The misdiagnosis of acute febrile illness (AFI) aetiology is associated with antibiotic overuse and improper patient management. To develop novel strategies, a more comprehensive understanding of the pathophysiological mechanisms underlying the early response to different causes of fever is essential.Here we examined the host response to AFI, through the retrospective investigation of serum samples from febrile patients with bacterial infection (n = 52) or malaria (n = 73). The systemic levels of CXCL10, IFNγ, IL-2, IL-4, IL-6, IL-8, procalcitonin (PCT), TRAIL, ICAM-1, VCAM-1, osteopontin, TNFα, MMP-2 and MMP-9 were measured by multiplex immunoassays, while the relative abundance of 37 different surface markers of circulating extracellular vesicles (EVs) was determined using the MACSplex kit (Miltenyi Biotec).Markers of endothelial activation (CD29+, CD62P+, CD9+ EVs) and immune cell migration (MMP-2 and MMP-9) appeared elevated in bacterial AFI (q-value < 0.05). Mediators associated with antigen recognition (CD8+, CD81+, HLA-DR/DP/DQ+ EVs) and cytokine storm (IFNγ, CXCL10, TNFα) were instead prominent in malaria infection (q-value < 0.005). Interestingly, HLA-DR/DP/DQ+ EVs distinguished between bacterial and malaria AFI with area under the ROC curve (AUC) of 0.87, not significantly different from platelets' AUC (0.92), which was the best individual discriminator.Our results showed different biological processes as associated with bacterial and malaria AFI, paving the way for the identification of novel potential markers for a timely and reliable AFI diagnosis. The study also provides novel insights on the potential role of EVs as mediators of pro-inflammatory signalling during acute fever, which should be investigated more comprehensively in vitro.
{"title":"Profiling of circulating immune factors and host-derived extracellular vesicles in response to bacterial or malaria acute fever.","authors":"Natalia Tiberti, Giulia Bertoli, Cristina Mazzi, Elisabetta Vezzelli, Serena Zanzoni, Francesca Alladio, Zeno Bisoffi, Francesca Tamarozzi, Chiara Piubelli, Dora Buonfrate, Federico Giovanni Gobbi","doi":"10.1007/s15010-025-02694-7","DOIUrl":"https://doi.org/10.1007/s15010-025-02694-7","url":null,"abstract":"<p><p>The misdiagnosis of acute febrile illness (AFI) aetiology is associated with antibiotic overuse and improper patient management. To develop novel strategies, a more comprehensive understanding of the pathophysiological mechanisms underlying the early response to different causes of fever is essential.Here we examined the host response to AFI, through the retrospective investigation of serum samples from febrile patients with bacterial infection (n = 52) or malaria (n = 73). The systemic levels of CXCL10, IFNγ, IL-2, IL-4, IL-6, IL-8, procalcitonin (PCT), TRAIL, ICAM-1, VCAM-1, osteopontin, TNFα, MMP-2 and MMP-9 were measured by multiplex immunoassays, while the relative abundance of 37 different surface markers of circulating extracellular vesicles (EVs) was determined using the MACSplex kit (Miltenyi Biotec).Markers of endothelial activation (CD29<sup>+</sup>, CD62P<sup>+</sup>, CD9<sup>+</sup> EVs) and immune cell migration (MMP-2 and MMP-9) appeared elevated in bacterial AFI (q-value < 0.05). Mediators associated with antigen recognition (CD8<sup>+</sup>, CD81<sup>+</sup>, HLA-DR/DP/DQ<sup>+</sup> EVs) and cytokine storm (IFNγ, CXCL10, TNFα) were instead prominent in malaria infection (q-value < 0.005). Interestingly, HLA-DR/DP/DQ<sup>+</sup> EVs distinguished between bacterial and malaria AFI with area under the ROC curve (AUC) of 0.87, not significantly different from platelets' AUC (0.92), which was the best individual discriminator.Our results showed different biological processes as associated with bacterial and malaria AFI, paving the way for the identification of novel potential markers for a timely and reliable AFI diagnosis. The study also provides novel insights on the potential role of EVs as mediators of pro-inflammatory signalling during acute fever, which should be investigated more comprehensively in vitro.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1007/s15010-025-02680-z
Gerd Fätkenheuer
{"title":"Language matters: the case of \"septic arthritis\".","authors":"Gerd Fätkenheuer","doi":"10.1007/s15010-025-02680-z","DOIUrl":"https://doi.org/10.1007/s15010-025-02680-z","url":null,"abstract":"","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1007/s15010-025-02690-x
Laura Lempinen, Riste Saat, Anu Laulajainen-Hongisto, Antti A Aarnisalo, Tea Nieminen, Jussi Jero
Purpose: Otogenic meningitis is a rare but potentially life-threatening intracranial complication of otitis media (OM). Our aim was to study the incidence of childhood otogenic meningitis and to compare clinical presentation, causative pathogens, diagnostics, treatment, and outcome of otogenic versus non-otogenic meningitis.
