Milo Gatti, Matteo Rinaldi, Cristiana Laici, Cecilia Bonazzetti, Luca Vizioli, Simone Ambretti, Maria Cristina Morelli, Antonio Siniscalchi, Maddalena Giannella, Pierluigi Viale, Federico Pea
Background To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections. Methods OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured. Multivariate logistic regression analyses were performed for testing independent variables associated with 30-day resistance occurrence. Results Fifty critical OLT recipients were treated with CI beta-lactam in mono- (n=34) or in combination (n=16) therapy for documented Gram-negative infections (46% hospital-acquired/ventilator-associated pneumonia). Combination therapy was selected more frequently for treating intraabdominal infections (P=0.03) and was associated with lower attainment of aggressive PK/PD target (P=0.03). No significant difference in clinical/microbiological outcome emerged between mono- and combination therapy. Four patients (8.0%) developed 30-day resistance occurrence. At multivariate analysis, failure in attaining an aggressive beta-lactam PK/PD target emerged as the only independent predictor of 30-day resistance development (OR 14.33; 95% CI 1.46-140.53; P=0.02). Conclusions Attaining an aggressive PK/PD target of CI beta-lactams in critical OLT recipients treated for documented Gram-negative infections could represent an effective strategy for minimizing the risk of 30-day resistance occurrence to the selected beta-lactam.
{"title":"Impact of attaining an aggressive PK/PD target with continuous infusion beta-lactams on the clinical efficacy of targeted therapy of early post-transplant Gram-negative infections in critically ill OLT recipients. An interim analysis of a 3-year prospective, observational, study","authors":"Milo Gatti, Matteo Rinaldi, Cristiana Laici, Cecilia Bonazzetti, Luca Vizioli, Simone Ambretti, Maria Cristina Morelli, Antonio Siniscalchi, Maddalena Giannella, Pierluigi Viale, Federico Pea","doi":"10.1093/infdis/jiaf048","DOIUrl":"https://doi.org/10.1093/infdis/jiaf048","url":null,"abstract":"Background To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections. Methods OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured. Multivariate logistic regression analyses were performed for testing independent variables associated with 30-day resistance occurrence. Results Fifty critical OLT recipients were treated with CI beta-lactam in mono- (n=34) or in combination (n=16) therapy for documented Gram-negative infections (46% hospital-acquired/ventilator-associated pneumonia). Combination therapy was selected more frequently for treating intraabdominal infections (P=0.03) and was associated with lower attainment of aggressive PK/PD target (P=0.03). No significant difference in clinical/microbiological outcome emerged between mono- and combination therapy. Four patients (8.0%) developed 30-day resistance occurrence. At multivariate analysis, failure in attaining an aggressive beta-lactam PK/PD target emerged as the only independent predictor of 30-day resistance development (OR 14.33; 95% CI 1.46-140.53; P=0.02). Conclusions Attaining an aggressive PK/PD target of CI beta-lactams in critical OLT recipients treated for documented Gram-negative infections could represent an effective strategy for minimizing the risk of 30-day resistance occurrence to the selected beta-lactam.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catherine Olal, Bianca S Bodmer, Monika Rottstegge, Beatriz Escudero-Pérez, Julia R Port, András Bencsik, Emily V Nelson, Michelle Heung, Stephanie Wurr, Olivia Blake, Elisa Adam, Lisa Oestereich, Maite Baz-Martínez, Jürgen Müller-Guhl, Yann Gallais, Fabienne Anjuère, Bernard Malliere, Juliana Idoyaga, Thomas Hoenen, César Muñoz-Fontela
Dendritic cells connect innate and adaptive immune responses. This is a particularly important immune checkpoint in the case of emerging infections against which most of the population does not have preexisting antibody immunity. In this study, we sought to test whether antibody-based delivery of Ebola virus (EBOV) antigens to dendritic cells could be used as a vaccination strategy against Ebola virus disease. Our approach was to use antibodies targeting the endocytic receptor DEC-205 present in murine and human dendritic cells, to deliver the EBOV nucleoprotein or the model antigen ovalbumin (OVA). Our findings indicate that DEC-205 targeting stimulated antigen-specific T-cell responses in mice, which resulted in protection from EBOV or recombinant EBOV-OVA challenge. An added value of this strategy was the generation of resident memory T cells. We propose that dendritic cell targeting could be used to improve T-cell responses against filoviruses, a strategy that may complement current vaccination strategies.
