Monobactams

Monobactams

1. MONOBACTAMS

2. Introduction
Monobactams is a subgroup of β-lactam antibiotics wherein the β-lactam ring is alone and not
fused to another ring, in contrast to most other β-lactams (such as penicillins, cephalosporins,
and carbapenems).
Monobactams were discovered in 1980s. Aztreonam was approved for medical use in the United
States in 1986.

4. Monobactams are effective only against aerobic Gram-negative bacteria (e.g., Neisseria,
Pseudomonas).

Siderophore-conjugated monobactams show promise for the treatment of multi drug-resistant
pathogens. (Siderophores: iron-chelating compounds)

5. Classification

Aztreonam is commercially available monobactam antibiotic. Other examples of monobactams
are tigemonam, nocardicin A, and tabtoxin.

6. Aztreonam

2-[(Z)-[1-(2-Amino-1,3-thiazol-4-yl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-
yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid

7. Tigemonam

2-[[1-(2-Amino-1,3-thiazol-4-yl)- 2-[[(3S)-2,2-dimethyl-4-oxo-1- sulfooxyazetidin-3-
yl]amino]-2- oxoethylidene]amino]oxyacetic acid

8. Nocardicin A

(2R)-2-Amino-4-[4-[N-hydroxy-C-[[(3S)-1- [(1R)-2-hydroxy-1-(4-hydroxyphenyl)-2-
oxoethyl]-2-oxoazetidin-3- yl]carbamoyl]carbonimidoyl]phenoxy]butanoic acid

9. Tabtoxin
also known as wildfire toxin

(2S,3R)-2-{(2S)-2-Amino-4-[(3S)-3-hydroxy-2-oxoazetidin-3-yl]butanamido}-3-
hydroxybutanoic acid

10. Mechanism of action

They inhibit synthesis of the bacterial cell wall, by blocking peptidoglycan crosslinking. They
have a very high affinity for penicillin-binding protein-3 and mild affinity for penicillin-binding
protein-1a. They bind the penicillin-binding proteins of Gram-positive and anaerobic bacteria
very poorly and are largely ineffective against them.

13. In absence of monobactams

14. In presence of monobactams

15. Video:

https://www.youtube.com/watch?v=WSpLwWyquoQ

https://www.youtube.com/watch?v=e6Ei6rBDaPo

16. Therapeutic Uses

Aztreonam, sold under the brand name Azactam used primarily to treat infections caused by
gram-negative bacteria such as Pseudomonas aeruginosa.

17. Mycobacterial disease
Infections in people who have received lung transplants
Bone infections
Endometritis
Intra-abdominal infections
Pneumonia
Urinary tract infections
Sepsis

18. Structure Activity Relationships

20. Stereochemistry of 4-methyl group should be identical to the penicillin and cephalosporin
antibiotics.

Beta lactam ring is essential for antibacterial activity. Any modification in the beta lactam ring
ring result in loss of activity.

Removal/ replacement of hetero N-atom by any other atom (such as C, S, or O) result in loss of
activity.

21. Adverse Effects

Skin rash

Occasional abnormal liver functions

Monobactams can trigger seizures in patients with history of seizures, although the risk is
lower than with penicillins.

22. Common side effects when given by injection include pain at the site of injection, vomiting,
skin rash, rarely toxic epidermal necrolysis.
Common side effects when inhaled include wheezing, cough, and vomiting. Serious side effects
include Clostridium difficile infection and allergic reactions including anaphylaxis.
Gastrointestinal side effects generally include diarrhoea, nausea and vomiting. There may be
drug-induced eosinophilia.
Those who are allergic to other β-lactams have a low rate of allergy to aztreonam. Use in
pregnancy appears to be safe.

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