Neonatal Early-Onset Sepsis Calculator and Antibiotic Therapy

To the Editor This letter is in response to the systematic review and meta-analysis by Achten et al¹ on the use of the neonatal early-onset sepsis (EOS) calculator. The meta-analysis clearly demonstrated that the use of the neonatal EOS calculator is associated with a reduction in the use of empirical antibiotics. However, the authors’ conclusion that “Available evidence regarding safety of the use of the EOS calculator is limited, but shows no indication of inferiority compared with conventional management strategies”¹ may not be true. Many of the cases of EOS in which the EOS calculator was applied were not included in the meta-analysis. The authors included 18 cases of EOS in which the management was guided by the use of the EOS calculator (Table 2) and 12 cases of EOS from retrospective studies for which the EOS calculator was hypothetically applied (Table 3).¹ Surprisingly, 39 cases of EOS from the landmark study by Kuzniewicz et al,² in which EOS management was assessed using the EOS calculator, are not included in the meta-analysis (eTable 1 in the Supplement). In this study, the EOS calculator was applied to 24 neonates during the baseline period and 15 infants during the learning period. Although management was not guided by the EOS calculator during these periods, the calculator would have failed to recommend empirical antibiotics in 29 of 39 infants (74%) with blood culture–positive EOS. Moreover, the calculator would not have recommended even a blood culture in 63% of infants (25 of 39) with blood culture–positive EOS. Similar concern was raised by others regarding missing cases of EOS during the baseline period.³ The authors¹ have reported that during the baseline period, 18 of 24 infants received empirical antibiotics before 24 hours by using a conventional method (Table 2). However, during this period, if the management was guided by the recommendations from the EOS calculator, only 6 of 24 infants would have received antibiotics before 24 hours with an additional 2 infants if their blood culture became positive within 24 hours (18 of 24 vs 8 of 24; P = .009). It is unclear why the authors have included these 12 cases of hypothetically managed infants from retrospective studies but excluded a large number of infants from such a seminal study. The number of infants with EOS (calculator applied) excluded in the meta-analysis was more than the combined infants with EOS included in the meta-analysis. Including these infants with EOS would likely change the conclusion of the meta-analysis.