Methods: Charts were reviewed for 47 children admitted to our tertiary center with bacterial meningitis (BM) between 2010 and 2020. Otoscopy and/or imaging were used to determine the otogenic meningitis ratio and the mean annual incidence was calculated.
Results: Eight (17%) of the 47 BM cases were otogenic [5 males; median age 1.3 years (range 2 months to 16 years)]. The otogenic meningitis incidence was 0.3/100 000/year. The classic triad of fever, altered level of consciousness, and meningeal irritation was more common in children with otogenic meningitis (50%, 4/8) than without OM (14%, 5/36) (P = 0.042). Streptococcus pneumoniae was a more common pathogen in children with OM (88%, 7/8) than without OM (14%, 4/29) (P < 0.001), whereas Neisseria meningitidis infection occurred only in children without OM (41%, 12/29) (P = 0.036). Neurological sequelae at discharge were present in 3 (38%) children with OM. Deafness was diagnosed in two children, both with otogenic backgrounds. Three children showed long-term sequelae: 2 had deafness (aged < 2 years) and 1 had aphasia/dysphasia.
Conclusion: The incidence of otogenic meningitis was 0.3/100 000/year, with S. pneumoniae the most common causative pathogen. Deafness was the most common long-term sequela and occurred only in children with otogenic meningitis.
{"title":"Otogenic meningitis in children.","authors":"Laura Lempinen, Riste Saat, Anu Laulajainen-Hongisto, Antti A Aarnisalo, Tea Nieminen, Jussi Jero","doi":"10.1007/s15010-025-02690-x","DOIUrl":"https://doi.org/10.1007/s15010-025-02690-x","url":null,"abstract":"<p><strong>Purpose: </strong>Otogenic meningitis is a rare but potentially life-threatening intracranial complication of otitis media (OM). Our aim was to study the incidence of childhood otogenic meningitis and to compare clinical presentation, causative pathogens, diagnostics, treatment, and outcome of otogenic versus non-otogenic meningitis.</p><p><strong>Methods: </strong>Charts were reviewed for 47 children admitted to our tertiary center with bacterial meningitis (BM) between 2010 and 2020. Otoscopy and/or imaging were used to determine the otogenic meningitis ratio and the mean annual incidence was calculated.</p><p><strong>Results: </strong>Eight (17%) of the 47 BM cases were otogenic [5 males; median age 1.3 years (range 2 months to 16 years)]. The otogenic meningitis incidence was 0.3/100 000/year. The classic triad of fever, altered level of consciousness, and meningeal irritation was more common in children with otogenic meningitis (50%, 4/8) than without OM (14%, 5/36) (P = 0.042). Streptococcus pneumoniae was a more common pathogen in children with OM (88%, 7/8) than without OM (14%, 4/29) (P < 0.001), whereas Neisseria meningitidis infection occurred only in children without OM (41%, 12/29) (P = 0.036). Neurological sequelae at discharge were present in 3 (38%) children with OM. Deafness was diagnosed in two children, both with otogenic backgrounds. Three children showed long-term sequelae: 2 had deafness (aged < 2 years) and 1 had aphasia/dysphasia.</p><p><strong>Conclusion: </strong>The incidence of otogenic meningitis was 0.3/100 000/year, with S. pneumoniae the most common causative pathogen. Deafness was the most common long-term sequela and occurred only in children with otogenic meningitis.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1007/s15010-025-02693-8
Kai Lu, Shilong Shu, Xuefeng Peng, Faqiang Zhang, Yong Cheng, Hua Yang
Background: Short-course antibiotic (SCA) therapy after appendectomy for complicated appendicitis (CA) has gained increasing attention, but its safety and efficacy remain insufficiently supported by meta-analyses. This study aimed to evaluate whether SCA therapy is as safe and effective as conventional long-course antibiotic (LCA) therapy following appendectomy for CA.
