Drug Information

Drug (ID: DG00055) and It's Reported Resistant Information

Name	Rifaximin
Synonyms	RCIFAX; Rifaximin (bioadhesive/ gastrointestinal extended release); Rifaximin (bioadhesive/ gastrointestinal extended release), Salix Pharmaceuticals Click to Show/Hide
Indication	In total 1 Indication(s) Bacterial infection [ICD-11: 1A00-1C4Z] Approved [1], [2], [3]
Structure
Drug Resistance Disease(s)	Disease(s) with Clinically Reported Resistance for This Drug (1 diseases) Mycobacterial diseases [ICD-11: 1B2Z ] [1], [2], [3] *Disease(s) with Resistance Information Validated by in-vivo* Model for This Drug** (1 diseases) Clostridioides difficile intestinal infection [ICD-11: 1A04] [4]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	C43H51N3O11
IsoSMILES	C[C@H]1/C=C/C=C(\\C(=O)NC2=C(C3=C(C4=C(C(=C3O)C)O[C@@](C4=O)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)C5=C2N6C=CC(=CC6=N5)C)O)/C
InChI	1S/C43H51N3O11/c1-19-14-16-46-28(18-19)44-32-29-30-37(50)25(7)40-31(29)41(52)43(9,57-40)55-17-15-27(54-10)22(4)39(56-26(8)47)24(6)36(49)23(5)35(48)20(2)12-11-13-21(3)42(53)45-33(34(32)46)38(30)51/h11-18,20,22-24,27,35-36,39,48-51H,1-10H3,(H,45,53)/b12-11+,17-15+,21-13-/t20-,22+,23+,24+,27-,35-,36+,39+,43-/m0/s1
InChIKey	NZCRJKRKKOLAOJ-XRCRFVBUSA-N
PubChem CID	6436173
ChEBI ID	CHEBI:75246
TTD Drug ID	D04ITO
VARIDT ID	DR00073
DrugBank ID	DB01220

Type(s) of Resistant Mechanism of This Drug

ADTT: Aberration of the Drug's Therapeutic Target

DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Click to Show/Hide the Resistance Disease of This Class

Clostridioides difficile intestinal infection [ICD-11: 1A04]

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)		Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB)			[4]
Molecule Alteration	Mutation	p.R505K	Molecule Info
Resistant Disease	Clostridium difficile infection [ICD-11: 1A04.0]		Disease Info
Experimental Note	Discovered Using In-vivo Testing Model
Mechanism Description	RIFs (rifampicin and rifaximin) have recently been used as another option for CDI treatment. Nevertheless, the resistance to RIFs in C. difficile has been reported. These drugs target on a DNA-dependent RNA polymerase (RNAP), resulting in the extension of short transcript blockage. Point mutations within the rpoB gene encoding for beta-subunit of RNAP cause resistance to RIFs. Among identified amino acid substitutions, the R505K substitution has been mostly evident to promote the high level of resistance.

Mycobacterial diseases [ICD-11: 1B2Z ]

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)		Click to Show/Hide
Key Molecule: Ribonuclease PH (RPH)			[1], [2], [3]
Molecule Alteration	Expression	Up-regulation	Molecule Info
Resistant Disease	MycoBacterial infection [ICD-11: 1B2Z.1]		Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Escherichia coli TOP10		83333
	Bacillus cereus RPH-Bc		1396
	Escherichia coli Rosetta(DE3) pLysS		866768
	L. monocytogenes		1639
Experiment for Molecule Alteration	Whole genome sequence assay
Experiment for Drug Resistance	MIC assay
Mechanism Description	RIF phosphotransferase (rph) led to the identification of a new resistance gene and associated enzyme responsible for inactivating rifamycin antibiotics by phosphorylation.

References

Ref 1	A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria. Proc Natl Acad Sci U S A. 2014 May 13;111(19):7102-7. doi: 10.1073/pnas.1402358111. Epub 2014 Apr 28.
Ref 2	Rifampin phosphotransferase is an unusual antibiotic resistance kinase. Nat Commun. 2016 Apr 22;7:11343. doi: 10.1038/ncomms11343.
Ref 3	Phosphorylative inactivation of rifampicin by Nocardia otitidiscaviarum. J Antimicrob Chemother. 1994 Jun;33(6):1127-35. doi: 10.1093/jac/33.6.1127.
Ref 4	Insights into drug resistance mechanisms in Clostridium difficile .Essays Biochem. 2017 Mar 3;61(1):81-88. doi: 10.1042/EBC20160062. Print 2017 Feb 28. 10.1042/EBC20160062