Daily Sepsis Research Analysis

IMPORTANCE: The Centers for Medicare & Medicaid Services reimburses remote monitoring to reduce hospital readmissions, yet its effectiveness remains uncertain. OBJECTIVE: To evaluate effectiveness of remote monitoring in reducing readmissions following hospitalizations for serious infections overall and across prespecified subgroups. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted from March 25, 2021, to December 9, 2024, using response adaptive randomization among postdischarge patients with sepsis or lower respiratory tract infection across 19 hospitals. Eligible patients were 21 years or older, lived in western Pennsylvania, were insured through the UPMC Health Plan or traditional fee-for-service Medicare, had a smartphone or other internet-connected device, had no cognitive impairment, and were at moderate or high risk for readmission at index hospitalization admission based on an internal predictive model. Analyses were based on intention to treat; data were analyzed from April to June 2025. INTERVENTION: Four remote monitoring strategies combining questionnaire intensity (low vs high) and clinical response teams (standard vs enhanced) compared with usual care. MAIN OUTCOMES AND MEASURES: The primary end point consisted of days at home at 90 days after discharge, assessed by posterior probability distribution for the cumulative odds ratios (CORs) in each study arm compared with usual care. Secondary end points included mortality, readmission, functional status, quality of life, and use of emergency department and hospice services. RESULTS: Among the 1286 patients included in the analysis, the median age was 63 (IQR, 54-71) years; 665 patients (51.7%) were female. The median Charlson Comorbidity Index was 6 (IQR, 3-9), and 386 patients (32.6%) received intensive care. Patients were randomized to usual care (n = 399) or remote patient monitoring (RPM) with low- or high-intensity questionnaires and standard or enhanced clinical response team combinations: RPM-low standard response (n = 204), RPM-high standard response (n = 129), RPM-low enhanced response (n = 383), and RPM-high enhanced response (n = 171). Of 887 patients assigned to remote monitoring arms, 529 (59.6%) enrolled in the remote monitoring program. The median home days were similar across all study arms: 90 (IQR, 83-90) for usual care, 90 (IQR, 84-90) for RPM-low standard response, 90 (IQR, 85-90) for RPM-high standard response, 90 (IQR, 83-90) for RPM-low enhanced response, and 90 (IQR, 84-90) for RPM-high enhanced response. Compared with usual care, the CORs were 0.96 (credible interval [CrI], 0.70-1.32) for RPM-low standard response, 0.86 (95% CrI, 0.60-1.23) for RPM-high standard response, 1.01 (95% CrI, 0.76-1.33) for RPM-low enhanced response, and 0.96 (95% CrI, 0.69-1.36) for RPM-high enhanced response, and superiority probability was less than 55% for all comparisons. At least 1 readmission occurred in 151 of 399 patients (37.8%) in the usual care arm, 81 of 204 (39.7%) in the RPM-low standard response arm, 57 of 129 (44.2%) in the RPM-high standard response arm, 143 of 383 (37.3%) in the RPM-low enhanced response arm, and 62 of 171 (36.3%) in the RPM-high enhanced response arm. Among patients 65 years and older, standard and enhanced response arms had fewer home days compared with usual care (COR, 0.56 [95% CrI, 0.36-0.85] and 0.67 [95% CrI, 0.45-0.98], respectively; inferiority probability, 99.6% and 97.9%, respectively). CONCLUSIONS AND RELEVANCE: Among trial patients discharged after hospitalization for serious infections, remote monitoring did not increase time spent alive at home but reduced it in those 65 years and older. These findings support reevaluating and tailoring remote monitoring after acute care for sepsis and lower respiratory tract infection to support further alignment with patients' needs and desire for personalized monitoring. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04829188.

