Improving empiric antibiotic prescribing in pediatric bloodstream infections: a potential application of weighted-incidence syndromic combination antibiograms (WISCA)

Abstract

Background: Increasing antibiotic resistance to WHO-recommended first- and second-line treatments of pediatric sepsis requires adaptation of prescribing guidelines. We discuss the potential and limitations of a weighted-incidence syndromic combination antibiogram (WISCA) as a practical tool for incorporating local microbiology data when assessing empiric coverage of commonly used antibiotics.

Research design and methods: A brief questionnaire of 18 clinically significant isolates from pediatric blood cultures (Jan-Dec 2018) was sent to a global network of pediatric hospitals in July 2019. Weighted coverage estimates of non-antipseudomonal third-generation cephalosporins (3GC) and meropenem were estimated using Monte-Carlo simulation for each site reporting >100 isolates.

Results: 52 hospitals in 23 countries in 5 WHO regions responded to the questionnaire; 13 sites met the sample size requirement. The most common isolates were S. aureus, Klebsiella spp., E. coli and Enterococcus spp. Coverage of 3GC ranged from 39% [95%CrI: 34-43%] to 73% (two sites: [95%CrI: 65-80%]; [95%CrI: 68-86%]) and meropenem coverage ranged from 54% [95%CrI: 47-60%] to 88% [95%CrI:84-91%].

Conclusions: A WISCA is a data-driven, clinically intuitive tool that can be used to compare empiric antibiotic regimens for pediatric sepsis using existing large datasets. The estimates can be further refined using more complex meta-analytical methods and patient characteristics.

Keywords: Antibiotic resistance; bloodstream infections; empiric antibiotics; pediatric sepsis; weighted incidence syndromic combination antibiogram (WISCA).