Is Aztreonam (a beta-lactam antibiotic) a beta-lactam?

From the Guidelines

Aztreonam is a beta-lactam antibiotic, but it can be safely used in patients with penicillin allergies, except for those with a history of ceftazidime allergy, due to its unique molecular structure that minimizes cross-reactivity. This is supported by the most recent and highest quality study, which suggests that aztreonam may be administered without prior testing in patients with a history of penicillin or cephalosporin allergy, unless there is a history of ceftazidime allergy 1. Aztreonam belongs to a specific class of beta-lactams called monobactams, which have a unique structure containing a single beta-lactam ring not fused to another ring.

Key Characteristics of Aztreonam

• Aztreonam is primarily active against aerobic gram-negative bacteria, including Pseudomonas aeruginosa, but lacks activity against gram-positive and anaerobic organisms.
• It works by binding to penicillin-binding proteins and inhibiting bacterial cell wall synthesis, leading to cell death.
• Clinically, aztreonam is often used for treating serious gram-negative infections, particularly in patients who cannot tolerate other antibiotics due to allergies or adverse effects.

Safety in Penicillin-Allergic Patients

• The study published in 2022 1 provides a consensus-based statement that aztreonam may be administered without prior testing in patients with a history of penicillin or cephalosporin allergy, unless there is a history of ceftazidime allergy.
• This is because aztreonam is less immunogenic and rarely causes hypersensitivity reactions, with no cross-reactivity for IgE- or T-cell–mediated hypersensitivity between penicillin and aztreonam, except for ceftazidime.
• Patients who are penicillin- and cephalosporin-allergic may safely receive aztreonam without prior testing, with the exception of patients who are confirmed allergic to ceftazidime.

Clinical Use

• Aztreonam has become a commonly used acute therapeutic drug for patients with penicillin or cephalosporin allergy histories.
• However, it does not have activity against aerobic and anaerobic gram-positive bacteria, is not as effective against gram-negative bacteria as other beta-lactams, has increasing rates of resistance, and is costly.
• Therefore, aztreonam is now a common target for antibiotic stewardship efforts, especially in patients with reported penicillin allergy 1.

From the FDA Drug Label

AZACTAM® (aztreonam for injection, USP) contains the active ingredient aztreonam, a monobactam. It was originally isolated from Chromobacterium violaceum. It is a synthetic bactericidal antibiotic. The monobactams, having a unique monocyclic beta-lactam nucleus, are structurally different from other beta-lactam antibiotics (eg, penicillins, cephalosporins, cephamycins)

• Aztreonam is a monobactam, which is a type of beta-lactam antibiotic, but it has a unique monocyclic beta-lactam nucleus that is structurally different from other beta-lactam antibiotics.
• The key point is that while aztreonam has a beta-lactam nucleus, it is not the same as other beta-lactam antibiotics like penicillins or cephalosporins.
• Therefore, aztreonam is technically a beta-lactam, but it belongs to a specific subclass called monobactams 2.

From the Research

Aztreonam Classification

• Aztreonam is classified as a beta-lactam antibiotic, specifically a monobactam, which is a unique class of beta-lactam antibiotics with a single ring configuration 3, 4, 5, 6, 7.

Characteristics of Aztreonam

• Aztreonam has a synthetic structure that determines its specific areas of activity, including enhanced activity against Pseudomonas species and gram-negative bacteria 3.
• It has a high affinity for the protein-binding protein 3 (PBP-3) of aerobic gram-negative bacteria, which contributes to its effectiveness against these organisms 3.
• Aztreonam is stable to beta-lactamases and lacks activity against gram-positive bacteria, making it a useful alternative to other antibiotics in certain situations 3, 4, 5, 6.

Spectrum of Activity

• Aztreonam is selectively active against gram-negative aerobic bacteria and inactive against gram-positive bacteria and anaerobes 4, 5, 6.
• It is effective against Enterobacteriaceae, Pseudomonas aeruginosa, and other gram-negative bacteria, but not against gram-positive bacteria or anaerobes 3, 4, 5, 6.

Pharmacokinetics and Pharmacodynamics

• Aztreonam is rapidly distributed to most body tissues and fluids when administered parenterally, with a serum half-life of 1.7 hours 3, 5, 7.
• It is primarily eliminated unchanged in the urine, with a small amount excreted as a microbiologically inactive metabolite 3, 5, 7.
• Aztreonam has been shown to be effective in treating various gram-negative infections, including urinary tract infections, lower respiratory tract infections, and septicemia 4, 5, 6.