Apramycin (sulfate)

Apramycin (EBL 1003) sulfate is an orally active, acidic pH tolerant and aminoglycoside-modifying-enzymes-tolerant aminoglycoside antibiotic which inhibits protein biosynthesis by targeting the bacterial ribosome. Apramycin sulfate is a potential anti-drug-resistance antibiotic^[1][2][3]. In Vitro:Apramycin (4 mg/L) sulfate inhibits 99% of K. pneumoniae and 93% of Enterobacter clinical isolates. Apramycin (8 mg/L) sulfate inhibits 99% of all E. coli, 98% of C. freundii, 96% of Providencia spp., 92% of S. marcescens, 97% of M. morganii and 100% of P. mirabilis clinical isolates, exhibiting significantly better antimicrobial activity than the clinical standard-of-care aminoglycosides Gentamicin and Amikacin sulfate^[1].
Apramycin (100 μM, 10 min) sulfate exerts an 11% decrease in cytoplasmic uptake of E.coli when lowering the pH from 7.3 to 5.7 while the amounts of Gentamicin and Amikacin are reduced by 62% and 51%, respectively^[3].
In Vivo:Apramycin (200 mg/kg/d, s.c., 9 d) sulfate demonstrates significant in vivo efficacy in lungs of M. tuberculosis low-dose aerosol infection model IFN-γ knockout mice^[2].
Apramycin (16, 32, 80 mg/kg, s.c., 24 h) sulfate dose-dependently reduces bacterial burden in the kidneys between 2-5 log₁₀ and in blood between 2-3 log₁₀ for neutropenic model of Staphylococcus aureus septicemia mice^[2].
Apramycin (50 mg/kg/d, s.c., 21 d) sulfate induces nephrotoxicity scores comparable to those induced by Gentamicin (10 mg/kg/d)^[3].