Methods: A comprehensive literature search was conducted to identify randomized controlled trials (RCTs) and observational studies comparing different durations of postoperative antibiotic therapy for CA. Data were analyzed using RevMan 5.3 for meta-analysis, and the GRADE approach was applied to assess the quality of evidence for key outcomes.
Results: Four RCTs and nine observational studies involving 3,251 patients were included. The meta-analysis revealed no significant increase in the risk of surgical site infection (SSI) (RR = 1.19, 95% CI: 0.52 to 2.73, P = 0.67, low-quality evidence) or intra-abdominal abscess (IAA) (RR = 1.18, 95% CI: 0.92 to 1.51, P = 0.19, moderate-quality evidence) with less than 3-day SCA therapy compared to LCA therapy. Secondary outcomes showed no significant differences between the two regimens (moderate to very-low quality evidence). However, SCA therapy was associated with a shorter length of hospital stay (low-quality evidence).
Conclusion: For patients with CA, less than 3-day SCA therapy does not increase the risk of SSI or IAA. Moreover, reducing the duration of antibiotic use may help minimize unnecessary antibiotic consumption.
{"title":"Is short-course antibiotic therapy as safe and effective as long-course therapy after surgery for complicated appendicitis? A systematic review and meta-analysis.","authors":"Kai Lu, Shilong Shu, Xuefeng Peng, Faqiang Zhang, Yong Cheng, Hua Yang","doi":"10.1007/s15010-025-02693-8","DOIUrl":"https://doi.org/10.1007/s15010-025-02693-8","url":null,"abstract":"<p><strong>Background: </strong>Short-course antibiotic (SCA) therapy after appendectomy for complicated appendicitis (CA) has gained increasing attention, but its safety and efficacy remain insufficiently supported by meta-analyses. This study aimed to evaluate whether SCA therapy is as safe and effective as conventional long-course antibiotic (LCA) therapy following appendectomy for CA.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted to identify randomized controlled trials (RCTs) and observational studies comparing different durations of postoperative antibiotic therapy for CA. Data were analyzed using RevMan 5.3 for meta-analysis, and the GRADE approach was applied to assess the quality of evidence for key outcomes.</p><p><strong>Results: </strong>Four RCTs and nine observational studies involving 3,251 patients were included. The meta-analysis revealed no significant increase in the risk of surgical site infection (SSI) (RR = 1.19, 95% CI: 0.52 to 2.73, P = 0.67, low-quality evidence) or intra-abdominal abscess (IAA) (RR = 1.18, 95% CI: 0.92 to 1.51, P = 0.19, moderate-quality evidence) with less than 3-day SCA therapy compared to LCA therapy. Secondary outcomes showed no significant differences between the two regimens (moderate to very-low quality evidence). However, SCA therapy was associated with a shorter length of hospital stay (low-quality evidence).</p><p><strong>Conclusion: </strong>For patients with CA, less than 3-day SCA therapy does not increase the risk of SSI or IAA. Moreover, reducing the duration of antibiotic use may help minimize unnecessary antibiotic consumption.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1007/s15010-025-02665-y
Sébastien Boutin, Sabrina Klein, Gerold Untergasser, Tobias P Loka, Suzan Jakob, Yasemin Caf, Elham Khatamzas, Ludwig Knabl, Georg Wrettos, Henri Knobloch, Dennis Nurjadi
Background: The detection of pathogens causing infections by conventional diagnostic methods can be challenging and next-generation sequencing (NGS) technology offers a promising alternative method. In this study, we evaluated the performance of real-time metagenomic next-generation sequencing (rt-mNGS) for the detection of pathogens in respiratory samples.
