Approximately 1% of well-appearing Infants in the third month of life who present as outpatients with fever were found to have an invasive bacterial infection (IBI), in a new meta-analysis1 of studies comprising over 34,000 infants.
"Most febrile young infants are well-appearing; however, they remain at increased risk of invasive bacterial infections, specifically bacteremia and bacterial meningitis," observe Brett Burstein, MDCM, PhD, MPH, Division of Pediatric Emergency Medicine, Montreal Children's Hospital and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada and colleagues.
They point out, further, that there are few IBI risk estimates for infants of this age, and in this current era marked by widespread group B Streptococcus intrapartum antibiotic prophylaxis and Haemophilus influenzae type b and pneumococcal conjugate vaccinations.
"Estimates for infants aged 60 to 90 days are imprecise, derived from heterogeneous populations with selective testing, and have not been consistently replicated across setting," Burstein and colleagues point out. "Updated, generalizable risk estimates are necessary to inform risk stratification, guideline development, and shared decision-making with families."
The investigators conducted the meta-analysis to estimate the prevalence of IBI, and specifically of bacteremia and bacterial meningitis in these infants.The meta-analysis of 59 studies published since 2000 involved 20 distinct cohorts with 34,835 infants aged 60 to 90 days who were evaluated for fever in an emergency or outpatient setting.Each cohort was restricted to infants who were well appearing, and excluded those with preexisting comorbidities or proven infections.
The investigators reported that 338 of the 34,835 infants had IBI, 315 of which were bactermia without bacterial meningitis and 40 with bacterial meningitis.The pooled prevalence of any IBI, then, was 1.11% (95% CI, 0.84 to 1.47%); with 1.01% bacteremia (0.76 to 1.34%), and 0.11% bacterial meningitis (0.08 to 0.16%).
They compare this with best estimates from the literature that indicate that risk for bacteremia and bacterial meningitis in the first month of life is 3.0 and 1.0%, respectively; and 1.6 and 0.4%, respectively, in the second month.
What You Need to Know
The meta-analysis found that approximately 1.1% of well-appearing infants in their third month of life had an invasive bacterial infection (IBI), including bacteremia or bacterial meningitis.
Rates of bacteremia and meningitis were lower in infants aged 60–90 days than in younger infants, supporting the idea that third-month infants represent a distinct, lower-risk group compared with those in the first two months of life.
Researchers emphasized that while clinicians must avoid missing serious infections, over testing and hospitalization can lead to complications, discomfort, disrupted breastfeeding and bonding, and unnecessary antibiotic exposure. Better risk stratification may help providers safely limit interventions in low-risk infants.
"When taken together, our findings highlight a continued downward risk gradient with increasing age and suggest that infants in the third month represent a distinct risk category," Burstein and colleagues indicate.
The investigators also cite the American Academy of Pediatrics, however, which has cautioned that "a number is not a decision;” and they acknowledge that risk estimates in the range of 1 in 100 for bacteremia and 1 in 1000 for bacterial meningitis "are inherently ambiguous and require judgment regarding what degree of risk is tolerable."
Burstein and colleagues also acknowledge the difficulty for clinicians seeking balance between the risk of missing an IBI and the potential harms of excessive testing and unnecessary treatment.That calculation, they suggest, should include the reported 20% to 30% of hospitalized febrile infants experiencing iatrogenic complications, the pain and discomfort from drawing samples, the disruption to breastfeeding and bonding, and disrupting the developing microbiome with broad-spectrum antibiotics.
"Efforts to 'safely do less,' however, must be grounded in accurate estimates of disease probability and supported by strategies that mitigate diagnostic uncertainty," the investigators advise.
Reference
1. Dionisopoulos Z, Sabhaney V, D'Arienzo D, et al. Prevalence of invasive bacterial infections among febrile infants aged 60 to 90 days. JAMA Pediatr. 2026. Published Online May 26. doi:10.1001/jamapediatrics.2026.1815.
