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DB00766 - Clavulanate


Identification
Name Clavulanate
Accession Number DB00766 (APRD00049)
Type small molecule
Description Clavulanic acid and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 199.1608
Groups approved
Monoisotopic Weight 199.048072403
Pharmacology
Indication For use with Amoxicillin, clavulanic acid is suitable for the treatment of infections with Staph. aureus and Bacteroides fragilis, or with beta-lactamase producing H. influenzae and E. coli.
Mechanism of action Clavulanic acid competitively and irreversibly inhibits a wide variety of beta-lactamases, commonly found in microorganisms resistant to penicillins and cephalosporins. Binding and irreversibly inhibiting the beta-lactamase results in a restauration of the antimicrobial activity of beta-lactam antibiotics against lactamase-secreting-resistant bacteria. By inactivating beta-lactamase (the bacterial resistance protein), the accompanying penicillin/cephalosporin drugs may be made more potent as well.
Absorption 75%
Protein binding Low (22 to 30%)
Biotransformation Hepatic
Route of elimination Not Available
Toxicity Gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Demeclocycline Possible antagonism of action
Doxycycline Possible antagonism of action
Ethinyl Estradiol This anti-infectious agent could decrease the effect of the oral contraceptive
Mestranol This anti-infectious agent could decrease the effect of the oral contraceptive
Methacycline Possible antagonism of action
Methotrexate The penicillin increases the effect and toxicity of methotrexate
Minocycline Possible antagonism of action
Oxytetracycline Possible antagonism of action
Rolitetracycline Possible antagonism of action
Tetracycline Possible antagonism of action
Food Interactions Not Available

Targets


Beta-lactamase
Name Beta-lactamase
Gene Name blaZ
Pharmacological action yes
Actions inhibitor
References
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Hugonnet JE, Blanchard JS: Irreversible Inhibition of the Mycobacterium tuberculosis beta-Lactamase by Clavulanate. Biochemistry. 2007 Oct 4;. - Pubmed
  • Poirel L, Brinas L, Verlinde A, Ide L, Nordmann P: BEL-1, a novel clavulanic acid-inhibited extended-spectrum beta-lactamase, and the class 1 integron In120 in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005 Sep;49(9):3743-8. - Pubmed
  • Pottumarthy S, Sader HS, Fritsche TR, Jones RN: Susceptibility patterns for amoxicillin/clavulanate tests mimicking the licensed formulations and pharmacokinetic relationships: do the MIC obtained with 2:1 ratio testing accurately reflect activity against beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis? Diagn Microbiol Infect Dis. 2005 Nov;53(3):225-31. Epub 2005 Oct 27. - Pubmed
  • Papp-Wallace KM, Taracila M, Hornick JM, Hujer AM, Hujer KM, Distler AM, Endimiani A, Bonomo RA: Substrate selectivity and a novel role in inhibitor discrimination by residue 237 in the KPC-2 beta-lactamase. Antimicrob Agents Chemother. 2010 Jul;54(7):2867-77. Epub 2010 Apr 26. - Pubmed
  • Sanchez PA, Toney JH, Thomas JD, Berger JM: A sensitive coupled HPLC/electrospray mass spectrometry assay for SPM-1 metallo-beta-lactamase inhibitors. Assay Drug Dev Technol. 2009 Apr;7(2):170-9. - Pubmed
DTHybrid score 0.6812

Predictions


Id Partner name Gene Name Score
2478 Beta-lactamase ampC 0.6812
2613 Beta-lactamase ampC 0.6812
2635 Beta-lactamase ampC 0.6812
2700 Beta-lactamase penP 0.6812
5445 Beta-lactamase blaB 0.6812
6019 Beta-lactamase SHV-7 0.6812
6701 Beta-lactamase cphA 0.6812
2858 Beta-lactamase TEM bla 0.099
6396 Beta-lactamase TEM bla 0.099
867 Penicillin-binding protein 3 pbpC 0.0611
6119 Penicillin-binding protein 3 pbp3 0.0611
7154 Penicillin-binding protein 3 pbp3 0.0611
7157 Penicillin-binding protein 3 LMHCC_2184 0.0611
7162 Penicillin-binding protein 3 pbpB 0.0611
7172 Penicillin-binding protein 3 pbp3 0.0611
115 Penicillin-binding protein 2 mrdA 0.049
6069 Penicillin-binding protein 2 mrdA 0.049
6118 Penicillin-binding protein 2 penA 0.049
6187 Penicillin-binding protein 2 pbpA 0.049
6686 Penicillin-binding protein 2 pbp2 0.049
6939 Penicillin-binding protein 2 mrdA 0.049
7163 Penicillin-binding protein 2 pbpA 0.049
543 Penicillin-binding protein 1B mrcB 0.0468
6186 Penicillin-binding protein 1B ponB 0.0468
6822 Penicillin-binding protein 1b pbp1b 0.0468
6844 Penicillin-binding protein 1b pbp1b 0.0468
645 Penicillin-binding protein 1A mrcA 0.0461
5805 Penicillin-binding protein 1A ponA 0.0461
6185 Penicillin-binding protein 1A mrcA 0.0461
6799 Penicillin-binding protein 1A pbpA 0.0461
633 Penicillin-binding proteins 1A/1B pbpA 0.035
1024 Solute carrier family 22 member 11 SLC22A11 0.0301
118 Organic cation/carnitine transporter 2 SLC22A5 0.0279
6142 Solute carrier family 22 member 8 SLC22A8 0.0263
1729 Solute carrier family 22 member 6 SLC22A6 0.0239
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