Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States
Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States
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DOI：
10.1089/107662903764736337
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发表时间：
2003-03-01
期刊：
影响因子：
--
通讯作者：
Ubukata, K
中科院分区：
文献类型：
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作者：
Hasegawa, K;Yamamoto, K;Ubukata, K
采用微量稀释法测试了来自日本（n = 296）和美国（n = 100）的流感嗜血杆菌临床分离株对 10 种 β-内酰胺抗生素的体外敏感性以及 β-内酰胺耐药性的分子机制。对于所有分离株，使用PCR来鉴定六个元件，包括产生β-内酰胺酶的氨苄青霉素（AMP）抗性（BLPAR）和不产生β-内酰胺酶的AMP抗性（BLNAR）基因，如下：（1）TEM-1型β-内酰胺酶基因，（2）ROB-1型β-内酰胺酶基因，（3）编码PBP3的正常ftsI基因的一部分，其参与间隔肽聚糖合成，(4) ftsI 基因的一部分，具有 BLNAR 菌株中常见的一些氨基酸取代，(5) 编码流感嗜血杆菌特异性 P6 膜蛋白的 p6 基因，以及 (6) b 血清型荚膜基因。 在日本和美国分离株中，日本和美国的每种耐药类别的流行率分别为 55.1% 和 46%，不产生 β-内酰胺酶， AMP 敏感 (BLNAS)； TEM-1型β-内酰胺酶基因为3.0%和26%； ROB-1 型为 0 % 和 10 %；低 BLNAR 和低 AMP 抗性的分别为 26.4 % 和 13 %； BLNAR 菌株为 13.2% 和 0%。剩下的一些分离株是产生 β-内酰胺酶的菌株，其 ftsI 基因发生突变。所有 β-内酰胺药物针对低 BLNAR 菌株的 MIC 比针对 BLNAS 的高 2-8 倍。头孢菌素类抗生素针对 BLNAR 菌株的 MIC 比针对 BLNAS 的高 16-32 倍。 β-内酰胺对 BLNAR 菌株的 MIC90 值的排序为哌拉西林 = 头孢曲松 = 头孢托仑 (0.25 mug/ml)、美罗培南 (0.5)、头孢噻肟 (1)、AMP = 头孢泊肟 (8)、头孢地尼 (16)、阿莫西林 (16) 和头孢克洛 (64)。 B 型血清分离株在这两个国家都很少（日本为 2.4%，美国为 3%）。两国流感嗜血杆菌分离株中各自 AMP 抗性基因比例的差异可能反映了通常用于社区获得性细菌感染门诊患者的抗生素药物的差异。
Clinical isolates of Haemophilus influenzae from Japan (n = 296) and the United States (n = 100) were tested by the microdilution method for susceptibility in vitro to 10 beta-lactam antibiotics and molecular mechanisms of beta-lactam resistance. For all isolates, PCR was used to identify six elements, including beta-lactamase-producing ampicillin (AMP)-resistance (BLPAR) and beta-lactamase-nonproducing AMP-resistance (BLNAR) genes as follows: (1) TEM-1 type beta-lactamase gene, (2) ROB-1 type beta-lactamase gene, (3) part of normal ftsI gene encoding PBP3, which is involved in septal peptidoglycan synthesis, (4) a portion of the ftsI gene possessing some amino acid substitutions commonly detected in BLNAR strains, (5) p6 gene encoding P6 membrane proteins specific to H. influenzae, and (6) serotype b capsule gene.In Japanese and U.S. isolates, respective prevalences of each resistance class in Japan and the United States were 55.1 % and 46 % for beta-lactamase-nonproducing, AMP-susceptible (BLNAS); 3.0 % and 26 % for the TEM-1 type beta-lactamase gene; 0 % and 10 % for the ROB-1 type; 26.4 % and 13 % for low-BLNAR with a low degree of AMP resistance; and 13.2% and 0% for BLNAR strains. A few remaining isolates were beta-lactamase-producing strains with a mutation in the ftsI gene. MICs of all beta-lactam agents against low-BLNAR strains were 2-8 times higher than against BLNAS. MICs of cephalosporin antibiotics against BLNAR strains were 16-32 times higher than against BLNAS. The rank order of beta-lactam MIC90 values against BLNAR strains was piperacillin = ceftriaxone = cefditoren (0.25 mug/ml), meropenem (0.5), cefotaxime (1), AMP = cefpodoxime (8), cefdinir (16), amoxicillin (16), and cefaclor (64). Serotype b isolates were few in both countries (2.4 % in Japan, 3 % in the United States). Differences in proportions of respective AMP-resistant genes in H. influenzae isolates between the two countries might reflect differences in antibiotic agents ordinarily given to outpatients with community-acquired bacterial infections.