Community-Acquired Infections

ImportanceThe novel Phoenix Sepsis Score and sepsis criteria were derived and validated using a multicountry dataset and proposed as a new definition for sepsis in children.ObjectiveTo externally validate the Phoenix Sepsis Score and sepsis criteria in a cohort of children hospitalized with suspected community-acquired sepsis.Design, setting, and participantsThis diagnostic study used data from the multicenter, multicountry Sepsis Epidemiology in Australian and New Zealand Emergency Departments (SENTINEL) study, collected from 2021 to 2023 and including 90-day follow-up. Children admitted to the hospital through 11 emergency departments in Australia and New Zealand and treated with parenteral antibiotics with either (1) a provisional diagnosis of sepsis or (2) treatment for sepsis (intravenous fluid bolus to treat poor perfusion) were included.ExposureDevelopment of organ dysfunction over the first 24 hours of hospitalization.Main outcomes and measuresThe main outcomes were (1) in-hospital mortality and (2) death or requirement for extracorporeal life support (ECLS) within 72 hours of hospitalization.ResultsA total of 6232 children were included in the analysis, with a median (IQR) age of 2.1 (0.3-7.1) years, 3386 (54.1%) male, in-hospital mortality of 60 (1.0%), and death or ECLS within 72 hours in 36 (0.6%). In this population, the worst Phoenix Sepsis Score calculated over the first 24 hours of hospitalization had an area under the precision recall curve of 0.17 (95% CI, 0.07-0.28) for predicting in-hospital mortality and 0.23 (95% CI, 0.11-0.36) for predicting death or ECLS within 72 hours. Overall, 306 children (4.9%) met the Phoenix sepsis criteria, of whom 33 (10.8%) died in the hospital (nearly half of the total number who died) and 28 (9.2%) died or required ECLS within 72 hours. The Phoenix sepsis criteria had a sensitivity of 55.0% (95% CI, 41.6%-67.9%) and positive predictive value (PPV) of 10.8% (95% CI, 7.6%-14.9%) for in-hospital mortality and sensitivity of 77.8% (95% CI, 60.8%-89.9%) and PPV of 9.2% (95% CI, 6.2%-13.0%) for death or ECLS within 72 hours. Coagulation data for the calculation of the Phoenix Sepsis Score were missing in more than 85% of children.Conclusions and relevanceIn this multicenter diagnostic study of children hospitalized with suspected sepsis, the Phoenix Sepsis Score and sepsis criteria had similar performance to the original derivation and validation cohorts. The small proportion of children meeting Phoenix sepsis criteria, missingness of data, timing of application, and lack of sensitivity for in-hospital mortality limit the clinical utility of the criteria.

BackgroundESBL-producing Enterobacteriaceae (ESBL-PE) represent a significant global health threat. In response to this growing concern and the lack of a surveillance system for ESBL-PE infections in Egypt, we conducted this meta-analysis. In this study, we aimed to quantify the prevalence of ESBL-PE based on the source of infection and characterize their molecular dissemination. Additionally, we sought to uncover temporal trends to assess the spread of ESBL-PE over time.MethodsA comprehensive literature search was conducted in PubMed, Scopus, Google Scholar, Web of Science, and the Egyptian Knowledge Bank to identify studies that: (1) report the prevalence of ESBL-PE in Egypt; (2) use valid detection methods; (3) involve clinical specimens; and (4) were published between 2010 and 2024. The quality of the included studies was evaluated using the "Joanna Briggs Institute Critical Appraisal Checklist". Meta-analysis was performed using the R meta package, reporting pooled prevalence with 95% confidence intervals (CI) via a random effects model.ResultsThis meta-analysis included 34 studies with 4,528 isolates, spanning 2007 to 2023. The overall prevalence of ESBL-PE in Egypt was 60% (95% CI: 54-65). The leave-one-out meta-analysis demonstrated the absence of influential outliers and Egger's test indicated no evidence of publication bias (P = 0.25). The prevalence of ESBL-PE was 62% (95% CI: 55-68) in nosocomial infections and 65% (95% CI: 52-75) in community-acquired infections, with no statistically significant difference (P = 0.68). The prevalence of ESBL producers in E. coli (64%) and K. pneumoniae (63%) is higher than in Proteus mirabilis (46%) (P = 0.06). Temporal analysis showed a stable ESBL prevalence over time. Moreover, in phenotypically confirmed ESBL-producing, E. coli harboring blaCTX-M was most prevalent (73%), followed by blaTEM (60%) and blaSHV (22%), with significant differences (P CTX-M-15 as the predominant variant of the blaCTX-M gene.ConclusionsThe prevalence of ESBL-PE in Egypt is alarmingly high at 60%. The observed high rates in both hospital and community-acquired infections underscore the need for public health strategies targeting both settings. One limitation of this study is the high heterogeneity, which partly attributed to regional and institutional variations in antibiotic use and stewardship practices.

