What are beta-lactamase inhibitors?

From the Guidelines

Beta-lactamase inhibitors are compounds that block bacterial enzymes (beta-lactamases) that would otherwise destroy beta-lactam antibiotics, making them ineffective. These inhibitors are typically combined with beta-lactam antibiotics to overcome bacterial resistance. Common beta-lactamase inhibitors include clavulanic acid, sulbactam, tazobactam, avibactam, vaborbactam, and relebactam. They're found in combination medications such as amoxicillin-clavulanate (Augmentin), ampicillin-sulbactam (Unasyn), piperacillin-tazobactam (Zosyn), ceftazidime-avibactam (Avycaz), and meropenem-vaborbactam (Vabomere) 1. These combinations are particularly useful for treating infections caused by resistant organisms that produce beta-lactamases. The inhibitors work by binding irreversibly to the beta-lactamase enzymes, preventing them from destroying the antibiotic component. This allows the antibiotic to reach its target and disrupt bacterial cell wall synthesis. When prescribing these combinations, it's essential to consider the specific resistance patterns in your region, potential side effects (which can include gastrointestinal disturbances, allergic reactions, and rarely liver dysfunction), and to adjust dosing in patients with renal impairment as most of these drugs are eliminated through the kidneys. Some key points to consider when using beta-lactamase inhibitors include:

• The choice of empiric antibiotic regimens should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.
• The use of carbapenems should be limited to preserve the activity of this class of antibiotics due to the concern of emerging carbapenem-resistance 1.
• Ceftazidime/avibactam plus aztreonam is recommended for the treatment of infections caused by metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) 1.
• Cefiderocol may also be considered as an alternative option for infections caused by MBL-producing CRE 1.
• Sulbactam-containing combination therapies have demonstrated clinical benefits, and ampicillin-sulbactam and cefoperazone-sulbactam are available options 1.

From the FDA Drug Label

Tazobactam sodium has little clinically relevant in vitro activity against bacteria due to its reduced affinity to penicillin-binding proteins. It is, however, a beta-lactamase inhibitor of the Molecular class A enzymes, including Richmond-Sykes class III (Bush class 2b & 2b') penicillinases and cephalosporinases. Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate some beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins.

Beta-lactamase inhibitors are compounds that inhibit the action of beta-lactamase enzymes, which are produced by some bacteria and can inactivate beta-lactam antibiotics, such as penicillins and cephalosporins.

• Examples of beta-lactamase inhibitors include tazobactam and clavulanic acid.
• These inhibitors work by binding to the beta-lactamase enzyme, preventing it from breaking down the antibiotic, and thereby extending the spectrum of activity of the antibiotic to include bacteria that would otherwise be resistant 2 3.

From the Research

Definition and Mechanism of Beta-Lactamase Inhibitors

• Beta-lactamase inhibitors are compounds that are used in combination with beta-lactam antibiotics to combat bacterial resistance mechanisms 4, 5, 6, 7, 8.
• These inhibitors work by inactivating beta-lactamases, which are enzymes produced by bacteria that break down beta-lactam antibiotics, thereby rendering them ineffective 5, 6, 7.

Types and Combinations of Beta-Lactamase Inhibitors

• There are several types of beta-lactamase inhibitors, including clavulanate, sulbactam, and tazobactam, which are often combined with beta-lactam antibiotics such as amoxicillin, ampicillin, piperacillin, and ticarcillin 6, 7, 8.
• Examples of beta-lactam/beta-lactamase inhibitor combinations include piperacillin/tazobactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid 4.

Clinical Applications and Efficacy

• Beta-lactamase inhibitors have been shown to be effective in treating a range of infections, including respiratory, intra-abdominal, and skin and soft tissue infections 5, 8.
• They are particularly useful against mixed infections and have a role in treating multi-resistant pathogens such as Acinetobacter species and Stenotrophomonas maltophilia 5.
• However, their efficacy against extended-spectrum beta-lactamase producers is limited, and their use may contribute to the emergence of resistance 4, 7.

Factors Influencing Activity and Pharmacodynamics

• The activity and pharmacodynamics of beta-lactamase inhibitors are influenced by several factors, including the potency of the inhibitor and the beta-lactam antibiotic, the type and quantity of beta-lactamase produced by the target bacterium, and the pharmacokinetics of the inhibitor 6.
• The choice of beta-lactamase inhibitor combination can also impact efficacy, with some combinations showing greater activity against certain types of bacteria 4, 6.