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Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial.

ABSTRACT: Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear.Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis.Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization.Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8-13.1%; 9/125) versus 15.3% (95% CI, 10.1-22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20-0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10-22.5%; 19/125) versus 28.2% (95% CI, 21.2-36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29-0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5-7) versus 10 (range, 7-15) days (P < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm.Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304).

SUBMITTER: Kyriazopoulou E

PROVIDER: S-EPMC7874409 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesMajor adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis.Design, setting, participants, & measurementsWe conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality.ResultsOf 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions.ConclusionsIn children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.

Project description:BackgroundLeft ventricular assist devices (LVADs) mechanically unload the heart and coupled with neurohormonal therapy can promote reverse cardiac remodeling and myocardial recovery. Minimally invasive LVAD decommissioning with the device left in place has been reported to be safe over short-term follow-up. Whether device retention reduces long-term safety, or sustainability of recovery is unknown.MethodsThis is a dual-center retrospective analysis of patients who had achieved responder status (left ventricular ejection fraction, LVEF ≥40% and left ventricular internal diastolic diameter, LVIDd ≤6.0 cm) and underwent elective LVAD decommissioning for myocardial recovery from May 2010 to January 2020. All patients had outflow graft closure and driveline resection with the LVAD left in place. Emergent LVAD decommissioning for an infection or device thrombosis was excluded. Patients were followed with serial echocardiography for up to 3-years. The primary clinical outcome was survival free of heart failure hospitalization, LVAD reimplantation, or transplant.ResultsDuring the study period 515 patients received an LVAD and 29 (5.6%) achieved myocardial recovery, 12 patients underwent total device explantation or urgent device decommissioning, 17 patients underwent elective LVAD decommissioning, and were included in the analysis. Median age of patients at LVAD implantation was 42 years (interquartile range, IQR: 25-54 years), all had a nonischemic cardiomyopathy, and 5 (29%) were female. At LVAD implantation, median LVEF was 10% (IQR: 5%-15%), and LVIDd 6.6 cm (IQR: 5.8-7.1 cm). There were 11 hydrodynamically levitated centrifugal-flow (65%), and 6 axial-flow LVADs (35%). The median duration of LVAD support before decommissioning was 28.7 months (range 13.5-36.2 months). As compared to the turndown study parameters, 1-month post-decommissioning, median LVEF decreased from 55% to 48% (p = 0.03), and LVIDd increased from 4.8 cm to 5.2 cm (p = 0.10). There was gradual remodeling until 6 months, after which there was no statistical difference on follow-up through 3-years (LVEF 42%, LVIDd 5.6 cm). Recurrent infections affected 41% of patients leading to 3 deaths and 1 complete device explant. Recurrent HF occurred in 1 patient who required a transplant. Probability of survival free of HF, LVAD, or transplant was 94% at 1-year, and 78% at 3-years.ConclusionsLVAD decommissioning for myocardial recovery was associated with excellent long-term survival free from recurrent heart failure and preservation of ventricular size and function up to 3-years. Reducing the risk of recurrent infections, remains an important therapeutic goal for this management strategy.

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Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial.

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