Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.

Introduction: Long-term health impairments are often experienced among survivors of critical illness, which may have a negative impact on their quality of life. The aim of this study was to characterize COVID-19 survivors of critical illness and to evaluate health-related quality of life and disability following hospital discharge.Material and Methods: This is a retrospective case-series study that included COVID-19 survivors admitted to the Intensive Care Medicine Department of a University Hospital. Follow-up evaluation was performed between the 30th and the 90th day after discharge. Quality of life was explored using the five-level version of the EQ-5D instrument (EQ-5D-5L) and functionality using the 12-question World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).Results: Forty-five survivors were enrolled, 28 (62.2%) men, median age 63.0 years. The EQ-5D-5L questionnaire showed moderate to extreme problems in some dimension in 29 patients (64.4%): mobility in six (13.3%), self-care in seven (13.3%), usual activities in 23 (51.1%), pain/discomfort in 14 (31.1%) and anxiety/depression in 17 (37.8%). When using the 12-question WHODAS 2.0 questionnaire, moderate to extreme disability was reported in some question in 37 patients (82.2%): 19 (42.2%) in standing for long periods, 18 (40.0%) in long-distance walking; 14 (31.1%) on taking care of household responsibilities and 17 (37.8%) in their day-to-day work; 23 (51.1%) felt emotionally affected by their health problems.Discussion: Based on COVID-19 survivors-reported outcomes after critical illness, mobility, pain/discomfort, and anxiety/depression were the main problems that persisted one to three months after hospital discharge.Conclusion: An organized follow-up structure is crucial to improve health-related quality of life in critical COVID-19 survivors.

Antimicrobial dosing can be a complex challenge. Although a solid rationale exists for a link between antibiotic exposure and outcome, conflicting data suggest a poor correlation between pharmacokinetic/pharmacodynamic targets and infection control. Different reasons may lead to this discrepancy: poor tissue penetration by β-lactams due to inflammation and inadequate tissue perfusion; different bacterial response to antibiotics and biofilms; heterogeneity of the host’s immune response and drug metabolism; bacterial tolerance and acquisition of resistance during therapy. Consequently, either a fixed dose of antibiotics or a fixed target concentration may be doomed to fail. The role of biomarkers in understanding and monitoring host response to infection is also incompletely defined. Nowadays, with the ever-growing stream of data collected in hospitals, utilizing the most efficient analytical tools may lead to better personalization of therapy. The rise of artificial intelligence and machine learning has allowed large amounts of data to be rapidly accessed and analyzed. These unsupervised learning models can apprehend the data structure and identify homogeneous subgroups, facilitating the individualization of medical interventions. This review aims to discuss the challenges of β-lactam dosing, focusing on its pharmacodynamics and the new challenges and opportunities arising from integrating machine learning algorithms to personalize patient treatment.

Before the development of transfusion medicine, severe anaemia was an important cause of morbidity and mortality. The discovery of haematopoietic mechanisms and essential nutrients made it possible to easily treat and prevent this condition. Nevertheless, it is often fatal in patients presenting with extreme anaemia (haemoglobin levels <2 g/dl). We report the rare case of a 54-year-old woman who presented with profound megaloblastic anaemia (haemoglobin of 1.7 g/dl) due to vitamin B12 deficiency, and was successfully treated.