Supplemental Files
Supplemental Files Table of Contents
1. Supplemental Figure 1. Fever Algorithm
2. Supplemental Figure 2. Survey questions
3. Supplemental Figure 3. U-chart of monthly central blood and peripheral blood culture
rates
4. Supplemental Figure 4. Sensitivity analysis excluding follow-up blood cultures obtained
within 72 hours of prior positive blood culture
5. Supplemental Figure 5. U-chart of monthly rates of broad-spectrum antibiotic treatment
6. Supplemental Figure 6. U-chart of monthly testing rates per device-days
7. Supplemental Table 1. Device days and microbiology testing rate per device-days before
and after implementation of the fever algorithm
Algorithm for Pediatric Intensive Care Unit Patients (PICU and PCICU)
with New Fever1 or New Instability2
COMPLETE ALL 4 STEPS
1 Time-sensitive
Obtain blood culture, urinalysis and Order antibiotics STAT release. Administer
< 2 months gestational age? Yes urine culture. Consider lumbar puncture within 60 minutes.
No (LP) for CSF. Consider HSV and acyclovir.
Yes If patient already on antibiotics, call peds
Concern for meningitis? Obtain blood and CSF culture. Consider ID fellow about broadening coverage.
head CT prior to LP.
No
Yes If burn patient, do not start antibiotics
Obtain simultaneous blood culture from
Immuno-compromised? 3 without consulting surgical burn team
every lumen in use, plus a peripheral
source.4, 5, 6 unless hemodynamically unstable from
No
sepsis.8 See BURN004 for details.
Yes Obtain optimal volume blood culture,
Concern for sepsis? 2
peripheral preferred. 6, 7 If concern for meningitis, consult peds ID.
No
2 Central line or ETT/Tracheostomy Presence of ETT/tracheostomy? No
Yes
ETA culture within 3 days?
Yes Defer respiratory culture.
Presence of central line? No
No
Yes
Is there at least one other supporting sign
Instability with use of central line
Obtain central line culture(s) in of respiratory infection?
or signs of local line site infection? Yes
addition to peripheral culture. • Increased quantity secretions from baseline? No
Concerns for contaminated or
Consider line removal. (changes in color or consistency not relevant)?
compromised line?
• New opacity on CXR concerning for consolidation
No • Sustained increase in ventilator settings (pressure
Yes or FiO2) due to poor oxygenation or ventilation
About to start or broaden Draw optimal volume blood
FOR AT LEAST 6 HOURS?
antibiotic coverage? Yes culture, peripheral preferred. 6, 7
Yes
No
Avoid a repeat culture if done within 48 hours. If still Consider ETA culture if there are sufficient
indicated, draw culture, peripheral is preferred. 6, 7 secretions, particularly if starting antibiotics.
3 Consider other sources CNS catheter? Does patient have
an EVD, VPS, or epidural?
Consider CSF studies after discussions with appropriate
consulting service (ped neurosurgery, ped ID, ped pain).
Surgical site infection (SSI)? Evaluate deep and superficial. If concerns, contact surgical
Sedation withdrawal? (↑ WAT Treat and re-assess patient Surgery within past 2 weeks? team, consider additional imaging. Low yield or evidence
scores) and sedation medications. for wound culture collection < 3 days from surgery.
Post-op fever? Surgery or anesthesia If consistent, treat and Infectious diarrhea? New diarrhea Consider C. difficile testing or other viral stool studies.
within 24 hours? Cardiac surgery or re-assess. (3 loose stools/24 hours) while not
catheterization within 48 hours? on laxatives
Thrombus? (DVT, PE, Line- Evaluate with US/duplex, CT Cellulitis? Examine for evidence of Consider wound or dermatology consult.
associated) Consider risk factors scan, and/or d-dimer. skin break down, prior PIV sites.
Drug fever? Review medication record. Viral URI symptoms or new apnea Send respiratory pathogen panel (RPP) if there are new
in neonates? signs or symptoms of respiratory illness.
Recent immunizations? Treat fever and re-assess.
AOM? Young child <6 years of age? Evaluate tympanic membranes.
Complication of Prematurity?9 E.g., IVH
4 Urine studies
May be reasonable to defer urine
studies. If patient has indwelling Consider urinalysis. Set aside a
catheter, remove if possible. portion for potential urine
culture (especially for
Another identified cause of fever?
