Rationalizing antimicrobial therapy in the ICU: a narrative review

Abstract

The massive consumption of antibiotics in the ICU is responsible for substantial ecological side effects that promote the dissemination of multidrug-resistant bacteria (MDRB) in this environment. Strikingly, up to half of ICU patients receiving empirical antibiotic therapy have no definitively confirmed infection, while de-escalation and shortened treatment duration are insufficiently considered in those with documented sepsis, highlighting the potential benefit of implementing antibiotic stewardship programs (ASP) and other quality improvement initiatives. The objective of this narrative review is to summarize the available evidence, emerging options, and unsolved controversies for the optimization of antibiotic therapy in the ICU. Published data notably support the need for better identification of patients at risk of MDRB infection, more accurate diagnostic tools enabling a rule-in/rule-out approach for bacterial sepsis, an individualized reasoning for the selection of single-drug or combination empirical regimen, the use of adequate dosing and administration schemes to ensure the attainment of pharmacokinetics/pharmacodynamics targets, concomitant source control when appropriate, and a systematic reappraisal of initial therapy in an attempt to minimize collateral damage on commensal ecosystems through de-escalation and treatment-shortening whenever conceivable. This narrative review also aims at compiling arguments for the elaboration of actionable ASP in the ICU, including improved patient outcomes and a reduction in antibiotic-related selection pressure that may help to control the dissemination of MDRB in this healthcare setting.

Novel Approaches to Hasten Detection of Pathogens and Antimicrobial Resistance in the Intensive Care Unit

“…However, it is important to realize that RDTs are simply a tool and needs effective implementation to optimize ICU patient and stewardship outcomes. 79 Studies have consistently demonstrated a shorter time to the administration of appropriate antibiotics, as well as decreased costs, length of stay, and mortality with RDTs. A recent meta-analysis reviewed 31 studies and found that mortality risk was significantly lower with the use of RDTs compared with conventional microbiology methods, and that the number needed to treat with such systems to save one life was 20.…”

“…[88][89][90] Currently, the greatest challenge to ICU clinicians is effective management of multidrug-resistant GNB infections. 79 IIAT of serious GNB infections is associated with increased mortality and has been the rationale for using broad-spectrum antibiotics upfront in critically ill patients. 32,46,[91][92][93] RDTs along with ASPs have been particularly effective in improving outcomes for these infections.…”

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

“…However, even very short exposure (1 to 3 days) to carbapenem is associated with a 5-fold higher risk of emergence of imipenem-resistant Gram-negative bacteria in the intestinal microbiota of ICU patients. 10 Intensivists are thus confronted with a permanent dilemma between the initiation of adequate antibiotic therapy and the risk of increasing MDR bacteria 3,11 by the prescription of broad-spectrum antibiotics.…”

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

“…However, even very short exposure (1 to 3 days) to carbapenem is associated with a 5-fold higher risk of emergence of imipenem-resistant Gramnegative bacteria in the intestinal microbiota of ICU patients. 10 Intensivists are thus confronted with a permanent dilemma between the initiation of adequate antibiotic therapy and the risk of increasing MDR bacteria 3,11 by the prescription of broad-spectrum antibiotics.…”