{"title":"Antibody-Based Antigen Delivery to Dendritic Cells as a Vaccination Strategy Against Ebola Virus Disease","authors":"Catherine Olal, Bianca S Bodmer, Monika Rottstegge, Beatriz Escudero-Pérez, Julia R Port, András Bencsik, Emily V Nelson, Michelle Heung, Stephanie Wurr, Olivia Blake, Elisa Adam, Lisa Oestereich, Maite Baz-Martínez, Jürgen Müller-Guhl, Yann Gallais, Fabienne Anjuère, Bernard Malliere, Juliana Idoyaga, Thomas Hoenen, César Muñoz-Fontela","doi":"10.1093/infdis/jiae613","DOIUrl":"https://doi.org/10.1093/infdis/jiae613","url":null,"abstract":"Dendritic cells connect innate and adaptive immune responses. This is a particularly important immune checkpoint in the case of emerging infections against which most of the population does not have preexisting antibody immunity. In this study, we sought to test whether antibody-based delivery of Ebola virus (EBOV) antigens to dendritic cells could be used as a vaccination strategy against Ebola virus disease. Our approach was to use antibodies targeting the endocytic receptor DEC-205 present in murine and human dendritic cells, to deliver the EBOV nucleoprotein or the model antigen ovalbumin (OVA). Our findings indicate that DEC-205 targeting stimulated antigen-specific T-cell responses in mice, which resulted in protection from EBOV or recombinant EBOV-OVA challenge. An added value of this strategy was the generation of resident memory T cells. We propose that dendritic cell targeting could be used to improve T-cell responses against filoviruses, a strategy that may complement current vaccination strategies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah M Bartsch, Kevin L Chin, Ulrich Strych, Danielle C John, Tej D Shah, Maria Elena Bottazzi, Kelly J O’Shea, McKaylee Robertson, Colleen Weatherwax, Jessie Heneghan, Marie F Martinez, Allan Ciciriello, Sarah Kulkarni, Kavya Velmurugan, Alexis Dibbs, Sheryl A Scannell, Yanhan Shen, Denis Nash, Peter J Hotez, Bruce Y Lee
Background Long COVID, which affects an estimated 44.69-48.04 million people in the U.S., is an ongoing public health concern that will continue to grow as SARS-CoV-2 continues to spread. Methods We developed a computational simulation model representing the clinical course, the health effects, and the associated costs of a person with Long COVID. Results Simulations show that the average total cost of a Long COVID case can range from $5,084-$11,646 (assuming symptoms only last 1 year) with 92.5%-95.2% of these costs being productivity losses. Therefore, the current number of Long COVID cases could end up costing society at least $2.01-$6.56 billion, employers at least $1.99-$6.49 billion in productivity losses, and third-party payers $21-68.5 million annually (6%-20% probability of developing Long COVID). These cases would accrue 35,808-121,259 QALYs lost and 13,484-45,468 DALYs. Moreover, each year, there may be an additional $698.5 million in total costs, 14,685 QALYs lost, and 5,628 DALYs, if the incidence of COVID is 100 per 10,000 persons (similar to that seen in 2023). Every 10-point increase in COVID incidence results in an additional $365 million in total costs, 5,070 QALYs lost, and 1,900 DALYs each year. Conclusion The current health and economic burden of Long COVID may already exceed that of a number of other chronic disease and will continue to grow each year as there are more and more COVID-19 cases. This could be a significant drain on businesses, third party payers, the healthcare system, and all of society.
