Pub Date : 2025-09-11Epub Date: 2025-05-29DOI: 10.1128/cmr.00107-24
Davinder S Gill, Sanjay Ram, Peter A Rice
SUMMARYSexually transmitted infections (STIs) represent a significant global health burden, with over one million new infections occurring daily. In some instances, the prevalence of antibiotic-resistant pathogens is rising, which exacerbates the challenge. STIs cause severe complications, including infertility, ectopic pregnancies, pre-term births, and heightened risks of HIV acquisition. These outcomes underscore the need for innovative therapeutic and prophylactic strategies. In this review, we provide a comprehensive analysis of the current state of biologic drug development targeting key STIs, focusing on Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus type 2 (HSV-2), and Treponema pallidum. We examine the complexity of host-pathogen interactions that inform biologic drug design, such as multiple mechanisms of infection, immune evasion strategies, and pathogenic latency. We also explore the role of mucosal immunity, highlighting advances in resident memory T cells and cytokine-driven responses that guide therapeutic targeting, concentrating on Chlamydia trachomatis and Neisseria gonorrhoeae, where recent advances in vaccine development appear promising. We conduct a comprehensive survey of platforms, including vaccines, and explore modalities such as monoclonal antibodies and protein therapeutics. Additionally, we examine emerging technologies like nucleic acid-based therapies, microbiome modulation, and phage-based interventions, highlighting their potential against challenging pathogens like HSV-2 and Treponema pallidum. By examining these established and emerging approaches, this review prioritizes critical opportunities for innovation in biologic therapeutics, addressing unmet needs in STI management. It advocates for integrated strategies leveraging antigenic conservation, host immunity modulation, and novel delivery platforms to achieve durable prophylaxis and effective treatment for high-burden infections globally.
{"title":"Biologic drug development for treatment and prevention of sexually transmitted infections.","authors":"Davinder S Gill, Sanjay Ram, Peter A Rice","doi":"10.1128/cmr.00107-24","DOIUrl":"10.1128/cmr.00107-24","url":null,"abstract":"<p><p>SUMMARYSexually transmitted infections (STIs) represent a significant global health burden, with over one million new infections occurring daily. In some instances, the prevalence of antibiotic-resistant pathogens is rising, which exacerbates the challenge. STIs cause severe complications, including infertility, ectopic pregnancies, pre-term births, and heightened risks of HIV acquisition. These outcomes underscore the need for innovative therapeutic and prophylactic strategies. In this review, we provide a comprehensive analysis of the current state of biologic drug development targeting key STIs, focusing on <i>Chlamydia trachomatis</i>, <i>Neisseria gonorrhoeae</i>, herpes simplex virus type 2 (HSV-2), and <i>Treponema pallidum</i>. We examine the complexity of host-pathogen interactions that inform biologic drug design, such as multiple mechanisms of infection, immune evasion strategies, and pathogenic latency. We also explore the role of mucosal immunity, highlighting advances in resident memory T cells and cytokine-driven responses that guide therapeutic targeting, concentrating on <i>Chlamydia trachomatis</i> and <i>Neisseria gonorrhoeae</i>, where recent advances in vaccine development appear promising. We conduct a comprehensive survey of platforms, including vaccines, and explore modalities such as monoclonal antibodies and protein therapeutics. Additionally, we examine emerging technologies like nucleic acid-based therapies, microbiome modulation, and phage-based interventions, highlighting their potential against challenging pathogens like HSV-2 and <i>Treponema pallidum</i>. By examining these established and emerging approaches, this review prioritizes critical opportunities for innovation in biologic therapeutics, addressing unmet needs in STI management. It advocates for integrated strategies leveraging antigenic conservation, host immunity modulation, and novel delivery platforms to achieve durable prophylaxis and effective treatment for high-burden infections globally.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0010724"},"PeriodicalIF":19.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-11Epub Date: 2025-05-29DOI: 10.1128/cmr.00011-25
Jacques G Mainil, Keiji Nakamura, Rie Ikeda, Florence Crombé, Jacob Diderich, Marc Saulmont, Denis Piérard, Damien Thiry, Tetsuya Hayashi
SUMMARYAttaching-effacing (AE) lesion- and Shiga toxin-producing Escherichia (E.) coli (AE-STEC), previously known as "enterohemorrhagic E. coli" (EHEC), are responsible for (hemorrhagic) enterocolitis (HC) and hemolytic uremic syndrome (HUS) in humans. The most frequent and pathogenic AE-STEC belong to a few O:H major serotypes that are responsible for the majority of cases and outbreaks worldwide. From time to time, one or another non-major O:H serotype can emerge, causing either local outbreaks or a a progressive increase in clinical cases. One of these minor serotypes is O80:H2, which has been progressively emerging in Western Europe, especially in France, since 2010. AE-STEC O80:H2 are responsible for not only HC and HUS but also invasive infections with bacteremia and internal organ infection. In parallel to their emergence in humans, AE-STEC and enteropathogenic E. coli (EPEC) O80:H2 have also been emerging in young calves suffering diarrhea and enteritis and, more rarely septicemia, in Belgium since 2009. In this manuscript, an overview of AE-STEC and EPEC O80:H2 infections in humans and calves is presented, with particular focus on the clinical manifestations, the prevalence and incidence in Western Europe, and the identification of the potential reservoir(s). In addition, the results of a large-scale whole genome-based phylogenetic analysis of 417 published and unpublished genome sequences currently available in the literature and in the NCBI and EnteroBase databases are presented with hypotheses on the origin and evolution of this new hybrid AE-STEC and EPEC serotype.
