Early Versus Late Antipseudomonal ß-Lactam Antibiotic Dose Adjustment in Critically Ill Sepsis Patients With Acute Kidney Injury: A Prospective Observational Cohort Study.

Background: Acute kidney injury (AKI) is a common complication of sepsis, contributing to an increased mortality rate. However, some studies have demonstrated that renal function improves in sepsis patients with AKI within 48 hours, raising questions about the necessity for early antibiotic adjustment. This study evaluates the association between the timing of antipseudomonal ß-lactam dose adjustment and the outcomes of critically ill sepsis patients with AKI. Methods: A prospective, multicenter observational study of critically ill patients aged ≥18 years admitted to the intensive care unit with sepsis and AKI and started on antipseudomonal ß-lactam therapy. After the initial dose, eligible patients were grouped as early ß-lactam antibiotic (E-BLA) or late ß-lactam antibiotic (L-BLA) dose adjustments based on the administration of subsequent renally adjusted doses within 24 hours and after 24 hours of sepsis recognition, respectively. The main outcome of interest was in-hospital mortality. Results: Among 1185 patients screened, 224 (mean age, 62.7 ± 16.8 years; 62% were male) met inclusion criteria. Eighty-four and 140 patients were included in the E-BLA and L-BLA groups, respectively. Approximately half of the cohort presented with AKI stage II, and piperacillin-tazobactam was prescribed as initial empirical therapy in more than 50% of the cohort. In the multivariable Cox proportional hazards model, L-BLA was associated with a significant reduction in in-hospital mortality compared to E-BLA (hazard ratio, 0.588 [95% confidence interval, .355-.974]). Conclusions: In sepsis patients with AKI, L-BLA was associated with in-hospital mortality benefits.

Prognostic accuracy of qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients presenting with suspected infection to the emergency department (PASSEM) Multicenter prospective external validation cohort study protocol.

BACKGROUND: Early identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department. METHODS AND ANALYSIS: PASSEM study is an international prospective external validation cohort study. For 9 months, each participating center will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalization. We will collect patients' demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., ≥72 hours), and 30- as well as 90-days all-cause mortality. The study started in December 2021 and planned to enroll 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses. DISCUSSION: PASSEM study will be the first international multicenter prospective cohort study that designated to externally validate qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients with suspected infection presenting to the ED in the Middle East region. STUDY REGISTRATION: The study is registered at ClinicalTrials.gov (NCT05172479).

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial.

Assessment of efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. This was an open-label, randomised clinical trial of ICU patients with life-threatening COVID-19 (positive RT-qPCR plus ARDS, sepsis, organ failure, hyperinflammation). Study was terminated after 87/120 patients enrolled. Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by PaO2/FiO2 ratio (>150 vs. ≤150), were compared. Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in SOFA score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length of stay (LOS). Eighty-seven patients [median age 49 (IQR 34-63) years; 82.8% male] were randomised (44 standard care; 43 standard care plus TPE). Days on MV (P = 0.007) and ICU LOS (P = 0.02) were lower in the TPE group. 35-Day mortality was non-significantly lower in the TPE group (20.9% vs. 34.1%; Kaplan-Meier, P = 0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity and decreased serum lactate, lactate dehydrogenase, ferritin, d-dimers and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO2/FiO2 ratio (HR, 0.98, 95% CI 0.96-1.00; P = 0.02]; ADAMTS-13 activity (HR, 0.89, 95% CI 0.82-0.98; P = 0.01); pulmonary embolism (HR, 3.57, 95% CI 1.43-8.92; P = 0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (P < 0.05). In critically-ill COVID-19 patients, addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.