Variation in antibiotic consumption in very preterm infants—a 10 year population-based study

Abstract

Objectives Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. Patients and Methods All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009–18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. Results We included 5296 infants: 3646 (69%) were born at 28–31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum β-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum β-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum β-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. Conclusions The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum β-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development.

Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants

“…The overall rate of VLBW infants exposed to antibiotics at any time during hospital stay is slightly lower in our centre (75% vs. 80%) than the one reported in a recent Norwegian nationwide study, although our overall antibiotic use during the hospital stay is higher (DOT/1000 PD 267 vs. 149) [14]. Among 5296 infants (with a comparable gestational age and birth weight), Norwegian investigators reported a reduction in DOT/1000 PD over 10 years [14]. Although the reasons for these discrepancies are unclear, repeated courses of antibiotics or prolonged therapies in cases of culture-positive sepsis would explain our results.…”

“…Wide variations exist in empirical antibiotic use in NICUs despite comparable infection rates and antibiotic resistance profiles [ 13 , 14 , 15 , 16 ]. There are many reasons for this, including limited pharmacokinetic and pharmacodynamic data in preterm and term infants and few high-quality clinical trials on which expert consensus or international guidelines for treatment and prophylaxis can rely [ 14 , 15 ]. However, comparing one’s NICU with population-based studies from different regions and centres may lead to revisiting one’s work and reconsidering one’s approaches [ 15 , 16 ].…”

“…Studies on AS in preterm and term infants are limited. VLBW infants are those at highest risk of sepsis and who benefit most from judicious use of antibiotics, especially in the first week of life, but the impact and safety of AS programs on preterm neonates are not clearly defined [ 3 , 14 , 18 ]. Quality improvement initiatives in NICUs have been proven to be effective in the short term [ 20 , 21 ].…”

“…In the short term, the feasibility of AS programs has been demonstrated both in industrialized and developing countries [ 23 , 24 ]. However, there are limited data on the long-term effects of systematic application of a standardized AS program, especially for infants of lower gestational age and lower birth weight [ 14 ].…”

“…Wide variations exist in empirical antibiotic use in NICUs despite comparable infection rates and antibiotic resistance profiles [13][14][15][16]. There are many reasons for this, including limited pharmacokinetic and pharmacodynamic data in preterm and term infants and few high-quality clinical trials on which expert consensus or international guidelines for treatment and prophylaxis can rely [14,15].…”