DT-Web

DB00355 - Aztreonam


Identification
Name Aztreonam
Accession Number DB00355 (APRD00815, EXPT00605)
Type small molecule
Description A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with gram-positive organisms. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 435.433
Groups approved
Monoisotopic Weight 435.051853925
Pharmacology
Indication For the treatment of the following infections caused by susceptible gram-negative microorganisms: urinary tract infections, lower respiratory tract infections, septicemia, skin and skin-structure infections, intra-abdominal infections, and gynecologic infections.
Mechanism of action The bactericidal action of aztreonam results from the inhibition of bacterial cell wall synthesis due to a high affinity of aztreonam for penicillin binding protein 3 (PBP3). By binding to PBP3, aztreonam inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that aztreonam interferes with an autolysin inhibitor.
Absorption Less than 1% absorbed from the gastrointestinal tract following oral administration. Completely absorbed following intramuscular administration.
Protein binding Serum protein binding averaged 56% and is independent of dose. Impaired renal function, 36 to 43%.
Biotransformation Approximately 6 to 16% metabolized to inactive metabolites by hydrolysis of the beta-lactam bond, resulting in an open-ring compound.
Route of elimination In healthy subjects, aztreonam is excreted in the urine about equally by active tubular secretion and glomerular filtration. Urinary excretion of a single parenteral dose was essentially complete by 12 hours after injection.
Toxicity Not Available
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
Minocycline Possible antagonism of action
Tetracycline Possible antagonism of action
Food Interactions Not Available

Targets


Penicillin-binding protein 3
Name Penicillin-binding protein 3
Gene Name pbpC
Pharmacological action yes
Actions inhibitor
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
  • 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
  • Rittenbury MS: How and why aztreonam works. Surg Gynecol Obstet. 1990;171 Suppl:19-23. - Pubmed
  • Mock CN, Jurkovich GJ, Dries DJ, Maier RV: Clinical significance of antibiotic endotoxin-releasing properties in trauma patients. Arch Surg. 1995 Nov;130(11):1234-40; discussion 1240-1. - Pubmed
  • Fung-Tomc J, Bush K, Minassian B, Kolek B, Flamm R, Gradelski E, Bonner D: Antibacterial activity of BMS-180680, a new catechol-containing monobactam. Antimicrob Agents Chemother. 1997 May;41(5):1010-6. - Pubmed
DTHybrid score 0.9145
Beta-lactamase
Name Beta-lactamase
Gene Name ampC
Pharmacological action yes
Actions potentiator
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
  • 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
  • Poirel L, Brinas L, Fortineau N, Nordmann P: Integron-encoded GES-type extended-spectrum beta-lactamase with increased activity toward aztreonam in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005 Aug;49(8):3593-7. - Pubmed
  • Diaz N, Suarez D, Sordo TL: Molecular dynamics simulations of class C beta-lactamase from Citrobacter freundii: insights into the base catalyst for acylation. Biochemistry. 2006 Jan 17;45(2):439-51. - Pubmed
  • Mirelis B, Rivera A, Miro E, Mesa RJ, Navarro F, Coll P: A simple phenotypic method for differentiation between acquired and chromosomal AmpC beta-lactamases in Escherichia coli. Enferm Infecc Microbiol Clin. 2006 Jun-Jul;24(6):370-2. - Pubmed
DTHybrid score 0.0611

Predictions


Id Partner name Gene Name Score
6119 Penicillin-binding protein 3 pbp3 0.9145
7154 Penicillin-binding protein 3 pbp3 0.9145
7157 Penicillin-binding protein 3 LMHCC_2184 0.9145
7162 Penicillin-binding protein 3 pbpB 0.9145
7172 Penicillin-binding protein 3 pbp3 0.9145
543 Penicillin-binding protein 1B mrcB 0.1109
6186 Penicillin-binding protein 1B ponB 0.1109
6822 Penicillin-binding protein 1b pbp1b 0.1109
6844 Penicillin-binding protein 1b pbp1b 0.1109
645 Penicillin-binding protein 1A mrcA 0.109
5805 Penicillin-binding protein 1A ponA 0.109
6185 Penicillin-binding protein 1A mrcA 0.109
6799 Penicillin-binding protein 1A pbpA 0.109
819 Penicillin-binding protein 4 dacB 0.0673
332 Beta-lactamase blaZ 0.0611
2478 Beta-lactamase ampC 0.0611
2613 Beta-lactamase ampC 0.0611
2700 Beta-lactamase penP 0.0611
5445 Beta-lactamase blaB 0.0611
6019 Beta-lactamase SHV-7 0.0611
6701 Beta-lactamase cphA 0.0611
115 Penicillin-binding protein 2 mrdA 0.0523
6069 Penicillin-binding protein 2 mrdA 0.0523
6118 Penicillin-binding protein 2 penA 0.0523
6187 Penicillin-binding protein 2 pbpA 0.0523
6686 Penicillin-binding protein 2 pbp2 0.0523
6939 Penicillin-binding protein 2 mrdA 0.0523
7163 Penicillin-binding protein 2 pbpA 0.0523
159 Penicillin-binding protein 2B penA 0.0224
6121 Penicillin-binding protein 2B penA 0.0224
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0181
1024 Solute carrier family 22 member 11 SLC22A11 0.0178
6143 Solute carrier family 22 member 7 SLC22A7 0.0173
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0173
6142 Solute carrier family 22 member 8 SLC22A8 0.0154
1729 Solute carrier family 22 member 6 SLC22A6 0.0141
↑