Secondary bacterial infections
Secondary
bacterial infections are a known complication of RSV bronchiolitis, of
which UTI is the most extensively studied. However, many of these
studies have used various UTI definitions with differing levels of
sensitivity and specificity. For instance, a recent meta-analysis
reported that 3.1% of children with bronchiolitis were also diagnosed
with a UTI. Many studies included only children under three months of
age and not 24 months. Early detection of UTI can profoundly impact the
clinical outcome of hospitalized infants.
In our cohort, 23 patients (1.2%) were diagnosed with UTI, with a
relative risk of 11 for the high CRP group in a multivariable analysis.
However, this association was highly sensitive but not specific. The
highest AUC was in children 3-12 months old with a threshold of 3.42
mg/dL (AUC 0.79), although further investigation is needed since UTI
incidence in our cohort was very low.
Lobar/alveolar
pneumonia is another important complication of RSV bronchiolitis, but
its definition varies in the literature and is based on clinical and
radiographic features, often assisted by laboratory markers. A recent
study from our center has demonstrated that RSV is associated with
community-acquired pneumonia in a multivariable model in 50% of cases,
most notably in children under 2 years of age (62%), indicating a
significant role in its pathogenesis. This finding is supported by the
decline in pneumonia and RSV prevalence during the COVID-19 pandemic
despite persistent nasopharyngeal carriage of S. pneumoniae.
Several studies have assessed the association of elevated CRP with
pneumonia in the context of RSV. One multinational study reported that
increased CRP levels (>4mg/dL) were associated with
bacterial rather than viral pneumonia in otherwise healthy children.
However, another study showed only a slightly elevated CRP level in
bacterial pneumonia (1.06 Vs. 0.62 mg/dL). In a prospective study of
children with bronchiolitis in a PICU setting, elevated CRP and
procalcitonin levels were significantly associated with pneumonia or
sepsis. These results are similar to our study in the association of CRP
with severe disease, but differ in the study population, which only
isolated RSV in 65% of patients and only included severe cases, who
often have other predisposing conditions that excluded them from our
study. Our study found that elevated CRP was associated with secondary
pneumonia (9% in the high-CRP group vs. 4.3% in the low group) with a
relative risk of 1.98 in a multivariable analysis. However, we found
that CRP had limited predictive ability, as the AUC for the suggested
cutoff was low.
The main strength of our research is the large cohort size, which is
larger than previous studies that have assessed CRP in acute
bronchiolitis in children. Additionally, being a single tertiary medical
center, SUMC was able to maintain a consistent clinical approach, with
standardized protocols for hospitalization, discharge, antibiotic
stewardship, and laboratory and radiologic evaluation, which further
strengthens the reliability and validity of our findings.
Limitations of this study include its retrospective nature, as the
inclusion and exclusion criteria may have resulted in the exclusion of
mild cases who were likely discharged without CRP measurement, as well
as critically ill patients with severe risk factors. Also, our
definition of secondary infection was based on the electronic medical
records, which were determined by the treating physicians and not based
on interpretation of radiological findings, with fixed criteria. As
such, there may be potential for under or overdiagnosis. Furthermore, an
elevated CRP level may have influenced the given pneumonia diagnosis,
which was also based on inflammatory markers and not merely based on
radiologic findings. Lastly, our medical documentation system prevented
us from further analyzing data on the use of high-flow nasal cannula in
the pediatric ward setting, which was implemented in 2020.
This study was conducted with the aim of providing clinicians an easy
and accessible tool to aid decision making and management of
hospitalized children with RSV bronchiolitis. Specifically, we sought to
determine the usefulness of CRP levels measured at ED admission as an
early detection method for severe disease. Our findings demonstrate that
CRP can be a valuable tool for informing decisions related to
hospitalization, diagnostic evaluation, and communication with parents
about the anticipated duration of hospitalization.