Sisomicin

Sisomicin (Antibiotic 6640, CAS No. 32385-11-8) is a broad-spectrum aminoglycoside antibiotic produced by Micromonospora inyoensis. Its core bioactivity is inhibition of bacterial protein synthesis, targeting the 30S subunit of the bacterial ribosome. By interfering with the binding of mRNA to the ribosome, it blocks the translation process and is effective against most Gram-negative bacteria, staphylococci and other Gram-positive bacteria, as well as some mycobacteria. The MIC is pathogen-specific. Among Gram-negative bacteria, ≥90% of Escherichia coli, Pseudomonas aeruginosa, Enterobacter spp., and Proteus spp. strains are inhibited by 1.56μg/ml, all Klebsiella spp. strains are inhibited by 0.39μg/ml, and 66% of Serratia marcescens strains are inhibited by 1.56μg/ml. Among Gram-positive bacteria, Staphylococcus aureus (including penicillin-resistant strains) are inhibited at ≤0.78μg/ml, and Streptococcus pneumoniae and Streptococcus pyogenes at ≤1.56μg/ml. Common application concentrations: for in vitro antibacterial testing, a gradient dilution method of 0.025~100μg/ml is used (Mueller-Hinton medium); in animal experiments, the dose in rat/dog infection models is 1~10mg/kg/day; in avian inner ear hair cell elimination experiments, a 50~75mg/mL solution (volume 0.8~2μL) is injected via the lateral semicircular canal. Clinically effective therapeutic concentrations correspond to an adult dose of 5mg/kg/day (divided into 3 intramuscular/intravenous injections), with steady-state serum peak concentrations of 5~10mg/L and trough concentrations < 2mg/L. In patients with renal impairment, the dose should be adjusted according to creatinine clearance; 40% of the drug can be removed by 6 hours of hemodialysis. It is suitable for severe Gram-negative infections of the respiratory tract, genitourinary system, abdominal cavity, etc., and requires monitoring for ototoxicity and nephrotoxicity. Strains resistant to gentamicin/tobramycin are often cross-resistant, and amikacin (Amikacin, CAS No. 37517-28-5, Cat. No.: B3431) is more effective against such strains.

References:

[1] Stewart D, Bodey GP. In vitro activity of sisomicin, an aminoglycoside antibiotic, against clinical isolates. J Antibiot (Tokyo). 1975 Feb;28(2):149-55. doi: 10.7164/antibiotics.28.149. PMID: 234415.

[2] Noone P. Sisomicin, netilmicin and dibekacin. A review of their antibacterial activity and therapeutic use. Drugs. 1984 Jun;27(6):548-78. doi: 10.2165/00003495-198427060-00003. PMID: 6376062.

[3] Sato MP, Huang AP, Heller S, Benkafadar N. Protocol for in vivo elimination of avian auditory hair cells, multiplexed mRNA detection, immunohistochemistry, and S-phase labeling. STAR Protoc. 2024 Jun 21;5(2):103118. doi: 10.1016/j.xpro.2024.103118. Epub 2024 Jun 8. PMID: 38852155; PMCID: PMC11217775.