In vitro activities of piperacillin against β-lactamase-negative ampicillin-resistant Haemophilus influenzae
In vitro activities of piperacillin against β-lactamase-negative ampicillin-resistant Haemophilus influenzae
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DOI：
10.1128/aac.48.4.1229-1234.2004
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发表时间：
2004-04-01
影响因子：
4.9
通讯作者：
Watanabe, Y
中科院分区：
文献类型：
--
作者：
Morikawa, Y;Kitazato, M;Watanabe, Y
将哌拉西林 (PIP) 体外抗 P-内酰胺酶阴性氨苄青霉素 (AMP) 耐药 (BLNAR) 流感嗜血杆菌的活性与头孢噻肟 (CTX) 和头孢曲松 (CRO) 进行比较，并讨论了 PIP 作为治疗 BLNAR 引起的脑膜炎的效力。 PIP对69株BLNAR菌株表现出良好的活性（抑制90%菌株的MIC，0.25μg/ml），其活性与CRO相当，优于CTX。 PIP 与 CTX 或 CRO 或 AMP 的 MIC 之间没有观察到显着相关性，而 CTX 和 CRO 的 MIC 之间观察到高度相关性。在杀灭研究中，与CTX和CRO相比，PIP显示出更强的杀菌活性。通过显微镜检查，PIP导致BLNAR菌株形成纺锤体和具有凸起的短丝状细胞，并诱导细胞裂解，而CTX和CRO处理导致形成大的球形细胞，但没有任何明显的裂解。 Bocillin FL（一种用于测定青霉素结合蛋白 (PBP) 50% 抑制浓度 (IC(50)s) 的荧光青霉素）与 BLNAR 菌株 PBP 3a 和 3b 的亲和力与 AMP 敏感菌株 (ATCC 33391) 相比显着降低。对于 BLNAR 菌株，PBP 1a、1b 和 2 的 IC50 与 ATCC 33391 的 PBP 相似。由于与 BLNAR 菌株的 PBP 3a 和 3b 的结合亲和力急剧下降，PBP 中的第二个靶标是 PIP 的 PBP 2，CTX 和 CRO 的 PBP1（1a 和 1b）。总之，PIP 以不同于头孢烯类抗生素的方式对 BLNAR 菌株表现出优异的活性，表明它可能成为治疗 BLNAR 菌株引起的脑膜炎的候选治疗剂。
The in vitro activities of piperacillin (PIP) against P-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae were compared with those of cefotaxime (CTX) and ceftriaxone (CRO), and the potency of PIP as therapy for meningitis caused by BLNAR is also discussed. PIP showed good activity (MIC at which 90% of strains are inhibited, 0.25 mug/ml) against 69 BLNAR strains, and its activity was comparable to that of CRO and superior to that of CTX. No significant correlation was observed between the MICs of PIP and CTX or CRO or AMP, whereas a high correlation was observed between the MICs of CTX and CRO. In the killing study, PIP showed potent bactericidal activity compared with those of CTX and CRO. By microscopic examination, PIP caused the formation of a spindle and short filamentous cells with bulges and induced cell lysis in BLNAR strains, while treatment with CTX and CRO resulted in the formation of large, spherical cells without any obvious lysis. The affinity of Bocillin FL, a fluorescent penicillin used for determination of the 50% inhibitory concentration (IC(50)s) for penicillin-binding proteins (PBPs), to PBPs 3a and 3b of BLNAR strains was drastically decreased compared with that to an AMP-susceptible strain (ATCC 33391). In the case of the BLNAR strains, the IC50s for PBPs 1a, 1b, and 2 were similar to those for the PBPs of ATCC 33391. Since the affinity of binding to PBPs 3a and 3b of the BLNAR strains decreased drastically, the second targets among the PBPs were PBP 2 for PIP, PBP1 (1a and 1b) for CTX and CRO. In conclusion, PIP showed excellent activities against BLNAR strains in a manner different from those of cephem antibiotics, suggesting that it could be a candidate therapeutic agent for the treatment of meningitis caused by BLNAR strains.