Details of the Drug Combination

General Information of Drug Combination (ID: DC7N7ZR)

• Drug Combination Name: Cephalexin + Cefazolin
• Indication: Surgical Site Infection; Status: Phase 4 [1]
• Component Drugs:
  Cephalexin (DMD5JU8): Small molecular drug
  Cefazolin (DMPDYFR): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cephalexin

Disease Entry	ICD 11	Status	REF
Acute otitis media	AB00	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Prostatitis	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]

Cephalexin 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]

Cephalexin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[7]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[8]
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[9]

Cephalexin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[11]
N-acylhomoserine lactone acylase (lacA)	DEIU0XN	A0A0A1VBK6_9BURK	Metabolism	[12]

Cephalexin 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]

Indication(s) of Cefazolin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[4]
Bacterial infection	1A00-1C4Z	Approved	[5]
Cholangitis	N.A.	Approved	[4]
Staphylococcal pneumonia	N.A.	Approved	[4]

Cefazolin 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	[14]

Cefazolin Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[15]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[16]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[17]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[18]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[18]

Cefazolin Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[19]
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[20]
Beta-lactamase (blaB)	DE7IH52	AMPC_CITFR	Metabolism	[21]
Beta-lactamase (blaB)	DENJ2SQ	BLAB_BACFG	Metabolism	[22]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Fractures, Open	DCDBRLB	N. A.	Phase 4	[23]

References

• [1] ClinicalTrials.gov (NCT04834310) Postoperative Antibiotics Following Primary and Secondary Breast Augmentation
• [2] Cephalexin FDA Label
• [3] 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: 4832).
• [4] Cefazolin FDA Label
• [5] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 065244.
• [6] Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics. J Med Microbiol. 2004 Mar;53(Pt 3):213-21.
• [7] Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
• [8] Direct evidence for efficient transport and minimal metabolism of L-cephalexin by oligopeptide transporter 1 in budded baculovirus fraction. Biol Pharm Bull. 2009 Aug;32(8):1459-61.
• [9] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [10] Transport and metabolic characterization of Caco-2 cells expressing CYP3A4 and CYP3A4 plus oxidoreductase. Pharm Res. 1999 Sep;16(9):1352-9.
• [11] Population pharmacokinetic analysis of mirtazapine. Eur J Clin Pharmacol. 2004 Sep;60(7):473-80.
• [12] A novel quorum-quenching N-acylhomoserine lactone acylase from Acidovorax sp. strain MR-S7 mediates antibiotic resistance. Appl Environ Microbiol. 2017 Jun 16;83(13). pii: e00080-17.
• [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.
• [14] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [15] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [16] Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012 Mar;40(3):515-21.
• [17] Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
• [18] Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004 Jan;21(1):61-7.
• [19] Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationship to hypoprothrombinemia. Drug Metab Dispos. 2002 Oct;30(10):1123-8.
• [20] 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.
• [21] Citrobacter freundii bacteremia: Risk factors of mortality and prevalence of resistance genes. J Microbiol Immunol Infect. 2018 Aug;51(4):565-572.
• [22] 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.
• [23] ClinicalTrials.gov (NCT06055712) Antibiotic Prophylaxis in Pediatric Open Fractures