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Procalcitonin Levels

in Febrile Infants

After Recent

Immunization

Andrew Dauber, Scott Weiss, VincenzoManiaci, Eric Nylen, Kenneth L. Becker and

Richard BachurPediatrics 2008;122;e1119-e1122

DOI: 10.1542/peds.2008-1884

BACKGROUNDProcalcitonin has beenidentified as a useful bloodmarker of serious bacterialinfection in febrile infants.

Many infants present with afebrile reaction after receivingimmunizations. The effects ofimmunization on procalcitoninhave not been investigated.

METHODSWe performed a prospectiveobservational cohort study at alarge, urban pediatric

emergency department.Infants 90 days of age with

fever of 38C were enrolled.Subjects were divided into 3groups: infants with seriousbacterial infection; subjectswithout serious bacterialinfection who received recent

( 48 hours) immunizations;and subjects without seriousbacterial infection who did not

recently receiveimmunizations. Procalcitoninwas measured by using aquantitative immunometricassay.

RESULTSOver 13 months, procalcitoninwas measured for 271 infants.There were 44 (16%) patients

with serious bacterial infection,35 in the recent-immunization

group, and 192 in the no-recent-immunization group.The median procalcitonin levelfor serious bacterial infectionwas 0.53 ng/mL, for recent

immunization was 0.29 ng/mL,and for no recentimmunizations was 0.17ng/mL. Procalcitonin valueswere elevated for patients withserious bacterial infectioncompared with patients bothwith and without recentimmunizations. Compared withpatients who had no recentimmunizations, procalcitoninlevels were elevated inpatients with recentimmunization. Using a cutpoint of .12 ng/mL, thesensitivity of procalcitonin forserious bacterial infection was96%, specificity was 23%, andnegative predictive value was96%. Two patients with recentimmunization who had serious

bacterial infection wereidentified with this cut point.

CONCLUSIONSAmong febrile infants with recent

immunization, procalcitonin levels are

increased compared with patients with

fever and no identified bacterial

infection. Despite this increase,

procalcitonin can still reliably

discriminate infants with serious

bacterial infection.

Fever may be the only sign ofa serious bacterial infection (SBI) For

infants 3 months of age. With the

advent of the Pediarix

(GlaxoSmithKline, Research Triangle

Park, NC) vaccine, there have been

reported rates of fever after vaccination

as high as 27.9% and no standart

evaluation or management for those

cases.

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Recent studies haveidentified procalcitonin as abiomarker of bacterialinfections. Procalcitonin wasfound to be a highly sensitive

marker of SBI in this cohort.The effect of immunization onprocalcitonin levels has notbeen well described andtheoretically might interferewith the use of procalcitonin asa diagnostic marker for SBI.

Fever is the mostfrequently reported seriousand nonserious adverseevent after immunizationaccording to the VaccineAdverse Event ReportingSystem. This presents a uniqueproblem in those infants 3months of age who are athigher risk of having an SBI.

Procalcitonin levels canbe modestly elevated aftervaccination in the absence ofinfection. Ours was a

prospective cohort study thatincluded 271 infants 90 daysold with documented

temperatures of 38C in apediatric emergencydepartment. We previouslyreported the utility of procalcitonin level forpredicting SBI in those patientswho had not receivedimmunizations in the previous48 hours. All cases of bacteremia were identifiedaccurately with the cut-pointvalue.

In the current study, we further

subcategorized the patients as those

with SBI, those without SBI who had

recently received immunizations, and

those without SBI who had not

recently received immunizations. The

median procalcitonin level wassignificantly higher in the group of

infants who had received

immunizations compared with those

who had not, but it was significantly

lower than in the SBI group. On the

basis of this, it seems that

immunization leads to an increase inserum procalcitonin values, but it can

still be used to identify a group at low

risk for SBI regardless of

immunization status.

The WBC count was also

elevated in the RI group when

compared with non-SBI patients

without recent immunization but was

similar to those with SBI. Therefore,

WBC count, a commonly used marker

for SBI, is less useful for patients whohave recently received vaccinations.

Overall, the addition of

vaccinated infants into the analysis of

the entire cohort led to a similar

sensitivity and NPV but decreased the

specificity of procalcitonin level as a

marker of SBI. This change is because

of the vast majority of immunized

patients having a procalcitonin value

that was greater than our cut point of

0.12 ng/mL. However, procalcitonin

levels can continue to be used to

identify patients at low risk for SBI,

and by using the same cut point, both

patients in our cohort with SBIs who

had recently received immunizations

were identified.

Our study has several

limitations. In addition, even among

those febrile infants who were recently

vaccinated and presented with fever,there may be a bias of who had any

laboratory evaluation.

Finally, our definitions of SBI

were intended to be conservative to

include all possible SBIs, because we

were hoping to identify a low-risk

group for SBI. We acknowledge that

some of the patients with low-colony-

count UTIs and radiographic

pneumonia may not have represented

true bacterial infections. Our initialstudy provides further analysis on

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definite and possible SBIs to account

for this difficulty in definitions.