Continuous infusion of β-lactam antibiotics for all critically ill patients?

Excerpt

Infections are common in critically ill patients and are associated with a significant increase in ICU mortality and total costs related to patient management [1]. One of the main therapeutic interventions in severe infections is the administration of antibiotics; however, the prescription of adequate antimicrobial therapy still represents a complex challenge for clinicians because of the late identification of microorganisms and the increasing spread of multidrug-resistant pathogens [2]. International guidelines recommend an early and broad-spectrum antibiotic therapy, typically given as combination therapy, for life-threatening infections [3]. Nevertheless, optimizing antibiotic therapy in critically ill patients also needs to consider the changes in drug pharmacokinetics (PKs), in particular an increased volume of distribution associated with either augmented or impaired renal clearance, which are responsible for variations in circulating antibiotic levels and, potentially, for therapeutic failure [4]. β-lactam antibiotics, which are the first-line therapy for severe infections, are the most effective when drug concentrations exceed the minimal inhibitory concentration (MIC) of the pathogen for an extended period of time between different administrations (T > MIC) [4]. Because of significant and unpredictable changes in drug PKs during critical illness when standard intermittent administrations (IA) are given [4], a continuous infusion (CI) of β-lactam antibiotics could rapidly obtain prolonged T > MIC in almost all patients and even for less susceptible pathogens, such as Pseudomonas aeruginosa or Acinetobacter baumannii, and should be preferred to optimize daily drug regimens in critically ill patients [5] (Fig. 1a). However, the evidence supporting that CI would also result in a better outcome when compared to standard regimens remains limited.

…