{"title":"The Current and Future Burden of Long COVID in the United States (U.S.)","authors":"Sarah M Bartsch, Kevin L Chin, Ulrich Strych, Danielle C John, Tej D Shah, Maria Elena Bottazzi, Kelly J O’Shea, McKaylee Robertson, Colleen Weatherwax, Jessie Heneghan, Marie F Martinez, Allan Ciciriello, Sarah Kulkarni, Kavya Velmurugan, Alexis Dibbs, Sheryl A Scannell, Yanhan Shen, Denis Nash, Peter J Hotez, Bruce Y Lee","doi":"10.1093/infdis/jiaf030","DOIUrl":"https://doi.org/10.1093/infdis/jiaf030","url":null,"abstract":"Background Long COVID, which affects an estimated 44.69-48.04 million people in the U.S., is an ongoing public health concern that will continue to grow as SARS-CoV-2 continues to spread. Methods We developed a computational simulation model representing the clinical course, the health effects, and the associated costs of a person with Long COVID. Results Simulations show that the average total cost of a Long COVID case can range from $5,084-$11,646 (assuming symptoms only last 1 year) with 92.5%-95.2% of these costs being productivity losses. Therefore, the current number of Long COVID cases could end up costing society at least $2.01-$6.56 billion, employers at least $1.99-$6.49 billion in productivity losses, and third-party payers $21-68.5 million annually (6%-20% probability of developing Long COVID). These cases would accrue 35,808-121,259 QALYs lost and 13,484-45,468 DALYs. Moreover, each year, there may be an additional $698.5 million in total costs, 14,685 QALYs lost, and 5,628 DALYs, if the incidence of COVID is 100 per 10,000 persons (similar to that seen in 2023). Every 10-point increase in COVID incidence results in an additional $365 million in total costs, 5,070 QALYs lost, and 1,900 DALYs each year. Conclusion The current health and economic burden of Long COVID may already exceed that of a number of other chronic disease and will continue to grow each year as there are more and more COVID-19 cases. This could be a significant drain on businesses, third party payers, the healthcare system, and all of society.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cornelius Clancy,Adam Lauring,Jonathan Li,Cynthia Sears
{"title":"Looking Forward: The Journal of Infectious Diseases in 2025.","authors":"Cornelius Clancy,Adam Lauring,Jonathan Li,Cynthia Sears","doi":"10.1093/infdis/jiaf020","DOIUrl":"https://doi.org/10.1093/infdis/jiaf020","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing-Rui Zhou, Yi Liao, Le-Qing Cao, Rui Ma, Yun He, Na Li, Dan-Ping Zhu, Xiao-Su Zhao, Xiao-Jun Huang, Yu-Qian Sun
Background Severe pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with high mortality. Given that cytokine, including Interleukin-6 (IL-6), play a critical role in immune-mediated organ injury in patients with severe COVID-19, we hypothesized that cytokines may also contribute to the pathogenesis of severe pneumonia after allo-HSCT. This study aimed to investigate the role of IL-6 in severe pneumonia post-allo-HSCT and explore its underlying mechanism. Methods Serum cytokine levels were prospectively measured in patients with severe and non-severe pneumonia following allo-HSCT. A mouse model of acute lung injury (ALI) and in vitro experiment using primary murine pulmonary microvascular endothelial cells (PMVECs) were conducted to assess the effects of IL-6 blockade, the mechanism of IL-6 in ALI, and immune-induced ALI. Results Serum IL-6 and sIL-6R levels were higher in the severe pneumonia group than in the non-severe group and were associated with disease progression. In a mouse model, preventive IL-6 blockade reduced ALI and improved survival. In vitro, the IL-6 trans-signaling complex caused more severe damage to mouse PMVECs than the classical signaling pathway. Soluble glycoprotein 130 and ruxolitinib effectively blocked the JAK1/STAT3 pathway activated by IL-6 trans-signaling in mouse PMVECs and reduced downstream inflammatory responses. Conclusions IL-6 levels were elevated in patients with severe pneumonia after allo-HSCT and were linked to disease progression. This injury may be driven by the IL-6/sIL-6R/JAK1/STAT3 pathway. This preliminary study suggests that targeting the IL-6 trans-signaling pathway may be a promising therapeutic approach for severe pneumonia/ALI following allo-HSCT.