{"title":"Emerging hybrid shigatoxigenic and enteropathogenic <i>Escherichia coli</i> serotype O80:H2 in humans and calves.","authors":"Jacques G Mainil, Keiji Nakamura, Rie Ikeda, Florence Crombé, Jacob Diderich, Marc Saulmont, Denis Piérard, Damien Thiry, Tetsuya Hayashi","doi":"10.1128/cmr.00011-25","DOIUrl":"10.1128/cmr.00011-25","url":null,"abstract":"<p><p>SUMMARYAttaching-effacing (AE) lesion- and Shiga toxin-producing <i>Escherichia</i> (<i>E</i>.) <i>coli</i> (AE-STEC), previously known as \"enterohemorrhagic <i>E. coli</i>\" (EHEC), are responsible for (hemorrhagic) enterocolitis (HC) and hemolytic uremic syndrome (HUS) in humans. The most frequent and pathogenic AE-STEC belong to a few O:H major serotypes that are responsible for the majority of cases and outbreaks worldwide. From time to time, one or another non-major O:H serotype can emerge, causing either local outbreaks or a a progressive increase in clinical cases. One of these minor serotypes is O80:H2, which has been progressively emerging in Western Europe, especially in France, since 2010. AE-STEC O80:H2 are responsible for not only HC and HUS but also invasive infections with bacteremia and internal organ infection. In parallel to their emergence in humans, AE-STEC and enteropathogenic <i>E. coli</i> (EPEC) O80:H2 have also been emerging in young calves suffering diarrhea and enteritis and, more rarely septicemia, in Belgium since 2009. In this manuscript, an overview of AE-STEC and EPEC O80:H2 infections in humans and calves is presented, with particular focus on the clinical manifestations, the prevalence and incidence in Western Europe, and the identification of the potential reservoir(s). In addition, the results of a large-scale whole genome-based phylogenetic analysis of 417 published and unpublished genome sequences currently available in the literature and in the NCBI and EnteroBase databases are presented with hypotheses on the origin and evolution of this new hybrid AE-STEC and EPEC serotype.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0001125"},"PeriodicalIF":19.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-11Epub Date: 2025-07-07DOI: 10.1128/cmr.00101-23
Susana Lopez-Alamillo, Pravallika Padyala, Megan Carey, Megan M Duffey, Jill E Weatherhead
SUMMARYHuman toxocariasis is a globally prevalent zoonotic parasitic infection caused by larvae of Toxocara species, primarily Toxocara canis and Toxocara cati. Toxocariasis is commonly transmitted to humans through the ingestion of embryonated Toxocara eggs found in contaminated soil, water, or on surfaces contaminated with animal feces. Unlike in dogs and cats, humans are not definitive hosts for Toxocara spp., and, as a result, Toxocara larvae do not complete their life cycle in humans. Instead, following accidental oral ingestion of embryonated eggs, Toxocara larvae undergo an aberrant larval migratory cycle to various organs including the lungs, liver, muscles, and central nervous system, and do not return to the intestines to develop into mature adult worms. As the Toxocara larvae do not complete their life cycle in the human host, they will ultimately die in human tissue. This comprehensive systematic review of human toxocariasis analyzes and synthesizes existing research to provide a detailed and updated understanding of this zoonotic parasitic infection of global importance. This review provides an in-depth analysis of various aspects of toxocariasis, including its epidemiology, microbiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies.
