Clinical Trials in Pediatric Sepsis: What’s the (End) Point?*

Weiss, Scott L.

doi:10.1097/pcc.0000000000001079

Cited by 4 publications

(2 citation statements)

References 13 publications

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“…Mortality as an end point in pediatric sepsis trials is limited by low incidence and fails to account for the potential effect of therapies on organ-specific morbidity (8). Composite outcomes that include both mortality and measures of morbidity more fully capture the health effect of sepsis on children and have the advantage of being more common with increased statistical efficiency (32). To be most useful, composite outcomes should be coherent without complete coincidence (i.e., each component should reflect related but different aspects of pathobiology), and each component must be of high importance to patients (33).…”

Section: Discussionmentioning

confidence: 99%

Major Adverse Kidney Events in Pediatric Sepsis

Weiss¹,

Balamuth²,

Thurm³

et al. 2019

CJASN

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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.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_04_18_CJASNPodcast_19_05_.mp3

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Section: Discussionmentioning

confidence: 99%

Major Adverse Kidney Events in Pediatric Sepsis

Weiss¹,

Balamuth²,

Thurm³

et al. 2019

CJASN

Self Cite

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“…8 A paucity of robust data obtained through appropriately-powered clinical trials in children with a sepsis-related critical illness is one of the main challenges being faced with guiding the management of children with severe sepsis. 9,10 This study aims to determine the early identification of bacteria and their patterns of susceptibility to antimicrobials to alert clinicians to the emerging pathogens that may pose a threat to the patients in the pediatric ward and serve as a guideline to the physician for empirical treatment with antibiotics of suspected bacteremia in children.…”

Section: Introductionmentioning

confidence: 99%

Microbial Patterns and Antibiotic Susceptibility in Blood Culture Isolates of Septicemia Suspected Children in the Pediatrics Ward of a Tertiary Care Hospital

et al. 2021

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Objectives This study aims to determine microbial patterns and antibiotic susceptibility to alert clinicians to the emerging pathogens that may pose a threat to the community, especially children. Materials and Methods This retrospective cross-sectional study was conducted in the Department of Pathology, Holy Family Hospital, Rawalpindi, Pakistan, from July 2019 to December 2019. Two samples were taken from two different sites of each patient at the time of fever (> 100° F) to avoid chances of contamination. A blood sample of 5 to 10 mL was drawn from each site. In a 50 mL brain heart infusion broth (BHIB), 5 to 10% blood was injected in two different bottles and incubated for 48 hours at 37°C. After 48 hours, subculture was done by streaking the drops of blood samples taken from BHIB on blood and MacConkey agar. Cultures were incubated in aerobic conditions at 37°C for 24 to 48 hours. For testing antibiotic susceptibility, criteria defined by the Clinical and Laboratory Standards Institute (CLSI) were followed. Microbes were identified under a microscope by observing their morphological characteristics after gram staining and applying biochemical tests. Antibiotic sensitivity test was performed using standard aseptic methods. Statistical Analysis Bacterial isolates and their susceptibility patterns were represented using frequencies and percentage charts. Results Out of 423 blood cultures, growth was recorded in 92 (21.75%) of the cultures with female to male ratio 2.1:1. The gram-positive bacteria accounted for 43.48% (n = 40), whereas gram-negative bacteria covered the majority 54.36% (n = 50). Among isolates, Staphylococcus aureus (42.39%) was the most common, followed by Acinetobacter spp. (17.39%) and Pseudomonas aeruginosa (14.13%). Acinetobacter spp. showed 0% susceptibility to amikacin and cefotaxime. All the isolates were 100% resistant to amoxicillin-clavulanic acid. S. aureus showed lower sensitivity for ceftazidime (0%), clindamycin (66.67%), ciprofloxacin (0%), clarithromycin (11.76%), and ceftriaxone (0%). Tigecycline showed 100% sensitivity for all isolates tested. Conclusion Gram-negative bacteria form the majority of isolates in our setup, with Acinetobacter as the most common species among them. The resistance against cephalosporins, penicillin, and fluoroquinolones shown by Acinetobacter, Pseudomonas, Salmonella, and Klebsiella is of grave concern. Among gram-positive bacteria, S. aureus has established resistance against multiple drugs. Limited and objective use of antibiotic therapy is a much-needed strategy under new guidelines.

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