Details of the Drug Combination

General Information of Drug Combination (ID: DCZ8GI2)

• Drug Combination Name: Cefotaxime + Azithromycin
• Indication: Cirrhosis; Status: Phase 4 [1]
• Component Drugs:
  Cefotaxime (DMEB837): N.A.
  Azithromycin (DMS6UOE): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cefotaxime

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[2]
Bacterial arthritis	N.A.	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Escherichia coli meningitis	N.A.	Approved	[2]
Meningococcal meningitis	N.A.	Approved	[2]
Neonatal sepsis	N.A.	Approved	[2]
Peritonitis	N.A.	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]

Cefotaxime Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial DD-carboxypeptidase (Bact vanYB)	TTLP6GN	VANY_ENTFA	Inhibitor	[7]

Cefotaxime Interacts with 19 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEAYSTX	C0W968_9FIRM	Metabolism	[8]
Beta-lactamase (blaB)	DEITMS0	Q9XBM2_ACIFE	Metabolism	[9]
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[10]
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Metabolism	[11], [12]
Beta-lactamase (blaB)	DE7IH52	AMPC_CITFR	Metabolism	[13], [14]
Ampc beta-lactamase (ampC)	DE0TCN3	B4EPS2_BURCJ	Metabolism	[15]
Beta-lactamase (blaB)	DE5HV8P	A0A4Q5I6I2_9BACE	Metabolism	[16]
Beta-lactamase (blaB)	DE47ARF	B5WXV2_9BACT	Metabolism	[16]
Beta-lactamase (blaB)	DEHJVX4	A0A414C8Y0_9BACT	Metabolism	[16]
Beta-lactamase (blaB)	DEG2PK9	B5WXV3_BACOV	Metabolism	[16]
Beta-lactamase (blaB)	DEWHJ7A	B5WXV7_BACT4	Metabolism	[16], [17]
Beta-lactamase (blaB)	DEU1RXB	BLAC_BACVU	Metabolism	[16]
Beta-lactamase (blaB)	DEMIUB2	BLAT_ECOLX	Metabolism	[12]
Beta-lactamase (blaB)	DEYIEO5	AMPC_SERMA	Metabolism	[18]
Beta-lactamase (blaB)	DEVHXAU	BLC2_SALTM	Metabolism	[17]
Beta-lactamase (blaB)	DEZLFV5	B8R6A5_9BURK	Metabolism	[15]
PenA beta-lactamase (penA1)	DE2ARDZ	O08350_BURCE	Metabolism	[19]
Beta-lactamase (blaB)	DE5AHG6	BLAC_CITKO	Metabolism	[20]
Beta-lactamase (blaB)	DEKGVS4	PENA_BURM1	Metabolism	[21]

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]

References

• [1] ClinicalTrials.gov (NCT01820026) Empirical vs 2nd Line Antibiotic Therapy in Health-care Associated Infections in Cirrhosis
• [2] Cefotaxime FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 064200.
• [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] Extended-spectrum cephalosporinases: structure, detection and epidemiology. Future Microbiol. 2007 Jun;2:297-307.
• [8] ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages. Environ Microbiol. 2018 Jun;20(6):2288-2300.
• [9] ACI-1 from Acidaminococcus fermentans: characterization of the first beta-lactamase in Anaerobic cocci. Antimicrob Agents Chemother. 2000 Nov;44(11):3144-9.
• [10] 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.
• [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] Oral streptococcal strains isolated from odontogenic infections and their susceptibility to antibiotics. Rev Med Chir Soc Med Nat Iasi. 2006 Oct-Dec;110(4):1012-5.
• [13] Citrobacter freundii bacteremia: Risk factors of mortality and prevalence of resistance genes. J Microbiol Immunol Infect. 2018 Aug;51(4):565-572.
• [14] Analyses of a ceftazidime-avibactam-resistant Citrobacter freundii isolate carrying blaKPC-2 reveals a heterogenous population and reversible genotype. mSphere. 2018 Sep 26;3(5). pii: e00408-18.
• [15] Cell wall recycling-linked coregulation of AmpC and PenB beta-lactamases through ampD mutations in Burkholderia cenocepacia. Antimicrob Agents Chemother. 2015 Dec;59(12):7602-10.
• [16] Presence of the cfxA gene in Bacteroides distasonis. Res Microbiol. 2003 Jun;154(5):369-74.
• [17] Cephalosporinases associated with outer membrane vesicles released by Bacteroides spp. protect gut pathogens and commensals against beta-lactam antibiotics. J Antimicrob Chemother. 2015 Mar;70(3):701-9.
• [18] 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.
• [19] Characterization of the penA and penR genes of Burkholderia cepacia 249 which encode the chromosomal class A penicillinase and its LysR-type transcriptional regulator. Antimicrob Agents Chemother. 1997 Nov;41(11):2399-405.
• [20] Novel TEM-type extended-spectrum beta-lactamase, TEM-134, in a Citrobacter koseri clinical isolate. Antimicrob Agents Chemother. 2005 Apr;49(4):1564-6.
• [21] Overcoming an extremely drug resistant (XDR) pathogen: avibactam restores susceptibility to ceftazidime for Burkholderia cepacia complex isolates from cystic fibrosis patients. ACS Infect Dis. 2017 Jul 14;3(7):502-511.