{"title":"Human toxocariasis.","authors":"Susana Lopez-Alamillo, Pravallika Padyala, Megan Carey, Megan M Duffey, Jill E Weatherhead","doi":"10.1128/cmr.00101-23","DOIUrl":"10.1128/cmr.00101-23","url":null,"abstract":"<p><p>SUMMARYHuman toxocariasis is a globally prevalent zoonotic parasitic infection caused by larvae of <i>Toxocara</i> species, primarily <i>Toxocara canis</i> and <i>Toxocara cati</i>. Toxocariasis is commonly transmitted to humans through the ingestion of embryonated <i>Toxocara</i> eggs found in contaminated soil, water, or on surfaces contaminated with animal feces. Unlike in dogs and cats, humans are not definitive hosts for <i>Toxocara</i> spp., and, as a result, <i>Toxocara</i> larvae do not complete their life cycle in humans. Instead, following accidental oral ingestion of embryonated eggs, <i>Toxocara</i> larvae undergo an aberrant larval migratory cycle to various organs including the lungs, liver, muscles, and central nervous system, and do not return to the intestines to develop into mature adult worms. As the <i>Toxocara</i> larvae do not complete their life cycle in the human host, they will ultimately die in human tissue. This comprehensive systematic review of human toxocariasis analyzes and synthesizes existing research to provide a detailed and updated understanding of this zoonotic parasitic infection of global importance. This review provides an in-depth analysis of various aspects of toxocariasis, including its epidemiology, microbiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0010123"},"PeriodicalIF":19.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linea Katharina Muhsal,Lisa Theis,Jörg Overmann,Axel Hamprecht
SUMMARYProteus spp. are members of the Enterobacterales order and are widely found in humans, animals, and the environment. Some species, particularly P. mirabilis, are highly pathogenic and are among the most frequent causes of urinary tract and bloodstream infections. Proteus spp. possess a variety of virulence factors, such as swarming and urease activity, leading to persistent and severe infections. An increasing resistance to antibiotics has been reported for isolates and poses a substantial threat to global health. In recent years, several new Proteus spp. have been described, but their potential as pathogens has not yet been determined. Here, we provide an update on the taxonomy, virulence factors, and antibiotic resistance of Proteus spp.
{"title":"Proteus spp.-taxonomy, clinical significance, and antibiotic resistance of a highly versatile pathogen.","authors":"Linea Katharina Muhsal,Lisa Theis,Jörg Overmann,Axel Hamprecht","doi":"10.1128/cmr.00181-24","DOIUrl":"https://doi.org/10.1128/cmr.00181-24","url":null,"abstract":"SUMMARYProteus spp. are members of the Enterobacterales order and are widely found in humans, animals, and the environment. Some species, particularly P. mirabilis, are highly pathogenic and are among the most frequent causes of urinary tract and bloodstream infections. Proteus spp. possess a variety of virulence factors, such as swarming and urease activity, leading to persistent and severe infections. An increasing resistance to antibiotics has been reported for isolates and poses a substantial threat to global health. In recent years, several new Proteus spp. have been described, but their potential as pathogens has not yet been determined. Here, we provide an update on the taxonomy, virulence factors, and antibiotic resistance of Proteus spp.","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":"3 1","pages":"e0018124"},"PeriodicalIF":36.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SUMMARYAntimicrobial resistance (AMR) poses a significant threat to global public health. Surveillance is a fundamental method for controlling AMR and guiding clinical decisions, public health interventions, and policymaking. Whole-genome sequencing (WGS) provides a comprehensive and accurate understanding of AMR mechanisms, gene profiling, and transmission dynamics. Public health authorities, academic scholars, hospitals, and laboratories have increasingly employed WGS-based surveillance for retrospective, real-time, and prospective monitoring of AMR and investigations of outbreaks. WGS-based surveillance has improved the accuracy and effectiveness of disease and AMR surveillance by identifying hidden transmissions and sources missed by conventional methods and by rapidly investigating and deploying infection control interventions. However, WGS analysis involves a complex combination of workflows of next-generation sequencing and bioinformatics data analysis, making it difficult to effectively compare surveillance results. It is crucial to understand the limitations of our existing WGS analyses by implementing rigorous validation practices across different WGS analyses, developing practice guidelines, and establishing appropriate quality assurance measures. These efforts will aid in the development of reliable and robust WGS systems, the harmonization and standardization of surveillance programs, and the development of public data sharing and governance frameworks. Despite these challenges, the expansion of WGS-based AMR surveillance is expected to be driven by technological advances, standardization efforts, and the recognition of its advantages among stakeholders. The integration of genomic data with nongenomic information, as well as interdisciplinary collaborations will further enhance knowledge regarding AMR and promote the development of countermeasures.