Method: We used rt-mNGS, using the Seqstant LiveGene Analysis platform, on 335 respiratory samples in comparison to conventional culture results.
Results: We observed an overall good concordance in 71.64% (240/335) of the methods. The rt-mNGS outperformed the gold standard culture in 16.12% (54/335) of the samples, while the culture was superior in detecting the clinically relevant pathogen in 12.24% (41/335) of the samples. The non-inferiority of rt-mNGS was statistically significant (δ = 10, α = 0.05, 1 - β = 0.8). We also observed that the real-time analysis of NGS data is beneficial in obtaining reliable, timely results, as the initial report at cycle 46 exhibits a Positive Predictive Value (PPV) of 93.75% at the species-level with a sensitivity of 32.09%.
Conclusion: Overall, our study showed the non-inferiority of rt-mNGS compared to the standard-of-care microbiology for respiratory samples with statistical significance. Moreover, the rt-mNGS method exhibited superior sensitivity and superior overall performance. It also uniquely detected certain organisms that are typically hard to culture. However, rt-mNGS reported a higher number of false positives and faced limitations in detecting Aspergillus spp. In conclusion, the study highlights the potential of rt-mNGS as a powerful tool in clinical diagnostics of respiratory infections and beyond.
{"title":"Evaluating Seqstant LiveGene Analysis in real-time assessment of metagenomic next-generation sequencing (mNGS) data from respiratory samples.","authors":"Sébastien Boutin, Sabrina Klein, Gerold Untergasser, Tobias P Loka, Suzan Jakob, Yasemin Caf, Elham Khatamzas, Ludwig Knabl, Georg Wrettos, Henri Knobloch, Dennis Nurjadi","doi":"10.1007/s15010-025-02665-y","DOIUrl":"https://doi.org/10.1007/s15010-025-02665-y","url":null,"abstract":"<p><strong>Background: </strong>The detection of pathogens causing infections by conventional diagnostic methods can be challenging and next-generation sequencing (NGS) technology offers a promising alternative method. In this study, we evaluated the performance of real-time metagenomic next-generation sequencing (rt-mNGS) for the detection of pathogens in respiratory samples.</p><p><strong>Method: </strong>We used rt-mNGS, using the Seqstant LiveGene Analysis platform, on 335 respiratory samples in comparison to conventional culture results.</p><p><strong>Results: </strong>We observed an overall good concordance in 71.64% (240/335) of the methods. The rt-mNGS outperformed the gold standard culture in 16.12% (54/335) of the samples, while the culture was superior in detecting the clinically relevant pathogen in 12.24% (41/335) of the samples. The non-inferiority of rt-mNGS was statistically significant (δ = 10, α = 0.05, 1 - β = 0.8). We also observed that the real-time analysis of NGS data is beneficial in obtaining reliable, timely results, as the initial report at cycle 46 exhibits a Positive Predictive Value (PPV) of 93.75% at the species-level with a sensitivity of 32.09%.</p><p><strong>Conclusion: </strong>Overall, our study showed the non-inferiority of rt-mNGS compared to the standard-of-care microbiology for respiratory samples with statistical significance. Moreover, the rt-mNGS method exhibited superior sensitivity and superior overall performance. It also uniquely detected certain organisms that are typically hard to culture. However, rt-mNGS reported a higher number of false positives and faced limitations in detecting Aspergillus spp. In conclusion, the study highlights the potential of rt-mNGS as a powerful tool in clinical diagnostics of respiratory infections and beyond.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1007/s15010-025-02681-y
Nitin Gupta, Martin P Grobusch, Jan Felix Drexler, José Ramón Paño-Pardo, Galadriel Pellejero-Sagastizabal, Sotirios Tsiodras, Aleksandra Barac, F-Xavier Lescure, Pikka Jokelainen
