Harnessing combination therapy to combat drug-resistant bacteria: toward effective treatments

Abstract

Antimicrobial resistance (AMR) occurs when microorganisms such as bacteria, viruses, fungi, and parasites evolve to withstand drugs designed to eliminate them, making infections harder to treat. This global health threat is driven largely by antibiotic misuse and overuse in humans, animals, and agriculture. Combination therapy using two or more agents with different mechanisms offers a promising approach to improve treatment outcomes and slow resistance development. FDA-approved drugs examples include amoxicillin–clavulanate and piperacillin–tazobactam, both of which pair a β-lactam antibiotic with a β-lactamase inhibitor to restore drug activity. This review followed a structured literature search of studies published in the last 15 years from databases such as PubMed, ScienceDirect, Google Scholar, and Springer Nature, focusing on resistance mechanisms, clinical applications, and therapeutic outcomes. This review aims to highlight combination therapy’s potential as a strategic tool against multidrug-resistant pathogens and to guide more effective, personalized treatment strategies in the era of rising AMR.