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A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study.

ABSTRACT: Biomarkers that identify critically ill children with systemic inflammatory response syndrome (SIRS) at low risk for bacterial infection may help clinicians reduce unnecessary antibiotic use.We conducted a prospective cohort study of children with SIRS and suspected infection admitted to a pediatric intensive care unit from January 5, 2012 to March 7, 2014. We enrolled patients upon initiation of new antibiotics (Time 0) and measured a panel of 8 serum biomarkers daily over 72 hours. Microbiology, imaging, and clinical data were reviewed to classify bacterial infections using Centers for Disease Control and Prevention definitions. We identified cut points of biomarker combinations to maximize the negative predictive value (NPV) and specificity for bacterial infection. Excess antibiotics were calculated as days of therapy beyond day 2 after SIRS onset in patients without bacterial infection.Infections were identified in 46 of 85 patients: bacterial (n = 22) and viral (24), whereas 39 patients had no infection identified. At Time 0, C-reactive protein (CRP) <5 mg/dL plus serum amyloid A <15.0 µg/mL had an NPV of 0.92 (95% confidence interval [CI], 0.79-1.0) and specificity of 0.54 (95% CI, 0.42-0.66) to identify patients without bacterial infection, whereas CRP <4 mg/dL plus procalcitonin <1.75 ng/mL had an NPV of 0.90 (95% CI, 0.79-1.0) and specificity of 0.43 (95% CI, 0.30-0.55). Patients without bacterial infection received a mean of 3.8 excess days of therapy.Early measurement of select biomarkers can identify children with SIRS in whom antibiotics might be safely discontinued when there is no other objective evidence of infection at 48 hours.

SUBMITTER: Downes KJ

PROVIDER: S-EPMC5907860 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study.

Downes Kevin J KJ Weiss Scott L SL Gerber Jeffrey S JS Klieger Sarah B SB Fitzgerald Julie C JC Balamuth Fran F Kubis Sherri E SE Tolomeo Pam P Bilker Warren B WB Han Xiaoyan X Nachamkin Irving I Garrigan Charles C Han Jennifer H JH Lautenbach Ebbing E Coffin Susan E SE

Journal of the Pediatric Infectious Diseases Society 20170601 2

<h4>Background.</h4>Biomarkers that identify critically ill children with systemic inflammatory response syndrome (SIRS) at low risk for bacterial infection may help clinicians reduce unnecessary antibiotic use.<h4>Methods.</h4>We conducted a prospective cohort study of children with SIRS and suspected infection admitted to a pediatric intensive care unit from January 5, 2012 to March 7, 2014. We enrolled patients upon initiation of new antibiotics (Time 0) and measured a panel of 8 serum biomar ...[more]

PMID: 27147715

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Project description:Background: Survivors of pediatric sepsis often develop new morbidities and deterioration in quality of life after sepsis, leading to a need for improved follow-up for children who survive sepsis. Objective: To implement a follow-up system for pediatric sepsis survivors in a pediatric health system. Methods: We performed a retrospective case series of patients treated for sepsis from October 2018 through October 2019 in a pediatric intensive care unit in a quaternary children's hospital, and describe implementation of a follow-up system for sepsis survivors. Program planning started in 2017 with multidisciplinary meetings including physical, occupational, and speech therapists, teachers, neuropsychologists, and coordinators from other survivorship programs (neonatology, stroke, and oncology). In 2018, a workshop was held to consult with local and national experts. The Pediatric Sepsis Survivorship Program launched in October 2018 led by a nurse coordinator who met with families to educate about sepsis and offer post-discharge follow-up. Patients with high pre-existing medical complexity or established subspecialty care were referred for follow-up through existing care coordination or subspecialty services plus guidance to monitor for post-sepsis morbidity. For patients with low-moderate medical complexity, the nurse coordinator administered a telephone-based health-assessment 2-3 months after discharge to screen for new physical or psychosocial morbidity. Patients flagged with concerns were referred to their primary physician and/or to expedited neuropsychological evaluation to utilize existing medical services. Results: Of 80 sepsis patients, 10 died, 20 were referred to care coordination by the program, and 13 had subspecialty follow-up. Five patients were followed in different health systems, four were adults not appropriate for existing follow-up programs, four remained hospitalized, and four were missed due to short stay or unavailable caregivers. The remaining 20 patients were scheduled for follow-up with the Pediatric Sepsis Program. Nine patients completed the telephone assessment. Four patients were receiving new physical or occupational therapy, and one patient was referred for neuropsychology evaluation due to new difficulties with attention, behavior, and completion of school tasks. Conclusions: Implementation of an efficient, low-cost pediatric sepsis survivorship program was successful by utilizing existing systems of care, when available, and filling a follow-up gap in screening for select patients.

