Rationale for Antimicrobial Combinations

Introduction & the monotherapy default

• Antimicrobial combination therapy — the concurrent use of more than one antimicrobial agent (AMA) for a single infectious indication — justified only with a specific purpose, never blindly in the hope that "if one is good, two should be better."
• Monotherapy is the rule — for definitive therapy, combination is the exception; once a pathogen is isolated a single agent is preferred unless compelling data favour a combination. Severity of infection is not in itself an indication to combine, and combinations are no substitute for an accurate diagnosis.
• Cost of needless combining — using multiple drugs where one would suffice increases toxicity and inflicts unnecessary damage on the protective bacterial/fungal flora; combinations are therefore reserved for defined "special circumstances."
• Scope — this answer concerns the rationale, mechanisms of synergy, resistance-prevention, disadvantages and in-vitro testing of antimicrobial combinations — not fixed-dose combinations generically, nor the molecular mechanisms of resistance per se.