Yes Obtain urinalysis catheterized specimens). If the
and urine culture. urinalysis is concerning for
No Remove urinary infection (>10 WBC/HPF), then
No
catheter if order and send a urine culture.
Indwelling urine catheter (Foley) Yes
Is the patient possible. Remove urinary catheters if
or intermittent catheterization?
immuno- possible.
Or does patient have risk factors Yes Urine culture without
compromised? No
for urinary tract infection10?
urinalysis is uninterpretable.
Supplemental Figure 1. Algorithm for pediatric intensive care unit patients with new fever
or new instability
Supplemental Figure 1 footnotes: The algorithm footnotes displayed on the reverse side:
This is not an exhaustive list of devices or sources of fever. Please evaluate patient on individual
basis and consider both risk factors for infections and non-infectious diagnoses.
1
New fever/hypothermia: New/first fever is at least 48 hours since last fever. Multiple
measurements taken 1 hour apart. For neonates <2 months gestational age: Hyperthermia 38 C
x1, hypothermia <36C x2, or increased need for temperature support. For immunocompetent:
38.3 C x2, 38.5 C x1, or <36 C x2.
For immunocompromised: 38 C x2 or 38.3 C x1 or <36 Cx2.
2
New instability or sepsis: rigors, hypothermia, hypotension (absolute or relative hypotension in
patient on anti-hypertensive medications), use of vasoactive medications, tachycardia, mental
status changes, poor perfusion, glucose instability, worsening organ dysfunction (lactemia, acute
kidney injury, metabolic acidosis), abnormal WBC, new apnea or bradycardia, or concern for
NEC/SIP in neonates.
3
Immunocompromised: immunocompromised patients may have masked signs of sepsis,
particularly patients on > 1 mg/kg/day steroids, induction chemotherapy for HLH, induction or
reduction therapy for Burkitt Lymphoma.
4
Differential time-to-positivity is a useful way to distinguish catheter-related bloodstream
infections from bacteremia unrelated to central line care. To be valid, equal volumes of blood
must be obtained simultaneously from each lumen and a peripheral source and inoculated in the
same culture media. Do not let difficulty obtaining peripheral blood cultures delay initiation of
appropriate antibiotics (standard is <60 min from neutropenic fever to broad-spectrum coverage).
5
Consider blood cultures from central line lumens and peripherally to distinguish line infections
from bacteremia and to inform possible salvage of the central line. If considering catheter
salvage, re-culture every lumen daily until negative.
6
See blood culture volume for pediatric patients in HPO.
7
After 2 unsuccessful peripheral attempts, attempt an arterial puncture sample. If unable to
obtain an arterial sample via arterial puncture, obtain blood culture via central line. If unable to
obtain central line culture, may consider changing the patient’s arterial line set up and then
obtaining an adequate specimen via arterial line. The arterial line should be the last option for
blood sampling.
8
Burn patients may have inflammatory response due to burns/debridement/grafting procedures.
Antibiotics should only be used when absolutely needed (i.e., septic shock or identified
infections). Antibiotics should be reviewed with PICU attending, surgical burn attending, and
following ID team.
9
Consider the differential for instability in premature neonates such as IVH, widened PDA, or
RDS.
10
Examples of UTI risk factors: structurally abnormal urinary tract, high-grade hydronephrosis,
neurogenic bladder.
Abbreviations: LP—lumbar puncture; CSF—cerebrospinal fluid; ETT—endotracheal tube; ETA—endotracheal aspirate, WAT—
withdrawal assessment tool; PE—pulmonary embolism; DVT—deep vein thrombosis; EVD—external ventricular drain; VPS—
ventriculoperitoneal shunt; AOM—acute otitis media; UTI—urinary tract infection; RPP—respiratory pathogen panel; CNS—
central nervous system; NEC—necrotizing enterocolitis; SIP—spontaneous intestinal perforation; IVH—intraventricular
hemorrhage; PDA—patent ductus arteriosus; RDS—respiratory distress syndrome of the newborn
Supplemental Figure 2. PICU/PCICU Fever Algorithm Physician Survey Questions
I am the:
• fellow
• attending
I started my week of service on this date:
Please select your team:
• Blue
• Red
• PCICU
Did you care for patient with new onset fever or new onset instability?
• Yes
• No
If yes, did you or someone on your team use the new fever culture algorithm?
• Yes
• No
• N/A - no patients with new onset fever or new onset instability
If you used the new fever culture algorithm, do you have any safety concerns related to this algorithm?
