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Reference: Florin TA, et al. Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study. Emerg Med J. 2023

Date: May 29, 2024

Guest Skeptic: Dr. Christina Lindgren is a Pediatric Emergency Medicine Attending at Children’s National Hospital and Assistant Professor of Pediatrics and Emergency Medicine at the The George Washington University School of Medicine and Health Sciences in Washington, DC. She also serves as the Associate Program Director for the Pediatric Emergency Medicine Fellowship.

Dr. Christina Lindgren

Guest Author: Dr. Todd Florin is a Pediatric Emergency Medicine Attending at Lurie Children’s Hospital of Chicago where he is also the Director of Research and Associate Professor of Pediatrics and Emergency Medicine at Northwestern University Feinberg School of Medicine. 

Case: A 6-week-old boy is brought by his family to the emergency department for fever. He was found to have a temperature of 38.4C at home this evening. His parents tell you that he has been congested for the past few days and his cough seems to have worsened. They have been using a bulb suction device at home to help him breathe better, and he is still tolerating breastmilk and formula. There is a school-age sibling at home with cough and congestion as well which she has successfully passed on to the rest of the family. On your physical exam, you note that he has clear nasal secretions, normal oxygen saturation, and appears well. His parents ask you, “He’s so little. Do you think he has pneumonia? His sister had pneumonia in the past and got a chest x-ray. Does he need a chest x-ray as well?”

Background: We’ve covered the topics of febrile infants and pediatric pneumonia multiple times on the SGEM:

  • SGEM #171: Step-by-Step Approach
  • SGEM #296: PECARN Clinical Prediction Rule for Low-Risk Febrile Infants 
  • SGEM #241: American Academy of Pediatrics (AAP) Guidelines for the Management of Febrile Infants 8-60 days old
  • SGEM #338: SAFER Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia
  • SGEM #359: SCOUT-CAP Short vs Standard-Course Antibiotics for Community-Acquired Pneumonia in Children
  • SGEM #387: Lumbar Punctures in Febrile Infants with Positive Urinalysis

Dr. Todd Florin

It only makes sense that today, we get to combine both topics in one episode and talk about pneumonia in febrile infants <60 days.

Pneumonia is tough to diagnose in this very young population based on just clinical examination alone. This can be particularly challenging because there is a lot of crossovers with bronchiolitis.

There is no evidence-based guidance as to who gets a chest X-ray (CXR) and who does not. This leads to a lot of practice variation. 

 

Clinical Question: What factors (demographic, clinical, laboratory) are associated with radiographic pneumonia in febrile infants?

Reference: Florin TA, et al. Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study. Emerg Med J. 2023

  • Population: Febrile infants ≤ 60 days with rectal temperature ≥38॰C with CXR performed
  • Excluded: Infants who appeared critically ill, already receiving antibiotics, premature <37 weeks gestation), significant comorbidities, indwelling devices, focal bacterial infections (cellulitis)
  • Intervention: Evaluation of radiographic pneumonia, classified into definite pneumonia, possible pneumonia, and no pneumonia.
  • Comparison: None
  • Outcome: Demographic, clinical, and laboratory factors associated with radiographic pneumonia.
  • Trial: Secondary analysis of data from previous PECARN study conducted from June 2016 to April 2019

Authors’ Conclusions: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonia, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

Quality Checklist for Observational Study:

  1. Did the study address a clearly focused issue? Yes
  2. Did the authors use an appropriate method to answer their question? Yes
  3. Was the cohort recruited in an acceptable way? Yes
  4. Was the exposure accurately measured to minimize bias? Unsure
  5. Was the outcome accurately measured to minimize bias? Yes
  6. Have the authors identified all-important confounding factors? Unsure
  7. Was the follow up of subjects complete enough? Yes
  8. How precise are the results? Unsure 
  9. Do you believe the results? Yes
  10. Can the results be applied to the local population? Unsure 
  11. Do the results of this study fit with other available evidence? Yes
  12. Were there any conflicts of Interest declared and who funded the study? Dr. Ramilo reported personal fees from Sanofi-Pasteur, Merck, and Pfizer, and grants from Janssen and the Bill & Melinda Gates Foundation, unrelated to this study. No other conflicts were reported. The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, and the Health Resources and Services Administration.

