Details of the Drug Combination

General Information of Drug Combination (ID: DCKBV2P)

• Drug Combination Name: Azithromycin + Tobramycin
• Indication: Cystic Fibrosis; Status: Phase 4 [1]
• Component Drugs:
  Azithromycin (DMS6UOE): Small molecular drug
  Tobramycin (DMUI0CH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Azithromycin

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[2]
Bronchitis	CA20	Approved	[3]
Chancroid	N.A.	Approved	[2]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]
Streptococcal pneumonia	N.A.	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
Pneumonia caused by chlamydia	N.A.	Investigative	[2]

Indication(s) of Tobramycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[5]
Bacterial infection	1A00-1C4Z	Approved	[6]
Blepharoconjunctivitis	N.A.	Approved	[5]
Corneal abrasion	NA06.4	Approved	[5]
Dacryocystitis	N.A.	Approved	[5]
Demodex blepharitis	1G07	Approved	[5]
Neonatal sepsis	N.A.	Approved	[5]
Peritonitis	N.A.	Approved	[5]
Rosacea	ED90.0	Approved	[5]
Staphylococcal pneumonia	N.A.	Approved	[5]
Staphylococcus aureus infection	N.A.	Approved	[5]

Tobramycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 30S ribosomal RNA (Bact 30S rRNA)	TTOVFH2	NOUNIPROTAC	Modulator	[8]

Tobramycin Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[9]
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Metabolism	[10]
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Metabolism	[11]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Metabolism	[11]
Aminoglycoside N-acetyltransferase (aacC2)	DEJADS9	AAC6_ACIBA	Metabolism	[10]

Tobramycin Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[7]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[7]
Beta-2-microglobulin (B2M)	OTDWN6NX	B2MG_HUMAN	Increases Expression	[12]
Survival motor neuron protein (SMN2)	OT54RLO1	SMN_HUMAN	Increases Expression	[13]
Phospholipase A2 (PLA2G1B)	OT1GG9FK	PA21B_HUMAN	Increases ADR	[14]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1)	OT9HYT7A	PLCB1_HUMAN	Increases ADR	[14]
Lysozyme C (LYZ)	OTD7H0G6	LYSC_HUMAN	Increases ADR	[14]
L-lactate dehydrogenase A chain (LDHA)	OTN7K4XB	LDHA_HUMAN	Increases ADR	[14]
Beta-hexosaminidase (nag1)	OTQCIZOD	P87258_TRIHA	Increases ADR	[14]

References

• [1] ClinicalTrials.gov (NCT02677701) Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
• [2] Azithromycin FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 065511.
• [4] ClinicalTrials.gov (NCT04332107) Azithromycin for COVID-19 Treatment in Outpatients Nationwide. U.S. National Institutes of Health.
• [5] Tobramycin FDA Label
• [6] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [7] A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
• [8] Mechanism of action of aminoglycoside antibiotics.Binding studies of tobramycin and its 6'-N-acetyl derivative to the bacterial ribosome and its subunits.Eur J Biochem.1979 Dec;102(1):73-81.
• [9] Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6'-N-acetyltransferase Ib and IIa proteins. J Bacteriol. 1992 May;174(10):3196-203.
• [10] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
• [11] Cloning and expression of novel aminoglycoside phosphotransferase genes from Campylobacter and their role in the resistance to six aminoglycosides. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: e01682-17.
• [12] The absence of nephrotoxicity and differential nephrotoxicity between tobramycin and gentamicin. South Med J. 1990 Oct;83(10):1149-52. doi: 10.1097/00007611-199010000-00008.
• [13] Translational readthrough by the aminoglycoside geneticin (G418) modulates SMN stability in vitro and improves motor function in SMA mice in vivo. Hum Mol Genet. 2009 Apr 1;18(7):1310-22. doi: 10.1093/hmg/ddp030. Epub 2009 Jan 15.
• [14] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.