Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies.

An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. We aimed to evaluate the clinical implications of adjusting beta-lactam dosages based on TDM in the critically ill population by performing a systematic review and meta-analysis of available investigations. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. The outcomes were evaluated using forest plots with random-effects modeling and subgroup analysis. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection [odds ratio (OR): 2.22 (95% confidence interval (CI): 1.78-2.76)] and microbiological eradication [OR: 1.72 (CI: 1.05-2.80)], as well as a lower probability of treatment failure [OR: 0.47 (CI: 0.36-0.62)], but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favorable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.

[Challenge in modern intensive care: chronic critical illness - pathophysiology and therapeutic options]. / A modern intenzív terápia kihívása: az elhúzódó kritikus állapot kórélettani háttere és terápiás lehetoségei.

The recent developments in intensive care have resulted in improved survival rates of patients treated with acute organ deficiency. As a consequence, the rate of those who survive the acute phase and subsequently require protracted organ support due to persisting organ dysfunction has been growing. Several survivors display chronic health status deterioration leading to prolonged rehabilitation or nursing, and repeated hospitalizations. The condition developed following the survival of the acute phase and requiring long-lasting intensive care is frequently termed as chronic critical illness (CCI). Several definitions exist, most of these are based on the number of ventilator days, or days of stay at the intensive care unit. Nevertheless, in spite of the initially heterogenous etiology of the acute illness, the complications associated with CCI, as well as the pathophysiological processes underlying these, are relatively uniform. This causes CCI to be a unique clinical syndrome characterized by the development of secondary infections, myopathy, central and peripheral neuropathy, and typical alterations of the hormonal and immune system functions. The outcome is heavily influenced by the frailty and comorbidities of the patient, in addition to the severity of the acute illness. The treatment of CCI patients presents a complicated task requiring multidisciplinary view and individualized therapeutic measures. Since the aging of the population and the continuously improving success rates in overcoming acute conditions also facilitate the development of CCI, the systematic overview of the underlying pathophysiological processes is pivotal for the optimization of the medical, nursing, social and economical burden presented by this syndrome. Orv Hetil. 2023; 164(18): 702-712.