Results: They enrolled 2,612 infants of whom 568 (22%) had CXRs performed. The median age was 38 days and 59% were male. Nineteen (3%) had a definite pneumonia and thirty-four (6%) had a possible pneumonia.

Key Results: Radiographic pneumonia in febrile infants was uncommon and associated with respiratory distress.

Demographic Factors: No statistically significant differences based on sex, age, race, or ethnicity amongst the groups that had no, possible, and definite pneumonias.

Clinical Factors: Infants who had definite or possible pneumonia were more likely to be tachypneic, have work of breathing, respiratory distress, require admission, or have influenza or RSV detected.

No statistical differences based on the YOS but a higher proportion of infants with definite pneumonias scored higher on YOS.

Lab Factors: The median white blood cell count (WBC), absolute neutrophil count (ANC), and procalcitonin (PCT) were higher in infants with possible or definite pneumonia. It’s important to note that only 324 infants (57%) had PCT results.

Higher proportion of infants with definite or possible pneumonia had influenza or respiratory syncytial virus (RSV) detected.

Bacteremia was rare and no infant who had possible or definite pneumonia had bacteremia.

Tune into the podcast to hear Dr. Florin’s full responses to our questions. We have included some key highlights.

Selection Bias:

In the initial PECARN study, CXRs were performed at the ED provider’s discretion. Unfortunately, researchers were unable to capture the ED provider’s clinical reasoning behind performing the CXR. Was it part of an institutional pathway for working up a febrile infant? Was it because the infant was exhibiting signs of respiratory distress? In the infants who did not have CXR performed, what proportion would also have potentially had evidence of radiographic pneumonia?

We are not advocating for irradiating all babies, but how do you think this selection bias may have impacted your results?

  • Authors did not know reasons why CXR were ordered (respiratory findings, institutional pathways/order sets, provider preference) but this reflects real world clinical practice.
  • Results largely consistent with previous studies.

Definite, Possible, No Pneumonia:

There are limitations to the use of CXRs in detecting pneumonia. We can’t tell based on CXR whether it is bacterial or viral. I think we’ve all gotten radiology reads along the lines of “atelectasis or developing pneumonia. Correlate clinically.” There’s even poor inter-rater reliability among radiologists. [1]

This study characterized the CXRs into “no, possible, and definite pneumonia”. 

What was the process of evaluating CXR by the study investigators? How many investigators reviewed each CXR? How was the inter-rater reliability amongst the study investigators and amongst the study investigators and the attending radiologists who performed the initial review?

  • Negative predictive value of chest radiography is very high. If CXR is read as definitely normal by radiologist, it is very unlikely that child will return with pneumonia. [2]
  • Authors did not review images but did review radiologist’s report and categorized them in a standard process.

Viral Testing:

In this study cohort, a large proportion of children tested positive for viruses. A higher proportion of children with possible or definite pneumonias tested positive for influenza or RSV. We know that detection of certain viruses such as influenza, RSV, or even SARS-CoV-2 may decrease the risk of invasive bacterial infections in this young age group. [3-6]

At the same time, we know that viral PCR testing is limited. Positive results can linger after active infection. Positive testing does not eliminate the possibility of bacterial co-infection.

How are you using respiratory viral testing in this population if at all?

  • Currently, there is little clinical utility in multiplex respiratory viral testing.
  • Dr. Florin makes an exception for influenza testing because oseltamivir can be considered in this population.
  • Knowledge of Covid status is less helpful.

