Tobramycin

Tobramycin is a parenterally administered aminoglycoside antibiotic with significant antibacterial activity against aerobic Gram-negative bacteria such as Pseudomonas aeruginosa^[1]. Tobramycin exerts its bactericidal effect by irreversibly binding to the bacterial 30S ribosomal subunit, thereby inhibiting protein synthesis^[2]. Tobramycin is commonly used to treat conditions such as ocular infections, respiratory tract infections in patients with cystic fibrosis, and urinary tract infections^[3,4].

In vitro, treatment of 96 clinically isolated P. aeruginosa strains with Tobramycin (0.39-25μg/mL) for 18h resulted in MICs ≤ 3.12μg/mL for 83/96 strains on Mueller Hinton agar, while its bacteriostatic activity was stronger in Mueller Hinton broth (MIC values were 2-8 times lower)^[5]. Pretreatment of human lung microvascular endothelial cells (HLMVEC) with Tobramycin (0.5mM) for 24h significantly inhibited platelet-induced T-cell migration (inhibition rate 66.5%)^[6].

In vivo, combined administration of Tobramycin (30mg/kg; once daily; s.c.) and Furanone C-30 (1mg/kg) to BALB/c mice implanted with a pre-infected P. aeruginosa silicone tube for up to 48h significantly reduced the bacterial load on the silicone implant. The synergistic clearance effect was significantly superior to monotherapy^[7]. Intratracheal single-dose administration of Tobramycin (250μg/mouse) on the first day after NMRI mice were infected with Klebsiella pneumoniae significantly increased the survival rate within 8 days post-infection by 33% compared to the untreated control group^[8]. Treatment of CBA/Ca mice with Tobramycin (200mg/kg/day; s.c. for 14 days) resulted in gap detection deficits in the gap pre-pulse inhibition of the acoustic startle (GPIAS) test in 36% of the mice, indicating tinnitus-like behavior. This behavior was most pronounced at 2 weeks post-administration and gradually diminished over time^[9].

References:
[1] FIEL S B, ROESCH E A. The use of tobramycin for Pseudomonas aeruginosa: A review[J]. Expert Review of Respiratory Medicine, 2022, 16(5): 503-509.
[2] KRAUS L, DUCHARDT-FERNER E, BRÄUCHLE E, et al. Development of a novel tobramycin dependent riboswitch[J]. Nucleic Acids Research, 2023, 51(20): 11375-11385.
[3] CHEER S M, WAUGH J, NOBLE S. Inhaled Tobramycin (TOBI®): A review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis[J]. Drugs, 2003, 63(22): 2501-2520.
[4] NEU H C. Tobramycin: an overview[J]. The Journal of Infectious Diseases, 1976, S3-S19.
[5] MEYER R D, YOUNG L S, ARMSTRONG D. Tobramycin (nebramycin factor 6): in vitro activity against Pseudomonas aeruginosa[J]. Applied Microbiology, 1971, 22(6): 1147-1151.
[6] GZIUT M, MACGREGOR H J, NEVELL T G, et al. Anti‐inflammatory effects of tobramycin and a copper–tobramycin complex with superoxide dismutase‐like activity[J]. British Journal of Pharmacology, 2013, 168(5): 1165-1181.
[7] CHRISTENSEN L D, VAN GENNIP M, JAKOBSEN T H, et al. Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model[J]. Journal of Antimicrobial Chemotherapy, 2012, 67(5): 1198-1206.
[8] VAN‘T VEEN A, MOUTON J W, GOMMERS D, et al. Pulmonary surfactant as vehicle for intratracheally instilled tobramycin in mice infected with Klebsiella pneumoniae[J]. British Journal of Pharmacology, 1996, 119(6): 1145.
[9] LONGENECKER R J, GU R, HOMAN J, et al. Development of Tinnitus and Hyperacusis in a mouse model of Tobramycin Cochleotoxicity[J]. Frontiers in Molecular Neuroscience, 2021, 14: 715952.

Tobramycin是一种胃肠外给药的，对需氧革兰氏阴性菌（如Pseudomonas aeruginosa）具有显著抗菌活性的氨基糖苷类抗生素^[1]。Tobramycin通过不可逆地结合细菌30S核糖体亚基，抑制蛋白质合成而发挥杀菌作用^[2]。Tobramycin通常用于眼部感染、囊性纤维化患者呼吸道感染及泌尿系统感染等疾病的治疗^[3,4]。

在体外，Tobramycin（0.39-25μg/mL）处理96株临床分离的P. aeruginosa菌株18h，在Mueller Hinton琼脂中，83/96株菌的MIC ≤ 3.12μg/mL，在Mueller Hinton肉汤中抑菌活性更强（MIC值低2-8倍）^[5]。Tobramycin（0.5mM）预处理人类肺微血管内皮HLMVEC细胞24h，显著抑制了血小板诱导的T细胞迁移（抑制率为66.5%）^[6]。

在体内，Tobramycin（30mg/kg; once daily; s.c.）与Furanone C-30（1mg/kg）联合处理植入了预感染P. aeruginosa硅胶管的BALB/c小鼠，持续至48h，显著降低了硅胶植入物上的细菌载量，协同清除效果显著优于单药治疗^[7]。Tobramycin（250μg/mouse）在NMRI小鼠感染肺炎Klebsiella pneumoniae后第一天给予气管内一次性滴注，较未治疗的对照组相比能显著提高感染后8天内的存活率（33%）^[8]。Tobramycin（200mg/kg/day; 14 days; s.c.）处理CBA/Ca小鼠后，36%的小鼠在脉冲前间隔抑制惊觉反射（GPIAS）测试中存在间隙检测缺陷，出现耳鸣样行为，且该行为在给药后2周最显著，随时间推移逐渐减轻^[9]。