Disease Information

General Information of the Disease (ID: DIS00044)
Name
Malaria
ICD
ICD-11: 1F45
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  DISM: Drug Inactivation by Structure Modification
  EADR: Epigenetic Alteration of DNA, RNA or Protein
Drug Resistance Data Categorized by Drug
Approved Drug(s)
7 drug(s) in total
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Cefotaxime
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cefotaxime
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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.
Cefoxitin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cefoxitin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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.
Ceftazidime
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Ceftazidime
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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.
Doripenem
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Doripenem
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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.
Meropenem
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Meropenem
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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.
Procainamide
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA (cytosine-5)-methyltransferase 1 (DNMT1) [2]
Sensitive Disease Malaria [ICD-11: 1F45.0]
Molecule Alteration Function
Inhibition
 Molecule Info 
Sensitive Drug Procainamide
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Mechanism Description The fusion of the histone deacetylase inhibitor SAHA and the DNMT inhibitor procainamide into a single compound, Proca-SAHA, resulted in an original family of antimalarials that is highly potent and selective for Plasmodium. Importantly, Proca-SAHA derivatives are highly active against multiple P. falciparum isolates from Cambodia, the epicenter of malaria drug-resistance, which makes them excellent drug candidates.
Imipenem
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Imipenem
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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.
Clinical Trial Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Ceftolozane sulfate
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Ceftolozane sulfate
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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.
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Piperacillin/Tazobactam
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: CAM-1 carbapenemase (CAM1) [1]
Resistant Disease Pseudomonas infection [ICD-11: 1F45.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Piperacillin/Tazobactam
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Pseudomonas aeruginosa N17-01167 287
Pseudomonas aeruginosa N17-01173 287
Pseudomonas aeruginosa N17-02436 287
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 Procainamide-SAHA Fused Inhibitors of hHDAC6 Tackle Multidrug-Resistant Malaria Parasites .J Med Chem. 2021 Jul 22;64(14):10403-10417. doi: 10.1021/acs.jmedchem.1c00821. Epub 2021 Jun 29. 10.1021/acs.jmedchem.1c00821

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