Details of the Drug Combination

General Information of Drug Combination (ID: DC7155H)

• Drug Combination Name: Linezolid + Aztreonam
• Indication: Bacterial Infection; Status: Phase 1 [1]
• Component Drugs:
  Linezolid (DMGFPU2): Small molecular drug
  Aztreonam (DMDNJHG): Small molecular drug

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	[7]

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	[8]
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Decreases Activity	[8]

Indication(s) of Aztreonam

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[5]
Endometritis	N.A.	Approved	[6]
Peritonitis	N.A.	Approved	[6]
Pseudomonas aeruginosa infectious disease	N.A.	Approved	[6]
Urinary tract infection	GC08	Approved	[6]
Pelvic inflammatory disease	GA05	Investigative	[6]

Aztreonam Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein 3 (Bact mrcA)	TT85JMW	FTSI_ECOLI	Binder	[9]

Aztreonam Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[10]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[10]
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[11]
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Metabolism	[12]

Aztreonam Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[13]

References

• [1] ClinicalTrials.gov (NCT00633152) Efficacy and Safety of Ceftaroline Versus Linezolid in Subjects With Complicated Skin and Skin Structure Infections
• [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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [6] Aztreonam FDA Label
• [7] Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance. Genome Res. 2009 Jul;19(7):1214-23.
• [8] 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.
• [9] Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole. Mol Microbiol. 2003 Jan;47(2):539-47.
• [10] Aztreonam decreases hepatic microsomal cytochrome P450 in cynomolgus monkeys. Pharmacology. 1994 Mar;48(3):137-42.
• [11] Analysis of the drug-resistant characteristics of Klebsiella pneumoniae isolated from the respiratory tract and CTX-M ESBL genes. Genet Mol Res. 2015 Oct 5;14(4):12043-8.
• [12] Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe. J Antimicrob Chemother. 1996 Sep;38(3):409-24.
• [13] 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.