[in Japanese]

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Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981. IKEMOTO et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed.
In 23 institutions around the entire Japan, 492 strains of presumably etiological bacteria were isolated mainly from the sputum of 421 patients with lower respiratory tract infections from October 1994 to September 1995. MICs of various antibacterial agents and antibiotics were determined against 70 strains of Staphylococcus aureus, 101 strains of Streptococcus pneumoniae, 92 strains of Haemophilus influenzae, 61 strains of Pseudomonas aeruginosa (non-mucoid strains), 25 strains of Pseudomonas aeruginosa (mucoid strains), 48 strains of Moraxella subgenus Branhamella catarrhalis, 14 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation.
1. S. aureus
S. aureus strains for which MICs of oxacillin were higher than 4μg/ml (methicillin-resistant S. aureus) accounted for 51.4%, but the frequency of the drug resistant bacteria decreased comparing to the previous year's 56.0%. Vancomycin showed the highest activity against S. aureus with MIC₈₀ of 0.5μg/ml.
2. S. pneumoniae
Most of the drugs tested showed potent activities against S. pneumoniae. Imipenem of carbapenems showed the most potent activity with MIC₈₀ was 0.063μg/ml. Erythromycin and clindamycin showed low activities with MIC₈₀s ≥256μg/ml. Among these strains, however, 46.5% and 68.3% of strains, were quite sensitive toward these agents, respectively, with MICs of 0.063μg/ml.
3. H. influenzae
The activities of all drugs were potent against H. influenzae tested. Cefmenoxime a cephem, showed the most potent activity, the MICs of this drug against all of the 92 strains were 0.063μg/ml. Ofloxacin also showed a potent activity, and inhibited about 96% of strains with MIC of 0.063μg/ml.
4. P. aeruginosa (mucoid strains) Tobramycin showed the most potent activity against P. aeruginosa (mucoid strains) with MIC₈₀ of 0.5μEg/ml. Gentamicin, arbekacin and ciprofloxacin showed next potent activities, and their MIC₈₀s were 2μg/ml.
5. P. aeruginosa (non-mucoid strains)
Tobramycin showed the most potent activity against P. aeruginosa (non-mucoid strains) with MIC₈₀ of 2μg/ml. Comparing to the activities against P. aeruginosa (mucoid strains), the activities of all the drugs tested were lower against P. aeruginosa (non-mucoid strains).
6. K. pneumoniae
Carumonam showed the most potent activity against K. pneumoniae with MIC₈₀ of 0.063μg/ml. Cefozopran showed the next most potent activity with MIC₈₀ of 0.125μg/ml. Ampicillin and cephems except cefpodoxime, cefozopran and cefditoren showed low activities and their MIC₈₀s were ≥16μg/ml, and their MICs were all higher than ≥4μg/ml.
7. M.(B.)catarrhalis
Imipenem and ofloxacin showed the most potent activities against M.(B.) catarrhalis, their MIC₈₀s were 0.063μg/ml. Erythromycin and minocycline showed the next highest activities with their MIC₈₀s at 0.25μg/ml.
Also, we investigated year to year changes in the background of patients, the respiratory infectious diseases, and the etiology of bacteria.

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Escherichia coli isolated from surgical infections during the period from July 1983 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained.
1. Although the isolation rate of E. coli was not high from postoperative infections, it was most frequently isolated from primary infections throughout the study period. E. coli, Klebsiella spp. and anaerobic bacteria were predominant from fresh infections. From the cases that had previous antibiotics treatment, Enterococcus spp. were the most predominant isolates followed by MRSA and Pseudomonas spp. in this order.
2. Against E. coli, cefozopran, carumonam and aztreonam had the strongest activity, followed by cefmenoxime, imipenem, latamoxef, gentamicin and ofloxacin. Recently, we have noticed that antibiotic resistant E. coli strains particuraly against cefazolin are incresing year by year.

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The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 567 bacterial strains isolated from patients with urinary tract infections in 10 hospitals during the period of June 1994 to May 1995. Of the above total bacterial isolates, Gram-positive bacteria accounted for 26.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 73.2% and most of them were Escherichia coli.
1. Enterococcus faecalis Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with urinary tract infections. The MIC₉₀s of them were 1μg/ml. Vancomycin (VCM) was also active with the MIC90 of 2μg/ml. Piperacillin (PIPC) and biapenem (BIPM) were also active with the MIC₉₀s of 4μg/ml and 8μg/ml, respectively. The others were not so active with the MIC₉₀s of 16μg/ml or above.
2. Staphylococcus aureus including MRSA
VCM showed the highest activities against S. aureus isolated from patients with urinary tract infections. Its MIC₉₀ was 1μg/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC₉₀ of 2μg/ml. The others except minocycline (MINO) were not so active with the MIC₉₀s of 64μg/ml or above.
3. Staphylococcus epidermidis
MINO showed the strongest activity against S. epidermidis isolated from patients with urinary tract infections. Its MIC₉₀ was 0.25μg/ml. ABK was also active with the MIC₉₀ of 1μg/ml. Cephems were active with the MIC₉₀s of 2-16μg/ml, but penicillins and quinolones were not so active with the MIC₉₀s of 64-128μg/ml.
4. Citrobacter freundii Gentamicin (GM) showed the highest activities against C. freundii isolated from patients with urinary tract infections. Its MIC₉₀ was 1μg/ml. IPM was also active with the MIC₉₀ of 2μg/ml. Cefpirome (CPR) and cefozopran (CZOP) were also active with the MIC₉₀s of 4μg/ml and 8μg/ml. The others were not so active with the MIC₉₀s of 32μg/ml or above.
5. Enterobacter cloacae
IPM showed the highest activities against E. cloacae. Its MIC₉₀ was 0.5μg/ml. GM and amikacin (AMK), ciprofloxacin (CPFX) and tosufloxacin (TFLX) were also active with the MIC₉₀s of 4μg/ml. Penicillins and cephems except latamoxef (LMOX), cefmenoxime (CMX), CPR and CZOP showed lower activities with the MIC₉₀s of 256μg/ml or above.
6. Escherichia coli
Most of antimicrobial agents were active against E. coli. CPR, CZOP, IPM, carumonam (CRMN), CPFX and TFLX showed the highest activities against E. coli. The MIC₉₀s of them were 0.125μg/ml or below. Cefotiam (CTM), flomoxef (FMOX), CMX, ceftazidime (CAZ), and LMOX were also active with the MIC₉₀s of 0.25μg/ml. Penicillins were not so active with the MIC₉₀s of 128μg/ml or above.
7. Klebsiella pneumoniae
CRMN showed the highest activities against K. pneumoniae. Its MIC₉₀ was?≤0.125μg/ml. CZOP was also active with the MIC₉₀ of 0.25μg/ml. Penicillins were not so active with the MIC₉₀s of 128μg/ml or above.
8. Proteus mirabilis
P. mirabilis was susceptible to a majority of drugs. CMX, CAZ, LMOX, CPR, cefpodoxime (CPDX), CRMN, CPFX and TFLX showed the highest activities against P. mirabilis isolated from patients with urinary tract infections. The MIC₉₀s of them were 0.125μg/ml or below. MINO was not so active with the MIC₉₀ of 128μg/ml.
9. Pseudomonas aeruginosa
Most of the agents were not so active against P. aeruginosa. IPM showed MIC₉₀ of 8μg/ml.

