Daily Sepsis Research Analysis

BACKGROUND: Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against ≥70% of K. pneumoniae infections, could avert ~400,000 cases and ~80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine-targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. METHODS AND FINDINGS: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20 K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and ≥70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n = 14 types). We estimate the top-5 (O1⍺β,2⍺, O1⍺β,2β, O2⍺, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ~99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. CONCLUSIONS: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover ≥70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.

BACKGROUND: Accurate monitoring of antimicrobial consumption is essential for developing effective stewardship interventions. Hospitals are mandated to report antibiotic treatment duration using the CDC's Standardized Antimicrobial Administration Ratio (SAAR). We aimed to create a metric for measuring antimicrobial spectrum to complement SAAR, benchmarked against local and individual resistance. METHODS: This retrospective cohort study utilised data from nine acute care hospitals within BJC Healthcare from January 2018 to December 2023. Adult patients meeting CDC sepsis event criteria were included, focussing on infections caused by Gram-negative bacilli (GNB). Data on patient characteristics, microbiology results, treatments, and timing were collected. We defined the antibiotic effective spectrum (AES) as the ratio of susceptible GNB to all GNB cultured. Mathematical optimisation identified the optimal antibiotic as the antibiotic with the narrowest effective spectrum active against the isolated GNB. We calculated the empirical (before culture results are available) and directed Optimal Spectrum Antibiotic Ratio (OSAR) as the ratio between the AES chosen clinically to the optimal AES, reported it for each hospital yearly, and compared it to SAAR and the Antibiotic Spectrum Index (ASI). Sensitivity analyses focused on empirical undertreatment (OSAR <1, where the empirical choice did not cover the cultured GNB). FINDINGS: We included 10,277 GNB cultured from clinical specimens in 7997 distinct patients. The AES ranged from 0.15 for ampicillin to 0.94 for amikacin. Empirical OSAR varied between 1.08 (95% CI 1.05-1.10) and 1.89 (95% CI 1.51-2.28), with undertreatment present in 1396 (13.6%) of cases overall and wide variations across hospitals. Directed OSAR was lower, ranging between 0.74 (95% CI 0.73-0.75) and 1.45 (95% CI 1.41-1.49). OSAR, SAAR and ASI had different trends across hospitals over the six study years. INTERPRETATION: The OSAR yielded different conclusions about antibiotic utilisation, complementing duration-based measures like SAAR. It determines the appropriateness of antibiotic spectrum based on local and individual resistance. FUNDING: The project was funded by the CDC (5U54CK000609).

AIMS: This retrospective study is aimed at evaluating the effect of SGLT2 inhibitors (SGLT2i) on the risk of sepsis among patients with Type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: An active-comparator new user design was utilized based on Taiwan's National Health Insurance Research Database. Adult patients diagnosed with T2DM between 2017 and 2020 who initiated either SGLT2i or DPP-4 inhibitors (DPP-4i) were included. After 1:2 matching by age, sex, and Charlson Comorbidity Index, the study enrolled 34,672 SGLT2i users and 69,344 DPP-4i users. The primary outcome was sepsis, with secondary outcomes including septic shock, organ dysfunction, and mortality. Hazard ratios (HRs) were estimated using Cox proportional hazards regression. RESULTS: SGLT2i users had a significantly lower risk of sepsis than DPP-4i users (10.1% vs. 15.5%; adjusted HR [aHR]: 0.77; 95% CI: 0.74-0.81). The risk of septic shock and mortality in SGLT2i users was also reduced by 30% (aHR: 0.70; 95% CI: 0.57-0.87) and 40% (aHR: 0.60; 95% CI: 0.54-0.66), respectively, compared with that of DPP-4i users. CONCLUSIONS: The findings suggest that SGLT2i is associated with a significantly lower risk of sepsis, septic shock, and mortality compared with that of DPP-4i in patients with T2DM.