Disease Information

General Information of the Disease (ID: DIS00119)
Name
Otitis media
ICD
ICD-11: AA80
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  ADTT: Aberration of the Drug's Therapeutic Target
  DISM: Drug Inactivation by Structure Modification
  EADR: Epigenetic Alteration of DNA, RNA or Protein
Drug Resistance Data Categorized by Drug
Approved Drug(s)
4 drug(s) in total
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Cefprozil
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Penicillin-binding protein 2B (PBP2B) [1], [2], [3]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
Molecule Alteration Missense mutation
p.T445A
 Molecule Info 
Resistant Drug Cefprozil
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 Agar dilution method assay
Mechanism Description MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.The PBP2b T445-A substitution found in all PISP and PRSP and one PSSP has been found in all low-level Beta-lactam-resistant pneumococci examined.
Gentamicin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside N(3)-acetyltransferase (AACC2) [4], [5]
Resistant Disease Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Gentamicin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli ATCC 25922 1322345
Pseudomonas aeruginosa ATCC 27853 287
Pseudomonas aeruginosa isolates 287
Staphylococcus aureus ATCC 25923 1280
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Agar dilution method assay
Mechanism Description Various aminoglycoside modifying enzymes were associated with overlapping phenotypes: 36.5% strains produced AAC(6')-I with either a serine (GEN-TOB-NET) or a leucine (TOB-NET-AMk) at position 119, or both variants (GEN-TOB-NET-AMk); 21.2% expressed ANT(2")-I (GEN-TOB), 7.7% AAC(3)-II (GEN-TOB-NET), 5.8% AAC(3)-I (GEN) and 1.9% AAC(6')-II (GEN-TOB-NET-AMk) or AACA7 (TOB-NET-AMk).
Netilmicin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside N(3)-acetyltransferase (AACC2) [4], [5]
Resistant Disease Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Netilmicin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli ATCC 25922 1322345
Pseudomonas aeruginosa ATCC 27853 287
Pseudomonas aeruginosa isolates 287
Staphylococcus aureus ATCC 25923 1280
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Agar dilution method assay
Mechanism Description Various aminoglycoside modifying enzymes were associated with overlapping phenotypes: 36.5% strains produced AAC(6')-I with either a serine (GEN-TOB-NET) or a leucine (TOB-NET-AMk) at position 119, or both variants (GEN-TOB-NET-AMk); 21.2% expressed ANT(2")-I (GEN-TOB), 7.7% AAC(3)-II (GEN-TOB-NET), 5.8% AAC(3)-I (GEN) and 1.9% AAC(6')-II (GEN-TOB-NET-AMk) or AACA7 (TOB-NET-AMk).
Tobramycin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside N(3)-acetyltransferase (AACC2) [4], [5]
Resistant Disease Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Tobramycin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli ATCC 25922 1322345
Pseudomonas aeruginosa ATCC 27853 287
Pseudomonas aeruginosa isolates 287
Staphylococcus aureus ATCC 25923 1280
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Agar dilution method assay
Mechanism Description Various aminoglycoside modifying enzymes were associated with overlapping phenotypes: 36.5% strains produced AAC(6')-I with either a serine (GEN-TOB-NET) or a leucine (TOB-NET-AMk) at position 119, or both variants (GEN-TOB-NET-AMk); 21.2% expressed ANT(2")-I (GEN-TOB), 7.7% AAC(3)-II (GEN-TOB-NET), 5.8% AAC(3)-I (GEN) and 1.9% AAC(6')-II (GEN-TOB-NET-AMk) or AACA7 (TOB-NET-AMk).
Investigative Drug(s)
2 drug(s) in total
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Ceragenin
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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: Interleukin-8 (IL8) [6]
Sensitive Disease Otitis media [ICD-11: AA80.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Ceragenin
 Drug Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation IL-8 pathway Regulation hsa04622
In Vitro Model Streptococcus pneumoniae ATCC 49619 1313
Experiment for
Molecule Alteration		 ELISA assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description Immobilization of ceragenins on the surface of nonspherical gold nanoparticles intensifies their antibacterial effects, against both planktonic and biofilm form of bacteria. At the same time, it reduces the secretion of IL-8 and reduces the inflammatory response.
