ImportanceMeropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes.ObjectiveTo determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis.Design, Setting, and ParticipantsA double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022.InterventionsPatients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304).Main Outcomes and MeasuresThe primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events.ResultsAll 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients).Conclusions and RelevanceIn critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28.Trial RegistrationClinicalTrials.gov Identifier: NCT03452839
This work aims to evaluate the prognostic value of the demographical and clinical data on long-term outcomes (up to 12 months) in patients with severe acquired brain injury with vegetative state/unresponsive wakefulness syndrome (VS/UWS/UWS) or a minimally conscious state (MCS). Patients (n = 211) with VS/UWS/UWS (n = 123) and MCS (n = 88) were admitted to the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology after anoxic brain injury (n = 53), vascular lesions (n = 59), traumatic brain injury (n = 93), and other causes (n = 6). At the beginning of the 12-month study, younger age and a higher score by the Coma Recovery Scale-Revised (CRS-R) predicted a survival. However, no reliable markers of significant positive dynamics of consciousness were found. Based on the etiology, anoxic brain injury has the most unfavorable prognosis. For patients with vascular lesions, the first three months after injury have the most important prognostic value. No correlations were found between survival, increased consciousness, and gender. The demographic and clinical characteristics of patients with chronic DOC can be used to predict long-term mortality in patients with chronic disorders of consciousness. Further research should be devoted to finding reliable predictors of recovery of consciousness.
Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota. In the present study, two complex phage cocktails targeting multiple bacterial species were used in the rehabilitation of thirty patients after COVID-19, and the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae was evaluated for the first time using real-time visualization on a 3D Cell Explorer microscope. Application of phage cocktails for two weeks showed safety and the absence of adverse effects. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, together with an erythrocyte sedimentation rate (ESR), was detected. This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.
There is ongoing debate about the role of nutrition during critical illness in terms of long-term outcomes. Even taking into account the inability to adequately assess all biological mechanisms associated with nutrition, it should be recognized that the available randomized trials, nutritional support during the early phase of critical illness, when considered in isolation from other treatment, may have very limited long-term functional value. This review focuses on recent clinical studies and evaluating the impact of critical nutrition on long-term physical and functional recovery. Critical survival is becoming an increasingly important subject of attention. Future research on nutritional support should consider specific factors that can provide measurable benefits in terms of both physical and functional recovery. These factors include the development of strategies to ensure adequate nutritional interventions, the provision of nutrition for a period of time in which biologically it is possible to observe differences in the results assessed, and the selection of appropriate methods of assessing the results recorded at clinically significant time points. One of these results is an assessment of muscle mass and function, as well as quality of life. In addition, selection of patients who are most likely to benefit from nutritional interventions and nutritional research after transfer from ICU deserves special attention.
В статье обсуждается проблема почечных осложнений при интервенционных вмешательствах на коронарных артериях. Представлен обзор последних исследований возникновения контраст-индуцированной нефропатии у больных с острым коронар-ным синдромом. Приведены определения контраст-индуцированной нефропатии, ее патогенез и факторы риска развития, характе-ристика рентгенконтрастных веществ, меры профилактики контраст-индуцированной нефропатии у больных с острым коронарным синдромом.Ключевые слова: острый коронарный синдром, контраст-индуцированная нефропатия, контраст-индуцированное острое почечное повреждение, рентгеноконтрастные вещества.
Chronic disorders of consciousness (DOC) develop after severe traumatic and non-traumatic brain damage and are characterized by the restoration of wakefulness in a patient after a coma without the recovery of consciousness. To optimize the diagnosis and treatment of patients with chronic DOC, a Russian working group on the problems of chronic DOC was organized, which included specialists in various areas, primarily anesthesiologists, critical care physicians and neurologists. While discussing the terminology of chronic DOC, the group identified that currently there is no definition for the state that falls into the period from the recovery of wakefulness and until 28 days after the brain damage when vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) may be diagnosed. In the intensive care unit (ICU) setting, there is often no consultant to provide critical care physicians with the correct diagnosis of the latter clinical syndromes, and neurophysiological tests are not feasible either. Therefore, there is a need to create a set of simple, understandable and easily reproducible strategies for managing this category of patients in the ICU. Thus, the working group proposed the term “prolonged disorders of consciousness” to be used for the patients with the signs of VS/UWS or MCS syndromes during their stay in the ICU until 28 days after initial brain damage and/or until the correct differential diagnosis of a type of chronic DOC is made. With the introduction of prolonged disorders of consciousness definition, the regular ICU staff will better understand how to provide an optimal set of supportive therapy and early rehabilitation activities in the lack of specific diagnostics techniques and dedicated specialists. Allocation of this category of patients allows us to create an algorithm for their better diagnosis and management and ensures consistent and effective interdisciplinary care at various levels. On the one hand, this approach will help us allow to free up ICU beds that are in high demand, while on the other, it will maximize the opportunity to realize the rehabilitation potential of DOC patients due to timely transfer to specialized centers. Conclusions. If the term “prolonged disorder of consciousness” is accepted by professional communities of specialists (critical care physicians, neurologists, neurosurgeons, etc.), it will be used in guidelines for the management of DOC patients.
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