Thiamphenicol glycinate acetylcysteine

Thiamphenicol glycinate acetylcysteine (TGA) is a pharmaceutical drug that is a combination of thiamphenicol glycinate ester (TAFGE), which is a derivative of the antibiotic thiamphenicol, and N-acetylcysteine (NAC), which is a mucus-thinning drug. Upon contact with tissue esterases, TGA releases both TAFGE and NAC. As a standalone medication, NAC is widely used in respiratory tract infections for its mucolytic activity.^[1]

Thiamphenicol glycinate acetylcysteine

Chemical structures of thiamphenicol glycinate (top) and acetylcysteine (bottom)
Combination of
Thiamphenicol glycinate	Antibiotic
Acetylcysteine	Mucoactive agent
Identifiers
CAS Number	20192-91-0
PubChem CID	44147002
UNII	7I3XBP3IFP
CompTox Dashboard (EPA)	DTXSID10942260
ECHA InfoCard	100.039.597
Chemical and physical data
Formula	C19H27Cl2N3O9S2
Molar mass	576.46 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(=O)NC(CS)C(=O)O.CS(=O)(=O)C1=CC=C(C=C1)C(C(COC(=O)CN)NC(=O)C(Cl)Cl)O

Medical uses

A vial of Thiamphenicol glycinate acetylcysteine produced in Italy

Thiamphenicol glycinate acetylcysteine (TGA) effectively treats upper respiratory tract infections, including otitis media, pharyngotonsillitis, and rhinosinusitis. It is also used to treat exacerbations of chronic obstructive pulmonary disease (COPD) and chronic bronchitis with bronchiectasis.^[1][2]

TGA is effective in eradicating biofilms in otolaryngologic infections,^[2] as biofilms are often resistant to treatment with antibiotics.^[3] Biofilms are complex communities of bacteria that can adhere to surfaces and are known to be highly resistant to antibiotic treatment and immune responses,^[4][5] so the ability of TGA to effectively eradicate biofilms represents an advantage over traditional antibiotics.^[2]

Mechanism of action

TGA works by releasing thiamphenicol glycinate ester (TAFGE) and N-acetylcysteine (NAC) upon contact with tissue esterases.^[1] Esterases are enzymes that break down esters into an acid and an alcohol in a chemical reaction with water called hydrolysis.^[6] Such reaction is needed to split TGA into its active components. TAFGE is an antibiotic, while NAC has mucolytic properties.^[1]

Thiamphenicol and TAFGE are related compounds, but they have different forms and uses: thiamphenicol is an antibiotic that is the methyl-and-sulfonyl analogue of chloramphenicol; it has a similar spectrum of activity to chloramphenicol but is 2.5 to 5 times as potent;^[7] it is used in many countries as a veterinary antibiotic, but is also used in some countries such as Brazil, China, Italy, Moldova and Morocco for use in humans. On the other hand, TAFGE is a form of thiamphenicol that is used in parenteral^[8] and aerosol dosage forms. After administration, TAFGE is rapidly hydrolysed by tissue esterases, releasing thiamphenicol. Its antibacterial activity is due to thiamphenicol.^[9]

Routes of Administration

TGA can be administered intramuscularly or by aerosol.^[1] It can be used by a sprayer or via a nebulizer.^[10][1]

Brand name

TGA is sold under various brand names, including "Fluimucil Antibiotic IT".

References

1. Serra A, Schito GC, Nicoletti G, Fadda G (2007). "A therapeutic approach in the treatment of infections of the upper airways: thiamphenicol glycinate acetylcysteinate in sequential treatment (systemic-inhalatory route)". International Journal of Immunopathology and Pharmacology. 20 (3): 607–617. doi:10.1177/039463200702000319. PMID 17880774.
2. Smith A, Buchinsky FJ, Post JC (March 2011). "Eradicating chronic ear, nose, and throat infections: a systematically conducted literature review of advances in biofilm treatment". Otolaryngology–Head and Neck Surgery. 144 (3): 338–347. doi:10.1177/0194599810391620. PMID 21493193.
3. Hawas S, Verderosa AD, Totsika M (2022). "Combination Therapies for Biofilm Inhibition and Eradication: A Comparative Review of Laboratory and Preclinical Studies". Frontiers in Cellular and Infection Microbiology. 12: 850030. doi:10.3389/fcimb.2022.850030. PMC 8915430. PMID 35281447.
4. Nazzari E, Torretta S, Pignataro L, Marchisio P, Esposito S (March 2015). "Role of biofilm in children with recurrent upper respiratory tract infections". European Journal of Clinical Microbiology & Infectious Diseases. 34 (3): 421–429. doi:10.1007/s10096-014-2261-1. PMID 25318897.
5. Wu H, Moser C, Wang HZ, Høiby N, Song ZJ (March 2015). "Strategies for combating bacterial biofilm infections". International Journal of Oral Science. 7 (1): 1–7. doi:10.1038/ijos.2014.65. PMC 4817533. PMID 25504208.
6. Firth J, Conlon C, Cox T, eds. (2020). Oxford Textbook of Medicine. Oxford University Press. doi:10.1093/med/9780198746690.001.0001. ISBN 9780191809019.
7. Fisch A, Bryskier A (2005). "Chapter 33 : Phenicols". In Bryskier A (ed.). Antimicrobial Agents. American Society for Microbiology. pp. 925–929. doi:10.1128/9781555815929.ch33. ISBN 978-1-68367-191-6.
8. Francis PG (1997). "Thiamphenicol". Residues of some veterinary drugs in animals and foods. FAO Food and Nutrition Paper (41/9). Rome: Food and Agriculture Organization (FAO), World Health Organization (WHO). ISBN 92-5-103972-0. Archived from the original on May 11, 2006. Retrieved August 21, 2024.
9. Fuchs FD (2004). "Tetraciclinas e cloranfenicol". In Fuchs FD, Wannmacher L, Ferreira MB (eds.). Farmacologia clínica: fundamentos da terapêutica racional (in Portuguese) (3rd ed.). Rio de Janeiro: Guanabara Koogan. pp. 375. ISBN 0-7216-5944-6.
10. Macchi A, Castelnuovo P (2009). "Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery". International Journal of Immunopathology and Pharmacology. 22 (2): 303–310. doi:10.1177/039463200902200207. PMID 19505384.