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Context: Clinical sign algorithms are a key strategy to identify young infants at risk of mortality., Objective: Synthesize the evidence on the accuracy of clinical sign algorithms to predict all-cause mortality in young infants 0-59 days., Data Sources: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials., Study Selection: Studies evaluating the accuracy of infant clinical sign algorithms to predict mortality., Data Extraction: We used Cochrane methods for study screening, data extraction, and risk of bias assessment. We determined certainty of evidence using Grading of Recommendations Assessment Development and Evaluation., Results: We included 11 studies examining 26 algorithms. Three studies from non-hospital/community settings examined sign-based checklists (n = 13). Eight hospital-based studies validated regression models (n = 13), which were administered as weighted scores (n = 8), regression formulas (n = 4), and a nomogram (n = 1). One checklist from India had a sensitivity of 98% (95% CI: 88%-100%) and specificity of 94% (93%-95%) for predicting sepsis-related deaths. However, external validation in Bangladesh showed very low sensitivity of 3% (0%-10%) with specificity of 99% (99%-99%) for all-cause mortality (ages 0-9 days). For hospital-based prediction models, area under the curve (AUC) ranged from 0.76-0.93 (n = 13). The Score for Essential Neonatal Symptoms and Signs had an AUC of 0.89 (0.84-0.93) in the derivation cohort for mortality, and external validation showed an AUC of 0.83 (0.83-0.84)., Limitations: Heterogeneity of algorithms and lack of external validation limited the evidence., Conclusions: Clinical sign algorithms may help identify at-risk young infants, particularly in hospital settings; however, overall certainty of evidence is low with limited external validation.

Context: Accurate identification of possible sepsis in young infants is needed to effectively manage and reduce sepsis-related morbidity and mortality., Objective: Synthesize evidence on the diagnostic accuracy of clinical sign algorithms to identify young infants (aged 0-59 days) with suspected sepsis., Data Sources: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials., Study Selection: Studies reporting diagnostic accuracy measures of algorithms including infant clinical signs to identify young infants with suspected sepsis., Data Extraction: We used Cochrane methods for study screening, data extraction, risk of bias assessment, and determining certainty of evidence using Grading of Recommendations Assessment Development and Evaluation., Results: We included 19 studies (12 Integrated Management of Childhood Illness [IMCI] and 7 non-IMCI studies). The current World Health Organization (WHO) 7-sign IMCI algorithm had a sensitivity of 79% (95% CI 77%-82%) and specificity of 77% (95% CI 76%-78%) for identifying sick infants aged 0-59 days requiring hospitalization/antibiotics (1 study, N = 8889). Any IMCI algorithm had a pooled sensitivity of 84% (95% CI 75%-90%) and specificity of 80% (95% CI 64%-90%) for identifying suspected sepsis (11 studies, N = 15523). When restricting the reference standard to laboratory-supported sepsis, any IMCI algorithm had a pooled sensitivity of 86% (95% CI 82%-90%) and lower specificity of 61% (95% CI 49%-72%) (6 studies, N = 14278)., Limitations: Heterogeneity of algorithms and reference standards limited the evidence., Conclusions: IMCI algorithms had acceptable sensitivity for identifying young infants with suspected sepsis. Specificity was lower using a reference standard of laboratory-supported sepsis diagnosis.

Context: Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear., Objectives: To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes., Data Sources: MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials., Study Selection: We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes., Data Extraction: We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence., Results: Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes., Conclusions: Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.