Isolated bacteria from respiratory tract infections were collected since 1981 in cooperation with institutions located throughout Japan, and have been investigated for their sensitivities to various antibacterial agents and antibiotics and reported by IKEMOTO,et al. Relationships between these isolates and backgrounds of the patients were also studied each year. These results are discussed in detail in this report.
In 20 institutions around the entire Japan from October 1991 to September 1992, 631 strains of bacteria were isolated mainly from sputa of 529 patients with respiratory tract infections and tentatively determined to be etiological agents. MICs of various antibacterial agents and antibiotics against 96 strains of Staphylococcus aureus, 112 strains of Streptococcus pneumoniae, 111 strains of Haemophilus influenzae, 114 strains of Pseudomonas aeruginosa non-mucoid, 41 strains of Moraxella subgenus Branhamella catarrhalis, 39 strains of Pseudomonas aeruginosa(mucoid),Klebsiella pneumoniae and some others, were determined, and the drug sensitivities of these strains were determined except for the strains that had been killed during transportation.
1.S. aureus strains for which MICs of methicillin were higher than 4μg/ml (methicillin-resistant S. aureus) accounted for 58.3% and the frequency of the drug resistant bacteria increased over previous year's 42.5%. As shown by the MICs, arbekacin was active as vancomycin against all the strains on S. aureus.
2.S. pneumoniae
Benzylpenicillin among the penicillins showed a potent activity against S. pneumoniae. Cefu zonam, cefmenoxime, cefozopran and cefotaxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; a penem antibiotic, showed the most potent activity with MIC₈₀ of 0.03μg/ml.
3.H. influenzae
Activities of all drugs were excellent against H. influenzae strains tested. Ampicillin showed MIC₈₀ of 1μg/ml against H. influenzae. Cefuzonam showed the most potent activity among cephems, it completely killed all bacteria at MIC 0.06μg/ml. Cefotaxime and cefmenoxime showed next most potent activities with MIC₈₀s of 0.06μg/ml. The antimicrobial activity of ofloxacin was equvalent to those of cephems.
4.P. aeruginosa(mucoid)
Ciprofloxacin and tobramycin showed the most potent activities against P. aeruginosa (mucoid), and their MIC₈₀s were 4μg/ml.
5.P. aeruginosa(non-mucoid)
Similarly, ciprofloxacin and tobramycin showed the most potent activities against P. aeruginosa(non-mucoid) with MIC₈₀ of 2μg/ml. Comparing to activities against P. aeruginosa(mucoid), all the drugs tested showed lower activities against P. aeruginosa(non-mucoid).
6.K. pneumoniae
The activities of all drugs except for penicillins were very high against K. pneumoniae. Flomoxef and cefixime showed the most potent activities and their MIC₈₀s were 0.06μg/ml.
7.M.(B.) catarrhalis
Imipenem; a penem antibiotic, showed the most potent activity against M.(B.) catarrhalis with MIC₈₀ of 0.06μg/ml. Cephems, cefmetazole and cefotaxime, all showed MIC₈₀ of 1μg/ml.
Also, we investigated annual changes in the background of patients. Types of respiratory infectious diseases, and their etiological bacteria were also studied.
As for the patients backgrounds, many infectious diseases were found in patients in the high age bracket, and the patients over age of 60 accounted for 64.9% of the diseases. As for the distribution by respiratory tract infections, chronic bronchitis and bacterial pneumonia accounted for the greatest numbers of cases with 37.2%, 32.1%, respectively, followed by bronchiectasis at 9.5%.

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We investigated the in vivo kinetics of sparfloxacin (SPFX), an oral quinolone, in the hemodialytic patients. SPFX was orally administrated in a single dose of 200 mg to each of five hemodialytic patients, on a day that they were not receiving hemodialysis therapy. After dosing, the blood samples were collected periodically at 2, 4, 6, 8, 12, 24, 25, 27, 29, 48, 72 hours. Concentration of the unchanged SPFX in the plasma samples were measured by HPLC. The peak plasma levels of SPFX in the hemodialytic patients did not differ greatly from patients with renal failure (5<Ccr<20ml/min). Average T1/2β of SPFX was 25.7 hours, and it was prolonged compared to the patients with renal failure (who were not receiving hemodialysis) and a group of young healthy volunteers. Based on these results, we believe those hemodialytic patients may be administrated with the drug once every other day, as long as normal doses are used.

