Cefotaxime (sodium salt) is a third-generation cephalosporins against a wide range of gram positive and gram negative organisms[1]. Cefotaxime inhibits both the monophenolase and diphenolase activities of tyrosinase with IC50 values of 3.2mM and 0.14mM, respectively[2]. Cefotaxime is effective in the treatment of various infections: complicated urinary tract infections, lower respiratory tract infections, bacteraemia, meningitis, uncomplicated gonorrhoea, infections of skin and soft tissue and of bone and joints, and obstetric and gynaecological infections[3].
In vitro, Cefotaxime (100μg/ml) treatment for 72h specifically promoted the apoptosis in nasopharyngeal carcinoma CNE2 cells treated by cisplatin (2μg/ml). Cefotaxime (200μg/ml) treatment combined with cisplatin (2μg/ml) for 48h on CNE2 cells significantly regulated 5 genes in direction favoring the enhancement of anticancer efficacy; of which, THBS1 and LAPTM5 were upregulated; PPP3CB, STAG1 and NCOA5 were downregulated jointly[4]. Cefotaxime (0.25, 0.5 and 1mg/mL) incubation for 24 or 48h after 1mg/mL LPS stimulation boosted IL-2 production from mononuclear cells (MC) isolated from cord blood (CBMC) of newborns and from peripheral venous blood (PBMC) of adults. Cefotaxime also induced dose-dependent inhibition of the spontaneous and LPS induced IL-1β production, but had no effect on the production of IL-6 by cells of the two groups[5].
In vivo, Cefotaxime (30mg/kg; i.p.) and Ciprofloxacin (8mg/kg; i.p.) were injected into V. vulnificus. infected female BALB/c mice every 6h or 12h respectively for total 42h. Cefotaxime failed to effectively clear V. vulnificus in vivo but the combination of Ciprofloxacin and Cefotaxime significantly increased 96h survival rate from 0% to 85%[6]. Sub-inhibitory concentration of Cefotaxime (0.065mg/L (0.5× MIC)) applied to pretreated bacteria. S. Typhimurium for 3 hours increased the systemic colonization of S. Typhimurium in BALB/c mice after intraperitoneal inoculation in part by the establishment of a fitness alteration conducive to anaerobic metabolism[7].
References:
[1] Woodfield J C, Van Rij A M, Pettigrew R A, et al. A comparison of the prophylactic efficacy of ceftriaxone and cefotaxime in abdominal surgery.Am J Surg. 2003 Jan;185(1):45-9.
[2] Hu Y H, Zhuang J X, Yu F, et al. Inhibitory effects of cefotaxime on the activity of mushroom tyrosinase. J Biosci Bioeng. 2016 Apr;121(4):385-9.
[3] Todd P A, Brogden R N. Cefotaxime. An update of its pharmacology and therapeutic use. Drugs. 1990 Oct;40(4):608-51.
[4] He X Q, Yao Q, Fan D, et al. Combination of Cefotaxime and Cisplatin Specifically and Selectively Enhances Anticancer Efficacy in Nasopharyngeal Carcinoma.Curr Cancer Drug Targets. 2023;23(7):572-584.
[5] Bessler H, Gurary N, Aloni D, Vishne T H, Sirota L. Effect of cefotaxime on cytokine production in newborns and adults in vitro. Biomed Pharmacother. 2000 Aug;54(7):410-4.
[6] Jang H C, Choi S M, Kim H K, et al. In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis. PLoS One. 2014 Jun 30;9(6):e101118.
[7] Molina-Quiroz R C, Silva C A, Molina C F, et al. Exposure to sub-inhibitory concentrations of cefotaxime enhances the systemic colonization of Salmonella Typhimurium in BALB/c mice. Open Biol. 2015 Oct;5(10):150070.
Cefotaxime (sodium salt)是第三代头孢菌素，对广泛的革兰氏阳性菌和革兰氏阴性菌均有效[1]。Cefotaxime可同时抑制酪氨酸酶的单酚酶和二酚酶活性，IC50值分别为3.2mM和0.14mM[2]。Cefotaxime适用于多种感染的治疗：复杂性尿路感染、下呼吸道感染、败血症、脑膜炎、单纯性淋病、皮肤及软组织感染、骨关节感染以及妇产科感染[3]。
在体外实验中，Cefotaxime（100μg/ml）处理72小时可特异性促进cisplatin（2μg/ml）诱导的鼻咽癌CNE2细胞的凋亡。Cefotaxime（200μg/ml）联合cisplatin（2μg/ml）处理CNE2细胞48小时，显著调控了5个基因，增强抗癌效果；其中THBS1和LAPTM5表达上调，PPP3CB、STAG1和NCOA5共同下调[4]。Cefotaxime（0.25、0.5和1mg/mL）在1mg/mL LPS刺激后的24或48小时内孵育，可促进从新生儿脐带血（CBMC）和成人外周静脉血（PBMC）中分离出的单核细胞（MC）产生IL-2。Cefotaxime还诱导了对自发和LPS诱导的IL-1β产生的剂量依赖性抑制，但对两组细胞产生的IL-6无影响[5]。
在体内实验中，Cefotaxime（30mg/kg）和Ciprofloxacin（8mg/kg）分别每6小时或12小时向感染V.vulnificus的雌性BALB/c小鼠进行腹腔注射，总共42小时。Cefotaxime在体内未能有效清除V. vulnificus，但Ciprofloxacin与Cefotaxime的组合显著提高了96小时生存率，从Cefotaxime单独注射组的0%提高到85%[6]。Cefotaxime的亚抑制浓度（0.065mg/L（0.5× MIC））被应用于预先处理的沙门氏菌S.Typhimurium 3小时。Cefotaxime暴露通过建立了有利于厌氧代谢的适应性改变增加了BALB/c小鼠腹腔接种后S.Typhimurium的系统定植[7]。