Drug Information

Drug (ID: DG00328) and It's Reported Resistant Information

• Name: Ceftolozane sulfate
• Synonyms: Ceftolozane; CXA-101; CXA-301; CXA-301); Cephalosporin derivatives, Astellas; Cephalosporinderivatives, Calixa Therapeutics; FR-193879; FR-264205; FR-295389; CXA-101 (inhaled), Calixa; CXA-101 (inhaled), Cubist; Cephalosporin derivative (H pylori/P aeruginosa infection), Astellas; CXA-101 (inhaled, bacterial lung infection), Cubist
• Indication:
  In total 1 Indication(s)
  Respiratory infection [ICD-11: CA07-CA4Z]; Phase 4; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Malaria [ICD-11: 1F45]; [1]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C23H32N12O12S3
• IsoSMILES: CC(C)(C(=O)O)O/N=C(\\C1=NSC(=N1)N)/C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C[N+]4=CC(=C(N4C)N)NC(=O)NCCN)C(=O)O.OS(=O)(=O)[O-]
• InChI: 1S/C23H30N12O8S2.H2O4S/c1-23(2,20(40)41)43-31-11(15-30-21(26)45-32-15)16(36)29-12-17(37)35-13(19(38)39)9(8-44-18(12)35)6-34-7-10(14(25)33(34)3)28-22(42)27-5-4-24;1-5(2,3)4/h7,12,18,25H,4-6,8,24H2,1-3H3,(H7,26,27,28,29,30,32,36,38,39,40,41,42);(H2,1,2,3,4)/b31-11+;/t12-,18-;/m1./s1
• InChIKey: UJDQGRLTPBVSFN-GZGOMJRCSA-N
• PubChem CID: 11592969
• TTD Drug ID: D03IUD
• DrugBank ID: DB09050

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [2]

• Molecule Alteration: Missense mutation; p.Y221H
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Escherichia coli EC13; 562
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: The CMY-136 Beta-lactamase, a Y221H point mutant derivative of CMY-2,confers an increased level of resistance to ticarcillin, cefuroxime, cefotaxime, and ceftolozane/tazobactam.

Malaria [ICD-11: 1F45]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: CAM-1 carbapenemase (CAM1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Pseudomonas infection [ICD-11: 1F45.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Pseudomonas aeruginosa N17-01167; 287
• In Vitro Model: Pseudomonas aeruginosa N17-01173; 287
• In Vitro Model: Pseudomonas aeruginosa N17-02436; 287
• In Vitro Model: Pseudomonas aeruginosa N17-02437; 287
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Experiment for Drug Resistance: Vitek 2 assay; Etest assay
• Mechanism Description: A novel class B Beta-lactamase gene, blaCAM-1, exhibited resistance to imipenem, meropenem, doripenem, cefotaxime, ceftazidime, cefoxitin, piperacillin/tazobactam, ceftazidime/avibactam and ceftolozane/tazobactam.

References

• Ref 1: Identification of a novel metallo-Beta-lactamase, CAM-1, in clinical Pseudomonas aeruginosa isolates from Canada. J Antimicrob Chemother. 2019 Jun 1;74(6):1563-1567. doi: 10.1093/jac/dkz066.
• Ref 2: Genetic, Biochemical, and Structural Characterization of CMY-136 Beta-Lactamase, a Peculiar CMY-2 Variant. ACS Infect Dis. 2019 Apr 12;5(4):528-538. doi: 10.1021/acsinfecdis.8b00240. Epub 2019 Mar 7.