Monday, October 7, 2019

Ruling out serious bacterial infections in the first weeks of life

- Jennifer Middleton, MD, MPH

Diagnosing serious bacterial infections (bacteremia, meningitis, and urinary tract infection) in the first 60 days of life can be challenging; the risks of missing these infections can be quite serious, but many infants with fever also receive empiric antibiotics and lumbar punctures that may be unnecessary. A new decision rule, reviewed in this October 1 AFP POEM, may help clinicians better predict which infants with fever are more likely to have a serious underlying cause.

The study researchers prospectively enrolled over 1800 infants aged 60 days or younger presenting to Emergency Departments (EDs) across the United States with fever. They excluded infants who appeared critically ill, had a history of prematurity, and/or had received antibiotics in the last 48 hours. Enrolled participants had an evaluation by a pediatric emergency medicine physician and received care however each physician felt was best indicated. All infants had blood and urine cultures obtained along with a complete blood count and serum procalcitonin. The researchers then followed these infants' outcomes; 9.3% (170) had a serious bacterial infection, and the researchers compared their lab values to those infants who did not end up with a diagnosed serious bacterial infection by using, as described by Dr. Barry in the AFP POEM summary, "a variety of statistical gymnastics" to derive their prediction rule:
Using the validation sample, the combination of a negative urinalysis, an absolute neutrophil count less than 4,090 per mL, and a procalcitonin level of less than 1.71 ng per mL was accurate at ruling out serious infections: 97.7% sensitivity (95% CI, 91.3 to 99.6) and 60.0% specificity (56.6 to 63.3). 
Procalcitonin has shown promise before as a predictor of serious illness. The Step-by Step approach, outlined in this 2018 AFP Point-of-Care Guide, uses urinalysis and procalcitonin but also includes c-reactive protein (CRP) to exclude serious bacterial infections in young infants with fever. Last year on the blog, though, Dr. Lin reviewed conflicting evidence regarding procalcitonin's utility in identifying adult respiratory illnesses that would benefit from antibiotics. There's a Choosing Wisely recommendation to not perform procalcitonin testing "without an established, evidence-based protocol." A recent review also reminds us that procalcitonin elevations can be due to several other physiologic processes besides infection, and warns that procalcitonin-guided "algorithms for antibiotic stewardship may not be universally applicable across heterogeneous patient settings and in the 'real world' outside the framework of clinical trials.

We should also resist the temptation to extrapolate this newest decision rule to settings beyond the Emergency Department, though further studies validating this rule (and possibly comparing it directly to the Step-by-Step approach) in those settings could cement its role in helping us better predict which young infants with fever need aggressive testing and treatment - and which do not. There's an AFP By Topic on Neonatology/Newborn Issues that includes several articles about neonatal infections, management of respiratory distress, and an overview of neonatal resuscitation if you'd like to read more.