Identification
Name Imipenem
Accession Number DB01598
Type small molecule
Description Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [PubChem]
Structure
Categories (*)
Molecular Weight 299.346
Groups approved
Monoisotopic Weight 299.093976737
Pharmacology
Indication For the treatment of bacterial infections caused by susceptible bacteria.
Mechanism of action Imipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria. This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to pencillin binding proteins (PBPs). In E. coli and selected strains of P. aeruginosa, imipenem has shown to have the highest affinity to PBP-2, PBP-1a, and PBP-1b. This preferential binding to PBP-2 and PBP-1b results in the direct conversion of the individual cell to a spheroblast, which leads to rapid cell lysis and death without filament formation.
Absorption Imipenem is not effectively absorbed from the gastrointestinal tract and therefore must be administered parenterally.
Protein binding 20% binds to plasma proteins
Biotransformation Renal.
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Cyclosporine Imipenem increases the effect and toxicity of cyclosporine
Valganciclovir Generalized convulsions have been reported in patients taking Ganciclovir and Imipenem-cilastatin. Concomitant therapy should be avoided. (Note: Valganciclovir is converted to Ganciclovir in vivo)
Food Interactions Not Available
Penicillin-binding protein 2
Name Penicillin-binding protein 2
Gene Name mrdA
Pharmacological action yes
Actions inhibitor
References
  • Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. - Pubmed
  • Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. - Pubmed
  • Neu HC: Carbapenems: special properties contributing to their activity. Am J Med. 1985 Jun 7;78(6A):33-40. - Pubmed
  • Luchi M, Morrison DC, Opal S, Yoneda K, Slotman G, Chambers H, Wiesenfeld H, Lemke J, Ryan JL, Horn D: A comparative trial of imipenem versus ceftazidime in the release of endotoxin and cytokine generation in patients with gram-negative urosepsis. Urosepsis Study Group. J Endotoxin Res. 2000;6(1):25-31. - Pubmed
DTHybrid score 0.0571
Penicillin-binding protein 1B
Name Penicillin-binding protein 1B
Gene Name mrcB
Pharmacological action yes
Actions inhibitor
References
  • Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. - Pubmed
  • Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. - Pubmed
DTHybrid score 0.6967
Penicillin-binding protein 1A
Name Penicillin-binding protein 1A
Gene Name mrcA
Pharmacological action yes
Actions inhibitor
References
  • Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. - Pubmed
  • Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. - Pubmed
DTHybrid score 0.7023
Penicillin-binding protein 3
Name Penicillin-binding protein 3
Gene Name pbpC
Pharmacological action yes
Actions inhibitor
References
  • Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. - Pubmed
  • Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. - Pubmed
DTHybrid score 0.6202
Beta-lactamase
Name Beta-lactamase
Gene Name blaZ
Pharmacological action yes
Actions other/unknown
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Pichardo C, Rodriguez-Martinez JM, Pachon-Ibanez ME, Conejo C, Ibanez-Martinez J, Martinez-Martinez L, Pachon J, Pascual A: Efficacy of cefepime and imipenem in experimental murine pneumonia caused by porin-deficient Klebsiella pneumoniae producing CMY-2 beta-Lactamase. Antimicrob Agents Chemother. 2005 Aug;49(8):3311-6. - Pubmed
  • Jeon BC, Jeong SH, Bae IK, Kwon SB, Lee K, Young D, Lee JH, Song JS, Lee SH: Investigation of a nosocomial outbreak of imipenem-resistant Acinetobacter baumannii producing the OXA-23 beta-lactamase in korea. J Clin Microbiol. 2005 May;43(5):2241-5. - Pubmed
  • Fenollar-Ferrer C, Donoso J, Frau J, Munoz F: Molecular modeling of Henry-Michaelis and acyl-enzyme complexes between imipenem and Enterobacter cloacae P99 beta-lactamase. Chem Biodivers. 2005 May;2(5):645-56. - Pubmed
  • Neu HC: Carbapenems: special properties contributing to their activity. Am J Med. 1985 Jun 7;78(6A):33-40. - Pubmed
  • Kahan FM, Kropp H, Sundelof JG, Birnbaum J: Thienamycin: development of imipenen-cilastatin. J Antimicrob Chemother. 1983 Dec;12 Suppl D:1-35. - Pubmed
DTHybrid score 0.8172
Id Partner name Gene Name Score
2478 Beta-lactamase ampC 0.8172
2613 Beta-lactamase ampC 0.8172
2635 Beta-lactamase ampC 0.8172
2700 Beta-lactamase penP 0.8172
5445 Beta-lactamase blaB 0.8172
6019 Beta-lactamase SHV-7 0.8172
6701 Beta-lactamase cphA 0.8172
5805 Penicillin-binding protein 1A ponA 0.7023
6185 Penicillin-binding protein 1A mrcA 0.7023
6799 Penicillin-binding protein 1A pbpA 0.7023
6186 Penicillin-binding protein 1B ponB 0.6967
6822 Penicillin-binding protein 1b pbp1b 0.6967
6844 Penicillin-binding protein 1b pbp1b 0.6967
6119 Penicillin-binding protein 3 pbp3 0.6202
7154 Penicillin-binding protein 3 pbp3 0.6202
7157 Penicillin-binding protein 3 LMHCC_2184 0.6202
7162 Penicillin-binding protein 3 pbpB 0.6202
7172 Penicillin-binding protein 3 pbp3 0.6202
819 Penicillin-binding protein 4 dacB 0.2702
6184 D-alanyl-D-alanine carboxypeptidase dacC dacC 0.1544
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.146
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.1256
1729 Solute carrier family 22 member 6 SLC22A6 0.1187
6142 Solute carrier family 22 member 8 SLC22A8 0.1008
2858 Beta-lactamase TEM bla 0.099
6396 Beta-lactamase TEM bla 0.099
633 Penicillin-binding proteins 1A/1B pbpA 0.0916
1024 Solute carrier family 22 member 11 SLC22A11 0.0831
587 Serum albumin ALB 0.0794
3760 Penicillin-binding protein 5 precursor dacA 0.0787
118 Organic cation/carnitine transporter 2 SLC22A5 0.0761
1 Peptidoglycan synthetase ftsI ftsI 0.0629
4155 Peptidoglycan synthetase ftsI ftsI 0.0629
115 Penicillin-binding protein 2 mrdA 0.0571
6118 Penicillin-binding protein 2 penA 0.0571
6187 Penicillin-binding protein 2 pbpA 0.0571
6686 Penicillin-binding protein 2 pbp2 0.0571
6939 Penicillin-binding protein 2 mrdA 0.0571
7163 Penicillin-binding protein 2 pbpA 0.0571
6067 Penicillin binding protein 2a mecA 0.0551
6113 MecA PBP2' (penicillin binding protein 2') mecA 0.0476
1198 Serum paraoxonase/arylesterase 1 PON1 0.0453
6223 Penicillin-binding protein 1C pbpC 0.0453
159 Penicillin-binding protein 2B penA 0.0397
6121 Penicillin-binding protein 2B penA 0.0397
6143 Solute carrier family 22 member 7 SLC22A7 0.033
1405 Thiopurine S-methyltransferase TPMT 0.0265
2164 Multidrug resistance-associated protein 4 ABCC4 0.0179
4512 Cytochrome P450 3A4 CYP3A4 0.0061