Details of the Drug Combination

General Information of Drug Combination (ID: DC8ZPFF)

• Drug Combination Name: Ertapenem + Ceftriaxone
• Indication: Liver Abscess, Pyogenic; Status: Phase 1 [1]
• Component Drugs:
  Ertapenem (DM4S3O8): Small molecular drug
  Ceftriaxone (DMCEW64): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ertapenem

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Endometritis	N.A.	Approved	[3]
Peptostreptococcus infectious disease	N.A.	Approved	[3]
Streptococcal pneumonia	N.A.	Approved	[3]

Ertapenem Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[6]

Ertapenem Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEC3G7M	A0A1S7IV31_ENTAS	Metabolism	[7]
Beta-lactamase (blaB)	DEMIUB2	BLAT_ECOLX	Metabolism	[8]
Beta-lactamase (blaB)	DECWSA9	AMPC_MORMO	Metabolism	[8]

Indication(s) of Ceftriaxone

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[4]
Bacteremia	1A73	Approved	[4]
Bacterial arthritis	N.A.	Approved	[4]
Bacterial infection	1A00-1C4Z	Approved	[5]
Chancroid	N.A.	Approved	[4]
Endometritis	N.A.	Approved	[4]
Escherichia coli meningitis	N.A.	Approved	[4]
Gonococcal infection of joint	N.A.	Approved	[4]
Meningococcal meningitis	N.A.	Approved	[4]
Pneumococcal meningitis	N.A.	Approved	[4]
Staphylococcal pneumonia	N.A.	Approved	[4]
Pelvic inflammatory disease	GA05	Investigative	[4]

Ceftriaxone 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	[9]

Ceftriaxone Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[10]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[12]

Ceftriaxone Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Metabolism	[13]
Beta-lactamase (blaB)	DEYIEO5	AMPC_SERMA	Metabolism	[14]
Beta-lactamase (blaB)	DEBKS91	A0A1B1FBM9_ACIBA	Metabolism	[15]

Ceftriaxone Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Activity	[16]

References

• [1] ClinicalTrials.gov (NCT01723150) Antibiotics for Klebsiella Liver Abscess Study
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Ertapenem FDA Label
• [4] Ceftriaxone FDA Label
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5326).
• [6] Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: evidence for the cooperative functioning of PBP2, PBP4, and PBP2A. JBacteriol. 2005 Mar;187(5):1815-24.
• [7] FRI-4 carbapenemase-producing Enterobacter cloacae complex isolated in Tokyo, Japan. J Antimicrob Chemother. 2018 Nov 1;73(11):2969-2972.
• [8] War wound treatment complications due to transfer of an IncN plasmid harboring bla(OXA-181) from Morganella morganii to CTX-M-27-producing sequence type 131 Escherichia coli. Antimicrob Agents Chemother. 2015;59(6):3556-62.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [11] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [12] Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes. Biol Pharm Bull. 2011;34(3):389-95.
• [13] 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.
• [14] Determination of the antibiotic resistance rates of Serratia marcescens isolates obtained from various clinical specimens. Niger J Clin Pract. 2019 Jan;22(1):125-130.
• [15] Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection. Chin Med J (Engl). 2010 Sep;123(18):2571-5.
• [16] Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity. J Biochem Mol Toxicol. 2015 Mar;29(3):135-9.