Daily ReportSep 23, 2026
Sepsis, September 23 edition
We read 34 papers and selected 3.
Summary
Today’s most impactful sepsis-related studies addressed preventable infection transmission, probiotic prevention of necrotizing enterocolitis in very preterm infants, and comparative infection risks of advanced immunomodulatory therapies. The strongest contributions combined prospective or large population-based designs with genomic epidemiology, causal-oriented statistical methods, or broad comparative evidence synthesis.
Research Themes
- Genomic epidemiology and infection prevention in neonatal sepsis
- Probiotic prevention of necrotizing enterocolitis and sepsis-related outcomes in very preterm infants
- Comparative serious infection and sepsis risks of advanced immunomodulatory therapies
Selected Articles
1. Transmission of extended-spectrum β-lactamase-producing Klebsiella pneumoniae in a Malawian neonatal unit: a clinical and genomic analysis of a prospective cohort study.
In a prospective cohort of 94 mother-neonate pairs, 49% of neonates became colonized with ESBL-producing Klebsiella pneumoniae, with a median time to colonization of 5 days. Whole-genome sequencing and transmission modeling implicated ward surfaces, particularly sinks and oxygen-delivery equipment, as major sources, with additional contributions from cots, maternal hands, and other neonates.
Impact: This study directly links clinical isolates to environmental and patient-associated reservoirs using genomic data and quantitative transmission models. It converts neonatal sepsis epidemiology into specific, actionable infection-prevention targets in resource-constrained settings.
Clinical Implications: Neonatal units should prioritize sink and surface decontamination, containment of neonatal stool, cot cleaning, maternal hand hygiene, and single-use oxygen-delivery equipment. These findings support targeted environmental interventions rather than relying only on patient-focused precautions.
Key Findings
- Among 90 evaluable neonates, 44 (49%) were colonized with ESBL-producing K pneumoniae at least once, with a median time to colonization of 5 days.
- Invasive isolates clustered genetically with stool and environmental isolates; 76% of invasive isolates clustered with these non-invasive sources.
- Transmission analyses attributed approximately 37%-65% of transmission to ward surfaces, 13%-29% to cots, 6%-13% to maternal hands, and 8%-13% to other neonates.
Methodological Strengths
- Prospective sampling of mother-neonate pairs, patients, cots, hands, swaddling cloths, and the ward environment enabled source attribution.
- Single-colony whole-genome sequencing, metagenomics, state-transition models, and timing-based transmission analyses provided convergent evidence.
Limitations
- The study was conducted in a single neonatal unit with 94 mother-neonate pairs, which may limit generalizability.
- Transmission estimates are probabilistic and may be affected by incomplete sampling, unobserved contacts, and the short follow-up period.
Future Directions: Multicentre implementation studies should test whether sink redesign, enhanced environmental cleaning, dedicated oxygen equipment, and improved stool containment reduce colonization and invasive infection. Longer-term genomic surveillance is also needed to determine whether targeted interventions alter antimicrobial-resistance transmission.
BACKGROUND: Klebsiella pneumoniae is an important cause of neonatal sepsis in sub-Saharan Africa and is frequently antimicrobial resistant. In this study, we investigated key transmission routes of extended-spectrum β-lactamase-producing K pneumoniae (ESBL-K pneumoniae) within a single neonatal unit to inform development of contextually appropriate infection prevention and control practices. METHODS: We recruited a prospective mother and neonate cohort of babies admitted for less than 48 h and expected to stay for 24 h or more, where the mother or guardian was aged 18 years or older. Participants were followed up until day 7 of admission or discharge, with samples taken on day 1 and 3, and at the final follow-up (maternal stool, neonatal stool, maternal hands, cots, and swaddling cloth (day 1 only)). We sampled the ward environment weekly and included contemporaneous invasive ESBL-K pneumoniae isolates in our analysis.
2. Probiotics and Risk of Death, Necrotizing Enterocolitis, and Sepsis in Very Preterm Infants.
In 4,695 very preterm infants in Sweden, probiotic supplementation was associated with lower risks of death and necrotizing enterocolitis, with an adjusted relative risk of 0.28 for the composite outcome. The association was not significant for death and culture-proven sepsis, and Bayesian modeling suggested that 42.3% of the mortality reduction was mediated through reduced necrotizing enterocolitis.
Impact: This large national cohort provides clinically relevant real-world evidence after implementation of a national probiotic recommendation. The separation of benefits for necrotizing enterocolitis from the absence of a clear sepsis benefit is particularly important for accurate counseling and policy decisions.
Clinical Implications: For very preterm infants born at 28 to 31 weeks’ gestation, multistrain probiotics may be considered to reduce necrotizing enterocolitis and possibly mortality, with shared decision-making about local product quality and safety. The findings do not support presenting probiotics as a proven strategy to prevent culture-proven sepsis and should not be generalized to infants born before 28 weeks.
Key Findings
- The cohort included 4,695 very preterm infants; probiotic use increased from 0% before 2020 to approximately 65% annually during 2021-2024.
- Death and/or necrotizing enterocolitis occurred in 0.8% of probiotic-exposed infants versus 3.4% of unexposed infants, with an adjusted relative risk of 0.28.
- Probiotics were not associated with death and/or culture-proven sepsis: 3.4% versus 4.4%, adjusted relative risk 0.86, 95% confidence interval 0.58-1.26.