Key Molecule: Interleukin-8 (IL8) [6]
Sensitive Disease Otitis media [ICD-11: AA80.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Ceragenin
 Drug Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation IL-8 pathway Regulation hsa04622
In Vitro Model Streptococcus pneumoniae ATCC 49619 1313
Experiment for
Molecule Alteration		 ELISA assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description Immobilization of ceragenins on the surface of nonspherical gold nanoparticles intensifies their antibacterial effects, against both planktonic and biofilm form of bacteria. At the same time, it reduces the secretion of IL-8 and reduces the inflammatory response.
Key Molecule: Interleukin-8 (IL8) [6]
Sensitive Disease Otitis media [ICD-11: AA80.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Ceragenin
 Drug Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation IL-8 pathway Regulation hsa04622
In Vitro Model Moraxella catarrhalis ATCC 25238 480
Experiment for
Molecule Alteration		 ELISA assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description Immobilization of ceragenins on the surface of nonspherical gold nanoparticles intensifies their antibacterial effects, against both planktonic and biofilm form of bacteria. At the same time, it reduces the secretion of IL-8 and reduces the inflammatory response.
Key Molecule: Interleukin-8 (IL8) [6]
Sensitive Disease Otitis media [ICD-11: AA80.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Ceragenin
 Drug Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation IL-8 pathway Regulation hsa04622
In Vitro Model Moraxella catarrhalis ATCC 25238 480
Experiment for
Molecule Alteration		 ELISA assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description Immobilization of ceragenins on the surface of nonspherical gold nanoparticles intensifies their antibacterial effects, against both planktonic and biofilm form of bacteria. At the same time, it reduces the secretion of IL-8 and reduces the inflammatory response.
Key Molecule: Interleukin-8 (IL8) [6]
Sensitive Disease Otitis media [ICD-11: AA80.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Ceragenin
 Drug Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation IL-8 pathway Regulation hsa04622
In Vitro Model Haemophilus influenzae ATCC 49766 727
Experiment for
Molecule Alteration		 ELISA assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description Immobilization of ceragenins on the surface of nonspherical gold nanoparticles intensifies their antibacterial effects, against both planktonic and biofilm form of bacteria. At the same time, it reduces the secretion of IL-8 and reduces the inflammatory response.
Key Molecule: Interleukin-8 (IL8) [6]
Sensitive Disease Otitis media [ICD-11: AA80.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Ceragenin
 Drug Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation IL-8 pathway Regulation hsa04622
In Vitro Model Haemophilus influenzae ATCC 49766 727
Experiment for
Molecule Alteration		 ELISA assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description Immobilization of ceragenins on the surface of nonspherical gold nanoparticles intensifies their antibacterial effects, against both planktonic and biofilm form of bacteria. At the same time, it reduces the secretion of IL-8 and reduces the inflammatory response.
Midecamycin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Oleandomycin glycosyltransferase oleD (OLED) [7]
Resistant Disease Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
Molecule Alteration Expression
Acquired
 Molecule Info 
Resistant Drug Midecamycin
 Drug Info 
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model Prostate cancer tissue .
Experiment for
Molecule Alteration		 SDS-PAGE analysis
Experiment for
Drug Resistance		 Broth microdilution antifungal susceptibility test assay
References
Ref 1 Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2006 Nov;50(11):3638-45. doi: 10.1128/AAC.00626-06. Epub 2006 Aug 28.
Ref 2 Resistance to Beta-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins. Antibiotics (Basel). 2016 Sep 28;5(4):35. doi: 10.3390/antibiotics5040035.
Ref 3 Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem. 2009 Jan 9;284(2):1202-12. doi: 10.1074/jbc.M805761200. Epub 2008 Nov 4.
Ref 4 Beta-lactam and aminoglycoside resistance rates and mechanisms among Pseudomonas aeruginosa in French general practice (community and private healthcare centres). J Antimicrob Chemother. 2008 Aug;62(2):316-23. doi: 10.1093/jac/dkn174. Epub 2008 May 8.
Ref 5 Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev. 1993 Mar;57(1):138-63. doi: 10.1128/mr.57.1.138-163.1993.
Ref 6 Targeting bacteria causing otitis media using nanosystems containing nonspherical gold nanoparticles and ceragenins .Nanomedicine (Lond). 2021 Dec;16(30):2657-2678. doi: 10.2217/nnm-2021-0370. Epub 2021 Nov 26. 10.2217/nnm-2021-0370
Ref 7 Midecamycin Is Inactivated by Several Different Sugar Moieties at Its Inactivation Site .Int J Mol Sci. 2021 Nov 23;22(23):12636. doi: 10.3390/ijms222312636. 10.3390/ijms222312636

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