Project description:BackgroundPediatric sepsis remains a significant cause of morbidity and mortality worldwide. This study aimed to identify the incidence of sepsis and septic shock among patients admitted to the pediatric intensive care unit (PICU) of a tertiary center in Saudi Arabia. Patients' demographics and risk factors associated with sepsis-related mortality were also investigated.MethodsA retrospective cohort study was conducted in the PICU of King Abdulaziz Medical City, Jeddah (KAMC-J). KAMC-J is a tertiary care hospital in the western region of Saudi Arabia. A total of 2389 patients admitted to the PICU of KAMC-J between January 1, 2013 and December 31, 2017 were screened and evaluated for sepsis using The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).ResultsOf the 2389 total admissions to the PICU, 113 patients (4.9%) met the definition of Sepsis-3; 50.4% of the 113 patients met the definition of septic shock. Most patients (66.3%) were less than 6 years old, and 52.2% were male. Eight-five patients (75.2%) had underlying comorbidities. The respiratory system was the most common primary site of infection (57.5%). Bacterial and viral infections were the most common infectious etiology with reported rates of 29.2 and 21.2%, respectively. The median duration of PICU stay was 8 days and the 28-day PICU mortality rate was 23.9%. A Pediatric Sequential Organ Failure Assessment (pSOFA) Score greater than four and a pre-existing percutaneous central venous catheter were associated with a significant increase in mortality, with adjusted odds ratios of 3.6 (95% confidence interval: 1.30-9.93) and 9.27 (95% confidence interval: 1.28-67.29), respectively.ConclusionsThe incidence of sepsis in our institution is comparable to that reported internationally; however, the mortality rate is higher than that of developed countries. Nationwide studies identifying sepsis epidemiology are needed to improve the outcome of pediatric sepsis. Following international guidelines for central-line insertion and maintenance is of paramount importance.

Project description:Background: The gut is thought to play an important role in the pathogenesis of sepsis. Changes in the gut microbiota are closely related to the occurrence and development of human diseases, but few studies have focused on taxonomic composition of gut microbiota in septic patients. Knowledge of changes in the gut microbiota is a key issue in intensive care. Clinicians must understand how an altered gut microbiota affects the susceptibility and prognosis of septic patients. Measurements and Main Results: In the single-center case control study, 20 septic patients and 20 healthy children were recruited. The taxonomic composition of gut microbiota was determined via 16S rRNA gene sequencing. Gut microbiota diversity in children with sepsis was significantly reduced compared with that in healthy children. The taxonomic composition of gut microbiota can effectively distinguish children with sepsis from healthy children. Thirteen taxa of gut microbiota were significantly increased in the guts of children with sepsis compared with those of healthy children. The increased abundances of Enterococcaceae, Enterococcus, and Enterococcus durans in gut of septic patients were significantly positively correlated with blood inflammation indicators CRP and WBC. The abundances of seven bacteria were significantly decreased in the guts of septic children compared with those of healthy children. The decreased abundance of Bifidobacteriales in gut of septic patients is significantly negatively correlated with blood inflammation index WBC. A machine-learning classifier was built for distinguishing sepsis and achieved the AUC value of 81.25%. It shows that the composition of gut microbiota has certain potential for diagnosis of sepsis. Conclusions: Gut microbiota alterations in septic patients exhibit proliferation of opportunistic pathogenic bacteria, the massive reduction of the commensal flora, and the significant decrease in the diversity of the gut microbiota. Dysbiosis may also account for some changes in the inflammation indexes.

Dataset Information

A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study.

Publications

A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study.

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