{"title":"Integrating whole-genome sequencing into antimicrobial resistance surveillance: methodologies, challenges, and perspectives.","authors":"Yasufumi Matsumura,Masaki Yamamoto,Ryota Gomi,Yasuhiro Tsuchido,Koh Shinohara,Taro Noguchi,Miki Nagao","doi":"10.1128/cmr.00140-22","DOIUrl":"https://doi.org/10.1128/cmr.00140-22","url":null,"abstract":"SUMMARYAntimicrobial resistance (AMR) poses a significant threat to global public health. Surveillance is a fundamental method for controlling AMR and guiding clinical decisions, public health interventions, and policymaking. Whole-genome sequencing (WGS) provides a comprehensive and accurate understanding of AMR mechanisms, gene profiling, and transmission dynamics. Public health authorities, academic scholars, hospitals, and laboratories have increasingly employed WGS-based surveillance for retrospective, real-time, and prospective monitoring of AMR and investigations of outbreaks. WGS-based surveillance has improved the accuracy and effectiveness of disease and AMR surveillance by identifying hidden transmissions and sources missed by conventional methods and by rapidly investigating and deploying infection control interventions. However, WGS analysis involves a complex combination of workflows of next-generation sequencing and bioinformatics data analysis, making it difficult to effectively compare surveillance results. It is crucial to understand the limitations of our existing WGS analyses by implementing rigorous validation practices across different WGS analyses, developing practice guidelines, and establishing appropriate quality assurance measures. These efforts will aid in the development of reliable and robust WGS systems, the harmonization and standardization of surveillance programs, and the development of public data sharing and governance frameworks. Despite these challenges, the expansion of WGS-based AMR surveillance is expected to be driven by technological advances, standardization efforts, and the recognition of its advantages among stakeholders. The integration of genomic data with nongenomic information, as well as interdisciplinary collaborations will further enhance knowledge regarding AMR and promote the development of countermeasures.","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":"30 1","pages":"e0014022"},"PeriodicalIF":36.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Grace Butel-SimoesMichael A. MosoPrashanth RamachandranMaryza GrahamDeborah A. WilliamsonChuan Kok Lim1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Doherty Institute for Infection and Immunity534133, Melbourne, Victoria, Australia2Department of Infectious Diseases, University of Melbourne, Peter Doherty Institute for Infection and Immunity2281https://ror.org/01ej9dk98, Melbourne, Victoria, Australia3Victorian Infectious Diseases Service, Royal Melbourne Hospital, Doherty Institute for Infection and Immunity534133, Melbourne, Victoria, Australia4Monash University2541https://ror.org/02bfwt286, Clayton, Victoria, Australia5School of Medicine, University of St Andrews7486https://ror.org/02wn5qz54, Fife, ScotlandAudrey N. SchuetzAaron M. T. BarnesAditya Shah
Clinical Microbiology Reviews, Ahead of Print.
临床微生物学评论,提前印刷。
{"title":"A review of post-exposure strategies for high-consequence viral pathogens in the laboratory","authors":"Grace Butel-SimoesMichael A. MosoPrashanth RamachandranMaryza GrahamDeborah A. WilliamsonChuan Kok Lim1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Doherty Institute for Infection and Immunity534133, Melbourne, Victoria, Australia2Department of Infectious Diseases, University of Melbourne, Peter Doherty Institute for Infection and Immunity2281https://ror.org/01ej9dk98, Melbourne, Victoria, Australia3Victorian Infectious Diseases Service, Royal Melbourne Hospital, Doherty Institute for Infection and Immunity534133, Melbourne, Victoria, Australia4Monash University2541https://ror.org/02bfwt286, Clayton, Victoria, Australia5School of Medicine, University of St Andrews7486https://ror.org/02wn5qz54, Fife, ScotlandAudrey N. SchuetzAaron M. T. BarnesAditya Shah","doi":"10.1128/cmr.00236-24","DOIUrl":"https://doi.org/10.1128/cmr.00236-24","url":null,"abstract":"Clinical Microbiology Reviews, Ahead of Print. <br/>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":"36 1","pages":""},"PeriodicalIF":36.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Corey SmithRajiv Khanna1Queensland Immunology Research Centre and Inflammation and Infection Program, QIMR Berghofer Medical Research Institutehttps://ror.org/004y8wk30, Brisbane, Australia2School of Biological Sciences, University of Queensland1974https://ror.org/00rqy9422, Brisbane, AustraliaGraeme N. Forrest
Clinical Microbiology Reviews, Ahead of Print.