{"title":"Interleukin-6 is significantly increased in severe pneumonia after allo-HSCT and might induce lung injury via IL-6/sIL-6R/JAK1/STAT3 pathway","authors":"Jing-Rui Zhou, Yi Liao, Le-Qing Cao, Rui Ma, Yun He, Na Li, Dan-Ping Zhu, Xiao-Su Zhao, Xiao-Jun Huang, Yu-Qian Sun","doi":"10.1093/infdis/jiaf041","DOIUrl":"https://doi.org/10.1093/infdis/jiaf041","url":null,"abstract":"Background Severe pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with high mortality. Given that cytokine, including Interleukin-6 (IL-6), play a critical role in immune-mediated organ injury in patients with severe COVID-19, we hypothesized that cytokines may also contribute to the pathogenesis of severe pneumonia after allo-HSCT. This study aimed to investigate the role of IL-6 in severe pneumonia post-allo-HSCT and explore its underlying mechanism. Methods Serum cytokine levels were prospectively measured in patients with severe and non-severe pneumonia following allo-HSCT. A mouse model of acute lung injury (ALI) and in vitro experiment using primary murine pulmonary microvascular endothelial cells (PMVECs) were conducted to assess the effects of IL-6 blockade, the mechanism of IL-6 in ALI, and immune-induced ALI. Results Serum IL-6 and sIL-6R levels were higher in the severe pneumonia group than in the non-severe group and were associated with disease progression. In a mouse model, preventive IL-6 blockade reduced ALI and improved survival. In vitro, the IL-6 trans-signaling complex caused more severe damage to mouse PMVECs than the classical signaling pathway. Soluble glycoprotein 130 and ruxolitinib effectively blocked the JAK1/STAT3 pathway activated by IL-6 trans-signaling in mouse PMVECs and reduced downstream inflammatory responses. Conclusions IL-6 levels were elevated in patients with severe pneumonia after allo-HSCT and were linked to disease progression. This injury may be driven by the IL-6/sIL-6R/JAK1/STAT3 pathway. This preliminary study suggests that targeting the IL-6 trans-signaling pathway may be a promising therapeutic approach for severe pneumonia/ALI following allo-HSCT.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"131 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hansheng Wang, Xiao Chen, Hui You, Yunyun Wang, Xianru Xia, Yijun Tang, Tao Ren, Meifang Wang
Background and Objective Multiplex polymerase chain reaction (PCR)-based targeted next-generation sequencing (tNGS) is a promising tool for distinguishing lower respiratory tract infections (LRTIs) in clinical practice, and its detectable pathogen spectrum can cover more than 95% of clinical cases. but there is limited information on systematic evaluation of the clinical use of multiplex PCR-based tNGS (mp-tNGS) in IPA cases. We aim to assess mp-tNGS in bronchoalveolar lavage fluid (BALF) for Aspergillus detection in suspected IPA patients, and to provide a reliable basis for initiating antifungal therapy without microbiological or histopathological evidence. Methods We prospectively enrolled a cohort of consecutive patients suspected of IPA, all of them had undergone serum/BALF galactomannan antigen (GM), BALF mp-tNGS, and traditional tests (direct smear and culture of respiratory specimens), EORTC/MSGERC and FUDICU criteria were used for IPA diagnosis. Results Thirty-two patients were diagnosed with IPA and 42 with non-IPA. Compared with the final diagnosis, the sensitivity of BALF mp-tNGS was 87.5%, while the sensitivity of traditional tests, serum GM and BALF GM assay was 43.8%, 21.9%, and 62.5%, respectively; the specificity of BALF mp-tNGS was 90.5%, which was similar to traditional tests. The average turnaround time (TAT) for Aspergillus detection by BALF mp-tNGS was 22.10±2.49h, which was significantly faster than that by traditional tests. Conclusion BALF mp-tNGS showed good performance in identification of Aspergillus in non-neutropenic IPA patients. Importantly, positive mp-tNGS in BALF can provide a basis for early antifungal therapy before microbiological evidence is available.
