Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Aug 2019
ReviewPharmacokinetics/Pharmacodynamics of β-Lactams and Therapeutic Drug Monitoring: From Theory to Practical Issues in the Intensive Care Unit.
Despite therapeutic advances over recent decades, the mortality rate for sepsis and septic shock is still approximately 25% worldwide. Early administration of appropriate intravenous antibiotics in the right dose is one of the cornerstones of treatment of sepsis. β-Lactam antibiotics are the most commonly prescribed in critically ill patients, and dosages that do not achieve specific pharmacokinetic/pharmacodynamic targets may increase the likelihood of treatment failure and even emergence of antibiotic resistance. Fluctuations in physiological parameters are often observed in critically ill patients, leading to altered pharmacokinetics and increased risk of suboptimal exposures, especially if standard dosing according to the product information is prescribed. ⋯ This review will investigate alternative β-lactam dose optimization strategies including prolonged infusions, guideline-based dosing, therapeutic drug monitoring (TDM), and the use of dose optimization software, all of which aim to increase the likelihood of achieving therapeutic drug concentrations and improve clinical outcomes as compared with the standard dosing approach. These dose optimization strategies have been the subject of a growing body of evidence; however, further investigation into the outcome benefits and validity of both non-TDM and TDM dosing strategies is required. For the clinician, it is important to select a feasible dosing strategy tailored for the individual patient, which will maximize the likelihood of achieving therapeutic concentrations at steady state and maintain these exposures throughout the course of therapy.
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Semin Respir Crit Care Med · Aug 2019
ReviewEarly Antimicrobial Therapy for Sepsis: Does Each Hour Really Count?
For the last decades, the timing of antimicrobial therapy has remained a hotly debated topic in sepsis as well as other infectious diseases like community-acquired pneumonia (CAP) or bacterial meningitis (CABM). In CAP, a relationship between the time to antibiotic administration and mortality was found only in the largest cohort, but all these studies were retrospective and of low quality. ⋯ Finally, in sepsis, if the 1-hour cut-off remains debatable for sepsis patients, early administration (within 3 hours) is recommended in sepsis and sepsis shock as suggested by the surviving sepsis campaign recommendations. To conclude, all these data are in favor of a potential link between the time to antibiotic administration and survival, but we still miss randomized controlled studies to give a definite answer.
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Semin Respir Crit Care Med · Aug 2019
ReviewDiagnosis and Treatment of Candidemia in the Intensive Care Unit.
Candidemia is the fourth most frequent health care-associated bloodstream infection, and the most frequent severe fungal infection developing in critically ill patients in intensive care units (ICUs). Diagnosis of candidemia in ICU patients is a complex task made of both early and late assessments involving both conventional diagnostic methods and novel rapid tests. Management strategies to optimize treatment of candidemia can be challenging and include starting early adequate therapy, use of an adequate dose and duration of therapy, de-escalating treatment whenever possible, and early discontinuation of useless antifungals in those with no definitive diagnosis of fungal infection. Herein, we will discuss recent epidemiological data on candidemia in ICUs and current diagnostic techniques before concentrating on antifungal treatments.
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Biomarkers are increasingly used in patients with serious infections in the critical care setting to complement clinical judgment and interpretation of other diagnostic and prognostic tests. The main purposes of such blood markers are (1) to improve infection diagnosis (i.e., differentiation between bacterial vs. viral vs. fungal vs. noninfectious), (2) to help in the early risk stratification and thus provide prognostic information regarding the risk for mortality and other adverse outcomes, and (3) to optimize antibiotic tailoring to individual needs of patients ("antibiotic stewardship"). Especially in critically ill patients, in whom sepsis is a major cause of morbidity and mortality, rapid diagnosis is desirable to start timely and specific treatment. ⋯ Without a doubt, the addition of blood biomarkers to clinical medicine has had a strong impact on the way we care for patients today. Recent trials show that as an adjunct to other clinical and laboratory parameters these markers provide important information about risks for bacterial infection and resolution of infection. Moreover, biomarkers can help to optimize management of patients with serious illness in the intensive care unit, thereby offering more individualized treatment courses with overall improvements in clinical outcomes.