临床微生物学评论,提前印刷。
{"title":"Adoptive T-cell therapy for virus-associated diseases","authors":"Corey SmithRajiv Khanna1Queensland Immunology Research Centre and Inflammation and Infection Program, QIMR Berghofer Medical Research Institutehttps://ror.org/004y8wk30, Brisbane, Australia2School of Biological Sciences, University of Queensland1974https://ror.org/00rqy9422, Brisbane, AustraliaGraeme N. Forrest","doi":"10.1128/cmr.00198-24","DOIUrl":"https://doi.org/10.1128/cmr.00198-24","url":null,"abstract":"Clinical Microbiology Reviews, Ahead of Print. <br/>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":"21 1","pages":""},"PeriodicalIF":36.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SUMMARYAcinetobacter baumannii has emerged as a formidable global health concern and is a major contributor to infection-related mortality in critically ill patients worldwide. This versatile Gram-negative bacterium is notorious for its highly plastic genome, which enables the rapid emergence and dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, severely limiting the available treatment options. The genetic flexibility of A. baumannii underpins its arsenal of molecular mechanisms, enabling it to resist a range of antibiotics, from traditional agents to the latest therapeutic advancements available. With the progress made in treatments against Acinetobacter infections and various drugs undergoing clinical trials, the effectiveness of these treatments is often outpaced by the pathogen's swift evolution of resistance, resulting in alarmingly high rates of treatment failure. In this systematic review of literature spanning 2004-2024, we highlight the high mortality rates associated with infections caused by XDR strains and carbapenem-resistant A. baumannii (CRAB). This review provides a comprehensive examination of the resistance mechanisms deployed by A. baumannii, encompassing both conventional antibiotics and novel agents used in global healthcare settings. In addition, we discuss emerging druggable targets and the inherent challenges in their development, offering strategic insights into next-generation therapeutic programs. A deep profound understanding of the pathogen's molecular defenses is essential to guide the design of innovative therapies aimed at mitigating the escalating threat posed by A. baumannii.
{"title":"Drug-resistant Acinetobacter baumannii: mortality, emerging treatments, and future pharmacological targets for a WHO priority pathogen.","authors":"Vineet Dubey,Nada Reza,William Hope","doi":"10.1128/cmr.00279-24","DOIUrl":"https://doi.org/10.1128/cmr.00279-24","url":null,"abstract":"SUMMARYAcinetobacter baumannii has emerged as a formidable global health concern and is a major contributor to infection-related mortality in critically ill patients worldwide. This versatile Gram-negative bacterium is notorious for its highly plastic genome, which enables the rapid emergence and dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, severely limiting the available treatment options. The genetic flexibility of A. baumannii underpins its arsenal of molecular mechanisms, enabling it to resist a range of antibiotics, from traditional agents to the latest therapeutic advancements available. With the progress made in treatments against Acinetobacter infections and various drugs undergoing clinical trials, the effectiveness of these treatments is often outpaced by the pathogen's swift evolution of resistance, resulting in alarmingly high rates of treatment failure. In this systematic review of literature spanning 2004-2024, we highlight the high mortality rates associated with infections caused by XDR strains and carbapenem-resistant A. baumannii (CRAB). This review provides a comprehensive examination of the resistance mechanisms deployed by A. baumannii, encompassing both conventional antibiotics and novel agents used in global healthcare settings. In addition, we discuss emerging druggable targets and the inherent challenges in their development, offering strategic insights into next-generation therapeutic programs. A deep profound understanding of the pathogen's molecular defenses is essential to guide the design of innovative therapies aimed at mitigating the escalating threat posed by A. baumannii.","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":"12 1","pages":"e0027924"},"PeriodicalIF":36.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David A Foley,David W Smith,Ian Barr,Hannah C Moore,Mark Nicol,Christopher C Blyth
SUMMARYRespiratory syncytial virus and human metapneumovirus are major causes of respiratory illness globally, particularly affecting children and older adults. Despite their clinical significance, substantial gaps persist in understanding the determinants of their transmission. This review examines the multifaceted factors shaping RSV and hMPV transmission, including viral structure and evolution, host behaviors and viral shedding dynamics, the influence of environmental conditions on viral survival, the roles of population- and community-level transmission networks, and the impact of SARS-CoV-2. Additionally, we explore prevention strategies, including immunizations and non-pharmaceutical interventions, to reduce transmission in high-risk settings.
