替莫西林

替莫西林
臨床資料
AHFS/Drugs.com	国际药品名称
ATC碼	J01CA17 (WHO) ;
识别信息
	IUPAC命名法 (2S,5R,6S)-6-[(Carboxy-3-thienylacetyl)amino]- 6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid,; ;
CAS号	66148-78-5
PubChem CID	171758;
ChemSpider	150149 ;
UNII	03QB156W6I;
KEGG	D06064 ;
ChEBI	CHEBI:51817 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID201009398 ;
ECHA InfoCard	100.060.148
化学信息
化学式	C16H18N2O7S2
摩尔质量	414.45 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C(O)[C@@H]2N3C(=O)[C@@](OC)(NC(=O)C(c1ccsc1)C(=O)O)[C@H]3SC2(C)C;
	InChI InChI=1S/C16H18N2O7S2/c1-15(2)9(12(22)23)18-13(24)16(25-3,14(18)27-15)17-10(19)8(11(20)21)7-4-5-26-6-7/h4-6,8-9,14H,1-3H3,(H,17,19)(H,20,21)(H,22,23)/t8?,9-,14+,16-/m0/s1 ; Key:BVCKFLJARNKCSS-DWPRYXJFSA-N ;

替莫西林（英语：Temocillin）是由比彻姆集团推出的一种耐β-内酰胺酶的青霉素，^[1]^[2]由Eumedica制药以商品名Negaban销售。它主要用于治疗多重耐药的革兰氏阴性菌。

它是一种6-甲氧基青霉素；它也是一种羧基青霉素。^[3]

药理学

替莫西林是一种耐 β-内酰胺酶的青霉素。它对革兰氏阳性菌或具有改变的青霉素结合蛋白的细菌没有活性。

它通常对卡他莫拉氏菌、流产布鲁氏菌、洋葱伯克氏菌、柠檬酸杆菌属的物种、大肠杆菌、流感嗜血杆菌、肺炎克雷伯氏菌、多杀性巴斯德氏菌、奇异变形杆菌、肠沙门氏菌肠亚种和小肠结肠炎耶尔森菌具有活性。它还对一些肠杆菌属的物种、摩氏摩根氏菌和沙雷氏菌属的物种具有活性。但是，替莫西林对不动杆菌属或铜绿假单胞菌没有有用的活性。

它的主要用途是对抗肠杆菌科，特别是对抗产生超广谱β-内酰胺酶或AmpC β-内酰胺酶的菌株。^[4]

剂量

常规剂量为每12小时静脉注射2克，而高剂量，特别是对于危重病患者，则为每8小时2克。在严重疾病中，有理论依据将替莫西林作为静脉持续输注：^[5]^[6]首先静脉注射2克的单次剂量，然后24小时内进行4克或6克的输注。根据SPC，以下溶剂在25°C下24小时内的化学和物理稳定性已被证明：注射用水、生理盐水（0.9%氯化钠）、5%葡萄糖、氯化钠复合物（林格氏液）、哈特曼氏液（乳酸钠复合物+林格乳酸液）。特莫西林用于静脉注射时，需在10至20毫升的无菌水中稀释；用于肌肉注射时，在不到2毫升的无菌水中稀释；持续输注为了方便给药而在48毫升的无菌水中稀释（每小时2毫升）。为了减轻疼痛，肌肉注射可以使用1%无菌利多卡因代替无菌水制备。

调整剂量后，肾功能不全的患者可使用替莫西林：

肌酸酐清除率 (毫升/分钟)	每次给药剂量	给药间隔
超过60	2克	12小时
60至30	1克	12小时
30至10	1克	24小时

在间歇性高通量血液透析的情况下：透析间每24小时期1克（静脉注射），最好在血液透析结束时（1克q24小时，2克q48小时，3克q72小时）。如果门诊患者进行连续腹膜透析：每24小时1克。

没有口服替莫西林制剂获得许可。

不良反应

替莫西林的不良反应与任何β-内酰胺类抗生素的不良反应相同。特别是，它与青霉素过敏患者的血管性水肿和过敏反应有关。动物研究未显示其对任何艰难梭菌感染的诱导。^[7]与任何其他青霉素一样，如果给予非常高的剂量，可能会发生抽搐。

