Evidence Based Strategies for Common Clinical Questions

Risk of Bacterial Meningitis in Febrile Infants

Author: Brittany Moore, MD | Pediatric Resident

Column Editor: Kathleen Berg, MD | Co-Director, Department of Evidence Based Practice | Pediatric Hospitalist, Division of Pediatric Hospital Medicine | Associate Professor of Pediatrics, UMKC School of Medicine 

Picture an 8-day-old who presents with fever, decreased oral intake, and irritability. Then imagine a 25-day-old with fever but reassuring physical exam. Last, consider a 59-day-old with fever and foul-smelling urine. Febrile infants pose a wide array of clinical questions. Recent studies have investigated epidemiology and risk stratification of serious and invasive bacterial infections. Urinary tract infections (UTIs) in the well-appearing febrile neonate have long been thought to place an infant at high risk for bacterial meningitis. This article will review bacterial meningitis in neonates and discuss the relationship between bacterial meningitis and UTI.   

The organisms causing serious or invasive bacterial infections have shifted over time in part due to increased vaccination, maternal screening and food safety. After introduction of the pneumococcal and Haemophilus influenzae vaccines, bacterial meningitis seen in children older than 2 months declined appreciably.¹ In infants less than 3 months old, the most common pathogens are Escherichia coli and group B streptococcus.^1-3 UTI is the most common serious bacterial infection.^4-6 

Neonates can present with fever or hypothermia, difficulty with feeding, bulging fontanelle, lethargy or irritability.⁷ Symptoms of meningitis whether viral, bacterial or other etiology can be nonspecific, and neonates may continue to appear well despite infection. For the ill-appearing infant, a full sepsis work-up should be performed including blood culture, urine culture, cerebrospinal fluid (CSF) cell counts, protein, glucose, and culture, and parenteral antimicrobials should be initiated. In the first six weeks of life, herpes simplex virus should also be considered, though outside the scope of this article. 

The full-term, well-appearing febrile infant presents a multitude of clinical questions that require carefully weighing the risks and benefits of invasive testing, empiric antimicrobials and hospitalization. In August 2021, the American Academy of Pediatrics (AAP) developed a clinical practice guideline to provide an evidence-based approach to the well-appearing infant with fever.⁶ These new guidelines distinguish between the 8- to 21-day-old, 22- to 28-day-old, and 29- to 60-day-old infants due to differences in their risk of bacteremia and bacterial meningitis. A full sepsis work-up including CSF studies and culture continues to be recommended for those 8-21 days. However, decisions to perform a lumbar puncture, provide parenteral antibiotics and admit to the hospital are more nuanced for the 22- to 28-day and 29- to 60-day age groups, and are based on urinalysis (UA) and inflammatory markers. CSF pleocytosis consistent with meningitis should prompt broad-spectrum antibiotics and observation in the hospital.^1,6 

In the past, an abnormal UA placed the infant in a high-risk category for bacterial meningitis, prompting CSF examination, parenteral antimicrobials and hospitalization. In 2019, a systematic review evaluated 20 studies of infants <90 days old with suspected or confirmed UTI. The frequency of coexisting UTI and bacterial meningitis was 0%-2.1%; none with bacterial meningitis were considered low risk (well appearing, >21 days of age, procalcitonin ≤0.5 ng/ml, and C-reactive protein ≤20 mg/L).⁸ The same year, a meta-analysis included infants 29-90 days old with evidence of UTI who underwent CSF examination. Prevalence of coexisting UTI and bacterial meningitis was 0.25% (95% CI, 0.09%-0.70%).⁵ In a 2021 systematic review of 48 studies evaluating infants 29-60 days old with positive UA, the prevalence of bacterial meningitis was 0.25%-0.44%. This percentage was no greater than that for infants with negative UA (0.50%).⁴ The findings of these studies suggest that for well-appearing febrile infants ≥29 days of age with evidence of UTI, CSF examination is not always indicated. The AAP guidelines recommend using inflammatory markers to guide this decision. There is less evidence for infants 22-28 days old; the guidelines offer more management options chosen with shared decision-making.⁶ 

The treatment of bacterial meningitis in the neonatal period varies by age. Ampicillin and ceftazidime are recommended empiric treatments in the 8- to 28-day-old infant.⁶ Ceftriaxone should be used in the 29- to 60-day-old infants without an identified focus of infection. If meningitis is suspected, then vancomycin should be added for the 29- to 60-day-olds.⁶  

Evidence-based evaluation for bacterial meningitis in the febrile infant requires careful consideration of age, risk factors, laboratory findings and coexisting infections. When it is suspected, empiric antimicrobials should be initiated without delay, as early treatment can improve survival and prevent progression of disease. The Children’s Mercy febrile infant clinical practice guideline can support decision-making in each neonatal age group.

 
 
References: 

1. Ouchenir L, Renaud C, Khan S, et al. The epidemiology, management, and outcomes of bacterial meningitis in infants. Pediatrics. 2017;140(1):e20170476. doi:10.1542/peds.2017-0476
2. Brouwer MC, van de Beek D. Epidemiology of community-acquired bacterial meningitis. Curr Opin Infect Dis. 2018;31(1):78-84. doi:10.1097/QCO.0000000000000417
3. Powell EC, Mahajan PV, Roosevelt G, et al. Epidemiology of bacteremia in febrile infants aged 60 days and younger. Ann Emerg Med. 2018;71(2):211-216. doi:10.1016/j.annemergmed.2017.07.488
4. Burstein B, Sabhaney V, Bone JN, Doan Q, Mansouri FF, Meckler GD. Prevalence of bacterial meningitis among febrile infants aged 29-60 days with positive urinalysis results: a systematic review and meta-analysis. JAMA Netw Open. 2021;4(5):e214544. Published online May 3, 2021. doi:10.1001/jamanetworkopen.2021.4544
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6. Pantell RH, Roberts KB, Adams WG, et al. Evaluation and management of well-appearing febrile infants 8 to 60 days old [published correction appears in Pediatrics. 2021 Nov;148(5):]. Pediatrics. 2021;148(2):e2021052228. doi:10.1542/peds.2021-052228
7. Johansson Kostenniemi U, Norman D, Borgström M, Silfverdal SA. The clinical presentation of acute bacterial meningitis varies with age, sex and duration of illness. Acta Paediatr. 2015;104(11):1117-1124. doi:10.1111/apa.13149
8. Poletto E, Zanetto L, Velasco R, Da Dalt L, Bressan S. Bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infection: a systematic review. Eur J Pediatr. 2019;178(10):1577-1587. doi:10.1007/s00431-019-03442-4