Drug Information

Drug (ID: DG00057) and It's Reported Resistant Information

• Name: Paromomycin
• Synonyms: Aminosidin; Catenulin; Humatin; Hydroxymycin sulfate; Paramomycin Sulfate; Paromomycin I; Paromomycin sulfate Rx346208; Aminosidine, sulfate; HATT & Paromomycin; Humatin (TN); Paromomycin (INN); Paromomycin (TN); Paromomycin (complex); PA1-PA2-PA3-PA4; Human .alpha.-1-antitrypsin & Paromomyin; PAROMOMYCIN I, AMMINOSIDIN, CATENULIN, CRESTOMYCIN, MONOMYCIN A, NEOMYCIN E; (1R,2R,3S,4R,6S)-4,6-diamino-2-{[3-O-(2,6-diamino-2,6-dideoxy-beta-L-idopyranosyl)-beta-D-ribofuranosyl]oxy}-3-hydroxycyclohexyl 2-amino-2-deoxy-alpha-D-glucopyranoside; (2S,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(2R,3S,4R,5S)-5-[(1R,2R,3S,5R,6S)-3,5-diamino-2-[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol; O-2-Amino-2-deoxy-.alpha.-D-glucopyranosyl-(1->4)-O-[O-2,6-diamino-2,6-dideoxy-.beta.-L-idopyranosyl-(1->3)-.beta.D-ribofuranosyl(1->5)]-2-deoxy-D-streptamine
• Indication:
  In total 1 Indication(s)
  Amoebiasis [ICD-11: 1A36]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Leishmaniasis [ICD-11: 1F54]; [2]
  Pneumonia [ICD-11: CA40]; [3]
• Target: Staphylococcus 30S ribosomal subunit (Stap-coc pbp2); F4NA87_STAAU; [1]
• Formula: C23H45N5O14
• IsoSMILES: C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)N)O[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O[C@@H]4[C@@H]([C@H]([C@@H]([C@@H](O4)CN)O)O)N)O)O)N
• InChI: 1S/C23H45N5O14/c24-2-7-13(32)15(34)10(27)21(37-7)41-19-9(4-30)39-23(17(19)36)42-20-12(31)5(25)1-6(26)18(20)40-22-11(28)16(35)14(33)8(3-29)38-22/h5-23,29-36H,1-4,24-28H2/t5-,6+,7+,8-,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+/m1/s1
• InChIKey: UOZODPSAJZTQNH-LSWIJEOBSA-N
• PubChem CID: 165580
• ChEBI ID: CHEBI:7934
• TTD Drug ID: D04NDM
• DrugBank ID: DB01421

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 3'-phosphotransferase (A3AP) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Stenotrophomonas maltophilia infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• Experiment for Molecule Alteration: PCR amplification assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Aph(3')-IIc significantly increases MICs of kanamycin, neomycin, butirosin, and paromomycin when expressed in Escherichia coli. Disruption of aph(3')-IIc results in decreased MICs of these drugs.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Serratia marcescens infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• In Vitro Model: Escherichia coli strain 83-125; 562
• In Vitro Model: Escherichia coli strain 83-75; 562
• In Vitro Model: Escherichia coli strain JM83; 562
• In Vitro Model: Escherichia coli strain JM83(pRPG101); 562
• In Vitro Model: Escherichia coli strain M8820Mu; 562
• In Vitro Model: Escherichia coli strain MC1065; 562
• In Vitro Model: Escherichia coli strain MC1065(pRPG101); 562
• In Vitro Model: Escherichia coli strain POII1681; 562
• In Vitro Model: Escherichia coli strain PRC930(pAO43::Tn9O3); 562
• In Vitro Model: Klebsiella pneumoniae strains; 573
• In Vitro Model: Serratia marcescens strains; 615
• Experiment for Molecule Alteration: Restriction enzyme treating assay
• Experiment for Drug Resistance: Cation-supplemented Mueller-Hinton broth assay; agar dilution with MH agar assay
• Mechanism Description: Clinical isolates of Klebsiella pneumoniae and Serratia marcescens at a hospital that had used amikacin as its principal aminoglycoside for the preceding 42 months demonstrated high-level resistance to amikacin (greater than or equal to 256 micrograms/ml), kanamycin (greater than or equal to 256 micrograms/ml), gentamicin (greater than or equal to 64 micrograms/ml), netilmicin (64 micrograms/ml), and tobramycin (greater than or equal to 16 micrograms/ml). The clinical isolates and transformants produced a novel 3'-phosphotransferase, APH(3'), that modified amikacin and kanamycin in vitro.

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• In Vitro Model: Escherichia coli strain 83-125; 562
• In Vitro Model: Escherichia coli strain 83-75; 562
• In Vitro Model: Escherichia coli strain JM83; 562
• In Vitro Model: Escherichia coli strain JM83(pRPG101); 562
• In Vitro Model: Escherichia coli strain M8820Mu; 562
• In Vitro Model: Escherichia coli strain MC1065; 562
• In Vitro Model: Escherichia coli strain MC1065(pRPG101); 562
• In Vitro Model: Escherichia coli strain POII1681; 562
• In Vitro Model: Escherichia coli strain PRC930(pAO43::Tn9O3); 562
• In Vitro Model: Klebsiella pneumoniae strains; 573
• In Vitro Model: Serratia marcescens strains; 615
• Experiment for Molecule Alteration: Restriction enzyme treating assay
• Experiment for Drug Resistance: Cation-supplemented Mueller-Hinton broth assay; agar dilution with MH agar assay
• Mechanism Description: Clinical isolates of Klebsiella pneumoniae and Serratia marcescens at a hospital that had used amikacin as its principal aminoglycoside for the preceding 42 months demonstrated high-level resistance to amikacin (greater than or equal to 256 micrograms/ml), kanamycin (greater than or equal to 256 micrograms/ml), gentamicin (greater than or equal to 64 micrograms/ml), netilmicin (64 micrograms/ml), and tobramycin (greater than or equal to 16 micrograms/ml). The clinical isolates and transformants produced a novel 3'-phosphotransferase, APH(3'), that modified amikacin and kanamycin in vitro.

References

• Ref 1: Aph(3')-IIc, an aminoglycoside resistance determinant from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2007 Jan;51(1):359-60. doi: 10.1128/AAC.00795-06. Epub 2006 Nov 6.
• Ref 2: Drug resistance in visceral leishmaniasis .J Biomed Biotechnol. 2010;2010:617521. doi: 10.1155/2010/617521. Epub 2009 Nov 1. 10.1155/2010/617521
• Ref 3: Isolation, characterization, and cloning of a plasmid-borne gene encoding a phosphotransferase that confers high-level amikacin resistance in enteric bacilli. Antimicrob Agents Chemother. 1988 Sep;32(9):1379-84. doi: 10.1128/AAC.32.9.1379.