Avian influenza remains a persistent global health threat, with Asia at its epicentre due to dense poultry production, live bird markets, and cross-species interfaces with ducks and swine. Several pathogenic subtypes continue to cause recurrent zoonotic spillovers with varying human case fatality, reinforcing the region's role as a pandemic hotspot. Surveillance highlights the main key ecological drivers: sustained viral circulation in live bird markets, subclinical infection in domestic ducks, wild birds serving as reservoirs, and multiple species with dual receptors that can act as mixing vessels enabling reassortment. Recent events in the United States, where H5N1 has emerged in dairy cattle with viral RNA detectable in retail milk and human cases arising from both poultry and dairy cattle exposures, further demonstrate the capacity of these viruses to invade new mammalian hosts and the food chain. Advances in poultry vaccination and next-generation antivirals show promise but are constrained by antigenic drift, incomplete protection, logistical barriers, and uneven uptake. Human preparedness remains weakened by diagnostic delays, limited access to therapeutics, and fragmented surveillance. Mitigation requires regionally tailored, One Health-driven strategies, market regulation, duck vaccination, swine surveillance, and rapid therapeutic deployment, together with equitable access to tools and transparent international collaboration to reduce zoonotic risk and strengthen global pandemic readiness. This review synthesizes recent evidence on avian influenza virus infections in Asia, outlining zoonotic risks, key drivers, and mitigation strategies, and concludes that the sustained circulation of these viruses in poultry and wild birds continues to present significant challenges for animal health, public health, and pandemic preparedness, highlighting the importance of strengthened One Health surveillance and control measures.
{"title":"Endemic avian influenza landscape in Asia: sustained zoonotic risks.","authors":"Nitin Gupta, Martin P Grobusch, Jan Felix Drexler, José Ramón Paño-Pardo, Galadriel Pellejero-Sagastizabal, Sotirios Tsiodras, Aleksandra Barac, F-Xavier Lescure, Pikka Jokelainen","doi":"10.1007/s15010-025-02681-y","DOIUrl":"https://doi.org/10.1007/s15010-025-02681-y","url":null,"abstract":"<p><p>Avian influenza remains a persistent global health threat, with Asia at its epicentre due to dense poultry production, live bird markets, and cross-species interfaces with ducks and swine. Several pathogenic subtypes continue to cause recurrent zoonotic spillovers with varying human case fatality, reinforcing the region's role as a pandemic hotspot. Surveillance highlights the main key ecological drivers: sustained viral circulation in live bird markets, subclinical infection in domestic ducks, wild birds serving as reservoirs, and multiple species with dual receptors that can act as mixing vessels enabling reassortment. Recent events in the United States, where H5N1 has emerged in dairy cattle with viral RNA detectable in retail milk and human cases arising from both poultry and dairy cattle exposures, further demonstrate the capacity of these viruses to invade new mammalian hosts and the food chain. Advances in poultry vaccination and next-generation antivirals show promise but are constrained by antigenic drift, incomplete protection, logistical barriers, and uneven uptake. Human preparedness remains weakened by diagnostic delays, limited access to therapeutics, and fragmented surveillance. Mitigation requires regionally tailored, One Health-driven strategies, market regulation, duck vaccination, swine surveillance, and rapid therapeutic deployment, together with equitable access to tools and transparent international collaboration to reduce zoonotic risk and strengthen global pandemic readiness. This review synthesizes recent evidence on avian influenza virus infections in Asia, outlining zoonotic risks, key drivers, and mitigation strategies, and concludes that the sustained circulation of these viruses in poultry and wild birds continues to present significant challenges for animal health, public health, and pandemic preparedness, highlighting the importance of strengthened One Health surveillance and control measures.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1007/s15010-025-02558-0
Miguel Mansilla-Polo, Daniel Martín-Torregrosa, Sara Becerril-Andrés, Javier López-Davia