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Clinical background was investigated on 628 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during period from June, 1994 to May, 1995.
1. Distribution of sex, age and urinary tract infections
Among over sixties males, the majority was taken by complicated urinary tract infections. Among females, the uncomplicated urinary tract infections was most frequent without a relation of age. As for over 40 females, the increase of complicated UTI was admitted.
2. Distribution of sex, age and pathogens isolated from UTIs
In uncomplicated UTIs, Escherichia coli was most frequently isolated without a relation of age, and next Enterococcus faecalis and CNS. In complicated UTIs without indwelling catheter, E. coli, Pseudomonas aeruginosa and E. faecalis were isolated the most frequent. In complicated UTIs with indwelling catheter, P. aeruginosa was most frequently isolated, and next E. faecalis and Staphylococcus aureus.
3. Administration of antimicrobial agents and pathogens isolated from UTIs
In uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from patients have obviously decreased from 216 to 32 isolates. And also, pathogens of complicated UTIs without indwelling catheter, have decreased from 127 to 50 isolates. However, in complicated UTIs with indwelling catheter, pathogens after or before administration of antibiotics, were not revealed an obvious change.
4. Pathogens and UTIs with or without factor and operation
In uncomplicated UTIs with or without factor and operation, E. coli was mainly detected. In complicated UTIs without indwelling catheter and with factor and operation E. faecalis was mainly detected, and next E. coli, S. aureus and P. aeruginosa. Without factor and operation, E. coli was mainly detected. In complicated UTIs with indwelling catheter and with factor and operation, P. aeruginosa, E. faecalis and S. aureus were mainly detected at 23.5%, 15.0%, 15.0%, respectively. Without factor and operation, Proteus spp. 22%, and next E. faecalis and P. aeruginosa 10% and 12%, were detected, respectively. The distribution of pathogens, in the case of Proteus spp. and P. aeruginosa has been obviously varied by the influence of factor and operation.

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[in Japanese]

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We investigated antibacterial activities of combination uses of isepamicin (ISP) and β-lactams in vitro against Pseudomonas aeruginosa, and the following conclusions were obtained.
1. ISP+piperacillin, ISP+ceftazidime, ISP+aztreonam, ISP+imipenem and ISP+panipenem against P. aeruginosa showed strong combined effects.
2. The minimum inhibitory concentrations (MICs) of these combinations were low and dependent on concentrations of ISP. And strong antibacterial activities were observed at ISP concentrations of sub-MIC levels. These results were similar to the results of previous reports, parts 1 and 2.
3. Concentrations of ISP sufficient to lower MIC90 values when by combined with β-lactam agents were 4-8μg/ml. These effects made it possible to lower the ISP dose to 400mg at a single dose and the enhancement of activities by combinations resulted in strong antibacterial activities against multiple drug resistant strains at sub-MIC levels of ISP. Strong antibacterial activities were also obtained against β-lactams-resistant strains of ISP-susceptible strains when ISP was combined with β-lactam agents.
4. All results reported in parts 1?
3 indicated that no antagonisms were produced by combining ISP+penicillins, ISP+cephems, ISP+monobactams and ISP+carbapenems against Staphylococcus aureus, Enterobacteriaceae and P. aeruginosa. These combinations showed strong antibacterial activities that were enhanced synergistically with wider spectra.

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The transferability of cefozopran (CZOP) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus.
The mean plasma concentration was 293±17.6μg/ml at 15 minutes after intravenous administration of CZOP at a dose level of 100mg/kg. The mean concentration in CSF reached its maximum, 16.5±2.74μg/ml at 60 minutes after administration.
Pharmacokinetic parameters calculated from these values were as follows: Cmax (CSF/plasma) 5.72%, AUC (CSF/plasma) 6.61% between 15 and 60 minutes, 9.38% between 15 and 120 minutes and 11.2% between 15 and 180 minutes, T1/2 for CZOP in CSF: 138 minutes, T1/2 (CSF/ plasma): 2.81.
In comparison to those of β-lactams that were obtained in the same way, the transferability of CZOP to CSF was moderate but concentration in CSF was high, hence, in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for CZOP.

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