Related Experiment Video
Updated: Mar 21, 2026
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing
Kevin J Downes1,2, Scott L Weiss3, Jeffrey S Gerber1,2,4
1Division of Infectious Diseases.
Insights
Biomarkers like C-reactive protein can help identify critically ill children with systemic inflammatory response syndrome (SIRS) who are unlikely to have bacterial infections, reducing unnecessary antibiotic use.
Area of Science:
- Pediatric critical care medicine
- Infectious disease diagnostics
- Biomarker research
Background:
- Systemic inflammatory response syndrome (SIRS) in children often leads to broad-spectrum antibiotic use.
- Identifying children at low risk for bacterial infection is crucial to prevent antibiotic resistance and overuse.
- Novel biomarkers are needed to guide clinical decisions in pediatric intensive care units (PICUs).
Purpose of the Study:
- To evaluate the utility of serum biomarkers in identifying critically ill children with SIRS who do not have bacterial infections.
- To determine optimal biomarker cut-points for maximizing negative predictive value (NPV) and specificity.
- To assess the potential for reducing unnecessary antibiotic therapy in this population.
Main Methods:
- Prospective cohort study of children with SIRS admitted to a PICU.
- Measurement of 8 serum biomarkers daily for 72 hours, starting at antibiotic initiation (Time 0).
- Classification of bacterial infections based on CDC definitions, microbiology, imaging, and clinical data.
Main Results:
- C-reactive protein (CRP) <5 mg/dL combined with serum amyloid A <15.0 µg/mL showed an NPV of 0.92 for identifying patients without bacterial infection.
- CRP <4 mg/dL combined with procalcitonin <1.75 ng/mL demonstrated an NPV of 0.90 for ruling out bacterial infection.
- Patients without bacterial infection received an average of 3.8 excess days of antibiotic therapy.
Conclusions:
- Early measurement of specific biomarkers can accurately identify children with SIRS unlikely to have bacterial infections.
- These biomarkers can inform decisions to safely discontinue antibiotics at 48 hours when objective evidence of infection is absent.
- This approach has the potential to significantly reduce unnecessary antibiotic exposure in critically ill children.
Background.:
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.
Methods.:
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.
Results.:
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.
Conclusions.:
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.
More Related Videos
03:22Author Spotlight: Advancing Pathogen Detection and Disease Assessment in Real-Time Using M-ROSE
Published on: March 1, 2024
09:26Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Related Concept Videos
01:24Automated Microbial Diagnostics
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
00:57Antibiotic Selection
01:25Clinical Significance of Antibiotic Resistance
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:30Pneumonia III: Complications and Assessment