Past, present, and future perspectives on aztreonam and avibactam

Area of Science:

• Antimicrobial resistance
• Pharmacology
• Infectious diseases

Background:

• Aztreonam, a monobactam antibiotic, lost clinical utility against Gram-negative bacteria due to resistance enzymes like extended-spectrum β-lactamases (ESBLs).
• Avibactam emerged as a novel non-β-lactam β-lactamase inhibitor, effectively combating these resistance mechanisms.
• Avibactam is approved in combination with ceftazidime and aztreonam to treat infections caused by bacteria producing various β-lactamases.

Purpose of the Study:

• To provide a historical perspective on the development of aztreonam, avibactam, and their combinations.
• To review preclinical and clinical data on these antimicrobial agents.
• To assess the clinical utility of avibactam combinations in treating multidrug-resistant Gram-negative infections.

Main Methods:

• Literature search of MEDLINE (Ovid) to identify relevant studies.
• Analysis of preclinical and clinical data on aztreonam and avibactam.
• Historical review of antimicrobial development and resistance patterns.

Main Results:

• Avibactam combinations with ceftazidime and/or aztreonam demonstrate efficacy against Gram-negative bacteria producing multiple β-lactamases.
• Aztreonam combinations show particular promise due to stability against metallo-β-lactamase hydrolysis.
• These combinations offer treatment options for previously untreatable infections, with aztreonam combinations being advantageous for penicillin-allergic patients.

Conclusions:

• Avibactam, in combination with ceftazidime and aztreonam, provides crucial treatment options for multidrug-resistant Gram-negative infections.
• Aztreonam-based combinations are valuable due to their stability against metallo-β-lactamases and safety profile.
• Ongoing development of other inhibitor combinations may present future therapeutic alternatives.