Is two (antibiotics) better than one?

Area of Science:

• Critical Care Medicine
• Infectious Diseases
• Pharmacology

Background:

• The optimal antibiotic strategy for severe sepsis and septic shock is debated.
• Some evidence suggests combination therapy improves outcomes in high-mortality patients.
• Recent trials present conflicting data regarding combination therapy efficacy.

Purpose of the Study:

• To discuss the reasons behind conflicting findings on antibiotic combination therapy in severe sepsis.
• To reconcile divergent results from randomized and non-randomized studies.

Main Methods:

• Review and discussion of existing literature, including a large randomized multicentric clinical trial.
• Comparison of findings from randomized controlled trials and non-randomized observational studies.

Main Results:

• A recent large randomized trial found no significant advantage of meropenem plus moxifloxacin over meropenem monotherapy for sepsis-related organ dysfunction.
• Mortality rates at 28 and 90 days were similar between combination and monotherapy groups in the trial.
• Non-randomized studies have reported contrasting observations.

Conclusions:

• Conflicting evidence exists regarding the benefit of antibiotic combination therapy in severe sepsis.
• Further investigation is needed to understand the discrepancies and guide clinical practice.
• The discussion aims to clarify the role of combination therapy in managing severe sepsis and septic shock.