Details of the Drug Combination

General Information of Drug Combination (ID: DCL6AED)

• Drug Combination Name: Linezolid + Vancomycin
• Indication: Complicated Skin and Structure Infection; Status: Phase 1 [1]
• Component Drugs:
  Linezolid (DMGFPU2): Small molecular drug
  Vancomycin (DM3JFIH): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Linezolid

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Staphylococcal pneumonia	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]
Skin infection	1F28-1G0Z	Investigative	[2]

Linezolid Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA)	TTLFGBV	NOUNIPROTAC	Binder	[8]

Linezolid Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Amine oxidase A (MAOA)	OT8NIWMQ	AOFA_HUMAN	Decreases Activity	[9]
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Decreases Activity	[9]

Indication(s) of Vancomycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[5]
Bacterial endocarditis	N.A.	Approved	[5]
Clostridioides difficile infection	1A04	Approved	[5]
Methicillin-resistant staphylococci infection	1A00-1A09	Approved	[6]
Neonatal sepsis	N.A.	Approved	[5]
Staphylococcal pneumonia	N.A.	Approved	[5]
Staphylococcus aureus infection	N.A.	Approved	[5]
MRSA infection	1D01.0Y	Investigative	[7]
Skin infection	1F28-1G0Z	Investigative	[5]

Vancomycin Interacts with 14 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
VanA ligase (vanA)	DEOFMQ7	Q0WYK7_ENTFL	Metabolism	[10]
VanA ligase (vanA)	DEO97D6	VANA_ENTFC	Metabolism	[10]
VanB ligase (vanB)	DE27YVU	Q58F99_ENTFC	Metabolism	[10]
VanC2 ligase (vanC)	DEIF4P9	VANC_ENTGA	Metabolism	[11]
VanG ligase (vanG)	DEPH3S7	A0A076ZC24_STRAP	Metabolism	[12]
VanA ligase (vanA)	DEO8E75	A0A437UFE2_ENTAV	Metabolism	[10]
VanB ligase (vanB)	DER7KFQ	VANB_ENTFA	Metabolism	[10]
VanC2 ligase (vanC)	DEH73ZC	Q47720_ENTCA	Metabolism	[13]
D-alanylalanine synthetase (ddl)	DE035GU	A0A1Q6S944_9FIRM	Metabolism	[12]
VanG ligase (vanG)	DEPN8F9	A0A076YRI6_STRAG	Metabolism	[12]
VanB ligase (vanB)	DEMDEJ8	Q58F99_ENTFC	Metabolism	[14]
VanB ligase (vanB)	DE2GMEK	Q58F99_ENTFC	Metabolism	[14]
VanA ligase (vanA)	DEN6VO0	A0A376GZ73_ENTGA	Metabolism	[15]
VanA ligase (vanA)	DESOXHP	A0A4U9YK96_ENTCA	Metabolism	[16], [15]

Vancomycin Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[17]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[18]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)	OT17HGXJ	DMB_HUMAN	Affects Expression	[17]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[17]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hip Prosthetic Joint Infection	DCAX3EB	N. A.	Phase 2	[19]

References

• [1] ClinicalTrials.gov (NCT01363271) Cost Study of Linezolid Versus Vancomycin Among Previously Hospitalized Patients
• [2] Linezolid FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 200222.
• [4] Therapeutic and Triage Strategies for 2019 Novel Coronavirus Disease in Fever Clinics. Lancet Respir Med. 2020 Mar;8(3):e11-e12.
• [5] Vancomycin FDA Label
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [8] Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance. Genome Res. 2009 Jul;19(7):1214-23.
• [9] Nonclinical Evaluation of Antibacterial Oxazolidinones Contezolid and Contezolid Acefosamil with Low Serotonergic Neurotoxicity. Chem Res Toxicol. 2021 May 17;34(5):1348-1354. doi: 10.1021/acs.chemrestox.0c00524. Epub 2021 Apr 29.
• [10] Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob Agents Chemother. 1993 Aug;37(8):1563-71.
• [11] Sequence of the vanC gene of Enterococcus gallinarum BM4174 encoding a D-alanine:D-alanine ligase-related protein necessary for vancomycin resistance. Gene. 1992 Mar 1;112(1):53-8.
• [12] vanG element insertions within a conserved chromosomal site conferring vancomycin resistance to Streptococcus agalactiae and Streptococcus anginosus. mBio. 2014 Jul 22;5(4):e01386-14.
• [13] Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10040-4.
• [14] vanI: a novel D-Ala-D-Lac vancomycin resistance gene cluster found in Desulfitobacterium hafniense. Microb Biotechnol. 2014 Sep;7(5):456-66.
• [15] Emergence of high-level resistance to glycopeptides in Enterococcus gallinarum and Enterococcus casseliflavus. Antimicrob Agents Chemother. 1994 Jul;38(7):1675-7.
• [16] vanA in Enterococcus faecium, Enterococcus faecalis, and Enterococcus casseliflavus detected in French cattle. Foodborne Pathog Dis. 2009 Nov;6(9):1107-11.
• [17] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [18] [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy]. Nihon Jinzo Gakkai Shi. 2003;45(1):37-41.
• [19] ClinicalTrials.gov (NCT01757236) Efficacy and Safety Study of Antibiotic Treatment to Treat Hip Prosthetic Joint Infection