ImportanceProlonged exposure to broad-spectrum antibiotics (BSA) may be associated with patient harm.ObjectiveTo assess outcomes of BSA de-escalation compared with continuation on encounter day 4 in patients hospitalized for community-onset sepsis.Design, setting, and participantsThis target trial emulation study was conducted at 67 hospitals participating in the Michigan Hospital Medicine Safety Consortium. Patients 18 years and older hospitalized for community-onset sepsis from June 2020 through September 2024 who initiated empiric BSA therapy without evidence of multidrug-resistant organism infection were included. Data were analyzed from September 2024 to November 2025.ExposureInverse probability of treatment-weighted cohort exposed to de-escalation of BSA vs continuation at day 4.Main outcomes and measuresThe primary outcome was 90-day all-cause mortality. Secondary outcomes included in-hospital mortality, 30-day mortality, length of hospitalization, and days of antibiotic therapy.ResultsAmong 36 924 patients with community-onset sepsis, 18 559 (50.3%) were female, 18 365 (49.7%) were male, and the median (IQR) age was 71 (61-80) years. A total of 6926 (18.8%) and 11 149 (30.2%) were eligible for target trial emulations evaluating de-escalation of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-Pseudomonas aeruginosa (PSA; or other resistant gram-negative bacteria) antibiotics, respectively. Of these, 2993 (43.2%) and 2493 (22.4%) were de-escalated from anti-MRSA and anti-PSA coverage. After weighting, patients who were de-escalated vs continued on BSA were well balanced on baseline characteristics. In weighted analyses, anti-MRSA and anti-PSA de-escalation were associated with similar 90-day mortality as continued BSA therapy (anti-MRSA: odds ratio, 1.00; 95% CI, 0.88-1.14; anti-PSA: odds ratio, 0.98; 95% CI, 0.86-1.13). Additionally, anti-MRSA and anti-PSA de-escalation were associated with fewer days of antibiotics to day 14 (anti-MRSA de-escalation: risk ratio [RR], 0.91; 95% CI, 0.89-0.93; anti-PSA de-escalation: RR, 0.91; 95% CI, 0.88-0.93) and shorter length of hospitalization (anti-MRSA de-escalation: RR, 0.88; 95% CI, 0.85-0.92; anti-PSA de-escalation: RR, 0.91; 0.88-0.93). All other secondary outcomes were similar. Across 67 hospitals, the proportion of eligible patients de-escalated from BSA varied more than 2-fold (anti-MRSA de-escalation, 27.3% to 61.7%; anti-PSA de-escalation, 6.9% to 37.7%).Conclusions and relevanceIn this study, de-escalation of empiric BSA therapy at day 4 was associated with similar safety outcomes, fewer antibiotic days, and shorter length of hospitalization among patients with community-onset sepsis compared with those who continued BSA therapy but varied widely in practice.