Abstract
Sepsis is life-threatening organ dysfunction due to a dysregulated host response to an underlying acute infection. Sepsis is a major worldwide healthcare problem. An annual estimated 48.9 million incident cases of sepsis is reported, with 11 million (20%) sepsis-related deaths. Administration of appropriate antimicrobials is one of the most effective therapeutic interventions to reduce mortality. The severity of illness informs the urgency of antimicrobial administration. Nevertheless, even used properly, they cause adverse effects and contribute to the development of antibiotic resistance. Both inadequate and unnecessarily broad empiric antibiotics are associated with higher mortality and also select for antibiotic-resistant germs. In this narrative review, we will first discuss important factors and potential confounders which may influence the occurrence of surgical site infection (SSI) and which should be considered in the provision of perioperative antibiotic prophylaxis (PAP). Then, we will summarize recent advances and perspectives to optimize antibiotic therapy in the intensive care unit (ICU). Finally, the major role of the microbiota and the impact of antimicrobials on it will be discussed. While expert recommendations help guide daily practice in the operating theatre and ICU, a thorough knowledge of pharmacokinetic/pharmacodynamic (PK/PD) rules is critical to optimize the management of complex patients and minimize the emergence of multidrug-resistant organisms.