Topic overview

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Combination therapy is considered in situations such as severe sepsis, neutropenia, polymicrobial infection, endocarditis, tuberculosis, and initial treatment of hospital-acquired or ventilator-associated pneumonia. The choice depends on the intended goal and the likely pathogens. Some combinations broaden coverage or improve killing, while others can interfere with antibiotic activity. Pharmacodynamic effects may be assessed using time-kill or checkerboard methods. Combinations also bring trade-offs, including renal toxicity with aminoglycoside-based regimens and broader risks from routine, unnecessary dual therapy. A key stewardship principle is to reassess therapy when the pathogen and susceptibilities are known, then stop the second agent when it is no longer needed.