relebaktam

Relebaktam is a beta-lactamase inhibitor used in combination with a beta-lactam antibiotic to counteract resistance in certain Gram-negative bacteria. It belongs to the diazabicyclooctane (DBO) class of inhibitors and is co-formulated most commonly with imipenem and cilastatin.

Mechanism of action and spectrum

Relebaktam inhibits serine beta-lactamases, particularly class A enzymes such as KPC and class C AmpC enzymes. By inhibiting these enzymes, it protects the partner beta-lactam (imipenem) from enzymatic degradation, restoring or extending its activity against susceptible bacteria. It does not inhibit metallo-beta-lactamases (class B) and its effectiveness depends on the presence of beta-lactamases that relebaktam can inhibit, as well as the bacterial strain’s permeability and other resistance mechanisms.

Clinical use

Relebaktam is approved for use in combination with imipenem/cilastatin for adults with complicated urinary tract infections, complicated intra-abdominal infections, and hospital-acquired or ventilator-associated bacterial pneumonia when caused by susceptible organisms. It is intended for use in settings where beta-lactamase–producing pathogens limit the activity of standard beta-lactams.

Administration and pharmacology

The combination is given by intravenous infusion, with dosing tailored to renal function. The typical regimen uses a fixed amount of relebaktam with imipenem and cilastatin every six hours, and dosing may be adjusted in patients with renal impairment. Relebaktam is primarily eliminated by the kidneys and achieves systemic and tissue concentrations sufficient for activity in the indicated infections.

Adverse effects and resistance

Common adverse events include gastrointestinal symptoms (nausea, diarrhea), headache, and potential hypersensitivity reactions. As with other carbapenem-containing regimens, there is a risk of Clostridioides difficile infection and, in high doses, seizure risk. Resistance may emerge through beta-lactamase variants not inhibited by relebaktam, porin changes, or efflux, and is influenced by the organism and site of infection.