Antibiotic Dose Optimization at Critically Ill Patient

Abstract

Summary A ntimicrobial agents are some of the most widely and often injudiciously used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection, understanding the difference between empiric and definitive therapy, identifying opportunities to switch to narrow spectrum, cost effective oral agents for the shortest duration necessary, understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection), accounting for host characteristics that influence antimicrobial activity and in turn, recognizing the adverse effects of antimicrobial agents on the host. Inappropriate use of antimicrobial drugs is responsible for therapeutic failures, increased mortality rates, and the emergence of resistance. Antimicrobial activity is determined by intrinsic pharmacokinetics/ pharmacodynamics (PK/ PD) concepts. In critically ill patients, an inappropriate dosing regimen can be caused by the inability of an antimicrobial drug to reach adequate concentrations at the infection site owing to alterations in the drug’s pharmacokinetics caused by pathophysiological changes. Understanding these concepts and changes in PK-PD parameters that occur in intensive care unit patients is crucial for the optimization of antimicrobial therapy in these patients. ICU patients have a higher use of antibiotics, which can result in the development and amplification of multidrug resistant (MDR) and even more resistant infections. The National Healthcare Safety Network found higher rates of antibiotic resistant pathogens in ICU patients than in non-ICU patients. The European Centre for Disease Prevention and Control and the Centers for Disease Control and Prevention recently proposed these definitions:  Multi drug resistant: acquired non susceptibility to at least one agent in three or more antimicrobial categories.  Extensively drug resistant: bacterial isolates remain susceptible to only one or two categories.  Pandrug-resistant: non susceptibility to all agents in all antimicrobial categories. Because of the higher rates of infections and higher rates of antibiotics resistance, the potential for initial inadequate antibiotic selection can be detrimental if clinicians are not vigilant. Inadequate antibiotic use, defined as the use of agents with lack of activity against the pathogen, has been associated with increased mortality, increased hospital and ICU length of stay, and increased cost to the health system. Successful prediction of a patient’s infecting pathogen is the most important initial treatment consideration for critically ill individuals. Considerations before implementing treatment regimens include typical bacterial pathogens for disease states, local susceptibility patterns and antibiogram data, and risk stratification for MDR organisms.