{"title":"Performance of multiplex PCR-based targeted next-generation sequencing in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients","authors":"Hansheng Wang, Xiao Chen, Hui You, Yunyun Wang, Xianru Xia, Yijun Tang, Tao Ren, Meifang Wang","doi":"10.1093/infdis/jiaf044","DOIUrl":"https://doi.org/10.1093/infdis/jiaf044","url":null,"abstract":"Background and Objective Multiplex polymerase chain reaction (PCR)-based targeted next-generation sequencing (tNGS) is a promising tool for distinguishing lower respiratory tract infections (LRTIs) in clinical practice, and its detectable pathogen spectrum can cover more than 95% of clinical cases. but there is limited information on systematic evaluation of the clinical use of multiplex PCR-based tNGS (mp-tNGS) in IPA cases. We aim to assess mp-tNGS in bronchoalveolar lavage fluid (BALF) for Aspergillus detection in suspected IPA patients, and to provide a reliable basis for initiating antifungal therapy without microbiological or histopathological evidence. Methods We prospectively enrolled a cohort of consecutive patients suspected of IPA, all of them had undergone serum/BALF galactomannan antigen (GM), BALF mp-tNGS, and traditional tests (direct smear and culture of respiratory specimens), EORTC/MSGERC and FUDICU criteria were used for IPA diagnosis. Results Thirty-two patients were diagnosed with IPA and 42 with non-IPA. Compared with the final diagnosis, the sensitivity of BALF mp-tNGS was 87.5%, while the sensitivity of traditional tests, serum GM and BALF GM assay was 43.8%, 21.9%, and 62.5%, respectively; the specificity of BALF mp-tNGS was 90.5%, which was similar to traditional tests. The average turnaround time (TAT) for Aspergillus detection by BALF mp-tNGS was 22.10±2.49h, which was significantly faster than that by traditional tests. Conclusion BALF mp-tNGS showed good performance in identification of Aspergillus in non-neutropenic IPA patients. Importantly, positive mp-tNGS in BALF can provide a basis for early antifungal therapy before microbiological evidence is available.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eunshin Cho, Jinshil Kim, Taehee Won, Sangryeol Ryu, Byeonghwa Jeon
Shiga toxin-producing Escherichia coli (STEC) infections pose a significant public health challenge, characterized by severe complications including hemolytic uremic syndrome (HUS) due to Shiga toxin (Stx) production. Current therapeutic approaches encounter a critical limitation, as conventional antibiotic treatment is contraindicated due to its propensity to trigger bacterial SOS response and subsequently enhance Stx production, which increases the likelihood of developing HUS in antibiotic-treated patients. The lack of effective, safe therapeutic options has created an urgent need for alternative treatment strategies for STEC infections. This study investigates the therapeutic potential of virulent bacteriophages (phages) against STEC O157:H7. Our findings demonstrate that these phages effectively reduce STEC populations to levels comparable to ciprofloxacin treatment, while crucially avoiding the induction of SOS response and subsequent enhancement of Stx production. This is a significant advantage over conventional antibiotics which increase Stx levels. Furthermore, these phages exhibited broad-spectrum antimicrobial activity against multiple clinical STEC isolates without triggering toxin expression. The capability of virulent phages to effectively control STEC without enhancing toxin production represents a promising therapeutic strategy that combines antimicrobial efficacy with safety considerations. These characteristics indicate that virulent phages represent a potential solution to address the current therapeutic challenges in STEC infections, particularly in mitigating the risk of HUS development in infected patients.
