Cloxacillin (sodium salt) is an orally active antibacterial agent and β-lactamase inhibitor with an IC50 value of 0.04µM [1]. Cloxacillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins and is resistant to the beta-lactamase enzyme produced by S. aureus [2]. Cloxacillin is widely used as an antibiotic in veterinary medicine against S. aureus and can be combined with plant essential oils to kill drug-resistant bacteria[3].
In vitro, Cloxacillin treatment for 5min significantly inhibited organic anion transporter (OAT) 1, OAT3, and OAT4 activities in OAT-overexpressing HEK293 cells with IC50 values of 550µM, 13µM, and 21µM, respectively[4]. Cloxacillin treatment (0.015625μg/ml) combined with thioridazine (0.25μg/ml) and tetracycline (0.03125μg/ml) for 6h significantly inhibited the expression of MAPK/NF-κB/NLRP3 proteins in RAW264.7 cells induced with S. aureus[5].
In vivo, Cloxacillin treatment via intraperitoneal injection (7.5mg/mouse; twice daily) for 3 day combined with IL-15 neutralizing antibodies, reduced synovitis and bone erosions in S. aureus-induced arthritis of mice[6].
References:
[1] Lupiola-Gómez P A, Gonzalez-Lama Z, Tejedor-Junco M T, et al. Group 1 β-lactamases of Aeromonas caviae and their resistance to β-lactam antibiotics[J]. Canadian journal of microbiology, 2003, 49(3): 207-215.
[2] Mani S S R, Iyyadurai R. Cloxacillin induced agranulocytosis: a rare adverse event of a commonly used antibiotic[J]. International Journal of Immunopathology and Pharmacology, 2017, 30(3): 297-301.
[3] Buldain D, Buchamer A V, Marchetti M L, et al. Combination of cloxacillin and essential oil of Melaleuca armillaris as an alternative against Staphylococcus aureus[J]. Frontiers in Veterinary Science, 2018, 5: 177.
[4] Lalanne S, Le Vée M, Lemaitre F, et al. Differential interactions of the β‐lactam cloxacillin with human renal organic anion transporters (OATs)[J]. Fundamental & Clinical Pharmacology, 2020, 34(4): 476-483.
[5] Zhou H, Luan W, Wang Y, et al. The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation[J]. International Journal of Biological Macromolecules, 2022, 198: 1-10.
[6] Bergmann B, Jirholt P, Henning P, et al. Antibiotics with Interleukin-15 inhibition reduce joint inflammation and bone erosions but not cartilage destruction in Staphylococcus aureus-induced arthritis[J]. Infection and Immunity, 2018, 86(5): 10.1128/iai. 00960-17.
Cloxacillin (sodium salt)是一种口服有效的抗菌剂和β-内酰胺酶抑制剂，IC50值为0.04µM[1]。Cloxacillin通过与青霉素结合蛋白结合抑制细菌细胞壁合成，并对金黄色葡萄球菌产生的β-内酰胺酶具有抗性[2]。Cloxacillin在兽医学中被广泛用作抗金黄色葡萄球菌的抗生素，并可与植物精油联合使用以杀灭耐药细菌[3]。
在体外，Cloxacillin处理5分钟显著抑制了过表达有机阴离子转运体（OAT）1、OAT3和OAT4的HEK293细胞中的相应活性，IC50值分别为550µM、13µM和21µM[4]。Cloxacillin（0.015625µg/ml）联合thioridazine（0.25µg/ml）和四环素（0.03125µg/ml）处理6小时，显著抑制了金黄色葡萄球菌诱导的RAW264.7细胞中MAPK/NF-κB/NLRP3蛋白的表达[5]。
在体内，每日两次腹腔注射Cloxacillin（7.5mg/只小鼠）连续3天，联合IL-15中和抗体治疗，减轻了金黄色葡萄球菌诱导的小鼠关节炎的滑膜炎和骨侵蚀[6]。