Drug Information

Drug (ID: DG00169) and It's Reported Resistant Information

• Name: Quinupristin
• Synonyms: Quinupristina; Quinupristine; Quinupristinum; SYB; RP 57669; Quinupristin [USAN:INN]; Quinupristina [INN-Spanish]; Quinupristine [INN-French]; Quinupristinum [INN-Latin]; RP-57669; Synercid (TN); Quinupristin (JAN/USAN/INN); 4-[4-(DIMETHYLAMINO)-N-METHYL-L-PHENYLALANINE]-5-[(2S,5R)-5-[[[(3S)-1-AZABICYCLO-[2.2.2]OCT-3-YL]THIO]METHYL]-4-OXO-2-PIPERIDINECARBOXYLIC ACID]VIRGINIAMYCIN; 5delta-(3-quinuclidinyl)thiomethylpristinamycin IA
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Bacterial meningitis [ICD-11: 1D02]; [2]
  Mycobacterial diseases [ICD-11: 1B2Z ]; [3]
  Surgical wound infection [ICD-11: NE81]; [1]
• Target: Bacterial Integral membrane LmrP (Bact lmrP); Q9CDQ3_LACLA; [1]
• Formula: C53H67N9O10S
• IsoSMILES: CC[C@@H]1C(=O)N2CCC[C@H]2C(=O)N([C@H](C(=O)N3C[C@H](C(=O)C[C@H]3C(=O)N[C@H](C(=O)O[C@@H]([C@@H](C(=O)N1)NC(=O)C4=C(C=CC=N4)O)C)C5=CC=CC=C5)CS[C@@H]6CN7CCC6CC7)CC8=CC=C(C=C8)N(C)C)C
• InChI: 1S/C53H67N9O10S/c1-6-37-50(68)61-23-11-14-38(61)51(69)59(5)40(26-32-16-18-36(19-17-32)58(3)4)52(70)62-28-35(30-73-43-29-60-24-20-33(43)21-25-60)42(64)27-39(62)47(65)57-45(34-12-8-7-9-13-34)53(71)72-31(2)44(48(66)55-37)56-49(67)46-41(63)15-10-22-54-46/h7-10,12-13,15-19,22,31,33,35,37-40,43-45,63H,6,11,14,20-21,23-30H2,1-5H3,(H,55,66)(H,56,67)(H,57,65)/t31-,35+,37-,38+,39+,40+,43-,44+,45+/m1/s1
• InChIKey: WTHRRGMBUAHGNI-LCYNINFDSA-N
• PubChem CID: 5388937
• TTD Drug ID: D0E2OU
• DrugBank ID: DB01369

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Mycobacterial diseases [ICD-11: 1B2Z ]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm (ERM39) [3]

• Molecule Alteration: Missense mutation; Putative initiation codon GTG>CTG
• Resistant Disease: Mycobacterium fortuitum infection [ICD-11: 1B2Z.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium peregrinum ATCC14467; 43304
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Mueller-Hinton (MH) broth assay
• Mechanism Description: The erm genes are a diverse collection of methylases that add one or two methyl groups to the adenine at position 2058 (Escherichia coli numbering) of the 23S rRNA; this modification impairs the binding of macrolides to ribosomes, and thus reduces the inhibitory activity of these agents.

Bacterial meningitis [ICD-11: 1D02]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: MsrC (MSRC) [2]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Enterococcus faecium meningitis [ICD-11: 1D01.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Enterococcus faecium TX2465; 1352
• In Vitro Model: Escherichia coli TX1330; 668369
• In Vitro Model: Escherichia coli TX2046; 668369
• In Vitro Model: Escherichia coli TX2597; 668369
• Experiment for Molecule Alteration: Southern blotting assay
• Experiment for Drug Resistance: Twofold dilutions assay
• Mechanism Description: The complete sequence (1,479 nucleotides) of msrC, part of which was recently reported by others using a different strain, was determined. This gene was found in 233 of 233 isolates of Enterococcus faecium but in none of 265 other enterococci. Disruption of msrC was associated with a two- to eightfold decrease in MICs of erythromycin azithromycin, tylosin, and quinupristin, suggesting that it may explain in part the apparent greater intrinsic resistance to macrolides of isolates of E. faecium relative to many streptococci. This endogenous, species-specific gene of E. faecium is 53% identical to msr(A), suggesting that it may be a remote progenitor of the acquired macrolide resistance gene found in some isolates of staphylococci.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: MsrC (MSRC) [2]

• Molecule Alteration: Truncated mutantion; Disruption (nt 1251 to 1879)
• Sensitive Disease: Enterococcus faecium meningitis [ICD-11: 1D01.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Enterococcus faecium TX2465; 1352
• In Vitro Model: Escherichia coli TX1330; 668369
• In Vitro Model: Escherichia coli TX2046; 668369
• In Vitro Model: Escherichia coli TX2597; 668369
• Experiment for Molecule Alteration: Southern blotting assay
• Experiment for Drug Resistance: Twofold dilutions assay
• Mechanism Description: Disruption of msrC was associated with a two- to eightfold decrease in MICs of erythromycin azithromycin, tylosin, and quinupristin, suggesting that it may explain in part the apparent greater intrinsic resistance to macrolides of isolates of E. faecium relative to many streptococci.

ICD-22: Injury/poisoning/certain external causes consequences

Surgical wound infection [ICD-11: NE81]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Erythromycin resistance protein (ERM38) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Mycobacterium smegmatis infection [ICD-11: 1B2Z.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium smegmatis mc2155; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pMIP12; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV20; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV30; 246196
• Experiment for Molecule Alteration: MALDI mass spectrometry assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Erm (38) is a specific dimethyltransferase. The strain obtained drug resistance by adding two methyl groups to A2058 in Mycobacterium 23SrRNA.

Key Molecule: Erythromycin resistance protein (ERM38) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Mycobacterium smegmatis infection [ICD-11: 1B2Z.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium smegmatis mc2155; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pMIP12; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV20; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV30; 246196
• Experiment for Molecule Alteration: MALDI mass spectrometry assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Erm (38) is a specific dimethyltransferase. The strain obtained drug resistance by adding two methyl groups to A2058 in Mycobacterium 23SrRNA.

References

• Ref 1: Mycobacterium smegmatis Erm(38) is a reluctant dimethyltransferase. Antimicrob Agents Chemother. 2005 Sep;49(9):3803-9. doi: 10.1128/AAC.49.9.3803-3809.2005.
• Ref 2: Disruption of an Enterococcus faecium species-specific gene, a homologue of acquired macrolide resistance genes of staphylococci, is associated with an increase in macrolide susceptibility. Antimicrob Agents Chemother. 2001 Jan;45(1):263-6. doi: 10.1128/AAC.45.1.263-266.2001.
• Ref 3: Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother. 2005 Feb;55(2):170-7. doi: 10.1093/jac/dkh523. Epub 2004 Dec 8.