Avibactam

Avibactam structure 2

Avibactam is a beta-lactamase inhibitor that is used in combination with antibiotics to treat certain bacterial infections. It works by inhibiting the action of beta-lactamase enzymes, which are produced by some bacteria to confer resistance against beta-lactam antibiotics such as penicillins, cephalosporins, and carbapenems. By blocking these enzymes, avibactam allows the accompanying antibiotic to remain effective against beta-lactamase producing bacteria. Avibactam is not effective on its own and is always used in combination with another antibiotic.

Mechanism of Action

Avibactam functions by binding to the active sites of beta-lactamase enzymes, thereby preventing these enzymes from breaking down the beta-lactam antibiotic. This action helps in preserving the antibacterial activity of the accompanying antibiotic against beta-lactamase producing bacteria. Avibactam has a broad spectrum of activity and can inhibit a wide range of beta-lactamase enzymes, including those belonging to the Ambler class A, class C, and some class D enzymes.

Clinical Uses

Avibactam is combined with ceftazidime, a third-generation cephalosporin, to form a combination drug known as ceftazidime/avibactam. This combination is used for the treatment of complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP). It is particularly useful in treating infections caused by multidrug-resistant Gram-negative bacteria, such as Klebsiella pneumoniae carbapenemase (KPC)-producing organisms, and certain Pseudomonas aeruginosa strains.

Development and Approval

The development of avibactam was motivated by the increasing prevalence of bacterial resistance to existing antibiotics, particularly the emergence of beta-lactamase producing bacteria that are resistant to multiple antibiotic classes. The combination of avibactam with ceftazidime was approved by regulatory agencies to address the critical need for new treatment options against these resistant bacteria.

Side Effects

The use of avibactam, in combination with ceftazidime, can lead to side effects similar to those associated with the use of other beta-lactam antibiotics. These may include gastrointestinal disturbances, such as nausea and diarrhea, as well as allergic reactions, which can range from mild skin rashes to severe anaphylaxis. As with all antibiotics, the use of avibactam/ceftazidime can also lead to the development of Clostridioides difficile-associated diarrhea (CDAD).

Conclusion

Avibactam represents a significant advancement in the fight against antibiotic-resistant bacteria. When used in combination with specific antibiotics, it offers a valuable option for treating infections caused by bacteria that produce beta-lactamase enzymes. Ongoing research and development efforts are focused on expanding the use of avibactam with other antibiotics to combat a broader range of resistant bacterial infections.

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