The effect of combining antibiotics on resistance: A systematic review and meta-analysis.

Antimicrobial resistance is a threat to human health. Antibiotic combinations potentially reduce resistance. However, conflicting data exists on its effectiveness. To test the effect of antibiotic combination therapy on resistance, we conducted a meta-analysis of clinical evidence, comparing higher and lower numbers of antibiotics across various bacterial infections and antibiotic combinations. We update and expand on previous work that focused on specific infections and antibiotic combinations. Overall, we found no statistical evidence for a difference in the risk of resistance acquisition due to lack of power. Thus, despite the increasing threat of antibiotic resistance, it remains unresolved whether combination therapy de- or accelerates resistance evolution of bacterial pathogens beyond the well-known conditions where combination therapy is the standard of care.