From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients′ characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneurnoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc.
Of 78 S. aureus strains, those with 4μg/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64μg/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S.pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063μg/ml. Generally, all drugs showed strong activities against H. influenzae with MIC₈₀s of 4μg/ml or below. MICs of ofloxacin ranged between 0.063μg/ml and 4μg/ml in 1998, however, those were 0.125μg/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC₈₀s of 1μg/ml. Number of isolated P aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M.(B.) catarrhalis. MIC₈₀s of all drugs were 2μg/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063μg/ml.
On the patients′ characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M.(B.) catarrhalis in 12.0% and S. aureus in 10.6%.

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Efficacy of panipenem/betamipron (PAPM/BP) against experimental pneumonia caused by penicillinesistant Streptococcus pneumoniae (PRSP: MIC of benzylpenicillin, ≥1.56μg/ml) in mice was compared with hose of imipenem/cilastatin (IPM/CS), meropenem (MEPM), cefozopran (CZOP), ceftriaxone (CTRX), mpicillin (ABPC), and vancomycin (VCM). The infection was induced by inoculating a PRSP clinical isolate, 9601 (serotype 6) or 10693 (serotype 19), into ddY male mice intranasally. Drugs were administered ubcutaneously at doses of 0.4, 2, and 10mg/kg, 18, 26, 42, and 50 hours post-infection. Viable cell counts in the ngs were determined 66 hours post-infection. PAPM/BP showed the greatest efficacy against the infections mong tested drugs. MICs of PAPM against PRSP 9601 and 10693 were both 0.125μg/ml, which were superior those of IPM (0.25 and 0.54μg/ml, respectively), MEPM (0.5 and 1μg/ml, respectively), CZOP (2 and 1μg/ml, respectively), CTRX (both 1 μg/ml), ABPC (both 4μg/ml), and VCM (0.5 and 0.25μg/ml, espectively). These results suggest that the potent in vivo activity of PAPM/BP reflects the potent in vitro activity of PAPM.
MICs of PAPM, IPM, MEPM, and CZOP against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of benzylpenicillin, ≤0.05μg/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of benzylpenicillin, 0.1-0.78μg/ml), and PRSP, were tested by an agar dilution method. MIC₉₀s of the drugs against the PSSP, PISP, and PRSP were as follows: PAPM, 0.012, 0.05, and 0.39μg/ml; IPM, ≤0.006, 0.1, and 0.78μg/ml; MEPM, 0.05, 0.39, and 1.56μg/ml; and CZOP, 0.2, 0.78, and 6.25μg/ml, respectively. Thus, PAPM showed the most potent activity among tested drugs against clinical isolates of PISP and PRSP.

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The effect of arbekacin (ABK), vancokmycin (VCM) and teicoplanin (TEIC) on the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus was examined. In logarithmicphase cultures, ABK, VCM and TEIC inhibited TSST-1 production by 85, 10 and 25%, respectively, at the concentration of one-fourth the each MIC. In stationary-phase cultures, ABK inhibited TSST-1 production by 50% or 90% compared with the control at the concentration of 4.0μg/ml or 5.0μg/ml respectively. VCM and TEIC did not inhibit TSST-1 production at the concentration of 8.0μg/ml or lower. In human blood cultures, TSST-1 production was inhibited by ABK by 50% at 0.04μg/ml (1/256 of C_max), but not inhibited by VCM and TEIC at the concentration of 1/16 of C_max or lower. It has been already known that ABK has higher bactericidal activity than VCM and TEIC. ABK combined the inhibition of TSST-1 production with high bactericidal activity in both bacterial growth phases, and therefore ABK should be considered for the treatment of TSST-1-mediated MRSA-infection.

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