RATIONALE: Empiric anti-pseudomonal coverage is an important part of treatment of sepsis, but there is limited data to guide antibiotic selection. The antibiotic choice on renal outcomes (ACORN) randomized trial found no difference in mortality when comparing cefepime and piperacillin-tazobactam, while an Instrumental Variable (IV) study found improved mortality with cefepime. OBJECTIVE: To determine if white blood cell (WBC) count modifies the effect of antibiotic choice on mortality. METHODS: We conducted post-hoc sub-group analyses of the ACORN trial and the IV study comparing cefepime to piperacillin-tazobactam. We performed regression modeling of interaction between treatment group and WBC on 28-day mortality with adjustment for relevant covariates, with evaluation for heterogeneity of treatment effect through likelihood ratio testing. MEASUREMENTS: The main outcome was 28-day mortality in both cohorts. Secondary outcomes in the secondary analysis of the ACORN trial included highest stage of acute kidney injury on an ordinal scale, a composite outcome of major adverse kidney events, and incidence of coma or delirium within 14 days. MAIN RESULTS: There was a significant interaction between WBC and treatment group in predicting 28-day mortality in both the ACORN trial and the IV study (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92-0.98, p = <0.01 and OR 0,95, CI 0.94-0.96, P < .01, respectively), with likelihood ratio testing revealing better model fit with inclusion of the interaction term (F = 8.17, p = <0.01 and F = 42.9, P < .01, respectively). In the ACORN cohort, patients with a baseline WBC count of 16 or higher had significantly lower odds of mortality when treated with piperacillin-tazobactam compared to cefepime (OR 0.51, CI 0.29-0.90). CONCLUSIONS: WBC modified the effect of antibiotic choice on mortality in two large clinical studies. Further research is needed to confirm this effect in prospective studies and to determine if WBC count could be used for predictive enrichment in future trials of anti-pseudomonal antibiotics.

IMPORTANCE: Neonatal sepsis causes substantial mortality. Topical antisepsis for laboring women or neonates may reduce pathogenic colonization and sepsis risk. OBJECTIVE: To evaluate the safety and effectiveness of various topical antiseptic regimens to reduce bacterial load in the maternal genital tract and on neonatal skin and assess suitability for future effectiveness trials. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted from March 7, 2022, to March 29, 2023, at Zomba Central Hospital, Malawi, with 28-day follow-up. Participant populations were laboring women and, separately, facility-born neonates (aged <24 hours and with birth weight >1000 g) not born to a mother recruited to the trial. Data were analyzed from May 17 to December 28, 2023. INTERVENTIONS: Participants were individually randomized in an unblinded factorial design to chlorhexidine 1% (1% CHG), chlorhexidine 2% (2% CHG), or octenidine 0.1% with phenoxyethanol 2% (OHP), each applied either once or multiple times (maternal: antiseptic applied every 4 hours during working hours for up to 6 applications; neonatal: antiseptic applied every 24 hours for up to 3 applications), or to standard of care (SOC; application of sterile water for mothers and no cleansing for neonates). Laboratory staff assessing primary outcomes were blinded. MAIN OUTCOMES AND MEASURES: Co-primary outcomes were change in total skin bacterial load (log10 colony-forming units [log10CFU]) from baseline at each follow-up, analyzed separately in the maternal and neonatal populations and adjusted for intervention variables. Secondary outcomes included skin condition score (range, 0-12 for neonates and 0-16 for women; lower scores indicate better condition), serious adverse events (SAEs), and neonatal temperature. RESULTS: A total of 149 women (mean [SD] age at enrollment, 25.7 [5.9] years) and 147 neonates (mean [SD] age at enrollment, 10.3 [6.3] hours; 82 [56%] male) participated. Mean (SD) infant gestational age was 37.7 (1.5) weeks in the maternal population and 36.7 (3.1) weeks in the neonatal population. Neonates' mean birth weight was 2729 g (712 g). Among mothers, compared with 1% CHG, bacterial load was higher (worse) with OHP (adjusted log10CFU difference, 1.7; 95% CI, 0.9-2.5) and SOC (3.5; 95% CI, 2.4-4.6); there was no clear log10CFU difference with 2% CHG (-0.6; 95% CI, -1.4 to 0.2). There was no evidence of difference in effectiveness between multiple vs single application (log10CFU difference, -0.4; 95% CI, -1.1 to 0.2). In neonates, 1% CHG showed greater effectiveness than SOC (log10CFU difference, 1.3; 95% CI, 0.2-2.4) but no difference vs 2% CHG (-0.2; 95% CI, -1.1 to 0.7) or OHP (0.7; 95% CI, -0.2 to 1.6). Multiple applications showed increasing benefits over time (frequency × time interaction). Skin scores were low (almost all were 0-1 and none ≥3). There were no significant differences in SAE rates between arms and no signal of postantiseptic neonatal hypothermia. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of topical antiseptics applied in laboring women and in neonates, 1% CHG reduced maternal and neonatal bacterial colonization without safety concerns, suggesting it would be the optimal regimen to evaluate in a larger pragmatic trial powered for clinical outcomes. TRIAL REGISTRATION: ISRCTN Registry Identifier: ISRCTN78026255.