Inflammatory Markers:

Previous PECARN low-risk febrile infant prediction tool risk stratified based on results of urinalysis, ANC, and PCT. That PCT cut-off was 0.5 ng/mL. This study also looked at WBC, ANC, and PCT. The PCT in this study even in the groups of possible or definite pneumonia ranged from 0.1 to 1.5 ng/mL.

How do you interpret an elevated PCT level >0.5 ng/mL and pneumonia on CXR? Does it reassure you (that you’ve found the source of infection)?

  • If you see an elevated PCT in the setting of fever and pneumonia, it is likely that you have found the source of infection. However, Dr. Florin still recommends following the PECARN low risk febrile infant prediction rule and obtaining blood and urine cultures.
  • If PCT is low and other PECARN markers are negative, it is unlikely the febrile infant has bacterial pneumonia.

In places without access to PCT, do the results of WBC or ANC help make a decision to perform CXR? There’s a lot of overlap in the ranges provided amongst the groups with no, possible, and definite pneumonia.

  • ANC and WBC should NOT be used to guide CXR use.

 The Future of Pneumonia: 

What’s next? Where do you think we’re going with the diagnosis of pneumonia in febrile infants and children?

  • Role of ultrasound
  • Many different “-omics”

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions.

SGEM Bottom Line: Consider obtaining CXR in febrile infants with clinical signs of respiratory distress.

Case Resolution: You let the family know that there are potential harms and benefits of ordering a CXR for their baby. There is little evidence to guide decision making around ordering a CXR. Given that the child appears well and does not appear to be in respiratory distress, you engage in shared decision making and opt to defer CXR at this time which has the added benefit of not exposing the child to radiation. However, you will plan to obtain urine and blood testing based on PECARN low risk febrile infant prediction tool.

Clinical Application: 

This work demonstrates that we should not uniformly include chest x-ray in the work-up of the febrile young infant, but in those where there is respiratory distress or signs of lower respiratory tract disease, it should be considered. In addition, although laboratory findings were not definitive in our study, I’d consider a chest x-ray in those infants whose ANC or PCT are through the roof.

There is a good deal of overlap between pneumonia and bronchiolitis in infants. Anecdotally, one of the key differentiators is the history – bronchiolitis starts with URI symptoms that then migrate down to the lower tract. On auscultation, generally there is wheezing and rhonchi. Wheezing tends to be negatively associated with pneumonia. Some of these findings may help to differentiate these two similar conditions.

What Do I Tell My Patient? 

Tune in to hear Dr. Florin’s response.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

References:

  1. Voigt GM, Thiele D, Wetzke M, et al. Interobserver agreement in interpretation of chest radiographs for pediatric community acquired pneumonia: Findings of the pedCAPNETZ-cohort. Pediatr Pulmonol. 2021;56(8):2676-2685.
  2. Lipsett SC, Monuteaux MC, Bachur RG, Finn N, Neuman MI. Negative chest radiography and risk of pneumonia. Pediatrics. 2018;142(3):e20180236.
  3. Mahajan P, Browne LR, Levine DA, et al. Risk of bacterial coinfections in febrile infants 60 days old and younger with documented viral infections. J Pediatr. 2018;203:86-91.e2.
  4. Krief WI, Levine DA, Platt SL, et al. Influenza virus infection and the risk of serious bacterial infections in young febrile infants. Pediatrics. 2009;124(1):30-39.
  5. Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics. 2004;113(6):1728-1734.
  6. Aronson PL, Louie JP, Kerns E, et al. Prevalence of urinary tract infection, bacteremia, and meningitis among febrile infants aged 8 to 60 days with sars-cov-2. JAMA Netw Open. 2023;6(5):e2313354.
  7. Stockmann C, Ampofo K, Killpack J, et al. Procalcitonin accurately identifies hospitalized children with low risk of bacterial community-acquired pneumonia. J Pediatric Infect Dis Soc. 2018;7(1):46-53.