What are beta-lactam (β-lactam) antibiotics?

Beta-Lactam Antibiotics: An Overview

Beta-lactam antibiotics are a major class of antibiotics characterized by their beta-lactam ring structure that inhibit bacterial cell wall synthesis, leading to bacterial death. 1, 2

Classification of Beta-Lactam Antibiotics

Beta-lactam antibiotics are divided into several major classes:

1. Penicillins

   • Natural penicillins (e.g., penicillin G)
   • Penicillinase-resistant penicillins (e.g., methicillin, oxacillin)
   • Aminopenicillins (e.g., amoxicillin, ampicillin)
   • Extended-spectrum penicillins (e.g., piperacillin)

2. Cephalosporins (grouped by generations)

   • First generation (e.g., cefazolin)
   • Second generation (e.g., cefuroxime)
   • Third generation (e.g., ceftriaxone)
   • Fourth generation (e.g., cefepime)
   • Fifth generation (e.g., ceftaroline)

3. Carbapenems

   • Imipenem, meropenem, ertapenem

4. Monobactams

   • Aztreonam

Mechanism of Action

Beta-lactam antibiotics work by:

• Binding to penicillin-binding proteins (PBPs) in bacterial cell walls
• Inhibiting cell wall biosynthesis by preventing cross-linking of peptidoglycan layers
• Causing bacterial cell lysis and death 1, 3

Spectrum of Activity

Different beta-lactam classes have varying spectra of activity:

• Penicillins: Generally effective against gram-positive bacteria, with extended-spectrum penicillins having broader activity against gram-negative organisms 3

• Cephalosporins: Broader spectrum with increasing generations; later generations have improved gram-negative coverage 1

• Carbapenems: Broadest spectrum among beta-lactams, active against most gram-positive and gram-negative bacteria including Pseudomonas (imipenem, meropenem) 4

• Monobactams (Aztreonam): Specifically active against aerobic gram-negative bacteria including Pseudomonas aeruginosa, with no activity against gram-positive or anaerobic bacteria 4

Resistance Mechanisms

The primary mechanism of resistance to beta-lactam antibiotics is:

• Beta-lactamase production: Bacterial enzymes that hydrolyze the beta-lactam ring, rendering the antibiotic inactive 5, 6
• Other mechanisms include altered penicillin-binding proteins and decreased permeability

Beta-Lactamase Inhibitors

To overcome beta-lactamase-mediated resistance, beta-lactamase inhibitors are often combined with beta-lactam antibiotics:

• Common inhibitors: Clavulanate, sulbactam, tazobactam
• Common combinations: Amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam
• These inhibitors protect the partner beta-lactam from degradation by beta-lactamases 6

Clinical Considerations

Dosing in Critical Illness

• Higher daily doses of beta-lactams are recommended in critically ill patients, especially those with preserved renal function 1
• Continuous or extended infusions may be preferred to maintain concentrations above the MIC (minimum inhibitory concentration) 1

Neurotoxicity Risk

• Beta-lactams can cause neurotoxicity, particularly at high concentrations
• Relative pro-convulsive activity varies among beta-lactams (from highest to lowest): cefazolin > cefepime > penicillin G > imipenem > aztreonam > other beta-lactams 1
• Risk increases with renal impairment and high plasma concentrations 1

Cross-Reactivity in Allergies

• Patients with penicillin allergies may safely receive aztreonam (except those with ceftazidime allergy due to shared side chains) 1
• Carbapenems can generally be administered to patients with penicillin or cephalosporin allergies, as long as the reaction was not a severe delayed cutaneous or organ-involved reaction 1

Antibiotic Stewardship Considerations

• Implementation of beta-lactam allergy pathways in healthcare systems is recommended to improve antibiotic stewardship 1
• Therapeutic drug monitoring (TDM) is valuable for optimizing beta-lactam dosing, particularly in critically ill patients 1
• Target plasma concentrations should generally be 4-8 times the MIC of the pathogen, while avoiding excessive concentrations that may cause neurotoxicity 1

Beta-lactams remain among the most important and widely used antibiotics in clinical practice, with ongoing development of new agents and inhibitor combinations to address evolving resistance patterns 5, 2.