Persistent bacteremia due to Enterococcus spp., without an identifiable source of infection, is a well-described phenomenon. Although often the preferred therapeutic agent, daptomycin resistance may develop, resulting in clinical failure. In North American isolates, mutations in the LiaFSR gene complex (specifically LiaR W73C and LiaS T120A) are associated with daptomycin resistance; however, these mutations also correlate with daptomycin-β-lactam synergistic activity. The case presented in this report had persistent vancomycin-resistant Enterococcus faecium bacteremia despite 26 days of daptomycin and β-lactam therapy. Initial daptomycin MICs were 2-4 µg/ml, and rose to 8 µg/ml during therapy. Whole-genome sequencing revealed a mutation in the LiaFSR gene complex (S19F of LiaR) previously reported only in Australian isolates. While other mutations involving LiaFSR are associated with synergy between daptomycin and β-lactams, clinical failure of combination therapy was observed in this case. Whenever possible, additional microbiological and genomic testing should be performed on isolates of E. faecium presenting with refractory bacteremia.
BACKGROUND Quantifying the risk of fluoroquinolone-associated musculoskeletal and neurological adverse event among children stratified supports clinicians to select the most appropriate antimicrobial regimen for children with bacterial infection. The objective of this study was to assess the risk of musculoskeletal and neurological disorders following fluoroquinolone exposure, compared with another antimicrobial class using the large-scale database. METHODS This retrospective study used the TriNetX platform, a multicenter health record database, to compare risk of musculoskeletal and neurological disorders following fluoroquinolone versus macrolide exposure in children aged <18 years. Propensity score matching was implemented to estimate odds ratio (OR) with 95% confidence interval (CI) of each musculoskeletal and neurological outcome. RESULTS In the United States, 423,880, 380,504 and 194,220 children aged <5, 5-11 and 12-17 years were matched from each group for the musculoskeletal cohort. The OR of any musculoskeletal outcomes, including disorders of tendon or synovium, in the fluoroquinolone was not increased. Conversely, the OR of peripheral neuropathy and sleep disorder following fluoroquinolone use were 2.22 [1.61-3.06]; p<0.001 and 1.57 [1.44-1.70]; p<0.001, 1.52 [1.20-1.93]; p<0.001 and 1.34 [1.26-1.43]; p<0.001, and 2.18 [1.75-2.72]; p<0.001) and 1.23 [1.13-1.35]; p<0.001 in children aged <5, 5-11, and 12-17 years, respectively. CONCLUSION This study showed the increased risk of peripheral neuropathy and sleep disorder following fluoroquinolones use among children compared with macrolide use. This study provided the data for clinicians to estimate risks of musculoskeletal or neurological adverse events.
OBJECTIVES We estimated human metapneumovirus (hMPV)-associated acute respiratory infection (ARI) hospitalisations in eastern China, and provided a direct comparison with RSV and influenza during 2020-2024. METHODS Leveraging a large regional medical database, we analysed weekly ARI hospitalisations and viral test-positives (hMPV, RSV and influenza) by age group and region, using negative binomial regression models with natural cubic splines, time-offsets for viral activity, excluding COVID-19 patients and adjusting for COVID-19 waves. RESULTS hMPV, RSV, and influenza were associated with 100,792 (5.35%), 266,826 (14.17%), and 409,599 (21.76%) ARI hospitalisations, respectively. RSV hospitalisations rebounded first in 2021/2022, followed by hMPV in 2022/2023, while influenza hospitalisations increased annually during the study period; meanwhile, hMPV- and influenza-associated hospitalisations shifted towards those aged 5-19 years, while RSV-associated hospitalisations shifted towards those aged ≥5 years. hMPV rates were highest among infants aged 0-5 months and 6-11 months (6.19 and 8.15 per 1,000 per year on average, respectively), followed by ages 12-23 months (18.54). RSV and influenza rates were highest in age groups within <1 year and 1-4 years, respectively. CONCLUSIONS Infants aged <1 year are the primary group for preventing severe hMPV infections, with a substantial additional burden observed in children aged 1-4 years. These findings support hMPV vaccine development and virus-specific intervention strategies.
BACKGROUND Dengue is expanding globally. Post-licensure vaccine effectiveness (VE) may differ from trial efficacy according to prior dengue exposure, circulating serotypes and programme conditions. We synthesised real-world evidence (RWE) on CYD-TDV and TAK-003. METHODS We searched four bibliographic databases, ScienceDirect and grey literature (January 2015-February 2026) for observational post-licensure studies in dengue-endemic settings. Outcomes were symptomatic and hospitalised laboratory-confirmed dengue, overall and by documented previous dengue, serostatus or serotype. Risk of bias (ROBINS-I) and certainty (GRADE) were assessed; synthesis was narrative. PROSPERO CRD420251058512. RESULTS Of 1,531 records, six eligible reports from three vaccination programmes (Cebu, Philippines; Paraná and São Paulo, Brazil) were included: five on CYD-TDV and one on TAK-003. CYD-TDV VE against symptomatic virologically confirmed dengue was 11.1% (three doses) and 21.3% (≥1 dose); estimates against hospitalisation were inconsistent, and VE was higher with documented previous dengue. TAK-003 VE was 61.7% against symptomatic dengue (two doses) and 67.5% against hospitalisation (one dose). Certainty was low to very low. CONCLUSIONS RWE remains scarce and largely non-independent. Serotype-specific outcomes, harmonised endpoints and characterisation of prior dengue exposure where feasible are needed to interpret the effectiveness of newer dengue vaccines.
