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Is Fever a Red Flag for Bacterial Pneumonia in Children With Viral

Bronchiolitis?

Introduction

Several previous studies have revealed potential morbidity from bacterial pneumonia

in patients with respiratory syncytial virus (RSV). RSV infection may increase the

risk for pneumococcal pneumonia.1 RSV increases the virulence of streptococcal pneumonia by binding to

penicillin-binding protein 1a. Coinfection with RSV and Streptococcus

pneumoniae is associated with severe and often fatal pneumonia.2 Physicians must be mindful of the potential for secondary bacterial pneumonia

in viral bronchiolitis so that it can be promptly treated.

As pediatricians, we follow the guidelines published by the American Academy of

Pediatrics. The 2014 guidelines dealing with evaluation and management of viral

bronchiolitis promote supportive care, and note that routine radiographic or

laboratory studies are not necessary.3 While these guidelines are paramount to treating viral illness, it is

imperative that the physician recognizes at what point further investigation is

warranted. Missing a secondary pneumonia could result in delay in antibiotic

treatment, transfer to the pediatric intensive care unit (PICU), or intubation.

Following a respiratory season at our institution, we noted that children with viral

illness who also had a fever tended to have a worse clinical course versus afebrile

patients. We hypothesized that fever may be a marker for secondary bacterial

pneumonia in patients with viral bronchiolitis. Fever is defined as temperature

≥100.4°F. If a patient developed a fever and the workup showed pneumonia, then

antibiotics could be started quickly rather than waiting until after worsening of

the patient’s clinical condition. Our hypothesis is based on the following anecdotal

evidence from our practice:

Our objective is to investigate whether children with viral bronchiolitis with fever

are more likely to have a diagnosis of secondary bacterial pneumonia than their

counterparts without fever.

Ethical Approval and Informed Consent

This research was submitted to our university institutional review board and was

approved. The IRBNet ID is 1083099-2.

Results

Of the 349 children included in the study, 178 were RSV positive. The majority of

children (56% or 100 children) with diagnoses of RSV were afebrile. Febrile children

who were RSV positive were more than twice as likely to be diagnosed with bacterial

pneumonia as those who were afebrile (47/78 or 60% vs 27/100 or 27%,

P < .001). In the 171 children who had RSV-negative

bronchiolitis (diagnosis of viral infection other than RSV), 88/171 (or 51%) were

afebrile. Febrile children with RSV-negative bronchiolitis were 8 times more likely

to be diagnosed with pneumonia as afebrile children (54/83 or 65% vs 7/88 or 8%,

P < .001).

Additional bivariate and trivariate analyses of both RSV-positive and RSV-negative

bronchiolitis did not show any significant difference between the occurrence of

pneumonia in children with fevers in the 100.4°F to 100.9°F range versus fevers in

the >102°F range.

Discussion

The study demonstrates that fever can be used as a marker indicating a need to

investigate for secondary bacterial pneumonia in children with RSV and other viral

illnesses. Children with viral illnesses who had a fever were more likely to have

diagnoses of pneumonia, whether they had RSV-positive or RSV-negative illness. The

literature supports the need to be wary of the possibility of bacterial pneumonia in

children with bronchiolitis. RSV infection decreases bacterial clearance,

potentially predisposing to secondary bacterial pneumonia despite increased lung

cellular inflammation, and suggests that functional changes occur in the recruited

neutrophils that may contribute to the decreased bacterial clearance.5 Bacterial infection, based on a significant rise of antibody titer and/or on

detection of pneumococcal antigen in serum or urine, was observed in 39% of the

children with RSV infection. We conclude that a bacterial pathogen should be

actively sought when managing patients with lower respiratory tract syndromes,

especially in those who have evidence of RSV infection.6 The interaction between viruses and bacteria is probably much more common and

clinically significant than previously understood. Respiratory viruses frequently

initiate the cascade of events that ultimately leads to bacterial infection. Early

recognition and treatment of these patients will lessen morbidity and mortality.6 Based on the findings at our institution, we believe that fever is a marker

indicating a need to investigate for bacterial pneumonia. There are several

limitations to our study. Since sputum cultures are not collected unless a patient

is intubated, a definitive bacterial cause cannot be confirmed in most cases. As

previously discussed in methods, the diagnosis of bacterial pneumonia is a physician

judgment. Part of the reason our study is important is that literature does not

elucidate any way to definitively determine the presence of bacterial pneumonia in a

non-intubated child. Several studies have tried to address this issue. CRP is

elevated when bacterial pneumonia is present, but it has less than desirable

specificity for distinguishing viral from bacterial pneumonia.7,8 Procalcitonin is a better

indicator than CRP. A procalcitonin less <0.1 has been found to rule out

bacterial infection; however, higher values show overlap in procalcitonin levels

found in viral and bacterial sources.9 Therefore, we are left with clinical judgement based on looking at multiple

factors. Since laboratory testing and imaging are discouraged in the initial

management of bronchiolitis, perhaps fever can indicate such testing is justified to

assist physicians in clinical decision making.

A subsequent study will further examine the prevalence of fever during RSV

bronchiolitis. Literature shows that some viruses such as adenovirus and enterovirus

definitely cause fever.10 Our anecdotal experience is that children with RSV alone usually do not have

fevers unless they have a secondary bacterial infection. For the sake of clarity in

our future study, we will exclude viral causes other than RSV. While our current

study shows the majority of children with bronchiolitis do not have fevers, we did

not investigate other causes of fever such as pyelonephritis and otitis media. The

future study will look for these additional possible bacterial causes of fever and

may show an even lower percentage of children with just RSV bronchiolitis who have a

fever.

Conclusion

Febrile children with viral bronchiolitis were 2 to 8 times more likely to be

diagnosed with a secondary bacterial pneumonia compared with their afebrile

counterparts. Delay in care of respiratory illnesses can significantly increase

morbidity and mortality. Further research is warranted to investigate the need for

more aggressive evaluation of febrile children with viral bronchiolitis. We are

aware of the limitations and plan to further investigate our findings. We feel this

study is relevant because the data discussed could result in a change in practice

for viral bronchiolitis in our young patient population.