{"title":"'Herpes simplex virus infection in a bipulmonary transplant recipient'.","authors":"Miguel Mansilla-Polo, Daniel Martín-Torregrosa, Sara Becerril-Andrés, Javier López-Davia","doi":"10.1007/s15010-025-02558-0","DOIUrl":"https://doi.org/10.1007/s15010-025-02558-0","url":null,"abstract":"","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145481877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1007/s15010-025-02686-7
Chandan Kumar, Anam Arshi, Anchal Yadav, Prashik Chavan, Susan Idicula-Thomas
Purpose: Candida spp. has emerged as major fungal pathogens, especially in immunocompromised individuals, posing significant challenges in clinical settings. Their growing prevalence and increasing resistance to antifungal agents underscore the urgent need for systematic investigation into resistance mechanisms. Constant monitoring of resistance-associated mutations is essential to mitigate drug resistance and develop effective therapeutic strategies.
Method: We developed CanDRes, a manually curated, open-access resource cataloging mutations linked to antifungal resistance in Candida spp. Mutations were systematically compiled from published literature, focusing on those identified in drug-resistant clinical isolates. Each entry was annotated with gene-level information, drug associations, organism specificity, resistance mechanisms, and evidence-based validation scores. 3D structures of mutant proteins were developed and are available for download from the CanDRes database.
Results: CanDRes encompasses 1053 unique mutations across 56 genes from drug-resistant strains of 13 Candida spp., assessed against 19 antifungal drugs. The database also includes resistance mechanisms, protein sequences, predicted 3D structural models, and mutation plots. These data provide a valuable foundation for understanding molecular resistance patterns and for guiding therapeutic decision-making.
Conclusion: Our study emphasizes the critical need to investigate antifungal resistance in Candida spp., which are among the most clinically challenging fungal pathogens. Understanding the mechanisms driving resistance to frontline antifungals can improve treatment strategies. CanDRes serves as a free and accessible resource for clinicians and researchers aiming to address antifungal resistance. Users can access CanDRes via https://candres.bicnirrh.res.in/ .
{"title":"CanDRes: Exploring the Mutation Landscape of Candida and its Role in Antifungal Resistance.","authors":"Chandan Kumar, Anam Arshi, Anchal Yadav, Prashik Chavan, Susan Idicula-Thomas","doi":"10.1007/s15010-025-02686-7","DOIUrl":"https://doi.org/10.1007/s15010-025-02686-7","url":null,"abstract":"<p><strong>Purpose: </strong>Candida spp. has emerged as major fungal pathogens, especially in immunocompromised individuals, posing significant challenges in clinical settings. Their growing prevalence and increasing resistance to antifungal agents underscore the urgent need for systematic investigation into resistance mechanisms. Constant monitoring of resistance-associated mutations is essential to mitigate drug resistance and develop effective therapeutic strategies.</p><p><strong>Method: </strong>We developed CanDRes, a manually curated, open-access resource cataloging mutations linked to antifungal resistance in Candida spp. Mutations were systematically compiled from published literature, focusing on those identified in drug-resistant clinical isolates. Each entry was annotated with gene-level information, drug associations, organism specificity, resistance mechanisms, and evidence-based validation scores. 3D structures of mutant proteins were developed and are available for download from the CanDRes database.</p><p><strong>Results: </strong>CanDRes encompasses 1053 unique mutations across 56 genes from drug-resistant strains of 13 Candida spp., assessed against 19 antifungal drugs. The database also includes resistance mechanisms, protein sequences, predicted 3D structural models, and mutation plots. These data provide a valuable foundation for understanding molecular resistance patterns and for guiding therapeutic decision-making.</p><p><strong>Conclusion: </strong>Our study emphasizes the critical need to investigate antifungal resistance in Candida spp., which are among the most clinically challenging fungal pathogens. Understanding the mechanisms driving resistance to frontline antifungals can improve treatment strategies. CanDRes serves as a free and accessible resource for clinicians and researchers aiming to address antifungal resistance. Users can access CanDRes via https://candres.bicnirrh.res.in/ .</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1007/s15010-025-02687-6
