Objectives– To identify the prevalence of occult bacteremia (OB) in well-appearing, previously healthy children aged 3 to 36 months who present to the emergency department (ED) with fever without source in the post-pneumococcal conjugate vaccine (PCV) era.
Methodology & Results–
This was a retrospective cohort study of children presenting to an urban pediatric ED between July 1, 2004, and June 30, 2007. Children were included if they were aged 3 to 36 months, febrile, and previously healthy; had no source of infection on examination; had a blood culture drawn; and were discharged from the ED. Outcome measures were rates of OB and contaminant rates.
A total of 8,408 children met all inclusion criteria. There were 21 true-positives, yielding an OB rate of 0.25% (95% confidence interval [CI] = 0.16% to 0.37%). There were 159 contaminant cultures yielding a contaminant rate of 1.89% (95% CI = 1.61% to 2.19%), or a ratio of 7.6 contaminants for each true-positive. There were 14 included patients who grew Streptococcus pneumoniae from the blood, for a rate of 0.17% (95% CI = 0.09% to 0.27%).
Conclusions– Given the current rate of OB in the post-PCV era, it may no longer be cost-effective to send blood cultures on well-appearing, previously healthy children aged 3 to 36 months who have fever without source.
For decades prior to the advent of the Haemophilus influenza type b vaccine (HIB) in 1990 and the pneumococcal conjugate vaccine (PCV7) in 2000, it had been common medical practice and guidelines were established to obtain a CBC and blood cultures in the well appearing, previously healthy young infant ages 3-36 months with fever without a source to assess for occult bacteremia (OB). [1, 2] Practice patterns have been slowly changing as new post-immunization data has emerged, but not quickly as many centers still assess these infants with blood cultures. Reasons for slow change likely include a lack of updated guidelines, concerns regarding adequate data, or possible legal repercussions.  Although this is a retrospective study, we are unlikely to see a prospective study addressing this question as the prevalence of the disease is low and decreasing, the cost of doing a prospective study would be high, and practice patterns for performing blood cultures in this patient population are changing.
In this well designed study from the Department of emergency medicine at Phoenix Children’s Hospital, it was standard practice at the study institution to send blood cultures on all well-appearing children with a temperature greater than or equal to 39o C. As a result of this practice, this likely increased the denominator of potentially eligible patients which more closely resembled a more conservative practice pattern. Due to its retrospective design, selection bias was possible as sicker appearing children may have been more likely to have had blood cultures drawn. This would likely have made the incidence of OB reported in the study higher and true rates potentially lower which should reassure the practitioner. The authors of the study acknowledged that it was possible well appearing children could have been evaluated and discharged without blood work, but they were unable to identify this subset of patients. This, however, would only add to the denominator of eligible patients and likely decrease the rate of OB that was reported. Immunization records of patients were not incorporated into this study so the OB rate actually represents the prevalence independent of immunization status. This could be pertinent if practicing in an under-immunized setting as rates of OB could be higher than reported here. However, vaccination rates by age in the study site’s county are very similar to those reported nationally in the U.S.Blood culture results were reviewed by a pediatric infectious disease physician and categorized as “true pathogen,” “contaminant,”, or “more information needed.” Chart review was performed for those cases categorized in the latter group in order to further categorize the blood culture as a “true pathogen” or a “contaminant.” All “true pathogen” charts were also reviewed in order to determine if these cases represented the healthy, well appearing child with occult bacteremia. This chart review was done by the pediatric infectious disease physician and adds consistency to the review process. Exclusion criteria were determined a priori, but due to study design restrictions, the authors were unable to exclude premature infants, children with recent antibiotic use, and children that had been recently hospitalized. Exclusion criteria included admitted patients and patients with the following: “indwelling catheters” (venous, foley, suprapubic), “any identifiable bacterial source of infection (except acute otitis media), croup, stomatitis, herpangina, varicella, or any chronic disease that may predispose to infection (e.g. cancer, immunodeficiency, but not including asthma).”
This large study adds significant validity to other similar smaller papers published after 2000 noting the marked decline in rates of occult bacteremia in the well appearing febrile child. This data provides strong support to change practice for those practitioners that still routinely send blood cultures. The noted total OB rate of 0.25% included 0.17% with S. pneumonia only. This is of importance as most pneumococcal bacteremias are felt to resolve spontaneously without sequelae. [4, 5] Before exclusion criteria were employed, the total OB rate was 0.39%. Of note, it has been reported that if the rate of OB falls below 0.5%, empiric testing and treatment is unlikely to be cost effective.  Noting the high rate of false positive cultures (almost 8-fold increase) obtained in this study also adds significantly to the cost of medicine as follow-up cultures and testing may be necessary.
Are you concerned regarding missing meningococcemia and feel this is why you still need to check a CBC and blood culture? Meningococcemia is rare and the WBC and band count have a low predictive value and have not been shown to be routinely useful in the laboratory diagnosis of unsuspected meningococcal disease.  In one case series, only 2 of 9 children with unsuspected meningococcemia had a WBC > 15,000.  Likely reasons to test include: contact with someone with meningococcemia, an outbreak of the disease in the region in which you practice, or fever with petechiae or purpura. (which would not be classified in the group “well appearing child with fever.”
In conclusion, routine blood cultures for the assessment of OB in the well appearing, previously healthy child (3-36 months) with fever without a source are of low yield, add to the cost of healthcare, and may lead to additional unnecessary testing and costs if false positive (contaminant) specimens are obtained. This is especially true in the fully immunized child. For unimmunized children, it may be prudent to evaluate with blood cultures. Final tips: Don’t forget to consider a U/A and urine culture for the age appropriate boy or girl. Ill appearing children should have an appropriate directed work-up including blood cultures if febrile or a clinical suspicion for sepsis.
1. Avner JR, Baker MD: Occult bacteremia in the post-pneumococcal conjugate vaccine era: does the blood culture stop here? Acad Emerg Med 2009;16(3):258-259.
2. Baraff LJ, Schriger DL, Bass JW et al: Practice guideline for the management of infants and children 0 to 36 months o age with fever without source. Pediatrics 1993;92(1):1-12.
3. Wilkinson M, Bulloch B, Smith M: Prevalence of occult bacteremia in children aged 3 to 36 months presenting to the emergency department with fever in the postpneumococcal conjugate vaccine era. Acad Emerg Med 2009;16(3):220-225.
4. Alter SJ: The evaluation of fever in infancy. In Baker RC: Pediatric Primary Care: Ill-Child Care. Lippincott, Williams & Wilkins, 2001; p277.
5. Alpern ER, Alessandrini EA, Bell LM, et al: Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome. Pediatrics 2000;106(3):505-511.
6. Lee GM, Fleisher GR, Harper MB: Management of febrile children in the age of the conjugate pneumococcal vaccine: a cost-effectiveness analysis. Pediatrics 2001;108(4):835-844.
7. Kuppermann N, Malley R, Inkelis SH et al: Clinical and hematologic features do not reliably identify children with unsuspected meningococcal disease. Pediatrics 1999;103(2):pe20.
8. Dashefsky B, Teele DW, Klein JO: Unsuspected meningococcemia. J Pediatr 1983;102:69-72.