A mortality benefit from combination antimicrobial therapy has not been clearly demonstrated in sepsis. However, when only the most severely-ill patients (i.e., septic shock) are considered in subgroup analysis, there appears to be a mortality benefit to using two antimicrobials against a suspected organism.
Combination antimicrobial therapy may reduce mortality through three mechanisms.
Increased probability that the causative organism will respond to at least one drug.
Preventing emergence of antimicrobial resistance.
Two antimicrobials may act synergistically.
Always obtain appropriate cultures before initiating therapy. Although identification and susceptibility of the organism may take some time, eventually narrowing antimicrobial therapy to monotherapy in the ICU is still recommended.
References
Abad, C. Antimicrobial Therapy of Sepsis and Septic Shock: When are Two Drugs Better Than One? Crit Care Clinic 27 (2011) e1-e27.