合成

替莫西林的合成^[8]

参考资料

^ Andrews JM, Jevons G, Walker R, Ashby J, Fraise AP. Temocillin susceptibility by BSAC methodology. J. Antimicrob. Chemother. July 2007, 60 (1): 185–7 [2023-03-03]. PMID 17550891. doi:10.1093/jac/dkm179  . （原始内容存档于2020-03-24）.
^ Van Landuyt HW, Pyckavet M, Lambert A, Boelaert J. In vitro activity of temocillin (BRL 17421), a novel beta-lactam antibiotic. Antimicrob. Agents Chemother. October 1982, 22 (4): 535–40. PMC 183789  . PMID 7181470. doi:10.1128/aac.22.4.535.
^ Chanal M, Sirot J, Cluzel M, Joly B, Glanddier Y. [In vitro study of the bacteriostatic and bactericidal activity of temocillin (BRL 17421)]. Pathol. Biol. June 1983, 31 (6): 467–70. PMID 6348653 （法语）.
^ Livermore DM et al. (2006) Activity of temocillin vs. prevalent ESBL- and AmpC-producing Enterobacteriaceae from SE England. J Antimicrob Chemother. 2006 May;57(5):1012-4.
^ De Jongh R et al. (2008) Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection. J Antimicrob Chemother. 2008 Feb;61(2):382-8.
^ Laterre PF et al. (2015) Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration. J Antimicrob Chemother. 2015 Mar;70(3):891-8.
^ Boon RJ, et al. Studies with temocillin in a hamster model of antibiotic-associated colitis. Antimicrob Agents Chemother. 1985, 27 (6): 980–1. PMC 180203  . PMID 3875312. doi:10.1128/aac.27.6.980.
^ Bentley, P. H.; Clayton, J. P.; Boles, M. O.; Girven, R. J. Transformations using benzyl 6-isocyanopenicillanate. Journal of the Chemical Society, Perkin Transactions 1. 1979: 2455. doi:10.1039/P19790002455.

延申阅读

Livermore DM, Tulkens PM. Temocillin revived. Journal of Antimicrobial Chemotherapy. February 2009, 63 (2): 243–5. PMID 19095679. doi:10.1093/jac/dkn511  .

[pmid17550891-1] Andrews JM, Jevons G, Walker R, Ashby J, Fraise AP. Temocillin susceptibility by BSAC methodology. J. Antimicrob. Chemother. July 2007, 60 (1): 185–7 [2023-03-03]. PMID 17550891. doi:10.1093/jac/dkm179  . （原始内容存档于2020-03-24）.

[pmid7181470-2] Van Landuyt HW, Pyckavet M, Lambert A, Boelaert J. In vitro activity of temocillin (BRL 17421), a novel beta-lactam antibiotic. Antimicrob. Agents Chemother. October 1982, 22 (4): 535–40. PMC 183789  . PMID 7181470. doi:10.1128/aac.22.4.535.

[pmid6348653-3] Chanal M, Sirot J, Cluzel M, Joly B, Glanddier Y. [In vitro study of the bacteriostatic and bactericidal activity of temocillin (BRL 17421)]. Pathol. Biol. June 1983, 31 (6): 467–70. PMID 6348653 （法语）.

[4] Livermore DM et al. (2006) Activity of temocillin vs. prevalent ESBL- and AmpC-producing Enterobacteriaceae from SE England. J Antimicrob Chemother. 2006 May;57(5):1012-4.

[5] De Jongh R et al. (2008) Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection. J Antimicrob Chemother. 2008 Feb;61(2):382-8.

[6] Laterre PF et al. (2015) Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration. J Antimicrob Chemother. 2015 Mar;70(3):891-8.

[7] Boon RJ, et al. Studies with temocillin in a hamster model of antibiotic-associated colitis. Antimicrob Agents Chemother. 1985, 27 (6): 980–1. PMC 180203  . PMID 3875312. doi:10.1128/aac.27.6.980.

[8] Bentley, P. H.; Clayton, J. P.; Boles, M. O.; Girven, R. J. Transformations using benzyl 6-isocyanopenicillanate. Journal of the Chemical Society, Perkin Transactions 1. 1979: 2455. doi:10.1039/P19790002455.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]