Reem Mahdi Saleh, Omar Mohammed Hassan
Chronic infections are a persistent global health problem and are frequently sustained by polymicrobial communities rather than by a single pathogen. This review brings together current evidence for the infectome concept, defined as the dynamic set of pathogenic or pathobiont taxa in the host, their shared functional capacities, and the interactions that connect them. We analyze how community-level processes promote persistence, cause diagnostic failure, and drive therapeutic resistance, with emphasis on multispecies biofilms, quorum sensing, horizontal gene transfer, metabolic cooperation, and immune modulation. We also highlight advances in multi-omics and computational integration that now permit high-resolution infectome profiling and reveal taxa and interspecies networks that are not captured by routine culture. Clinical examples such as periodontitis, bacterial vaginosis, chronic rhinosinusitis, device-associated infections, and recurrent urinary tract infections show the translational value of this shift. On the therapeutic side, we discuss infectome-informed options including antivirulence agents, biofilm-disrupting enzymes, bacteriophages and lysins, community-wide susceptibility-guided regimens, and microbiome-restoration strategies. Finally, we identify the main requirements for the field: standardized sampling and analytic workflows, reproducible infectome signatures linked to clinical outcomes, and trial designs able to capture ecological dynamics and meet regulatory expectations for community-targeted interventions. Adopting an infectome perspective can enable precision infectiology and reshape the management of chronic and recurrent infections.
{"title":"The infectome framework: linking polymicrobial ecology and biofilm dynamics to precision diagnostic approaches.","authors":"Reem Mahdi Saleh, Omar Mohammed Hassan","doi":"10.1007/s15010-025-02687-6","DOIUrl":"https://doi.org/10.1007/s15010-025-02687-6","url":null,"abstract":"<p><p>Chronic infections are a persistent global health problem and are frequently sustained by polymicrobial communities rather than by a single pathogen. This review brings together current evidence for the infectome concept, defined as the dynamic set of pathogenic or pathobiont taxa in the host, their shared functional capacities, and the interactions that connect them. We analyze how community-level processes promote persistence, cause diagnostic failure, and drive therapeutic resistance, with emphasis on multispecies biofilms, quorum sensing, horizontal gene transfer, metabolic cooperation, and immune modulation. We also highlight advances in multi-omics and computational integration that now permit high-resolution infectome profiling and reveal taxa and interspecies networks that are not captured by routine culture. Clinical examples such as periodontitis, bacterial vaginosis, chronic rhinosinusitis, device-associated infections, and recurrent urinary tract infections show the translational value of this shift. On the therapeutic side, we discuss infectome-informed options including antivirulence agents, biofilm-disrupting enzymes, bacteriophages and lysins, community-wide susceptibility-guided regimens, and microbiome-restoration strategies. Finally, we identify the main requirements for the field: standardized sampling and analytic workflows, reproducible infectome signatures linked to clinical outcomes, and trial designs able to capture ecological dynamics and meet regulatory expectations for community-targeted interventions. Adopting an infectome perspective can enable precision infectiology and reshape the management of chronic and recurrent infections.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}