Drug Information

Drug (ID: DG00448) and It's Reported Resistant Information

• Name: Amoxicillin/Clavulanic acid
• Synonyms: Amoxicillin + clavulanic acid; Amoxicillin and clavulanic acid; 79198-29-1; Amoxicillin + clavulinic acid; (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2R,3Z,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; Amoksiclav; Amoxyclav; Synulox; Amox-clav; Amoxicillin clavulanate; Augmentin (free acid); Amoxicillin & Clavulanate; Amoxicillin clavulanate acid; Amoxicillin & Clavulanic acid; SCHEMBL591660; CHEMBL2097107; Amoxicillin-clavulanic acid mixt.; DTXSID80872429; Amoxicillin mixture with Clavulanate; Clavulanate mixture with amoxicillin; Clavulanic acid - amoxicillin mixt.; NCGC00188989-01; (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2R,3Z,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 4-Oxa-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3-(2-hydroxyethylidene)-7-oxo-, (2R,3Z,5R)-, mixt. with (2S,5R,6R)-6-(((2R)-amino(4-hydroxyphenyl)acetyl)amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid; 4-Oxa-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3-(2-hydroxyethylidene)-7-oxo-, (2R-(2alpha,3Z,5alpha))-, mixt. with (2S-(2alpha,5alpha,6beta(S*))-6-((amino(4-hydroxyphenyl)acetyl)amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Pneumonia [ICD-11: CA40]; [2]
• Formula: C24H28N4O10S
• IsoSMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=C(C=C3)O)N)C(=O)O)C.C1[C@@H]2N(C1=O)[C@H](/C(=C/CO)/O2)C(=O)O
• InChI: 1S/C16H19N3O5S.C8H9NO5/c1-16(2)11(15(23)24)19-13(22)10(14(19)25-16)18-12(21)9(17)7-3-5-8(20)6-4-7;10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4/h3-6,9-11,14,20H,17H2,1-2H3,(H,18,21)(H,23,24);1,6-7,10H,2-3H2,(H,12,13)/b;4-1-/t9-,10-,11+,14-;6-,7-/m11/s1
• InChIKey: QJVHTELASVOWBE-AGNWQMPPSA-N
• PubChem CID: 6435924

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: Beta-lactamase (BLA) [1]

• Molecule Alteration: Missense mutation; p.Y104A+p.N110D+p.E175Q+p.S179A
• 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: Acinetobacter baumannii CIP70.10; 470
• In Vitro Model: Klebsiella pneumoniae kP3; 1290996
• In Vitro Model: Pseudomonas aeruginosa PU21; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: K. pneumoniae kP3 was resistant to all Beta-lactams, including carbapenems, and expressed the carbapenem-hydrolyzing Beta-lactamase OXA-181, which differs from OXA-48 by four amino acid substitutions. Compared to OXA-48, OXA-181 possessed a very similar hydrolytic profile.

Key Molecule: Beta-lactamase (BLA) [3], [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli JM101; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Beta-lactamases (Beta-lactamhydrolase, EC 3.5.2.6), responsible for most of the resistance to Beta-lactam antibiotics, are often plasmid mediated.The OXA-1 beta-lactamase gene is part of Tn2603, which is borne on the R plasmid RGN238.

References

• Ref 1: Characterization of OXA-181, a carbapenem-hydrolyzing class D beta-lactamase from Klebsiella pneumoniae. Antimicrob Agents Chemother. 2011 Oct;55(10):4896-9. doi: 10.1128/AAC.00481-11. Epub 2011 Jul 18.
• Ref 2: Pathogens and drug-resistance of hospital-acquired pneumonia in an EICU in Tianjin, ChinaInt J Biochem Mol Biol. 2021 Apr 15;12(2):49-54. eCollection 2021.
• Ref 3: Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7378-82. doi: 10.1073/pnas.84.21.7378.
• Ref 4: Identifying novel Beta-lactamase substrate activity through in silico prediction of antimicrobial resistance. Microb Genom. 2021 Jan;7(1):mgen000500. doi: 10.1099/mgen.0.000500.