Hasegawa Keiko, Kobayashi Reiko, Takada Emi, Ono Akiko, Chiba Naoko, Morozumi Miyuki, Iwata Satoshi, Sunakawa Keisuke, Ubukata Kimiko
Laboratory of Infectious Agents Surveillance, Kitasato Institute for Life Sciences, Kitasato University 5-9-1, Shirokane, Minato-ku, Tokyo, Japan.
J Antimicrob Chemother. 2006 Jun;57(6):1077-82. doi: 10.1093/jac/dkl142. Epub 2006 Apr 14.
To study yearly changes in resistance and to identify ftsI mutations in beta-lactamase-non-producing ampicillin-resistant (BLNAR) and TEM-1 beta-lactamase-producing amoxicillin/clavulanic acid-resistant (BLPACR) isolates of Haemophilus influenzae from patients with meningitis.
Between January 2000 and December 2004, we received 621 isolates of H. influenzae from 285 member institutions of the Nationwide Surveillance Study Group for Bacterial Meningitis. All isolates were analysed by PCR to identify resistance genes and tested for susceptibility to beta-lactams. The ftsI gene was sequenced in all BLNAR and BLPACR isolates.
All but four isolates were of serotype b. The isolates could be divided into six classes, namely beta-lactamase-non-producing ampicillin-susceptible (25.0%), TEM-1 beta-lactamase-producing ampicillin-resistant (11.0%), beta-lactamase-non-producing low-level ampicillin-resistant with N526K or R517H substitution in the ftsI gene (30.4%), BLNAR with an S385T substitution together with either N526K or R517H substitution in ftsI (22.2%), BLPACR-I with either a N526K or R517H substitution in ftsI (9.5%) and BLPACR-II with an S385T substitution together with either a N526K or R517H substitution in ftsI (1.9%). The prevalence of BLNAR has increased rapidly, from 5.8% in 2000 to 34.5% in 2004. All BLNAR and BLPACR-II strains were classified into nine subgroups on the basis of substitution patterns in the ftsI gene. The MICs of cephalosporin antibiotics for H. influenzae transformants into which the ftsI genes from BLNAR strains of each of the nine subgroups were introduced increased to varying degrees depending on the mutations.
The results suggest that introduction of H. influenzae type b (Hib) vaccination into infants and children is necessary for the prevention of severe Hib infections in Japan.
研究脑膜炎患者中流感嗜血杆菌的β-内酰胺酶非产生型氨苄西林耐药（BLNAR）和TEM-1β-内酰胺酶产生型阿莫西林/克拉维酸耐药（BLPACR）菌株的耐药性年度变化，并鉴定ftsI基因突变。
2000年1月至2004年12月期间，我们从全国细菌性脑膜炎监测研究组的285个成员机构收到了621株流感嗜血杆菌分离株。所有分离株均通过PCR分析以鉴定耐药基因，并检测对β-内酰胺类药物的敏感性。对所有BLNAR和BLPACR分离株的ftsI基因进行测序。
除4株外，所有分离株均为b型血清型。这些分离株可分为六类，即β-内酰胺酶非产生型氨苄西林敏感（25.0%）、TEM-1β-内酰胺酶产生型氨苄西林耐药（11.0%）、ftsI基因中具有N526K或R517H替代的β-内酰胺酶非产生型低水平氨苄西林耐药（30.4%）、ftsI基因中具有S385T替代以及N526K或R517H替代之一的BLNAR（22.2%）、ftsI基因中具有N526K或R517H替代之一的BLPACR-I（9.5%）以及ftsI基因中具有S385T替代以及N526K或R517H替代之一的BLPACR-II（1.9%）。BLNAR的患病率迅速上升，从2000年的5.8%升至2004年的34.5%。所有BLNAR和BLPACR-II菌株根据ftsI基因中的替代模式分为九个亚组。将九个亚组中每个亚组的BLNAR菌株的ftsI基因导入的流感嗜血杆菌转化株对头孢菌素抗生素的最低抑菌浓度（MIC）根据突变不同程度增加。
结果表明，在日本，对婴幼儿接种b型流感嗜血杆菌（Hib）疫苗对于预防严重的Hib感染是必要的。
