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Question 2:  What does the literature say regarding the work up for serious bacterial infection (SBI) in well-appearing febrile infants and children who have not received conventional routine immunizations?

With the conventional utilization of vaccines in infants and young children, the workup of the well appearing febrile infant/child has grown simpler with less routine bloodwork overall. Today, the more complicated patient evaluation might be the child who has not received routine immunizations. While Covid vaccinations in children has been a recent hot topic, this discussion focuses on conventional routine vaccinations in infants and young children.

The literature is extremely limited on this specific topic. We were only able to identify two articles. The first is a five-year retrospective study of children aged two to 36 months and their association with occult bacteremia.⁵ Children with high-risk medical conditions were excluded. A total of 5,534 blood cultures were obtained. Unvaccinated children were defined as not receiving any Haemophilus B (Hib) or pneumococcal (PCV) vaccines. Under-vaccinated children were defined as receiving only one set of vaccines by five months of age or one to two sets by seven months of age. Children over seven months of age were defined as under-vaccinated if they had received less than three sets of immunizations. The primary outcome was the rate of positive blood cultures in three groups: unvaccinated, under-vaccinated, and vaccinated.

The authors randomly selected 200 blood cultures per year for a total number of 1,000 blood cultures—of which 143 were excluded because patients either had co-morbidities predisposing to bacteremia or a lack of vaccination records—leaving 857 blood cultures for analysis. These results were then extrapolated back to a total number of 5,534 blood cultures. This extrapolation method seems to be one of the limitations of the study.

Unvaccinated and under-vaccinated children represented 15.2 percent and 6.6 percent of the total study population, respectively. The relative risks of occult bacteremia in unvaccinated (0.79; 95 percent CI 0.39-1.59) and under-vaccinated (1.20; 95 percent CI 0.52-2.75) children were not significant when compared to fully vaccinated children. This might suggest that herd immunity plays a role in the rate of bacteremia in this study. The reported rate of positive blood cultures was 6.8 percent. However, after contaminants were removed, the rate was only 1.5 percent suggesting a three-fold ratio of contaminant to true positive blood cultures. These data may help you to sleep a tiny bit better if a blood culture is not drawn on an unvaccinated or under-vaccinated well-appearing febrile child.

The second article on this topic provides a very brief review of fever without a source and offers a potential evaluation algorithm for febrile well-appearing unvaccinated children three to 24 months of age.⁶

Summary

Overall, the data on occult bacteremia in unvaccinated well-appearing febrile children in the post-vaccine era is extremely limited. At this time, no literature suggests that their work up should deviate from that of the vaccinated child.

References

1. Oskoui M, Pringsheim T, Holler-Managan Y et al. Practice guideline update summary: acute treatment of migraine in children and adolescents: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2019;93(11):487–499.
2. Richer L, Billinghurst L, Lindsdell MA et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database Syst Rev. 2016;4(4):CD005220.
3. Backur RG, Monuteaux MC, Neuman MI. A comparison of acute treatment regimens for migraine in the emergency department. Pediatrics. 2015;135(2):232–238.
4. migraine in the emergency room. Pediatr Neuro. 2012 Oct; 47(4):233-41.
5. Dunnick J, Taft M, Tisherman, RT et al. Association of bacteremia with vaccination status in children aged 2 to 36 months. J Pediatric. 2021;232(5):207–213.e2
6. Finkel L, Ospina-Jimenez C, Byers M et al. Fever without source in unvaccinated children aged 3 to 24 months: what workup is recommended? Pediatr Emerg Care. 2021;37(12):e882–e885.