When are combinations of antibiotics clinically useful?

Antimicrobial resistance is a global crisis. Prescribing antibacterial combinations may be one way of reducing the development of resistance in target pathogens, as in the treatment of tuberculosis. Combinations may be useful for ascertaining synergy, broadening antimicrobial cover to reduce the risk of non-susceptibility, antimicrobial stewardship reasons, and immune modulation. The current research literature and/or prevailing global standards of clinical care suggest that combination therapy may be advantageous in: severe community-acquired pneumonia; severe hospital-acquired or ventilator-associated pneumonia or when there is a high risk of resistance in hospital-acquired or ventilator-associated pneumonia; multi-drug or extensively drug-resistant Gram-negative infections; and severe group A streptococcal infections. In other situations, combinations may be harmful. Overall, outside of tuberculosis, combination antibacterial therapy is likely to improve outcomes only in specific circumstances and there is little evidence to suggest that this prevents the development of bacterial resistance. Further high-quality research is essential.