Details of the Drug Combination

General Information of Drug Combination (ID: DCIWS8I)

• Drug Combination Name: Ceftriaxone + Azithromycin
• Indication: Community-Acquired Pneumonia (CAP); Status: Phase 4 [1]
• Component Drugs:
  Ceftriaxone (DMCEW64): Small molecular drug
  Azithromycin (DMS6UOE): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ceftriaxone

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[2]
Bacteremia	1A73	Approved	[2]
Bacterial arthritis	N.A.	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Chancroid	N.A.	Approved	[2]
Endometritis	N.A.	Approved	[2]
Escherichia coli meningitis	N.A.	Approved	[2]
Gonococcal infection of joint	N.A.	Approved	[2]
Meningococcal meningitis	N.A.	Approved	[2]
Pneumococcal meningitis	N.A.	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]
Pelvic inflammatory disease	GA05	Investigative	[2]

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	[7]

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	[8]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[10]

Ceftriaxone Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Metabolism	[11]
Beta-lactamase (blaB)	DEYIEO5	AMPC_SERMA	Metabolism	[12]
Beta-lactamase (blaB)	DEBKS91	A0A1B1FBM9_ACIBA	Metabolism	[13]

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	[14]

Indication(s) of Azithromycin

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[4]
Bronchitis	CA20	Approved	[5]
Chancroid	N.A.	Approved	[4]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[4]
Staphylococcus aureus infection	N.A.	Approved	[4]
Streptococcal pneumonia	N.A.	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Pneumonia caused by chlamydia	N.A.	Investigative	[4]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Uncomplicated Urogenital Gonorrhea	DCO5GSI	N. A.	Phase 3	[15]
Chlamydia	DC54EZM	N. A.	Phase 1	[16]

References

• [1] ClinicalTrials.gov (NCT00035347) Intravenous Azithromycin Plus Intravenous Ceftriaxone Followed by Oral Azithromycin With Intravenous Levofloxacin Followed by Oral Levofloxacin for the Treatment of Moderate to Severely Ill Hospitalized Patients With Community Acquired Pneumonia
• [2] Ceftriaxone 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: 5326).
• [4] Azithromycin FDA Label
• [5] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 065511.
• [6] ClinicalTrials.gov (NCT04332107) Azithromycin for COVID-19 Treatment in Outpatients Nationwide. U.S. National Institutes of Health.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] 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.
• [9] 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.
• [10] Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes. Biol Pharm Bull. 2011;34(3):389-95.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] ClinicalTrials.gov (NCT02210325) Efficacy and Safety Study of Oral Solithromycin Compared to Intramuscular Ceftriaxone Plus Oral Azithromycin in the Treatment of Patients With Gonorrhea
• [16] ClinicalTrials.gov (NCT01150747) Chlamydia Trachomatis Immunology and Vaccinology Study