosage was given as one daily dose. Of the patients who were treated with 600 mg/day of AT-2266 in 3 divided doses, 93 were evaluated for the therapeutic efficacy. At the end of 3 days 57.0% were "excellent" cases, 39.8% were "good" cases and 3.2% were "fair" cases, and at the end of 7 days of therapy, 67 patients were 74.6% "excellent" cases, 23.9% were "good" cases and 1.5% were "fair" cases. The clinical efficacy rate was thus quite high. Those cases in which the secretion and leukocytes had not disappeared from the urine even at the end of the 7 days of therapy were probably cases of mixed infection involving Chlamydia, etc. Eight of the 77 gonococcal isolates (10.4%) were beta-lactamase producers. The MIC of AT-2266 hardly differed with the size of the bacterial inoculum. With an inoculum of 10(6)CFU/ml, the MIC distribution showed two peaks, i.e., at 0.05-0.2 micrograms/ml and 3.16-12.5 micrograms/ml. Only 11.7% of the strains were found to have high MICs. The distribution of these high MICs was found to be unrelated to the ability to produce beta-lactamase. Mild side effects of AT-2266 were seen in 2 out of 128 patients. (1.6%), an extremely low incidence.

[Therapeutic studies on male non-gonorrheal urethritis--use of AT-2266--Sapporo Clinical Research Group for STD].

AT-2266 tablets were administered orally in a daily dosage of 600 mg for 7 consecutive days as treatment of non-gonorrheal urethritis in 106 cases. The therapeutic results in 90 cases were investigated, and a detailed analysis of various background factors was also performed. Most of the patients were between 15 and 35 years old; 11.3% of the patients were between 15 and 19 years old. The source of infection was a "professional" woman such as a prostitute in 37 cases, and a non-professional woman in 53 cases. This is noteworthy because the source is more often a "professional" women in the case of gonorrhea. Bacterial isolates were obtained by culture of the urethral secretions. Most were gram-positive cocci, especially S. epidermidis, but, in 51.7% of the patients, no bacteria could be cultured. The urethral secretion was purulent in 51.9% of the patients, and serous in the remaining 48.1%. The efficacy rates obtained when AT-2266 was administered in a daily dosage of 600 mg (in 3 divided oral doses) for 7 days were as follows. In the purulent secretion group, the 3-day and 7-day therapeutic efficacy (elimination of the secretion) rates were 24.2% and 61.2%. In the serous secretion group, the corresponding efficacy rates were 36% and 71.4%. Thus the therapeutic efficacy was slightly inferior in the purulent secretion group. Oral administration of AT-2266 resulted in side effects in 5 of the patients (5.5%). These side effects consisted primarily of mild gastrointestinal disturbances, which did not require discontinued drug administration.

[Therapeutic studies on chronic prostatitis--use of AT-2266--Sapporo Clinical Research Group for STD].

AT-2266 is a new antibiotic of the pyridone carboxylic acid class which possesses a broad, low-MIC antibacterial spectrum. Therapeutic studies were carried out on the use of this drug in the treatment of chronic prostatitis, and at the same time a pathological analysis was performed on chronic prostatitis. The subjects were 97 chronic prostatitis patients for whom the prostate fluid had been confirmed to contain at least 30 leukocytes per 400-power magnification field. An analysis of the background factors revealed that 71% of these patients had a past history of gonorrheal or non-gonorrheal urethritis. Culture of the prostate fluid yielded gram-positive cocci (S. epidermidis in most cases) in 44.1% of the patients. E. coli was detected in 3.2% of the patients, while the remaining cases gave negative cultures. In 53.9% of the patients who had not been receiving therapy prior to inclusion in this study, the subjective symptoms consisted of urethral irritation or irritation upon urination. In the other patients, the relationship of the complaints to the disease could not be clearly established. In the patients who had been receiving therapy, the majority did not complain of subjective symptoms. AT-2266 was administered in a daily dosage of 600 mg (in 3 divided doses) for 14 days. The therapeutic efficacy was evaluated. At the end of 7 days of AT-2266 therapy, 15.5% of the previously-untreated group and 8% of the previously-treated group were "excellent" cases, and the efficacy rate was 32.8% and 36%, respectively, when the "good" cases were also included. At the end of the full 14 days of therapy, the corresponding efficacy rates were 21.7% and 17.4%, and 54.3% and 56.5%. Considerable improvement was achieved in the subjective symptoms of urethral irritation and irritation upon urination at the end of 7 days of therapy, and the improvement was even greater following the next 7 days of treatment. With regard to the complaints for which the relationship to the disease could not be clearly established, however, the improvement was not very good: there was not much difference between the results on the 7th and 14th days, and the elimination rate even after 14 days was slightly below 30%. In the previously-untreated patients, improvement in leukocyte count in the prostate fluid to 10 or fewer cells per microscopic field was achieved in 15.6% at 7 days and 21.7% at 14 days. As side effects of AT-2266, mild symptoms were observed to occur in only 1.8% of the patients.

