Daily Sepsis Research Analysis

OBJECTIVES: Guidelines recommend targeting a mean arterial pressure (MAP) greater than or equal to 65 mm Hg in septic shock. Although experts advocate for individualized targets, no validated bedside tool exists. An increased renal resistive index (RRI) is associated with acute kidney injury, and increasing MAP can reduce RRI. This study investigated the physiologic impact of a higher MAP on renal function based on RRI evolution during a transient high MAP target test. DESIGN: Prospective physiologic and randomized study. SETTING: Medical ICU of a university hospital. PATIENTS: Patients in the early phase of septic shock (norepinephrine ≥ 0.05 µg/kg/min base within 9 hr of initiation, with or without lactate > 2 mmol/L) without chronic kidney disease or immediate need for renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a standardized 2-hour MAP test (65-70 followed by 80-85 mm Hg) with RRI measured at each period. RRI responders were defined by an RRI decrease greater than or equal to 0.05 during the MAP test. Following the MAP test, patients were randomized according to the "low" (65-70) or "high" (80-85 mm Hg) MAP target for 5 days, stratified by RRI response during the MAP test. Eighty patients were randomized; 23 (29%) were RRI responders. Among RRI responders, the higher MAP target was not associated with improved renal outcomes (i.e., diuresis, Kidney Disease: Improving Global Outcomes stage, need for renal replacement therapy, or serum creatinine). RRI nonresponders had higher urine output with a high MAP target, whereas no other renal parameter differed significantly; these findings should be considered exploratory. CONCLUSIONS: In early septic shock, a decrease in RRI during a MAP test did not identify patients who would benefit from higher MAP targets to improve renal function. Conversely, the absence of an RRI decrease during the MAP test may help identify patients in whom increasing MAP is associated with increased urine output.

OBJECTIVES: The release of neutrophil extracellular traps is a key immune host defense mechanism that can contribute to organ damage during sepsis if excessive. We evaluated presentation H3.1 nucleosome levels in patients with sepsis, septic shock, and sepsis-associated acute kidney injury (AKI). We sought to determine if plasma H3.1 nucleosome levels could serve as predictive biomarkers for both renal replacement therapy (RRT) requirements and 28-day mortality. DESIGN: A secondary analysis of prospectively collected samples from the large multicenter Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients with Severe Sepsis or Septic Shock (SISPCT) trial. SETTING: Patients from 33 ICUs in Germany recruited between November 6, 2009, and June 6, 2013, including a 90-day follow-up period. PATIENTS: A total of 971 patients with complete data on plasma H3.1 admission levels with sepsis and septic shock, and 927 patients with complete data on RRT requirements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated associations between H3.1 levels and mortality and the time to commencement of RRT using multivariable Cox regression. A total of 443 patients (45.6%) presented with sepsis, and 520 patients (53.6%) had septic shock. Admission H3.1 levels were higher in patients with septic shock than sepsis (median, 921.84 vs. 432.71 ng/mL; p < 0.001). In a multivariable analysis for 28-day mortality, a one unit increase in log10 H3.1 levels was associated with a 48% increase in 28-day mortality (adjusted hazard ratio [HR], 1.48, 95% CI, 1.07-2.04; p = 0.02). Plasma H3.1 was also higher in patients with stage 3 AKI requiring RRT with septic shock vs. sepsis (1832 vs. 801.4 ng/mL; p = 0.01). In a multivariable Cox regression controlling for maximum lactate, procalcitonin, and C-reactive protein levels, plasma H3.1 levels were significantly higher in patients who developed AKI requiring RRT when compared with patients who did not develop AKI, with one log10 increase of H3.1 increasing the risk of 28-day RRT by 80% (adjusted HR, 1.8; 95% CI, 1.34-2.40; p < 0.001). CONCLUSIONS: Elevated levels of H3.1 nucleosomes at admission are associated with mortality and AKI requiring RRT. TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov, identifier: NCT00832039.

BACKGROUND: Extraintestinal pathogenic E. coli (ExPEC) can colonize and infect body sites outside the intestines, which can lead to invasive E. coli disease potentially resulting in sepsis or death. We evaluated O-serotype distribution, antimicrobial resistance profiles, and sequence types (STs) of ExPEC bloodstream isolates collected during 17 global surveillance studies conducted from 2011 through 2023. METHODS: E. coli clinical blood isolates from an adult population were analyzed for O-serotype, ST, and multidrug-resistance (MDR) using data obtained by agglutination, whole-genome sequencing, and determination of minimal inhibitory concentrations of antimicrobial drugs. RESULTS: Globally, 10 098 E. coli isolates were collected; 4925 (48.8%) from men and 5136 (50.9%) from women, median (range) age was 72 (18-104) years. The most prevalent ExPEC O-serotypes were O25 (18.7%), O2 (8.2%), O6 (8.2%), and O1 (7.0%). Highest MDR rates were observed in India (83.3%), Mexico (76.6%), and China (69.4%); lowest rates were in Sweden (10.6%), New Zealand (11.6%), and Netherlands (12.1%). Among MDR isolates (n=3343), serotype O25 was the most prevalent in all countries (range: 11.3% China to 56.2% Mexico). We observed a resistance rate of 1.1% and 0.7% to last-resort carbapenem and colistin antibiotics, respectively, distributed over diverse STs and O-serotypes. CONCLUSIONS: Overall, serotypes O25, O2, O6, and O1 were the most prevalent. MDR levels showed large regional variation. O25 was dominant within the subset of MDR isolates across all countries. O153-ST648, O101/O162-ST744, O102-ST405, and O25-ST131 were associated with MDR.