Caffeine exposure and acute kidney injury in premature infants with necrotizing enterocolitis and spontaneous intestinal perforation.

BACKGROUND: Acute kidney injury (AKI) is common in preterm infants, but specific therapies remain scarce. Recent studies have demonstrated an association between caffeine exposure and less frequent AKI in the first 7-10 days after birth. We hypothesized that patients with necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) would provide a better natural model of AKI to evaluate this association. METHODS: We reviewed all premature patients diagnosed with NEC or SIP at our institution from 2008 to 2014. AKI was defined by change in serum creatinine using the neonatal Kidney Disease: Improving Global Outcomes definition. Caffeine was prescribed for apnea of prematurity and caffeine exposure was determined by chart review. RESULTS: A total of 146 patients with NEC/SIP were reviewed. Of these, 119 (81.5%) received caffeine, and 91 (62.3%) developed AKI. AKI occurred less frequently in patients who received caffeine than in those who did not (55.5% vs. 92.6%; odds ratio (OR) 0.10; 95% confidence interval (CI) 0.02-0.44). This association persisted in multivariable models after adjustment for potential confounders (adjusted OR 0.08; 95% CI 0.01-0.42; number needed to be exposed to caffeine to prevent one case of AKI = 2.6). Although baseline serum creatinine did not differ by caffeine exposure, patients receiving caffeine had lower peak creatinine (median 1.0 mg/dl vs. 1.5 mg/dl; p = 0.008) and absolute creatinine change (median 0.42 mg/dl vs. 0.68 mg/dl; p = 0.003) than those who did not. CONCLUSIONS: Caffeine exposure in preterm infants with NEC/SIP is associated with decreased incidence and severity of AKI.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.