Culture Negative Sepsis and Outcomes in Children

Background: Sepsis and its sequelae of multiple organ dysfunction remain a significant cause of morbidity and mortality in the pediatric population. There are an estimated 1.2 million cases of childhood sepsis per year, accounting for 8% of PICU admissions in high-income countries (1). Patients are diagnosed with “culture negative” sepsis when a bacterial agent cannot be identified. There is limited evidence guiding management of culture negative sepsis. Consequentially, patients are treated with empiric antibiotics for extended durations. This may lead to the development of multi-drug resistant organisms and adverse events from prolonged medication use (2).
In a recent study, one third of septic adult patients were culture negative. These patients had a mortality rate of 40.6% and stayed an average of 3 weeks in the hospital (3). However, there are few reports of culture negative sepsis in pediatric literature. The purpose of this work is to describe the clinical course of children with culture negative sepsis.

Methods: 1. Data requested for patients presenting to Nemours Children’s Hospital (NCH) with a diagnosis of sepsis according to SIRS criteria (≥2 criteria must be true: body temperature instability, (>38.3 °C or <36 °C,) tachycardia > 90 BPM, tachypnea or hypocapnia, or abnormal leukocyte count (>12,000/µL, <4,000/µL, or normal WBC count and >10% band forms) (4)
2. Culture negative sepsis defined as clinical sepsis with blood cultures that remained sterile after ≥ 48 hours
3. PELOD-2 scores and predicted mortality rates calculated using the PELOD-2 score calculator as a measure of severity of multiple organ dysfunction (5)
4. Average PELOD-2 score, corresponding predicted death rate, and morbidity risk factors recorded
Inclusion Criteria
1. Age 1 month-18 years
2. Sepsis diagnosed in history and physical upon PICU admission
3. Negative blood cultures drawn within 48 hours of admission to NCH
Exclusion Criteria
1. Culture positive sepsis

Results: 228 patients presented to the NCH PICU with clinical sepsis between 2016-2019. 155 were reviewed and 19 met criteria for culture negative sepsis (incidence rate=12%, 95% CI: 8%-16%.) Average PELOD-2 score was 5.68 (95% CI: 4.49-6.87) and corresponding average predicted death rate was 3.88% (95% CI: 1.056% -6.27%.) Actual mortality rate was 10.5%. 57.9% of our patients with culture negative sepsis were treated with an antibiotic course lasting > 72 hours.

Conclusion: Culture negative sepsis in children may be associated with poor prognostic factors and unfavorable outcomes. Antibiotic courses were prescribed in most patients and may be promoting bacterial resistance. Our study demonstrates the necessity of further study in this population and creation of treatment guidelines.

References:
1. Pediatr Crit Care Med. 2020;21:e52-e106.
2. Biomed Pharmacother. 2017;96:936-943.
3. Crit Care Med. 2018;46:506-512.
4. Crit Care Med. 2013;41:580-637.
5. Crit Care Med. 2013;41:1761-73.