Kaeriyama Makoto, Mizunaga Shingo, Mitsuyama Junichi, Yamaoka Kazukiyo, Asano Yuko, Sawamura Haruki, Suematsu Hiroyuki, Teraji Mayumi, Tsuchiya Masako, Hashido Hikonori, Matsukawa Yoko, Matsubara Shigenori, Miyabe Takanori, Watanabe Kunitomo, Mikamo Hiroshige
Research Laboratories of Toyama Chemical Co., Ltd.
Jpn J Antibiot. 2008 Aug;61(4):195-208.
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 beta-lactamase (BL) production, the mutation 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) beta-lactamase-negative ampicillin-susceptible (BLNAS) strains, which showed BL negative, ampicillin (ABPC) and ampicillin/sulbactam (ABPC/SBT)-MIC < or = microg/ml, (2) beta-lactamase producing ampicillin-resistant (BLPAR) strains, which showed BL producing and ABPC/SBT-MIC < or =2 microg/ml, (3) beta-lactamase-negative ampicillin-resistant (BLNAR) strains, which showed BL negative, ABPC and ABPC/SBT-MIC > or =2 microg/ml, (4) beta-lactamase-producing amoxicillin/clavulanic acid-resistant (BLPACR) strains, which showed BL producing and ABPC/SBT-MIC > or =4 microg/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, 0.0156 microg/ml for garenoxacin, 0.0078, 0.0156 microg/ml for tosufloxacin and ciprofloxacin, 0.0156, 0.0313 microg/ml for levofloxacin, 0.0313, 0.0625 microg/ml for norfloxacin, 0.0625, 0.25 microg/ml for piperacillin/ tazobactam, 0.0625, 0.5 microg/ml for piperacillin, 0.125, 0.25 microg/ml for ceftriaxone and cefditoren, 0.5, 1 microg/ml for cefteram, chloramphenicol and tetracycline, 0.5, 2 microg/ml for cefotaxime, 2, 8 microg/ml for ampicillin, ampicillin/sulbactam and cefdinir. In comparison with the values for the strains isolated between 1999 and 2000, the MIC50s of beta-lactam for the strains isolated between 2005 and 2006 increased over 4 times.
我们调查了2005年至2006年间从岐阜县医疗机构分离出的194株流感嗜血杆菌对抗菌药物的敏感性，并将这些结果与1999年至2000年间分离出的280株流感嗜血杆菌的结果进行了比较。此外，对2005年至2006年间分离出的菌株进行了β-内酰胺酶（BL）产生情况、编码PBP3的ftsI基因的突变、编码TEM型BL的bla基因以及血清型的检测。参照CLSI断点，流感嗜血杆菌菌株被分为以下几类：（1）β-内酰胺酶阴性氨苄西林敏感（BLNAS）菌株，其BL呈阴性，氨苄西林（ABPC）和氨苄西林/舒巴坦（ABPC/SBT）的MIC≤μg/ml；（2）产β-内酰胺酶氨苄西林耐药（BLPAR）菌株，其BL呈阳性且ABPC/SBT的MIC≤2μg/ml；（3）β-内酰胺酶阴性氨苄西林耐药（BLNAR）菌株，其BL呈阴性，ABPC和ABPC/SBT的MIC≥2μg/ml；（4）产β-内酰胺酶阿莫西林/克拉维酸耐药（BLPACR）菌株，其BL呈阳性且ABPC/SBT的MIC≥4μg/ml。1999年至2000年间分离出的菌株中，各耐药类别的流行率分别为：BLNAS为71.8%，BLPAR为7.9%，BLNAR为19.6%，BLPACR为0.7%。但在2005年至2006年间分离出的菌株中，它们分别为：BLNAS为38.1%，BLPAR为4.6%，BLNAR为54.6%，BLPACR为2.6%，这表明从1999 - 2000年到2005 - 2006年，BLNAS和BLPAR的百分比下降，而BLNAR和BLPACR的百分比上升。基于ftsI替代和拥有bla基因，2005年至2006年间分离出的菌株分类如下分布：gBLNAS为24.2%，gBLPAR为4.1%，gLow - BLNAR为10.8%，gBLNAR为57.7%，gBLPACR - II为3.1%。基于ftsI替代和拥有bla基因的属于gBLNAR和gLow - BLNAR的BLNAR比例高于基于药敏模式的比例。2005年至2006年间分离出的那些菌株的MIC50和MIC90如下：加替沙星为0.0039、0.0156μg/ml，妥舒沙星和环丙沙星为0.0078、0.0156μg/ml，左氧氟沙星为0.0156、0.0313μg/ml，诺氟沙星为0.0313、0.0625μg/ml，哌拉西林/他唑巴坦为0.0625、0.25μg/ml，哌拉西林为0.0625、0.5μg/ml，头孢曲松和头孢地尼为0.125、0.25μg/ml，头孢特仑、氯霉素和四环素为0.5、1μg/ml，头孢噻肟为0.5、2μg/ml，氨苄西林、氨苄西林/舒巴坦和头孢地尼为2、8μg/ml。与1999年至2000年间分离出的菌株的值相比，2005年至2006年间分离出的菌株的β-内酰胺类的MIC50增加了4倍多。