Methodological Strengths
- Population-based national registry data captured routine clinical practice across Sweden and included a large sample of very preterm infants.
- Results were replicated using modified Poisson regression, propensity-score matching, inverse probability weighting, and Bayesian mediation modeling.
Limitations
- As an observational cohort study, probiotic exposure was not randomly assigned and residual confounding by center, clinical practice, or infant characteristics may remain.
- The findings apply to infants born at 28 to 31 weeks’ gestation in Sweden and should not be generalized to extremely preterm infants or other probiotic formulations without further evidence.
Future Directions: Pragmatic randomized trials and harmonized surveillance should evaluate strain-specific effects, product safety, long-term neurodevelopment, and outcomes in higher-risk extremely preterm infants. Mechanistic studies should clarify why reduced necrotizing enterocolitis did not translate into a clear reduction in culture-proven sepsis.
IMPORTANCE: Probiotics are reported to benefit preterm infants, but population-based clinical evidence is limited. In 2020, the Swedish Neonatal Society issued a national recommendation to supplement very preterm infants (28 weeks 0 days' to 31 weeks 6 days' gestation) with probiotics. OBJECTIVE: To investigate whether probiotic supplementation was associated with risk of death, necrotizing enterocolitis (NEC), and/or culture-proven sepsis in infants born very preterm. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study examined data from the Swedish Neonatal Quality Register from January 1, 2017, through December 31, 2024. Live-born, very preterm infants, excluding those who died within the first 3 days of life or due to congenital or chromosomal abnormalities, were included. EXPOSURE: Daily probiotic supplementation of 1 billion colony-forming units of freeze-dried Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus initiated following birth and discontinued at postmenstrual week 34.
3. Comparative serious infection and sepsis risks with advanced therapies in IMIDs: a Bayesian network meta-analysis.
This Bayesian network meta-analysis included 261 studies and 86,844 person-years of exposure across immune-mediated inflammatory diseases. Janus kinase inhibition was associated with higher serious infection rates than control and tumor necrosis factor inhibition, whereas tumor necrosis factor inhibition was associated with a lower sepsis rate than control; interleukin-23 inhibition and CTLA4 inhibition ranked among the safer options in specified disease networks.
Impact: The study provides a cross-disease framework for balancing efficacy and infection risk when selecting advanced immunomodulatory therapy. Its finding that infection risk differs materially by therapeutic class can inform individualized treatment decisions and safety monitoring.
Clinical Implications: When treating patients with immune-mediated inflammatory diseases, clinicians should incorporate baseline infection risk, disease context, and drug class into shared treatment decisions. Particular caution and enhanced infection surveillance may be appropriate with Janus kinase inhibitors in high-risk populations, while the apparently lower sepsis rate with tumor necrosis factor inhibition requires confirmation rather than immediate guideline reversal.
Key Findings
- The analysis included 261 studies representing 86,844 person-years of exposure across rheumatoid arthritis, psoriasis or psoriatic arthritis, inflammatory bowel disease, and a global immune-mediated inflammatory disease network.
- Janus kinase inhibition increased serious infection risk versus control, with a rate ratio of 1.44 and a 95% credibility interval of 1.12-1.89.
- Tumor necrosis factor inhibition was associated with lower sepsis rates than control, with a rate ratio of 0.54 and a 95% credibility interval of 0.30-0.99.
Methodological Strengths
- The large evidence base covered multiple immune-mediated inflammatory diseases and therapeutic classes, improving comparative scope.
- A Bayesian network meta-analysis enabled indirect comparisons and quantified uncertainty using credibility intervals and posterior probabilities.
Limitations
- The analysis integrates evidence from heterogeneous trials, diseases, comparators, follow-up periods, and definitions of serious infection and sepsis.
- Many comparisons are indirect, and differences in patient selection, background therapies, and reporting may bias relative estimates.
Future Directions: Future analyses should use individual-participant data or harmonized prospective registries to evaluate absolute infection risks by age, comorbidity, vaccination status, prior infection, and treatment sequence. Head-to-head pragmatic trials and postmarketing surveillance should test whether the observed class differences persist in routine care.
OBJECTIVES: Evidence on serious infection (SI)-risk with advanced therapies across immune-mediated inflammatory diseases (IMIDs) is limited. We compared SI- and sepsis-rates within a global-IMID network and assessed whether these are consistent across IMIDs. METHODS: We included studies evaluating advanced therapies across four networks: rheumatoid arthritis (RA), psoriasis/psoriatic arthritis (Pso/PsA), inflammatory bowel disease (IBD) and a global-IMID network. We used a Bayesian framework to present SI- and sepsis-rates as rate-ratios (RR) and 95% credibility intervals (CrI). RESULTS: 261 studies providing 86,844 person-years-of-exposure were included. In the global-network, JAK-inhibition was associated with a greater SI-rate than control, (placebo/methotrexate), (RR 1.44, 95% CrI 1.12-1.89, posterior probability (pp) >99%), corresponding to 2.1 additional SI-events per 100-PYE in high-risk populations (95% CrI 0.6-4.3). JAK-inhibition was associated with greater SI-rate than TNF-inhibition (RR 1.34, 95% CrI 1.00-1.81, pp 97.3%). TNF-inhibition was associated with lower sepsis-rate than control (RR 0.54, 95% CrI 0.30-0.99, pp 98%).