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PurposeThis Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients. MethodsLiterature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes.ResultsTDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients.ConclusionAlthough TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide.

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more components of combination empirical therapy, and/or the change from a broad-spectrum to a narrower spectrum antimicrobial. It is most commonly recommended in the intensive care unit (ICU) patient who is treated with broad-spectrum antibiotics as a strategy to reduce antimicrobial pressure of empirical broad-spectrum therapy and prevent antimicrobial resistance, yet this has not been convincingly demonstrated in a clinical setting. Even if it appears beneficial, ADE may have some unwanted side effects: it has been associated with prolongation of antimicrobial therapy and could inappropriately be used as a justification for unrestricted broadness of empirical therapy. Also, exposing a patient to multiple, sequential antimicrobials could have unwanted effects on the microbiome. For these reasons, ADE has important shortcomings to be promoted as a quality indicator for appropriate antimicrobial use in the ICU. Despite this, ADE clearly has a role in the management of infections in the ICU. The most appropriate use of ADE is in patients with microbiologically confirmed infections requiring longer antimicrobial therapy. ADE should be used as an integral part of an ICU antimicrobial stewardship approach in which it is guided by optimal specimen quality and relevance. Rapid diagnostics may further assist in avoiding unnecessary initiation of broad-spectrum therapy, which in turn will decrease the need for subsequent ADE.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Background Decompressive laparotomy has been advised as potential treatment for abdominal compartment syndrome (ACS) when medical management fails; yet, the effect on parameters of organ function differs markedly in the published literature. In this study, we sought to investigate the effect of decompressive laparotomy on intra-abdominal pressure and organ function in critically ill adult and pediatric patients with ACS, specifically focusing on hemodynamic, respiratory, and kidney function and outcome. Methods A systematic review and meta-analysis of the literature was performed. Articles reporting data on intra-abdominal pressure (IAP), hemodynamic (mean arterial pressures [MAP], central venous pressure [CVP], cardiac index [CI], heart rate [HR], systemic vascular resistance index [SVRI] and/or pulmonary capillary wedge pressure [PCWP]), respiratory (positive end-expiratory pressure [PEEP], peak inspiratory pressure [PIP] and/or ratio of partial pressure arterial oxygen and fraction of inspired oxygen [P/F ratio]), and/or urinary output (UO) following decompressive laparotomy were analyzed. Results A total of 15 articles were included; 3 included children only (aged 18 years or younger). Of the 286 patients who were included, 49.7% had primary ACS. The baseline mean IAP in adults decreased with an average of 18.2 ± 6.5 mmHg following decompression, from 31.7 ± 6.4 mmHg to 13.5 ± 3.0 mmHg. There was a decrease in HR (12.2 ± 9.5 beats/min; p  = 0.04), CVP (4.6 ± 2.3 mmHg; p  = 0.022), PCWP (5.8 ± 2.3 mmHg; p  = 0.029), and PIP (10.1 ± 3.9 cmH 2 O; p  < 0.001) and a mean increase in P/F ratio (70.4 ± 49.4; p  < 0.001) and UO (95.3 ± 105.3 ml/h; p  < 0.001). In children, there was a significant increase in MAP (20.0 ± 2.3 mmHg; p  = 0.006), P/F ratio (238.2; p  < 0.001), and UO (2.88 ± 0.64 ml/kg/h; p  < 0.001) and a decrease in CVP (7 mmHg; p  = 0.016) and PIP (9.9 cmH 2 O; p  = 0.002). The overall mortality rate was 49.7% in adults and 60.8% in children following decompressive laparotomy. Conclusions Decompressive laparotomy resulted in a significantly lower IAP and had beneficial effects on hemodynamic, respiratory, and renal parameters. Mortality after decompressive laparotomy remains high in both adults and children.

The application of machine learning (ML) in healthcare has surged, yet its adoption in high-stakes clinical domains, like the Intensive Care Unit (ICU), remains low. This gap is largely driven by a lack of clinician trust in AI decision support. Explainable AI (XAI) techniques aim to address this by explaining how an AI reaches its decisions, thereby improving transparency. However, rigorous evaluation of XAI methods in clinical settings is lacking. Therefore, we evaluated the perceived explainability of a dashboard incorporating three XAI methods for an ML model that predicts piperacillin plasma concentrations. The dashboard was evaluated by seven ICU clinicians using five distinct patient cases. We assessed the interpretation and perceived explainability of each XAI component through a targeted survey. The overall dashboard received a median score of seven out of ten for completeness of explainability, with Ceteris Paribus profiles identified as the most preferred XAI method. Our findings provide a practical framework for evaluating XAI in critical care, offering crucial insights into clinician preferences that can guide the future development and implementation of trustworthy AI in the ICU.

Introduction The term invasive candidiasis (IC) refers to both bloodstream and deep-seated invasive infections, such as peritonitis, caused by Candida species. Several guidelines on the management of candidemia and invasive infection due to Candida species have recently been published, but none of them focuses specifically on critically ill patients admitted to intensive care units (ICUs). Material and Methods In the absence of available scientific evidence, the resulting recommendations are based solely on epidemiological and clinical evidence in conjunction with expert opinion. The task force used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the recommendations and assign levels of evidence. The recommendations and their strength were decided by consensus and, if necessary, by vote (modified Delphi process). Descriptive statistics were used to analyze the results of the Delphi process. Statements obtaining > 80% agreement were considered to have achieved consensus. Conclusions The heterogeneity of this patient population necessitated the creation of a mixed working group comprising experts in clinical microbiology, infectious diseases and intensive care medicine, all chosen on the basis of their expertise in the management of IC and/or research methodology. The working group’s main goal was to provide clinicians with clear and practical recommendations to optimize microbiological diagnosis and treatment of IC. The Systemic Inflammation and Sepsis and Infection sections of the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) therefore decided to develop a set of recommendations for application in non-immunocompromised critically ill patients.

Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P = .05 to .002), when more agents were used (P = .002), and in the absence of multidrug-resistant pathogens (P < .05). Where invetigated, lower or improving severity scores were consistently associated with ADE (P = .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52–.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance.

Keywords: Sepsis, Septic shock, Infection, Diagnosis, Antibiotic therapy