Daily Sepsis Research Analysis

OBJECTIVE: Early-onset neonatal sepsis (EONS) due to ascending infection is a potentially preventable complication of preterm premature rupture of membranes (PPROM). Our objective was to determine whether the analysis of bacteria from vaginal swab samples is predictive of the risk of EONS in PPROM. STUDY DESIGN: In a prospective 3-center observational cohort, patients with PPROM were enrolled between 22 and 36 weeks' gestation (WG) + 6 days. Vaginal swab samples at delivery were analyzed using two different approaches, classical bacterial cultures and shotgun metagenomic sequencing analysis. A metagenomics score was constructed combining the characterization of the vaginal microbiome and the presence of pathogens and the optimal cut-off to predict EONS was tested on a receiver operating curve. RESULTS: 563 PPROM cases were enrolled, with 646 liveborn neonates. PPROM occurred < 32 WG in 41.9% and deliveries were < 34 WG in 41.0%. The incidence of EONS was 29/646 (4.5%). When considering all central and peripheral microbiological samples available for 26 neonates, the main pathogens isolated were Escherichia coli in 14 cases (53.8 %), other gram-negatives in 5 (19.2%), strict anaerobes in 3 (11.5%); there was a single case (3.8%) each with Group B Streptococcus (GBS), Streptococcus anginosus, Staphylococcus aureus and Ureaplasma urealyticum. We studied the prediction of EONS among 272 mothers and their 310 neonates (20 EONS, 6.4%) with both culture and metagenomic data available. A culture positive for a major or intermediate pathogen in the vaginal sample at delivery had a sensitivity of 80.0 % (95% CI=56.3-94.3) and a specificity of 37.9% (95% CI=32.3-43.8), adjusted odds ratio (aOR) of 1.6 (95 % CI [0.5-5.0]) to predict EONS. The presence of E. coli was associated with an EONS risk of 10.6% vs 4.9%, in the absence of E. coli (p=0.07). The metagenomics score was highly associated with EONS, with an area under the receiver operating curve of 0.75 (95% CI, 0.61-0.90). At the optimal cutoff value, sensitivity was 70% (95% CI, 64-95%), specificity was 85% (95% CI, 81-89%). A metagenomics score greater than 40 was associated with a significantly increased risk of EONS with an aOR of 8.9 (95 % CI [3.5; 22.3]) in multivariate analysis adjusted for latency period and gestational age, p<0.001. CONCLUSION: In PPROM, conventional microbial culture of maternal vaginal samples was associated with EONS, but its predictive values remain insufficient to guide perinatal care. Metagenomic microbial signatures improved predictive values. This opens the perspective for a rapid point-of-care test.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in critically ill patients, but the association between hypoxemia and renal dysfunction remains uncertain. METHOD: We retrospectively analyzed 2292 patients with SA-AKI from the MIMIC-IV database and stratified them into four groups based on their highest arterial partial pressure of oxygen (PO₂) within 24 h of admission: < 60 mmHg, ≥ 60 to < 80 mmHg, ≥ 80 to  < 100 mmHg, and ≥ 100 mmHg. Associations between PO₂ and renal injury markers (serum creatinine [SCr] and blood urea nitrogen [BUN]) were evaluated using multivariable regression analyses, and survival outcomes were compared with Kaplan-Meier methods. To explore mechanistic pathways, a murine model was established with four experimental conditions: normoxia, hypoxia (10% O₂), lipopolysaccharide (LPS)-induced sepsis, and combined sepsis plus hypoxia. Serum biochemical parameters, histological injury, and protein expression of hypoxia-inducible factor-1α (HIF-1α) were measured at 6, 24, and 48 h. Mitochondrial autophagy was assessed by LC3 and TOMM20 immunofluorescence colocalization. RESULT: Patients with lower PO₂ had higher illness severity and unadjusted BUN and SCr levels, multivariable analyses revealed no independent association between PO₂ and renal injury markers. Survival differed significantly across groups, with the ≥ 100 mmHg group showing the best outcomes (log-rank P < 0.001). In animal experiments, sepsis groups developed increased SCr and BUN at 24 and 48 h, but combined hypoxia did not exacerbate these parameters compared to sepsis alone. Histological analysis revealed severe tubular injury with no significant aggravation in the sepsis-plus hypoxia group. HIF-1α expression was lowest in sepsis-only kidneys but markedly upregulated in the sepsis-plus-hypoxia group at 6 h. Immunofluorescence demonstrated less colocalization of LC3 and TOMM20 in the sepsis-only group than in sepsis-plus-hypoxia mice, suggesting more efficient mitophagy with hypoxemia. CONCLUSIONS: These clinical and experimental findings indicate that hypoxemia was not independently associated with aggravated renal injury in SA-AKI and may activate HIF-1α and promote adaptive mitophagy. This challenges the conventionally held belief that hypoxemia is uniformly detrimental to renal function during sepsis.

INTRODUCTION: Procalcitonin (PCT) has been a blue-eyed-boy in diagnosing sepsis in previous years. The aim of this systematic review and meta-analysis was to assess the accuracy of PCT for the diagnosis of sepsis, according to the recent Sepsis-3 criteria, in adult patients admitted to the intensive care unit (ICU). METHODS: We searched several electronic databases, including PubMed, Science Direct, Wiley, Cochrane, and Google Scholar from the inception of the Sepsis-3 diagnostic criteria (January 1, 2016) until May 31, 2025, for randomized controlled trials, cohort, and case-control studies that assessed the diagnostic accuracy of PCT for sepsis using the Sepsis-3 criteria among critically ill adult patients with suspected infection. We performed a random effect diagnostic meta-analysis, evaluated the risk of bias of individual studies using the QUADAS tool, and assessed certainty of evidence using GRADE methodology. RESULTS: We included 10 studies comprising 1098 patients. Of these, 635 patients were diagnosed with sepsis based on Sepsis-3 criteria, including 89 patients with septic shock. The pooled sensitivity of PCT for diagnosing sepsis was 0.72 (95 % CI [confidence interval], 0.68-0.75, low certainty) and the pooled specificity was 0.65 (95 % CI, 0.61-0.69, low certainty). The pooled positive likelihood ratio was 2.45 (95 % CI [confidence interval], 1.62-3.68), The negative likelihood ratio was 0.38 (95 % CI, 0.28-0.53), and the pooled diagnostic odds ratio was 7.08 (95 % CI, 3.69-13.58). The area under the summary receiver operating characteristic curve of PCT was 0.79 (95 % CI 0.73-0.86). CONCLUSION: Based on pooled analysis, PCT has a moderate sensitivity and specificity for diagnosis of sepsis in ICU patients with suspected infection. These results suggest clinicians should be cautious about using PCT to facilitate the diagnosis of sepsis in critically ill adults with suspected infection. Given the ongoing uncertainty, further high-quality data in this population is needed.