These investigations have been continued since 1981. In this year the isolation frequencies and sensitivities to antibiotics were investigated for 654 bacterial strains isolatedfrom respiratory tract infections in 20 institutions during the period of October 1990 to September 1991.
Among Staphylococcus aureus isolated from inpatients, many were methicillin-resistant S. aureus (MRSA), and the frequency of their isolation was 56.3% for inpatients and 4.3% for outpatients. Of the relation to antibiotic administration, the isolation frequency of MRSA before administration of antibiotics was 19.6% (10/51), and after administration was 75.0% (27/36).
The sensitivities of S. aureus to imipenem and clindamycin (MIC₈₀) decreased from 0.2μg/ml to 64μg/ml and from 0.2μg/ml to 128μg/ml, respectively. We investigated year to year changes in the backgrounds of patients with respiratory tract infections. Bacterial pneumonia was 31.6% among respiratory tract infections in the period of the study, this trend has increase from 1989.
Frequencies of different etiological bacteria in respiratory tract infections did not change appreciably from year to year, and S. aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa were the most showing some frequent pathogens.

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S-1108 in granules, a new oral cephem antibiotic, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained.
1. Pharmacokinetics
S-1108 was administered at single doses of 2, 3, 4, 6 mg/kg orally and the following results were obtained on C_max, T1/2 and AUC, respectively: C_max: 0.79, 1.03, 1.39, 1.06 μg/ml, T1/2: 1.28±0.40, 1.27±0.65, 1.10±0.29, 1.83hrs., AUC: 2.65±0.63, 3.99±2.77, 5.25±1.83, 5.15μg ·hr/ml. These values indicated a dose-dependent pharmacokinetic behavior. Urinary recovery rates were 12.5-30.0% in the first 8 (6) hours after administration.
2. Clinical results
The clinical efficacy of S-1108 was evaluated in 456 patients with various infections. S-1108 was administered at a dose of 2-4 mg/kg three time a day to most patients.
The overall clinical efficacy rate was 95.0%. In 294 cases with identified causative pathogen, the clinical efficacy rate was 96.9%, and the bacteriological eradication rate was 89.0%.
Side effects occurred in 18 (3.23%) of 558 patients subjected to safety analyses. The main side effect was diarrhea but those side effects were mild and reversible. Abnormal laboratory test results were observed in 25 cases,(eosinophilia and elevated GOT and GPT). These abnormalities were not dose-dependent and also seen with other cephems to a similar extent. No particular and serious problems were associated with administration of this drug.
Based on the above results, S-1108 is considered to be very useful at a standard dose of 2-4mg/kg t. i. d. against most infections encountered in the pediatric field out-patient clinic.

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We performed clinical studies on sulbactam/cefoperazone (SBT/CPZ) for the treatment of geriatric patients with respiratory tract infections.
Seven patients with pneumonia, 7 with acute bronchitis, 6 with chronic respiratory tract infections were treated with SBT/CPZ. The patients were administered with a daily dose of 2.0g or 4.0g for 4-14 days. The clinical responses were excellent in 3, good in 13, fair in 3, and poor in 1 patients. The efficacy rate was 80.0%. No side effects were observed in any patients, but elevations of GOT, GPT were observed in two cases. Causative organisms were E. coli (2 strains), P. aeruginosa (2), MSSA (1), MRSA (1), S. pneumoniae (1), H. influenzae (1), K. oxytoca (1), and E. aerogenes (1). The bacteriological effect rate was 60%. One strain of MRSA and one of two strains of P. aeruginosa persisted in 2 patients.

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We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT-PI) in community-acquired respiratory tract infections and obtained the following findings.
1. Of the 420 respiratory tract infection cases that were treated with CEMT-PI according to a same protocol at a total of 42 institutions in Tokyo, Kanagawa-ken, Saitama-ken and Chiba-ken from February to the beginning of April 1994, 359 cases in which clinical evaluations were considered possible were selected as the subjects of the clinical study. Regarding genders of patients, slightly more females (56.3%) than males were included. Diagnoses given to these patients included laryngopharygealitis (60.7%), tonsillitis (14.2%) and acute bronchitis (13.6). Outpatients accounted for 94.4% of the subjects.
2. For the bacteriological study, a written material describing the method of collecting specimens, storage and transport in detail was distributed to the above mentioned institutions. The isolation and identification of suspected causative bacteria, determination of minimum inhibitory concentrations (MIC) and investigation of β-lactamase production were conducted all together. Suspected causative bacteria were detected from 238 (66.3%) out of the 359 cases. They included 85 strains of Haemophilus influenzae, 76 strains of Streptococcus pneumoniae, 20 strains of Streptococcus pyogenes and 17 strains of Moraxella subgenus Branhamella catarrhalis.
3. Clinical efficacy rates (the ratio of those excellent+good) among those who were treated with 1 CEMT-PI tablet (194mg, titer) twice a day was 76.5% and among those who were given 2 tablets twice a day was 87.4%. The improvement rate of the latter was higher at a significant level of P<0.05.
4. The clinical efficacies classified by suspected causative bacteria (single bacterium) were 93.3% against M (B.) catarrhalis, 91.7% against β-streptococci, 87.1% against H. influenzae and 78.4% against S. pneumoniae, etc.
Though 7 (9.2%) of the 76 strains of S. pneumoniae were benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), the bacteriological efficacy was assessed either excellent or good in all of the 7 patients from whom PISP were detected. The clinical efficacy was assessed 100.0% in those from which a plural number of bacteria were detected. The 13 cases from which small numbers of Staphylococcus aureus was detected with other bacterium were also included in these cases.

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The ofloxacin (OFLX) concentration in serum, saliva and pleural effusion was measured in 12 patients with pleural effusion after oral administration at a dose of 200mg three times a day (600mg daily). Three patients had non-small cell lung cancer and the others had pulmonary tuberculosis. The mean OFLX levels in the serum, saliva and pleural effusion at 2 hours after the first administration on day 3 was 3.15±1.52, 3.36±2.23 and 2.86±1.77μg/ml respectively. There was a strong correlation among these concentrations. The OFLX concentration of pleural effusion was predictable from that of saliva. A 3-day oral administration is sufficient to achieve the OFLX level of pleural effusion similar to that of the serum. It is possible that OFLX is effective for pleuritis caused not only by common infectious pathogens but also by Mycobacterium tuberculosis.

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