Details of the Drug Combination

General Information of Drug Combination (ID: DCL12QF)

• Drug Combination Name: Meropenem + Tigecycline
• Indication: Bloodstream Infections (BSI) Due to CRE; Status: Phase 3 [1]
• Component Drugs:
  Meropenem (DM62UHC): Small molecular drug
  Tigecycline (DMLE7IO): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Meropenem

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Meningococcal meningitis	N.A.	Approved	[3]
Peritonitis	N.A.	Approved	[3]
Pneumococcal meningitis	N.A.	Approved	[3]
Pseudomonas aeruginosa infectious disease	N.A.	Approved	[3]

Meropenem Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Modulator	[5]

Meropenem Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[6]

Meropenem Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEC3G7M	A0A1S7IV31_ENTAS	Metabolism	[7]
Beta-lactamase (blaB)	DENJ2SQ	BLAB_BACFG	Metabolism	[8]
Beta-lactamase (blaB)	DEBKS91	A0A1B1FBM9_ACIBA	Metabolism	[9]
Beta-lactamase (blaB)	DECWSA9	AMPC_MORMO	Metabolism	[10]
Carbapenemase (cphA)	DEB90AL	BLAB_AERHY	Metabolism	[11]
New delhi metallo-beta-lactamase NDM-1 (blaNDM)	DEBGCYQ	A0A345N7K5_SALET	Metabolism	[12]

Meropenem Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class II histocompatibility antigen, DO beta chain (HLA-DOB)	OTKADDUB	DOB_HUMAN	Affects Expression	[13]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[13]

Indication(s) of Tigecycline

Disease Entry	ICD 11	Status	REF
Skin infection	1F28-1G0Z	Approved	[4]

Tigecycline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[4]

References

• [1] ClinicalTrials.gov (NCT01970371) A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE). U.S. National Institutes of Health.
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Meropenem FDA Label
• [4] Tigecycline: first of a new class of antimicrobial agents. Pharmacotherapy. 2006 Aug;26(8):1099-110.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Characterization of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, and meropenem as substrates of human renal transporters. Drug Metab Pharmacokinet. 2007 Feb 25;22(1):41-7.
• [7] FRI-4 carbapenemase-producing Enterobacter cloacae complex isolated in Tokyo, Japan. J Antimicrob Chemother. 2018 Nov 1;73(11):2969-2972.
• [8] Prevalence of antimicrobial resistance genes in Bacteroides spp. and Prevotella spp. Dutch clinical isolates. Clin Microbiol Infect. 2019 Sep;25(9):1156.e9-1156.e13.
• [9] A high mortality rate associated with multidrug-resistant Acinetobacter baumannii ST79 and ST25 carrying OXA-23 in a Brazilian intensive care unit. PLoS One. 2018 Dec 28;13(12):e0209367.
• [10] Molecular investigation of extended-spectrum beta-lactamase genes and potential drug resistance in clinical isolates of Morganella morganii. Ann Saudi Med. 2016 May-Jun;36(3):223-8.
• [11] A carbapenem-resistant clinical isolate of Aeromonas hydrophila in Japan harbouring an acquired gene encoding GES-24 beta-lactamase. J Med Microbiol. 2018 Nov;67(11):1535-1537.
• [12] Genomic characterization of an extensively-drug resistance Salmonella enterica serotype Indiana strain harboring bla NDM-1 gene isolated from a chicken carcass in China. Microbiol Res. 2017 Nov;204:48-54.
• [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.