Details of the Drug Combination

General Information of Drug Combination (ID: DCKU834)

• Drug Combination Name: Vancomycin + Aztreonam
• Indication: Complicated Skin and Soft Tissue Infection; Status: Phase 3 [1]
• Component Drugs:
  Vancomycin (DM3JFIH): N.A.
  Aztreonam (DMDNJHG): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vancomycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[2]
Bacterial endocarditis	N.A.	Approved	[2]
Clostridioides difficile infection	1A04	Approved	[2]
Methicillin-resistant staphylococci infection	1A00-1A09	Approved	[3]
Neonatal sepsis	N.A.	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]
MRSA infection	1D01.0Y	Investigative	[4]
Skin infection	1F28-1G0Z	Investigative	[2]

Vancomycin Interacts with 14 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
VanA ligase (vanA)	DEOFMQ7	Q0WYK7_ENTFL	Metabolism	[7]
VanA ligase (vanA)	DEO97D6	VANA_ENTFC	Metabolism	[7]
VanB ligase (vanB)	DE27YVU	Q58F99_ENTFC	Metabolism	[7]
VanC2 ligase (vanC)	DEIF4P9	VANC_ENTGA	Metabolism	[8]
VanG ligase (vanG)	DEPH3S7	A0A076ZC24_STRAP	Metabolism	[9]
VanA ligase (vanA)	DEO8E75	A0A437UFE2_ENTAV	Metabolism	[7]
VanB ligase (vanB)	DER7KFQ	VANB_ENTFA	Metabolism	[7]
VanC2 ligase (vanC)	DEH73ZC	Q47720_ENTCA	Metabolism	[10]
D-alanylalanine synthetase (ddl)	DE035GU	A0A1Q6S944_9FIRM	Metabolism	[9]
VanG ligase (vanG)	DEPN8F9	A0A076YRI6_STRAG	Metabolism	[9]
VanB ligase (vanB)	DEMDEJ8	Q58F99_ENTFC	Metabolism	[11]
VanB ligase (vanB)	DE2GMEK	Q58F99_ENTFC	Metabolism	[11]
VanA ligase (vanA)	DEN6VO0	A0A376GZ73_ENTGA	Metabolism	[12]
VanA ligase (vanA)	DESOXHP	A0A4U9YK96_ENTCA	Metabolism	[13], [12]

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	[14]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[15]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)	OT17HGXJ	DMB_HUMAN	Affects Expression	[14]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[14]

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	[16]

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	[17]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[17]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[17]
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[18]
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Metabolism	[19]

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	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Complicated Skin and Soft Tissue Infection	DCSGHS2	N. A.	Phase 1	[20]

References

• [1] ClinicalTrials.gov (NCT02202135) Evaluation of Ceftaroline Fosamil vs Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections.
• [2] Vancomycin FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [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] Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob Agents Chemother. 1993 Aug;37(8):1563-71.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] vanI: a novel D-Ala-D-Lac vancomycin resistance gene cluster found in Desulfitobacterium hafniense. Microb Biotechnol. 2014 Sep;7(5):456-66.
• [12] Emergence of high-level resistance to glycopeptides in Enterococcus gallinarum and Enterococcus casseliflavus. Antimicrob Agents Chemother. 1994 Jul;38(7):1675-7.
• [13] vanA in Enterococcus faecium, Enterococcus faecalis, and Enterococcus casseliflavus detected in French cattle. Foodborne Pathog Dis. 2009 Nov;6(9):1107-11.
• [14] 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.
• [15] [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy]. Nihon Jinzo Gakkai Shi. 2003;45(1):37-41.
• [16] 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.
• [17] Aztreonam decreases hepatic microsomal cytochrome P450 in cynomolgus monkeys. Pharmacology. 1994 Mar;48(3):137-42.
• [18] 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.
• [19] 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.
• [20] ClinicalTrials.gov (NCT01499277) Evaluation of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections