Drug Information

Drug (ID: DG00375) and It's Reported Resistant Information

• Name: Dibekacin
• Synonyms: Dibekacin; Panamicin; Dideoxykanamycin B; 34493-98-6; 3',4'-Dideoxykanamycin B; UNII-45ZFO9E525; BRN 1441606; CHEBI:37945; 45ZFO9E525; Debecacin; DKB; DKM; O-3-Amino-3-deoxy-alpha-D-glucopyranosyl-(1-4)-O-(2,6-diamino-2,3,4,6-tetradeoxy-alpha-D-erythro-hexopyranosyl-(1-6))-2-deoxy-L-streptamine; Dibekacina; Dibekacine; Dibekacinum; Kappati; (1R,2S,3S,4R,6S)-4,6-diamino-3-(3-amino-3-deoxy-alpha-D-glucopyranosyloxy)-2-hydroxycyclohexyl 2,6-diamino-2,3,4,6-tetradeoxy-alpha-D-erythro-hexopyranoside; (1R,2S,3S,4R,6S)-4,6-diamino-3-[(3-amino-3-deoxy-alpha-D-glucopyranosyl)oxy]-2-hydroxycyclohexyl 2,6-diamino-2,3,4,6-tetradeoxy-alpha-D-erythro-hexopyranoside; Dibekacin [INN:BAN]; Dibekacine [INN-French]; Dibekacinum [INN-Latin]; Dibekacina [INN-Spanish]; Dibekacin (INN); D-Streptamine, O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1-6)-O-(2,6-diamino-2,3,4,6-tetradeoxy-alpha-D-erythro-hexopyranosyl)-(1-4)-2-deoxy-; EINECS 252-064-6; Spectrum_001398; Spectrum2_001528; Spectrum3_000960; Spectrum4_001074; Spectrum5_001613; NCGC00095276-01; DSSTox_CID_2915; DSSTox_RID_76787; DSSTox_GSID_22915; SCHEMBL49816; KBioGR_001428; KBioSS_001878; SPBio_001316; CHEMBL560976; DTXSID2022915; KBio2_001878; KBio2_004446; KBio2_007014; KBio3_002060; HY-B1129; ZINC8214383; Tox21_111496; AC-315; AKOS025402025; CCG-213771; CS-4725; DB13270; NCGC00389765-01; CAS-34493-98-6; D07811; AB01563356_01; Q3706873; (2S,3R,4S,5S,6R)-4-amino-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2R,3R,6S)-3-amino-6-(aminomethyl)tetrahydropyran-2-yl]oxy-2-hydroxy-cyclohexoxy]-6-(hydroxymethyl)tetrahydropyran-3,5-diol; 84D
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (9 diseases)
  Bacterial genitourinary infection [ICD-11: GA0Z-GC8Z]; [1]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [3]
  Gram-negative bacterial infection [ICD-11: 1B74-1G40]; [1]
  Infective endocarditis [ICD-11: BB40]; [1]
  Mycobacterial diseases [ICD-11: 1B2Z ]; [4]
  Peritonitis [ICD-11: DC50]; [1]
  Respiratory trac infection [ICD-11: CA45]; [1]
  Sepsis [ICD-11: 1G40]; [1]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Mycobacterial diseases [ICD-11: 1B2Z ]; [5]
• Formula: C18H37N5O8
• IsoSMILES: C1C[C@H]([C@H](O[C@@H]1CN)O[C@@H]2[C@H](C[C@H]([C@@H]([C@H]2O)O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)N)O)N)N)N
• InChI: 1S/C18H37N5O8/c19-4-6-1-2-7(20)17(28-6)30-15-8(21)3-9(22)16(14(15)27)31-18-13(26)11(23)12(25)10(5-24)29-18/h6-18,24-27H,1-5,19-23H2/t6-,7+,8-,9+,10+,11-,12+,13+,14-,15+,16-,17+,18+/m0/s1
• InChIKey: JJCQSGDBDPYCEO-XVZSLQNASA-N
• PubChem CID: 470999
• INTEDE ID: DR2603
• DrugBank ID: DB13270

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: Aminoglycoside N(6')-acetyltransferase type 1 (A6AC1) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Escherichia coli intestinal infection [ICD-11: 1A03]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside acetyltransferase (AAC) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli SCH92111602; 562
• Experiment for Molecule Alteration: Dot blot hybridizations assay
• Experiment for Drug Resistance: Standard broth microdilution method assay
• Mechanism Description: Escherichia coli SCH92111602 expresses an aminoglycoside resistance profile similar to that conferred by the aac(6')-Ie-aph(2")-Ia gene found in gram-positive cocci and was found to contain the aminoglycoside resistance genes aph(2")-Ib and aac(6')-Im (only 44 nucleotides apart). SCH92111602 is an Escherichia coli clinical isolate resistant to a number of aminoglycoside antibiotics, including gentamicin, tobramycin, and amikacin, and contains an approximately 50-kb plasmid.

Key Molecule: Aminoglycoside acetyltransferase (AAC) [3]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli SCH92111602; 562
• Experiment for Molecule Alteration: Dot blot hybridizations assay
• Experiment for Drug Resistance: Standard broth microdilution method assay
• Mechanism Description: Plasmid DNA isolated from this strain was introduced into Escherichia coli DH5alpha by transformation, and colonies were selected on Luria-Bertani agar plates containing 10 ug of tobramycin per ml. Analysis of restriction digests on agarose gels of DNA from a tobramycin-resistant transformant confirmed the presence of the same 50-kb plasmid that was isolated from Escherichia coli SCH92111602.

Mycobacterial diseases [ICD-11: 1B2Z ]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 2'-N-acetyltransferase (A2NA) [5]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Mycobacterium smegmatis infection [ICD-11: 1B2Z.3]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain DH5a; 668369
• In Vitro Model: Mycolicibacterium smegmatis strain EP10; 1772
• In Vitro Model: Mycolicibacterium smegmatis strain mc2155; 246196
• Experiment for Molecule Alteration: Southern blot hybridizations assay
• Experiment for Drug Resistance: Agar macrodilution assay
• Mechanism Description: The introduction of a plasmid-located copy of either the aac (2')-Ib or the aac (2')-Id genes into M. smegmatis mc2155 produces an increase in the level of resistance over those values observed in M. smegmatis mc2155. However, the introduction of the plasmid-located aac (2') Ic gene did not lead to an increase in the MICs. In this experiment, an increase of at least two dilutions in the MIC values over those observed in M. smegmatismc2155 with the vector pSUM36 has been assumed to be due to the increase in the activity of the AAC (2') enzyme. The MICs for the 2'-ethylnetilmicin do not change since this aminoglycoside is not a substrate of the AAC (2') enzyme.

Key Molecule: Aminoglycoside 2'-N-acetyltransferase (A2NA) [4]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Mycobacterium smegmatis infection [ICD-11: 1B2Z.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli XL1-Blue; 562
• In Vitro Model: Streptomyces lividans strain 1326; 1200984
• In Vitro Model: Mycolicibacterium fortuitum strain FC1k; 1766
• In Vitro Model: Mycolicibacterium smegmatis strain mc2 155; 246196
• Experiment for Molecule Alteration: Southern blot hybridizations assay
• Experiment for Drug Resistance: Twofold dilution of antibiotics assay
• Mechanism Description: The aac(2')-Ib gene cloned in a mycobacterial plasmid and introduced in Mycobacterium smegmatis conferred resistance to gentamicin, tobramycin, dibekacin, netilmicin, and 6'-N-ethylnetilmicin.

Gram-negative bacterial infection [ICD-11: 1B74-1G40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative pathogens infection [ICD-11: 1B74-1G40]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Sepsis [ICD-11: 1G40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

ICD-11: Circulatory system diseases

Infective endocarditis [ICD-11: BB40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Infective endocarditis [ICD-11: BB40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

ICD-12: Respiratory system diseases

Respiratory trac infection [ICD-11: CA45]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

ICD-13: Digestive system diseases

Peritonitis [ICD-11: DC50]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative pathogens infection [ICD-11: 1B74-1G40]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

ICD-16: Genitourinary system diseases

Bacterial genitourinary infection [ICD-11: GA0Z-GC8Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative pathogens infection [ICD-11: 1B74-1G40]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

References

• Ref 1: Novel aminoglycoside 2''-phosphotransferase identified in a gram-negative pathogen. Antimicrob Agents Chemother. 2013 Jan;57(1):452-7. doi: 10.1128/AAC.02049-12. Epub 2012 Nov 5.
• Ref 2: Identification and characterization of a novel aac(6')-Iag associated with the blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa. PLoS One. 2013 Aug 12;8(8):e70557. doi: 10.1371/journal.pone.0070557. eCollection 2013.
• Ref 3: Aminoglycoside resistance genes aph(2")-Ib and aac(6')-Im detected together in strains of both Escherichia coli and Enterococcus faecium. Antimicrob Agents Chemother. 2001 Oct;45(10):2691-4. doi: 10.1128/AAC.45.10.2691-2694.2001.
• Ref 4: Characterization of the chromosomal aminoglycoside 2'-N-acetyltransferase gene from Mycobacterium fortuitum. Antimicrob Agents Chemother. 1996 Oct;40(10):2350-5. doi: 10.1128/AAC.40.10.2350.
• Ref 5: Aminoglycoside 2'-N-acetyltransferase genes are universally present in mycobacteria: characterization of the aac(2')-Ic gene from Mycobacterium tuberculosis and the aac(2')-Id gene from Mycobacterium smegmatis. Mol Microbiol. 1997 Apr;24(2):431-41. doi: 10.1046/j.1365-2958.1997.3471717.x.