{"title":"Determinants of respiratory syncytial virus and human metapneumovirus transmission.","authors":"David A Foley,David W Smith,Ian Barr,Hannah C Moore,Mark Nicol,Christopher C Blyth","doi":"10.1128/cmr.00203-24","DOIUrl":"https://doi.org/10.1128/cmr.00203-24","url":null,"abstract":"SUMMARYRespiratory syncytial virus and human metapneumovirus are major causes of respiratory illness globally, particularly affecting children and older adults. Despite their clinical significance, substantial gaps persist in understanding the determinants of their transmission. This review examines the multifaceted factors shaping RSV and hMPV transmission, including viral structure and evolution, host behaviors and viral shedding dynamics, the influence of environmental conditions on viral survival, the roles of population- and community-level transmission networks, and the impact of SARS-CoV-2. Additionally, we explore prevention strategies, including immunizations and non-pharmaceutical interventions, to reduce transmission in high-risk settings.","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":"20 1","pages":"e0020324"},"PeriodicalIF":36.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rémy A Bonnin,Agnès B Jousset,Aymeric Jacquemin,Cécile Emeraud,Delphine Girlich,Thierry Naas,Laurent Dortet
SUMMARYMetallo-beta-lactamases are an ever-growing problem. Since the discovery of the beta-lactamase of Bacillus cereus in the late 1960s, many class B beta-lactamases have been reported, with three main families being NDM-, IMP-, and VIM-like. IMP- and VIM-like carbapenemases have been identified in a wide variety of Gram-negative bacteria. VIM-type carbapenemases are widely distributed, primarily represented by two main clusters, VIM-1 and VIM-2, and have been found in both Enterobacterales and non-fermenters. IMP-type carbapenemases are characterized by a significant genetic diversity and low identity between subgroups. This carbapenemase is more prevalent in Asia but has been identified globally, in both Enterobacterales and non-fermenters, as observed for VIM-type carbapenemases. The genetic diversity of IMP- and some VIM-type carbapenemases limits their detection. This review aims to discuss the genetic diversity, epidemiology, and biochemical characteristics of VIM- and IMP-type carbapenemases. It also evaluates the efficacy of commercially available detection tests and the in vitro activity of recently developed inhibitors.
{"title":"Genetic diversity, biochemical properties, epidemiology, and detection methods of IMP- and VIM-type carbapenemases.","authors":"Rémy A Bonnin,Agnès B Jousset,Aymeric Jacquemin,Cécile Emeraud,Delphine Girlich,Thierry Naas,Laurent Dortet","doi":"10.1128/cmr.00129-23","DOIUrl":"https://doi.org/10.1128/cmr.00129-23","url":null,"abstract":"SUMMARYMetallo-beta-lactamases are an ever-growing problem. Since the discovery of the beta-lactamase of Bacillus cereus in the late 1960s, many class B beta-lactamases have been reported, with three main families being NDM-, IMP-, and VIM-like. IMP- and VIM-like carbapenemases have been identified in a wide variety of Gram-negative bacteria. VIM-type carbapenemases are widely distributed, primarily represented by two main clusters, VIM-1 and VIM-2, and have been found in both Enterobacterales and non-fermenters. IMP-type carbapenemases are characterized by a significant genetic diversity and low identity between subgroups. This carbapenemase is more prevalent in Asia but has been identified globally, in both Enterobacterales and non-fermenters, as observed for VIM-type carbapenemases. The genetic diversity of IMP- and some VIM-type carbapenemases limits their detection. This review aims to discuss the genetic diversity, epidemiology, and biochemical characteristics of VIM- and IMP-type carbapenemases. It also evaluates the efficacy of commercially available detection tests and the in vitro activity of recently developed inhibitors.","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":"27 1","pages":"e0012923"},"PeriodicalIF":36.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}