Details of the Drug Combination

General Information of Drug Combination (ID: DCNQ18C)

• Drug Combination Name: Levofloxacin + Cloxacillin
• Indication: Staphylococcus; Status: Phase 3 [1]
• Component Drugs:
  Levofloxacin (DMS60RB): Small molecular drug
  Cloxacillin (DMUTL7O): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levofloxacin

Disease Entry	ICD 11	Status	REF
Acute maxillary sinusitis	N.A.	Approved	[2]
Anthrax	1B97	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Latent tuberculosis infection	N.A.	Approved	[2]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[2]
Pyelonephritis	N.A.	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]
Streptococcal pneumonia	N.A.	Approved	[2]
Pneumonia caused by chlamydia	N.A.	Investigative	[2]

Levofloxacin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial DNA gyrase (Bact gyrase)	TTN6J5F	GYRA_STAAU; GYRB_STAAU	Modulator	[6]
Staphylococcus Topoisomerase IV (Stap-coc parC)	TTIXTO3	PARC_STAAS	Modulator	[6]

Levofloxacin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[8]

Levofloxacin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[9]

Levofloxacin Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[10]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[10]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Decreases Expression	[10]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[11]

Indication(s) of Cloxacillin

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[4]
Staphylococcal pneumonia	N.A.	Approved	[5]
Staphylococcus aureus infection	N.A.	Approved	[5]
Sinusitis	CA0A.Z	Investigative	[5]

Cloxacillin 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	[12]

Cloxacillin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[13]

References

• [1] ClinicalTrials.gov (NCT01875263) Efficacy of a Short-term Sequential Therapy in Non-complicated Catheter Related Bacteremia by Methicillin- Susceptible S.Aureus.
• [2] Levofloxacin FDA Label
• [3] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [4] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 061454.
• [5] Cloxacillin FDA Label
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] 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.
• [8] Identification of influx transporter for the quinolone antibacterial agent levofloxacin. Mol Pharm. 2007 Jan-Feb;4(1):85-94.
• [9] 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.
• [10] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [11] TNF enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy. Toxicol Lett. 2021 May 15;342:73-84. doi: 10.1016/j.toxlet.2021.02.009. Epub 2021 Feb 17.
• [12] Development of a receptor-based microplate assay for the detection of beta-lactam antibiotics in different food matrices. Anal Chim Acta. 2007 Mar 14;586(1-2):296-303.
• [13] Potential cholestatic activity of various therapeutic agents assessed by bile canalicular membrane vesicles isolated from rats and humans. Drug Metab Pharmacokinet. 2003;18(1):16-22.