What non-penicillin antibiotics can potentiate the effects of penicillin (antibiotic)?

From the Guidelines

Non-penicillin antibiotics that can potentiate the effects of penicillin include beta-lactamase inhibitors such as clavulanic acid, sulbactam, and tazobactam, as well as aminoglycosides like gentamicin and tobramycin. These compounds work by either inhibiting bacterial enzymes that degrade penicillins or by synergistically enhancing antibacterial activity through different mechanisms. Some key combinations that potentiate the effects of penicillins include:

• Amoxicillin-clavulanate (Augmentin)
• Ampicillin-sulbactam (Unasyn)
• Piperacillin-tazobactam (Zosyn)
• Gentamicin or tobramycin in combination with penicillins for severe infections 1. The beta-lactamase inhibitors bind to and inactivate bacterial enzymes (beta-lactamases) that would otherwise destroy penicillin antibiotics, allowing the antibiotic to reach its target and disrupt bacterial cell wall synthesis 1. Aminoglycosides, on the other hand, work synergistically with penicillins through different mechanisms, enhancing overall antibacterial activity when used in combination therapy for severe infections 1. It's worth noting that the most recent and highest quality study 1 does not directly address the question of non-penicillin antibiotics that can potentiate the effects of penicillin, but the principles of antibiotic combination therapy are well-established in the medical literature 1.

From the FDA Drug Label

The potential for pharmacokinetic drug interactions between piperacillin and tazobactam and aminoglycosides, probenecid, vancomycin, heparin, vecuronium, and methotrexate has been evaluated [see Drug Interactions (7)]. 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.

The non-penicillin antibiotics that can potentiate the effects of penicillin are:

• Aminoglycosides 2 Note that the label does not provide a comprehensive list of non-penicillin antibiotics that can potentiate the effects of penicillin. The information provided is limited to the specific drug interactions evaluated for piperacillin and tazobactam.

From the Research

Non-Penicillin Antibiotics that Potentiate the Effects of Penicillin

• The following non-penicillin antibiotics can potentiate the effects of penicillin:
  • Tazobactam 3, 4, 5, 6, 7
  • Clavulanic acid 4, 6, 7
  • Sulbactam 3, 4, 7

Mechanism of Action

• These antibiotics work by inhibiting beta-lactamase enzymes, which are produced by certain bacteria to resist the effects of penicillin 4, 6, 7

Examples of Combinations

• Piperacillin/tazobactam 3, 4, 5, 6, 7
• Ticarcillin/clavulanic acid 3, 4
• Ampicillin/sulbactam 4
• Amoxicillin/clavulanate 4

Spectrum of Activity

• These combinations have a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria 5, 6, 7

Clinical Efficacy

• Clinical trials have demonstrated the efficacy of these combinations in treating various infections, including intra-abdominal infections, skin and soft tissue infections, and lower respiratory tract infections 5, 6