Synergistic Antibiotic Combinations

Synergy between antibiotics is a strictly defined microbiological phenomenon, requiring two bioactive agents to exhibit enhanced bacterial killing when the two are combined. Because of increasing antibiotic resistance, and few new drugs to treat multidrug-resistant bacteria, combination therapy is often used in the clinical setting. Frequently, these combinations have demonstrated synergistic activity both in vitro and in animal models before being used therapeutically. Antibiotic combinations are more likely to be used in patients with drug-resistant staphylococcal or enterococcal infections, as well as in patients whose diseases are caused by carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, or Acinetobacter spp. Although well-defined combinations have been approved by regulatory authorities as single agents, such as trimethoprim–sulfamethoxazole or β-lactamase inhibitor combinations, many combinations are used empirically with no clinical data to support their use. Because combination therapy will continue to be used in the absence of supportive clinical data, it will be important in the future to investigate mechanistic principles that may lead to predictive models for successful patient outcomes.