We investigated the susceptibility to antibacterials of 194 strains of Haemophilus influenzae isolated from medical facilities in Gifu prefecture between 2005 and 2006, and compared these results with those of 280 strains of H.influenzae isolated between 1999 and 2000. Additionally, the strains that had been separated between 2005 and 2006 were examined for β-lactamase (BL) production, the muta tion of ftsI gene coding for PBP3, the bla gene coding for TEM type of BL and the serotype.
Referring to the CLSI breakpoint, H.influenzae strains were classified into the following categories: (1) β-lactamase-negative ampicillin-susceptible (BLNAS) strains, which showed BL negative, ampicillin (ABPC) and ampicillin/sulbactam (ABPC/SBT)-MIC<1μg/ml,(2) β-lactamase producing ampicillinresistant (BLPAR) strains, which showed BL producing and ABPC/SBT-MIC<2μg/ml,(3) β-lactamasenegative ampicillin-resistant (BLNAR) strains, which showed BL negative, ABPC and ABPC/SBT-MIC>μ g/ml,(4) β-lactamase-producing amoxicillin/clavulanic acid-resistant (BLPACR) strains, which showed BL producing and ABPC/SBT-MIC>2μg/ml.
The prevalence of each resistance class were 71.8% for BLNAS, 7.9% for BLPAR, 19.6% for BLNAR and 0.7% for BLPACR in strains isolated between 1999 and 2000. But they were 38.1% for BLNAS, 4.6% for BLPAR, 54.6% for BLNAR and 2.6% for BLPACR in strains isolated between 2005 and 2006, indicating that the percentage of BLNAS and BLPAR decreased and that of BLNAR and BLPACR increased from 1999-2000 to 2005-2006.
On the basis of ftsI substitutions and having bla gene, the strains isolated between 2005 and 2006 were classified into the following distribution: 24.2% for gBLNAS, 4.1% for gBLPAR, 10.8% for gLow-BLNAR, 57.7% for gBLNAR, and 3.1% for gBLPACR-II. Ratio of BLNAR belonging to gBLNAR and gLow-BLNAR based on the ftsI substitutions and having bla gene was higher than that based on the susceptibility pattern.
The MIC₅₀ and MIC₉₀ for those strains isolated between 2005 and 2006 were as follows; 0.0039, 0.0156μg/ml for garenoxacin, 0.0078, 0.0156μg/ml for tosufloxacin and ciprofloxacin, 0.0156, 0.0313μg/ml for levofloxacin, 0.0313, 0.0625μg/ml for norfloxacin, 0.0625, 0.25μg/ml for piperacillin/ tazobactam, 0.0625, 0.5μg/ml for piperacillin, 0.125, 0.25μg/ml for ceftriaxone and cefditoren, 0.5, 1μg/ml for cefteram, chloramphenicol and tetracycline, 0.5, 2μg/ml for cefotaxime, 2, 8μg/ml for ampicillin, ampicillin/sulbactam and cefdinir. In comparison with the values for the strains isolated between 1999 and 2000, the MIC₅₀s of β-lactam for the strains isolated between 2005 and 2006 increased over 4 times.

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From October 2005 to September 2006, we collected the specimen from 366 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 411 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 406strains were examined. The isolated bacteria were: Staphylococcus aureus 70, Streptococcus pneumoniae 85, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 46, P aeruginosa (mucoid) 14, Klebsiella pneumoniae 21, and Moraxella subgenus Branhamella catarrhalis 40.
Of 70 S. aureus strains, those with 2 yg/ml or less of MIC of oxacillin (methicillin-susceptible S.aureus: MSSA) and those with 4 μg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 38 (54.3%) and 32 (45.7%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of 37 strains (97.4%) at 0.063 μg/ml or less. Against MRSA, arbekacin and vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 Jug/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 μg/ml or less. Faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 μg/ml. In contrast, there were high-resistant strains (MIC: over 128 μg/ml) for erythromycin (38.1%) and clindamycin (22.6%). Against H.influenzae, levofloxacin showed the most potent activity and its MIC₉₀ was 0.063 μg/ml or less.Meropenem showed the most potent activity against P aeruginosa (mucoid) and its MIC₉₀ was 0.5 μg/ml.Against P aeruginosa (non-mucoid), arbekacin had the most potent activity and its MIC₉₀ was 8 μg/ml. Against K pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 μg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M.(B.) catarrhalis and the MIC₉₀ of them were 2 μg/ml or less.
The approximately half the number (53.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 44.3% and 29.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (15.4%), S. pneumoniae (23.4%), and H. influenzae (21.3%). S. aureus (25.4%) and S.pneumoniae (18.0%) also were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.0%) and H. influenzae (21.4%). The bacteria frequently isolated from the patients treated with macrolides were S.pneumoniae and P aeruginosa, and their isolation frequencies were each 35.3%.

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We conducted 3 nationwide surveillance studies between 2001 and 2005 at 39 participating institutions throughout Japan according to the special survey plan to investigate susceptibility to ciprofloxacin (CPFX) and various parenteral antimicrobials using clinical isolates from patients with severe infection during the reexamination period of parenteral CPFX. Results ofthe first special survey (2001) were already reported in this journal. The current third special survey (2005) was conducted at 34 participating institutions throughout Japan to determine susceptibility to CPFXand 22 various parenteral antimicrobials with the use of the microdilution method with respect to 1696 strains isolated and identified from various clinical specimens between January and June 2005. The results of CPFX in this survey were compared with those in the first and second special surveys.
The minimum inhibitory concentration of CPFX at which 90% of isolates were susceptible (MIC₉₀) ranged from <0.063 to 2, μg/mL for methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella spp., Citrobacter freundii, Enterobacter spp., Proteus spp., Serratia marcescens, and Acinetobacter baumannii, revealing no marked change from results of the first and second surveys. However, the CPFX-susceptibility rate of Escherichia coli decreased in the second and third surveys compared to that in the first survey. For Morganella morganii and Pseudomonas aeruginosa, the MIC₉₀ of CPFX tended to increase with time. The CPFX-susceptibility rates calculated from the pneumoniabreakpoint were 85.2% for P. aeruginosa and 67.9% for Stenotrophomonas maltophilia. With the exception of these 2 species, major causative organisms of respiratory tract infection had susceptibility rates as high as 90% or more for CPFX, which were similar to results of the first and second special surveys. These susceptibility rates for CPFX were similar to the rates for cefozopran and imipenem. These values generally indicated favorable CPFX susceptibility testing results of major bacteria and the potent antimicrobial activity of CPFX particularly against Gram-negative bacteria. Further surveillance is required regarding the trend in susceptibility of E. coli, M. morganii, and P. aeruginosa, which tended to become less susceptible with time.

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Because the drug-induced severe adverse reaction (SAR) is rare and often occur in the unexpectedorgans, the physician could be unfamiliar to SAR. In that case the early stage of the SAR is easy to overlook. So the Ministry of the Health and Welfare of Japan (MHLW) started the “Comprehensive project to deal with the disorders due to adverse drug reactions” as a four years plan since 2005. In this project, the MHLW published “the manual for handling disorders due to adverse drug reactions” in corporation with the academia. This manual is constituted by two parts, one is intended for the parents, and the other is for the general healthcare providers. In this article, the aim and the progress of the manuals and the brief summary of the SAR induced by the antibiotics will be explained. By the end of the June 2008, 29 manuals have been released, and 16 of them are antibiotics-related. It is needless to say that antibiotics are essential in the modern medical care, close monitoring of the symptom of SAR in untargeted organ is required in use of the antibiotics.

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