{"title":"Virulent Bacteriophages for Controlling Shiga Toxin-Producing Escherichia coli (STEC) Without Inducing Toxin Production","authors":"Eunshin Cho, Jinshil Kim, Taehee Won, Sangryeol Ryu, Byeonghwa Jeon","doi":"10.1093/infdis/jiaf035","DOIUrl":"https://doi.org/10.1093/infdis/jiaf035","url":null,"abstract":"Shiga toxin-producing Escherichia coli (STEC) infections pose a significant public health challenge, characterized by severe complications including hemolytic uremic syndrome (HUS) due to Shiga toxin (Stx) production. Current therapeutic approaches encounter a critical limitation, as conventional antibiotic treatment is contraindicated due to its propensity to trigger bacterial SOS response and subsequently enhance Stx production, which increases the likelihood of developing HUS in antibiotic-treated patients. The lack of effective, safe therapeutic options has created an urgent need for alternative treatment strategies for STEC infections. This study investigates the therapeutic potential of virulent bacteriophages (phages) against STEC O157:H7. Our findings demonstrate that these phages effectively reduce STEC populations to levels comparable to ciprofloxacin treatment, while crucially avoiding the induction of SOS response and subsequent enhancement of Stx production. This is a significant advantage over conventional antibiotics which increase Stx levels. Furthermore, these phages exhibited broad-spectrum antimicrobial activity against multiple clinical STEC isolates without triggering toxin expression. The capability of virulent phages to effectively control STEC without enhancing toxin production represents a promising therapeutic strategy that combines antimicrobial efficacy with safety considerations. These characteristics indicate that virulent phages represent a potential solution to address the current therapeutic challenges in STEC infections, particularly in mitigating the risk of HUS development in infected patients.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eloise Williams, Jane S Hocking, Christopher K Fairley, Marcus Y Chen, Deborah A Williamson, James S McCarthy, Euzebiusz Jamrozik
Infection with Neisseria gonorrhoeae, the causative agent of gonorrhoea, causes significant morbidity worldwide and can have long-term impacts on reproductive health. The greatest global burden of gonorrhoea occurs in low- and middle-income settings. Global public health significance is increasing due to rising antimicrobial resistance (AMR), which threatens future gonorrhoea management. The oropharynx is an important asymptomatic reservoir for gonorrhoea transmission and a high-risk site for development of AMR and treatment failure. Controlled human infection model (CHIM) studies using N. gonorrhoeae may provide a means to accelerate the development of urgently needed therapeutics, vaccines and other biomedical prevention strategies. A gonorrhoea urethritis CHIM has been used since the 1980s with no reported serious adverse events. Here, we describe the rationale for an oropharyngeal gonorrhoea CHIM, including analysis of potential ethical issues that should inform the development of this novel study design.
{"title":"Rationale and Ethical Assessment of an Oropharyngeal Gonorrhoea Controlled Human Infection Model","authors":"Eloise Williams, Jane S Hocking, Christopher K Fairley, Marcus Y Chen, Deborah A Williamson, James S McCarthy, Euzebiusz Jamrozik","doi":"10.1093/infdis/jiaf029","DOIUrl":"https://doi.org/10.1093/infdis/jiaf029","url":null,"abstract":"Infection with Neisseria gonorrhoeae, the causative agent of gonorrhoea, causes significant morbidity worldwide and can have long-term impacts on reproductive health. The greatest global burden of gonorrhoea occurs in low- and middle-income settings. Global public health significance is increasing due to rising antimicrobial resistance (AMR), which threatens future gonorrhoea management. The oropharynx is an important asymptomatic reservoir for gonorrhoea transmission and a high-risk site for development of AMR and treatment failure. Controlled human infection model (CHIM) studies using N. gonorrhoeae may provide a means to accelerate the development of urgently needed therapeutics, vaccines and other biomedical prevention strategies. A gonorrhoea urethritis CHIM has been used since the 1980s with no reported serious adverse events. Here, we describe the rationale for an oropharyngeal gonorrhoea CHIM, including analysis of potential ethical issues that should inform the development of this novel study design.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eva Kozanli, Angelique M A M Winkel, Alvin X Han, Sharon van den Brink, Annemarie van den Brandt, Milly E Haverkort, Sjoerd Euser, Colin A Russell, Menno D de Jong, Marlies A van Houten, Steven F L van Lelyveld, Dirk Eggink
This study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens the viral RNA shedding duration and lowers viral load peaks. Frequent saliva sampling can be a convenient tool to study viral load dynamics.
{"title":"Shortened SARS-CoV-2 viral RNA shedding in saliva during early Omicron compared to wild-type pandemic phase","authors":"Eva Kozanli, Angelique M A M Winkel, Alvin X Han, Sharon van den Brink, Annemarie van den Brandt, Milly E Haverkort, Sjoerd Euser, Colin A Russell, Menno D de Jong, Marlies A van Houten, Steven F L van Lelyveld, Dirk Eggink","doi":"10.1093/infdis/jiaf031","DOIUrl":"https://doi.org/10.1093/infdis/jiaf031","url":null,"abstract":"This study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens the viral RNA shedding duration and lowers viral load peaks. Frequent saliva sampling can be a convenient tool to study viral load dynamics.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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