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Lytic action of cefminox (CMNX) against slowly growing Escherichia coli (E. coli) K-12 JE1011 was compared with that of the related cephamycin cefmetazole (CMZ) or ampicillin (ABPC). The growth rate in doubling time was 30 min. at 37°C. Minimal concentrations of CMNX, CMZ and ABPC showing clear lysis were 0.39, 3.13 and 12.5μg/ml, respectively, under these conditions. When E. coli was cultured at 12°C, the doubling time was 720 and 816 min. which were 24 and 27.2 fold as slow as those at 37°C, respectively. In 12°C culture, the minimal concentrations showing clear lysis were 0.78 (2 fold at 37°C), 25 (8 fold) and 100μg/ml and higher (8 fold or more) with CMNX, CMZ and ABPC, respectively. Therefore, it appeared that the lytic activity of CMNX was not significantly affected by bacterial growth rate and was demonstrated effectively against slowly growing bacteria at a low concentration. We determined release activity of cell wall peptidoglycan fragments by 5 β-lactam antibiotics in addition to the above-mentioned 3 antibiotics. The results showed that the release activity was not proportional to the MIC and that of CMNX was the strongest among those antibiotics. The rapid and strong bactericidal action of CMNX against bacteria at the early stationary phase was suggested to result from the characteristic lytic action against slowly growing bacteria.

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In order to evaluate antimicrobial activity of norfloxacin (NFLX), minimum inhibitory concentration (MICs) of NFLX and control drugs were determined against clinical isolates from ocular infections that were obtained in our laboratory from July, 1993 to December, 1994.
The results are summarized as follows;
1. Compared to MIC distributions of NFLX against clinical isolates from ocular infections studied in 1986 and 1987, the MIC₈₀ of NFLX against Corynebacterium spp.,Enterobacter spp.,Serratia spp.,Burkholderia cepacia, Flavobacterium spp., Alcaligenes spp. increased 8 times.
Almost all of NFLX-resistant strains among them were ofloxacin (OFLX)-resistant, new quinolones resistant strains, and a part of them were aminoglycosides, β-lactams-resistant as well, thus all of these strains were multiple drug resistant.
2. MIC of NFLX against Pseudomonas aeruginosa were lower than that of OFLX.
3. NFLX showed strong antimicrobial activities against so-called “particular bacteria” including Staphylococcus aureus subsp. aureus, Moraxella spp.,Haemophilus spp., and P. aeruginosa from ocular infections. And MIC₈₀ of NFLX against these bacteria was 0.05-1.56μg/ml. We observed that NFLX eye drops was administered so that concentrations above the MIC against these clinical isolates were maintained.

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A study was done to determine susceptibilities of Haemophilus influenzae that were obtained in our laboratory in 1994 to new quinolones (NQ) and other drugs.
The results were as follows;
1. Among the 300 isolates, the detection frequency of NQ-resistant strains was 8.7%(26 strains), including isolates from chronic lower respiratory tract infections (22 strains) and those from middle meatus of nose (2 strains), etc. NQ-resistant strains were not isolated from children.
2. The cross resistance was studied for different NQs against NQ-resistant strains. Clavulanic acid/amoxicillin, cefteram, cefpodoxime, cefditoren, cefodizime (CDZM) and cefpirome showed strong antimicrobial activities against NQ-resistant strains. MIC₉₀ of CEPs against all isolated strains including NQ-resistant strains and β-lactamase producers was low. And the MIC₉₀ of CDZM was ≤0.025μg/ml, which was the lowest among all the antibiotics tested.
3. We found 47 strains (15.7%) of β-lactamase producers among the 300 isolates, the frequency of β-lactamase producing strains was high among strains obtained from children.

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