Cethromycin

Cethromycin (ABT-773; Abbott-195773) is a ketolide antibiotic derived from erythromycin A, with broad-spectrum antibacterial activity. Cethromycin binds to domains II/V of 23S rRNA of the 50S subunit, inhibiting bacterial protein synthesis. Cethromycin can accumulate in lung tissue, alveolar macrophages, epithelial lining fluid, and human polymorphonuclear leukocytes. Cethromycin has potent in vitro activity against a variety of respiratory pathogens, including Mycoplasma pneumoniae. Cethromycin exhibits significant intracellular and pulmonary enrichment and anti-inflammatory effects against mycoplasma pneumonia in mouse models, improving airway obstruction and airway hyperresponsiveness. Cethromycin can disrupt the apicoplast and reduce liver-stage parasite burden against Plasmodium berghei liver stages. Cethromycin can be used in research related to pneumonia, Staphylococcus aureus infection, gonorrhea, and malaria^{[1][2][3][4][5][6][7][8][9][10]}. In Vitro:Cethromycin exhibits potent in vitro activity against a variety of respiratory pathogens, including Streptococcus pneumoniae (MIC₉₀ 0.004 to 0.25 µg/mL), Chlamydia pneumoniae (MIC₉₀ 0.015 µg/mL), and Mycoplasma pneumoniae (MIC₉₀ ≤ 0.001 µg/mL)^[1].
Cethromycin exhibits significant in vitro activity against Neisseria gonorrhoeae^[1].
Cethromycin exhibits potent in vitro activity against Borrelia burgdorferi, with MIC₉₀/MBC₉₀ of 0.0019/0.125 µg/mL^[1].
Cethromycin (4-16 × MIC) selected resistant mutants at a significantly lower frequency than erythromycin in S. pneumoniae, S. aureus , and S. pyogenes ^[1].
Cethromycin resistance is associated with specific erm genes and the MLS_B phenotype in S. aureus, where ermA MRSA and ermB/ermC MSSA show higher resistance rates, and the cMLS_B phenotype exhibits higher resistance than iMLS_B in both MRSA and MSSA^[7].
Cethromycin (20 µM; 48 h) disrupts plastid development in the liver stage of P. berghei in Hepa-1-6 hepatocytes, resulting in parasites with a single malformed plastid^[8].
Cethromycin (20 μM; 42 h) inhibits P. berghei liver-stage parasite growth in Hepa1-6 cells^[3].
Cethromycin (10 μg/mL; 3 h) was extensively taken up by human PMNs and did not reach saturation during the incubation period, with an I/E ratio exceeding 500^[4].
Cethromycin (10 μg/mL; 3 h) uptake in THP-1 promonocytes is saturable and reaches a plateau within 60 min^[4].
Cethromycin (10 μg/mL; 1 h) was rapidly released from preloaded human PMNs, with approximately 90% effluxed within the first hour of incubation in substance-free medium^[4].
Cethromycin (10 μg/mL; 3 h) was released in large amounts from preloaded THP-1 promonocytes, with approximately 90% excreted within the first 30 min^[4].
Cethromycin (72-144 h) exhibits delayed lethal activity against the blood stages of P. falciparum 3D7^[8]. In Vivo:Cethromycin (12-50 mg/kg; oral; single administration) reduced P. berghei liver-stage parasite burden at a single oral dose of 50 mg/kg, achieving greater than 99% inhibition when combined with 15 mg/kg Primaquine (HY-12651A)^[3].
Cethromycin (0.1-800 mg/kg/day; oral; once to four times daily) demonstrated significant bactericidal activity against both macrolide-susceptible and macrolide-resistant Streptococcus pneumoniae in a neutropenic mouse pneumonia model, and improved survival^[6].
Cethromycin (15-120 mg/kg; oral; 0-3 doses) exhibits potent causal prophylactic activity and curative effects against the liver stage of P. berghei malaria^[8].
Cethromycin (60 mg/kg; oral; daily; 7 days) exhibits curative efficacy in a blood-stage malaria model in mice with high parasitemia^[8].
Cethromycin (25 mg/kg; subcutaneous injection; once daily; 10 days) significantly reduced M. pneumoniae culture titers, lung inflammation, BAL cytokine and chemokine concentrations, and disease severity defined by airway obstruction and airway hyperresponsiveness in a mouse model of M. pneumoniae pneumonia^[9].