[Epidemiological and therapeutic studies of gonorrheal infection--clinical efficacy of sultamicillin].

We conducted an epidemiological study including analyses of background factors of 192 male and 13 female patients with gonorrheal infection in the Sapporo area and at the same time, investigated the therapeutic efficacy of sultamicillin, an ester linked prodrug of ampicillin and beta-lactamase inhibitor sulbactam in the treatment of these patients. The percentage of infections in Sapporo was rather high in the young generation, being as high as 13.5% in teen-age boys and 30.8% in teen-age girls, which were higher than the 6.1% and 6.3% of corresponding groups in Honshu island. The source of infections was so-called special public bath-ouse which accounted for about 31.8% of all cases which however, was lower than the 50% in Honshu island. By contrast, the percentage of their friends or so-called pick-up friends as a source of infection in Sapporo was as high as 46.9% which was significantly higher than the 19.9% in Honshu. Juveniles who had nonprostitutes of the other sex as a source of infection are a characteristic of the patients in Sapporo. The isolation rate of PPNG was 13.8%. The MIC (10(6) CFU/ml) of sultamicillin ranged from 0.05 to 0.39 micrograms/ml in beta-lactamase non-producing strains and from 0.20 to 1.56 micrograms/ml in beta-lactamase producing strains showing no trend of higher MIC against beta-lactamase producing strains. There was almost no difference in the efficacy of sultamicillin between a daily dose of 750 mg (2 tablets) and 1125 mg (3 tablets) nor in side effects. The eradication rate (efficacy rate) of gonococcus following a 3-day therapy was 96.2% (38.9% excellent cure rate) in male patients and 83.3% (8.3%) in female patients. In 31% of the male patients who underwent a 7-day therapy, residual serous secretion was found though some inaccuracy is involved in this data since dropouts were not counted. This suggests the need of concurrent therapy with other appropriate drugs in consideration of possible mixed infection involving Chlamydia trachomatis or other microorganisms.

[Epidemiological and therapeutic studies of gonorrheal infections (I)--clinical efficacy of long acting amoxicillin (L-AMPC)].

During the period from October of 1981 through March of 1982, our research group in Sapporo treated 178 patients (158 males and 20 females) for gonorrheal infections. We performed epidemiological and therapeutic studies on these patients. The youngest of the 158 male patients with acute gonorrheal urethritis was 15 years old. The age distribution was 32 patients (20.3%) under 20 years, 46 patients (29.1%) aged 20 to 24, 34 patients (21.5%) aged 25 to 29, 22 patients (13.9%) aged 30 to 34, 10 patients (6.3%) aged 35 to 39, and 14 patients (8.9%) aged 40 to 54. The fact that 20% of gonorrheal urethritis occurred in youths under 20 years of age, is especially noteworthy. The infection in the teenage boys was found to be picked up mostly from girls met at discos , etc., On the other hand, the patients in their 20s, were infected more frequently by contact with hostesses at massage parlors and bars, these sources making up the majority of male patients who were 25 years or older. These findings are quite interesting because they reflect the socio-economic status of the patients. In addition, the fact that hostesses working at massage parlors are a frequent source of gonorrheal urethritis infections can represent a considerable problem in terms of public hygiene. The 20 female patients with gonorrheal infections were all found to be cases of cervicitis, except for a 1-year-old girl with gonorrheal infection of external genitals. The fact that about half of these female patients were teenagers, aged 16 to 19 years is worth special note. The duration of the latent period was less than 5 days in 83 male patients (58.9%) with urethritis, 6 approximately 10 days in 39 patients (27.7%), 11 approximately 20 days in 13 patients (9.2%), 21 approximately 30 days in 4 patients (2.8%), and over 30 days in 2 patients (1.4%), It can thus be said that the number of cases showing a long incubation period is increasing. The MICs of 154 gonococci strains isolated from the urethral or vaginal discharge were determined. Thirteen (8.4%) of these clinically isolated strains were found to be beta-lactamase producers. When a bacterial inoculation level of 10(6) cells/ml was used in the in vitro MIC determination, the MIC was 1.56 micrograms/ml or higher for 12 of these beta-lactamase-producing strains; the MIC of the 13th strain was 0.78 microgram/ml. At the same time, the MICs of these beta-lactamase-producing strains to doxycycline were also high; 1.56 micrograms/ml or higher.(ABSTRACT TRUNCATED AT 400 WORDS)