European Society of Clinical Microbiology and Infectious Diseases

The global rise of multidrug-resistant (MDR) bacteria has rendered many conventional antibiotics ineffective, creating an urgent need for alternative therapeutic strategies. Among these, bacteriophage-based approaches offer targeted, self-amplifying antimicrobial activity with the potential to complement or restore antibiotic efficacy. We report the isolation, characterization and host-adaptation of phages from environmental samples using a set of standard experimental procedures. Using wastewater as the source, we isolated four Caudoviricetes phages infecting an MDR Acinetobacter baumannii clinical strain (Abau1). Genome sequencing and host‐prophage filtering identified two strictly lytic phages (ΦAb1-SL1 and ΦAb1-SL2) for characterization, whilst two phages were host-integrated. ΦAb1-SL1 demonstrated potent synergistic killing with cephalosporin antibiotics: checkerboard assays revealed strong synergy with cefiderocol, ceftazidime and cefotaxime, the first result confirmed by a time-killing assay. Conversely, no synergy was seen with carbapenems. Under our host‐adaptation protocol, ΦAb1-SL1 broadened its host-spectrum infecting a previously resistant A. baumannii strain (Abau2). The resulting adapted phage (ΦAb2-SL1) retained infectivity of both hosts, albeit at a lower titer on the new host. The observed phage–antibiotic synergy with cefiderocol underscores the therapeutic promise of combined phage–antibiotic regimens against MDR A. baumannii and highlights the efforts of a translational approach for assembling phage libraries.

BACKGROUNDCommunity-acquired Legionnaires’ disease (LD) has increased globally, including Europe. Climatic exposures may contribute to this rise, yet evidence from high-incidence countries, such as Italy, is limited.AIMWe aimed to assess LD seasonality at the national level and the effects of temperature, relative humidity and precipitation on LD incidence at the municipality level.METHODSWe analysed data on notified community-acquired LD cases and national climatic data from 2005 to 2023. Seasonality was assessed (peak-to-trough ratio (PTR)). A case time-series design with distributed lag nonlinear models was applied to estimate 1–10 week lagged effects of climatic exposures on LD incidence at the municipality level, as incidence rate ratios (IRRs).RESULTSOf the 28,662 notified LD cases, 27,458 (95.8%) were included. A clear seasonality was observed in the incidence, with a trough in early spring and a peak in autumn (PTR = 3.62; 95% confidence interval (CI): 2.45–5.34). Higher temperature and relative humidity had the strongest effects 10–9 weeks before disease onset (for 5°C increase above 15°C: IRR = 1.45; 95% CI: 1.33–1.58 and for 5% increase above 60%: IRR = 1.19; 95% CI: 1.12–1.26). Precipitation showed more immediate effects, particularly with a 1-week lag (for 5 mm increase above 10 mm: IRR = 1.07; 95% CI: 1.06–1.09). Findings were consistent among individuals aged ≥ 60 years.CONCLUSIONA clear seasonal pattern was seen in the LD incidence, peaking in summer and autumn. Temperature and humidity increased LD risk over longer lags, while precipitation had shorter-term effects, suggesting climatic exposures influence environmental proliferation and immediate transmission of Legionella.

Nipah virus (NiV) is a highly lethal zoonotic virus that has caused sporadic but severe outbreaks in South and Southeast Asia since its emergence in 1998. Despite the relatively small size of most outbreaks, NiV poses a substantial public health challenge due to its high case fatality rate. To examine the evolving epidemiology, clinical features, virological insights, and preparedness challenges associated with NiV infection in South Asia. We conducted a narrative review synthesising epidemiological, clinical, and public health data from national surveillance systems, WHO Disease Outbreak News reports, and published outbreak investigations. We describe the shift from pig-amplified transmission observed in Malaysia to bat-driven spillover and human-to-human transmission, particularly within household and hospital settings, as characterised by recent outbreaks in Bangladesh and eastern India, and specifically review Kerala's experience since 2018. Particular attention is given to the re-emergence of NiV in West Bengal in early 2026, involving a limited cluster of infections among healthcare workers that was rapidly contained but remains epidemiologically important given the region's prior history of nosocomial spread. We discuss persistent challenges in early diagnosis, access to high-containment laboratory testing, and clinical management, alongside emerging roles for mobile Biosafety Level 3 laboratories and point-of-care diagnostics. Overall, the South Asian experience underscores that NiV represents a persistent zoonotic threat rather than an episodic emergence, necessitating sustained preparedness, pathogen-agnostic clinical vigilance, and proportionate risk communication to mitigate future outbreaks. Sustained preparedness, rather than episodic alarm, must guide future responses.

Chronic hepatitis E virus (HEV) infection is increasingly recognized as a significant cause of post-transplant hepatitis in immunosuppressed patients. Although HEV genotype 3 is the most prevalent in Europe, the clinical significance of subgenotypic diversity remains poorly defined. We report two kidney transplant recipients (KTR) diagnosed with chronic HEV infection during routine follow-up. Both patients presented with abnormal liver function tests in the absence of overt clinical symptoms. A broad-spectrum nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene of the ORF1 region of the HEV genome was performed, followed by sequencing and phylogenetic analysis. Viral sequences detected in stool samples clustered with HEV-3c and HEV-3ra subtypes, the latter being a zoonotic variant associated with rabbits. Immunosuppressive reduction alone was insufficient for viral clearance, and both patients achieved sustained virologic response after six-month ribavirin therapy. These findings are consistent with established features of chronic HEV infection in KTR but also extend current knowledge by documenting the first case of HEV-3ra in this population. The present work underscores the importance of systematic HEV surveillance and routine molecular characterization in transplant medicine, reinforcing the need for timely initiation of antiviral therapy to prevent progression to advanced forms of liver disease.

Heterogeneity of the host response in sepsis hampers development of effective treatments. Several immunobiologically distinct subphenotypes (or endotypes) have been identified using data-driven analyses of single-timepoint biomarker data, but their temporal stability remains uncertain due to dynamic biology and statistical limitations. We analyzed data from 345 sepsis patients across two ICU cohorts. 30 immune biomarkers were measured every 8h for up to 7days. Latent profile analysis was used to identify classes upon admission and re-classify patients at later timepoints. Temporal robustness was assessed by (1) inter-class transition rates, and (2) intra-class cohesion (regardless of label) using the Rand Index (RI). At ICU admission, three immune profiles were identified: profile A (149 patients, 43%) reflected adaptive immune activation (elevated IL-4, IL-5, RANTES, and GM-CSF); profile B (60 patients, 17%) a hyperinflammatory state (high IL-6, IL-8, IL-1Ra, and low protein C); and profile C (136 patients, 39%) broadly attenuated inflammation. By 48h, the prevalences of A and B declined to 31% and 13%, while C increased to 56%. Inter-class transitions occurred most in patients assigned to A (41% of all 8-hourly transitions), compared to 39% and 22% for B and C. Intra-class cohesion across intervals was poor (median RI 65%, IQR 62-64%), indicating that patients classified together at admission did not remain consistently together. Sepsis patients were frequently reclassified across immune profiles over short intervals, with approximately one-third of subgroup peers changing at each timepoint. This instability challenges the clinical utility of biomarker-derived endotypes.