Low β-lactamase-negative ampicillin-resistant Haemophilus influenzae strains are best detected by testing amoxicillin susceptibility by the broth microdilution method
Low β-lactamase-negative ampicillin-resistant Haemophilus influenzae strains are best detected by testing amoxicillin susceptibility by the broth microdilution method
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DOI：
10.1128/aac.00214-08
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发表时间：
2008-07-01
影响因子：
4.9
通讯作者：
Oteo, Jesus
中科院分区：
文献类型：
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作者：
Garcia-Cobos, Silvia;Campos, Jose;Oteo, Jesus
由于青霉素结合蛋白(β-内酰胺酶阴性氨基青霉素耐药[BLNAR])的改变，流感嗜血杆菌对氨苄西林的耐药性日益受到临床和流行病学的重视。在欧洲和美国，BLNAR菌株的氨苄青霉素最低抑菌浓度(MIC)较低(0.5至4微克/毫升)，但将它们与敏感菌株分离是具有挑战性的。为了探讨鉴定低BLNAR菌株的最佳方法，我们用微量稀释法、Etest和纸片扩散法研究了94株临床分离的流感嗜血杆菌对抗生素的敏感性：25株没有耐药机制(GBLNAS)，34株只有FTSI基因突变(GBLNAR)，20株只产β-内酰胺酶(GBLPAR)，15株产生β-内酰胺酶并有FTSI基因突变(GBLPACR)。根据目前的CLSI断裂点，大多数gBLNAR分离株对微量稀释法(76.5%)或Etest(88.2%)敏感。用微量稀释法检测时，大多数gBLNAR菌株(79.4%)对阿莫西林(美国和欧洲最广泛使用的社区抗生素)不敏感。经Etest检测，15%的β-内酰胺酶阳性菌株对氨苄西林或阿莫西林不耐药。Etest和微量稀释法结果之间的一致性最差的是gBLPAR分离株(氨苄西林25%，阿莫西林15%，头孢克洛10%)。低强度的氨苄西林和阿莫西林-克拉维酸纸片对低BLNAR分离株鉴定不佳，不推荐作为筛查方法。我们建议BLNAR分离株新的阿莫西林临界点如下：敏感，最低抑菌浓度(MIC)=4微克/毫升(存在耐药机制，PK/PD数据不利)。
Ampicillin resistance in Haemophilus influenzae due to alterations in penicillin-binding proteins (beta-lactamase negative ampicillin resistant [BLNAR]) is acquiring increasing clinical and epidemiological importance. BLNAR strains with low ampicillin MICs (0.5 to 4 mu g/ml) represent the majority of this population in Europe and the United States, but separating them from susceptible isolates is challenging. To investigate the best method to identify low-BLNAR strains, we studied the antibiotic susceptibilities of 94 clinical isolates of H. influenzae by microdilution, Etest, and disk diffusion: 25 had no resistance mechanisms (gBLNAS), 34 had mutations in the ftsI gene only (gBLNAR), 20 were beta-lactamase producers only (gBLPAR), and 15 showed beta-lactamase production and mutations in the ftsI gene (gBLPACR). By current CLSI breakpoints, most gBLNAR isolates were ampicillin susceptible by microdilution (76.5%) or by Etest (88.2%). Most gBLNAR strains (79.4%) were nonsusceptible to amoxicillin (the most widely used community antibiotic in the United States and Europe) when tested by microdilution. By Etest, 15% of beta-lactamase-positive isolates were nonresistant to ampicillin or amoxicillin. The poorest agreement between Etest and microdilution results was for the gBLPAR isolates (25% for ampicillin, 15% for amoxicillin, and 10% for cefaclor). Low-strength disks of ampicillin and amoxicillin-clavulanic acid poorly identified low-BLNAR isolates and are not recommended as a screening method. We suggest new amoxicillin breakpoints for BLNAR isolates as follows: susceptible, MIC = 4 mu g/ml (resistance mechanisms present and PK/PD data unfavorable).