Drug Information

Drug (ID: DG00336) and It's Reported Resistant Information

• Name: Pleuromutilins
• Synonyms: BC-3004; BC-3080; BC-3291; Pleuromutilins (oral, bacterial infection); Pleuromutilins (oral, bacterial infection), Nabriva
• Indication:
  In total 1 Indication(s)
  Gram-positive bacterial infection [ICD-11: 1B74-1F40]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2], [3]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
• Formula: C22H34O5
• IsoSMILES: C[C@@H]1CC[C@@]23CCC(=O)[C@H]2[C@@]1([C@@H](C[C@@]([C@H]([C@@H]3C)O)(C)C=C)OC(=O)CO)C
• InChI: 1S/C22H34O5/c1-6-20(4)11-16(27-17(25)12-23)21(5)13(2)7-9-22(14(3)19(20)26)10-8-15(24)18(21)22/h6,13-14,16,18-19,23,26H,1,7-12H2,2-5H3/t13-,14+,16-,18+,19+,20-,21+,22+/m1/s1
• InChIKey: ZRZNJUXESFHSIO-BKUNHTPHSA-N
• PubChem CID: 9886081
• TTD Drug ID: D0R5JP

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

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

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Tiamulin efflux ATP-binding protein (TAEA) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Paenibacillus sp. LC231; 1120679
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: These new resistance elements are discussed below. We also identified two predicted ABC-transporters that confer resistance to tetracycline (TetAB(48)) and tiamulin (TaeA).

Key Molecule: ABC transporter ATP-binding protein (ABCP) [2], [3]

• Molecule Alteration: Missense mutation; p.T450I
• 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: Enterococcus faecium HM1070; 1352
• In Vitro Model: Enterococcus faecium UCN80; 1352
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: ABC systems constitute one of the largest families of proteins, with most of them being involved in import and export, often called ABC transporters.Several of these class 2 ABC systems have been involved in MLS resistance, such as Msr-, Vga-, or Lsa-like proteins.The observed profile of cross-resistance to lincosamides, streptogramins A, and pleuromutilins conferred by Eat(A)v was similar to those conferred by other Lsa-like proteins.

References

• Ref 1: A diverse intrinsic antibiotic resistome from a cave bacterium. Nat Commun. 2016 Dec 8;7:13803. doi: 10.1038/ncomms13803.
• Ref 2: Comparative analysis of the first complete Enterococcus faecium genome. J Bacteriol. 2012 May;194(9):2334-41. doi: 10.1128/JB.00259-12. Epub 2012 Feb 24.
• Ref 3: Genetic basis for in vitro and in vivo resistance to lincosamides, streptogramins A, and pleuromutilins (LSAP phenotype) in Enterococcus faecium. Antimicrob Agents Chemother. 2013 Sep;57(9):4463-9. doi: 10.1128/AAC.01030-13. Epub 2013 Jul 8.