• Yes, list concerns:
• No
• N/A - no patients with new onset fever or new onset instability
If you used the new fever culture algorithm, do you think the algorithm improved patient care in the
past week?
• Yes, elaborate:
• No
• N/A - no patients with new onset fever or new onset instability
Other comments or suggestions:
Supplemental Figure 3. U-chart of monthly central blood and peripheral blood culture
rates
Supplemental Figure 3 footnotes:
Abbreviations: T1—timepoint 1, staff education began late June 2020; T2—timepoint 2, first
algorithm was introduced in July 2020; T3—timepoint 3, introduction of 2nd algorithm version
with education in September 2020; T4—timepoint 4, introduction of 3rd algorithm version with
education in March 2021.
Supplemental Figure 4. Sensitivity analysis excluding follow-up blood cultures obtained
within 72 hours of prior positive blood culture
Supplemental Figure 4 footnotes:
Abbreviations: T1—timepoint 1, staff education began late June 2020; T2—timepoint 2, first
algorithm was introduced in July 2020; T3—timepoint 3, introduction of 2nd algorithm version
with education in September 2020; T4—timepoint 4, introduction of 3rd algorithm version with
education in March 2021.
Supplemental Figure 5. U-chart of monthly rates of broad-spectrum antibiotic treatment
Supplemental Figure 5 footnotes:
Abbreviations: T1—timepoint 1, staff education began late June 2020; T2—timepoint 2, first
algorithm was introduced in July 2020; T3—timepoint 3, introduction of 2nd algorithm version
with education in September 2020; T4—timepoint 4, introduction of 3rd algorithm version with
education in March 2021.
Supplemental Figure 6 U-chart of monthly blood, endotracheal, and urine cultures and urinalysis
rates per 1,000 device-days
Supplemental Figure 6 footnotes:
Device days are as follows: Blood cultures per central venous catheter-days; endotracheal cultures per
ventilator-days; urine cultures and urinalysis per urinary catheter-days. The device-days do not exclude
device-days contributed to by adult patients aged >25 years temporarily admitted to this unit during the
COVID-19 pandemic (April 16, 2020, to May 4, 2020, and January 18, 2021, to February 19, 2021)
Abbreviations: T1—timepoint 1, staff education began late June 2020; T2—timepoint 2, first algorithm
was introduced in July 2020; T3—timepoint 3, introduction of 2nd algorithm version with education in
September 2020; T4—timepoint 4, introduction of 3rd algorithm version with education in March 2021.
Supplemental Table 1. Device-days and microbiology testing rate per device-days
before and after implementation of the fever algorithm
Device-days Baseline1 Post- P-value
2
implementation
Central-venous catheter- 428 (355, 491) 515 (480, 563) 0.00
days, median (IQR)
Ventilator-days, median 277 (224, 326) 317 (287, 380) 0.03
(IQR)
Urine catheter-days, median 123 (87, 162) 118 (96, 129) 0.64
(IQR)
Monthly testing rate per Baseline1 Post- IRR 95% CI P-value
1,000 device-days4 implementation3
Blood Cultures 193.3 143.8 0.74 0.69 0.80 < 0.001
Peripheral blood cultures 140.1 103.8 0.74 0.69 0.80 < 0.001
Central line blood cultures 53.2 40.0 0.75 0.68 0.86 < 0.001
Endotracheal cultures 67.7 42.6 0.63 0.54 0.73 < 0.001
Urine cultures 221.2 161.1 0.73 0.64 0.83 < 0.001
Urinalysis 545.0 689.8 1.27 1.18 1.36 < 0.001
Supplemental Table 1 Footnotes:
1
The baseline period was defined as July 1, 2018, through June 30, 2020
2
The post-implementation period was defined as July 1, 2020, through December 31, 2021
3
The post-implementation period was defined as the first month of the new centerline shift
observed in the statistical process control U-chart and went through December 31, 2021. Blood
cultures in July 2020, endotracheal cultures in July 2020, urine cultures in April 2021, urinalysis
in November 2020.
4
Device days are as follows: Blood cultures per central venous catheter-days; endotracheal
cultures per ventilator-days; urine cultures and urinalysis per urinary catheter-days. The device-
days do not exclude device-days contributed to by adult patients aged >25 years temporarily
admitted to this unit during the COVID-19 pandemic (April 16, 2020, to May 4, 2020, and
January 18, 2021, to February 19, 2021)
Abbreviations: IRR- incident rate ratio; CI- confidence interval; IQR- interquartile range