A clinical isolate expresses a plasmid-encoded beta-lactamase that hydrolyzes the beta-lactam ring. Which modification to therapy directly targets this resistance mechanism?

Switch empirically to a bacteriostatic macrolide that will restore the function of PBPs by competitive displacement of beta-lactamase from the periplasmic compartment.

Administer a subinhibitory dose of the same beta-lactam to induce stress responses in bacteria that downregulate plasmid maintenance and reduce enzyme production within hours.

Increase dosing frequency of the original beta-lactam to flood the enzyme until spontaneous degradation pathways in bacteria eliminate the plasmid-encoded gene.

Combine a beta-lactam antibiotic with a beta-lactamase inhibitor (e.g., clavulanate) that irreversibly or competitively inhibits the enzyme, preserving the antibiotic's intact beta-lactam ring and activity.