Antibiotic exposure in very low-birth-weight infants associated with mortality, major morbidity

Issue: May 2019

A recent study found that prolonged empirical antibiotic exposure could potentially cause harm when used within the first week after birth in very low-birth-weight infants.

This follows a 2016 study that found antibiotics were overused among neonates who were considered low risk for sepsis. Another study found that although overall prolonged exposure to antibiotics decreased in extremely low-birth-weight infants (ELBW), antibiotics were still associated with mortality.

“Epidemiologic studies have shown that prolonged initial empirical treatment is associated with adverse outcomes, including development of hospital-acquired infections (HAIs), necrotizing enterocolitis (NEC), or death,” explained the study authors.

Researchers used the Canadian Neonatal Network database to collect data from very low-birth-weight (VLBW) infants (<1,500 g) admitted to one of the 29 participating NICUs in Canada from Jan. 1, 2010, to Dec. 31, 2016. The infants were classified into three groups based on antibiotic exposure: none, 1 to 3 days, and 4 to 7 days. Each additional day of antibiotic use was analyzed to determine its impact on a composite outcome of mortality or major morbidity — including severe intraventricular hemorrhage, periventricular leukomalacia, stage 3 through 5 retinopathy of prematurity in either eye, at least stage 2 NEC, chronic lung disease or HAI.

A study published in Pediatrics linked longer durations of empirical antibiotic exposure in low-birth-weight infants during the first week of after birth with an increased risk for morbidity and mortality.

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The researchers included data from 14,207 infants during the study period in their analysis. Of these infants, 2,950 (21%) did not receive antibiotics, 5,401 (38%) received 1 to 3 days of antibiotics and 5,856 (41%) received 4 to 7 days of antibiotics. Researchers found that prolonged antibiotic exposure for 4 to 7 days in the first week after birth was associated with higher adjusted odds of the composite outcome than not receiving antibiotics (adjusted OR = 1.24; 95% CI 1.09-1.41) or receiving them for 1 to 3 days (aOR = 1.38; 95% CI 1.25-1.51).

Each additional day of antibiotic use was associated with a 4.7% higher odds (95% CI 2.6%-6.8%) of the composite outcome in VLBW infants, 7.3% higher odds (95% CI 3.3%-11.4%) in low-risk infants, and 7% higher odds (95% CI: 3.8-10.4) in ELBW infants. Researchers found that 42% of VLBW infants were given more than 3 days of antibiotic treatment despite having no evidence of culture-proven sepsis.

“Although it can be debatable whether to start empirical antibiotics in an individual infant with critical conditions right after birth, any prolonged antimicrobial course of more than 3 days without a positive microbiology finding should be the exception rather than the rule,” the study authors said. – by Erin Michael

References:

Greenberg RG, et al. Abstract 2720A.5. Presented at: Pediatric Academic Societies Meeting; April 30-May 3, 2016; Baltimore.

Mukhopadhyay S, et al. Abstract 2720A.3. Presented at: Pediatric Academic Societies Meeting; April 30-May 3, 2016; Baltimore.

Ting JY, et al. Pediatrics. 2019;doi:10.1542/peds.2018-2286.

Disclosures: The authors report no relevant financial disclosures.