Pub Date : 2024-09-12Epub Date: 2024-07-29DOI: 10.1128/cmr.00044-24
Maria Siopi, Dimitrios Skliros, Paschalis Paranos, Nikoletta Koumasi, Emmanouil Flemetakis, Spyros Pournaras, Joseph Meletiadis
SUMMARYDespite the early recognition of their therapeutic potential and the current escalation of multidrug-resistant (MDR) pathogens, the adoption of bacteriophages into mainstream clinical practice is hindered by unfamiliarity with their basic pharmacokinetic (PK) and pharmacodynamic (PD) properties, among others. Given the self-replicative nature of bacteriophages in the presence of host bacteria, the adsorption rate, and the clearance by the host's immunity, their PK/PD characteristics cannot be estimated by conventional approaches, and thus, the introduction of new considerations is required. Furthermore, the multitude of different bacteriophage types, preparations, and treatment schedules impedes drawing general conclusions on their in vivo PK/PD features. Additionally, the drawback of acquired bacteriophage resistance of MDR pathogens with clinical and environmental implications should be taken into consideration. Here, we provide an overview of the current state of the field of PK and PD of bacteriophage therapy with a focus on its application against MDR Gram-negative infections, highlighting the potential knowledge gaps and the challenges in translation from the bench to the bedside. After reviewing the in vitro PKs and PDs of bacteriophages against the four major MDR Gram-negative pathogens, Klebsiella pneumoniae, Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Escherichia coli, specific data on in vivo PKs (tissue distribution, route of administration, and basic PK parameters in animals and humans) and PDs (survival and reduction of bacterial burden in relation to the route of administration, timing of therapy, dosing regimens, and resistance) are summarized. Currently available data merit close scrutiny, and optimization of bacteriophage therapy in the context of a better understanding of the underlying PK/PD principles is urgent to improve its therapeutic effect and to minimize the occurrence of bacteriophage resistance.
{"title":"Pharmacokinetics and pharmacodynamics of bacteriophage therapy: a review with a focus on multidrug-resistant Gram-negative bacterial infections.","authors":"Maria Siopi, Dimitrios Skliros, Paschalis Paranos, Nikoletta Koumasi, Emmanouil Flemetakis, Spyros Pournaras, Joseph Meletiadis","doi":"10.1128/cmr.00044-24","DOIUrl":"10.1128/cmr.00044-24","url":null,"abstract":"<p><p>SUMMARYDespite the early recognition of their therapeutic potential and the current escalation of multidrug-resistant (MDR) pathogens, the adoption of bacteriophages into mainstream clinical practice is hindered by unfamiliarity with their basic pharmacokinetic (PK) and pharmacodynamic (PD) properties, among others. Given the self-replicative nature of bacteriophages in the presence of host bacteria, the adsorption rate, and the clearance by the host's immunity, their PK/PD characteristics cannot be estimated by conventional approaches, and thus, the introduction of new considerations is required. Furthermore, the multitude of different bacteriophage types, preparations, and treatment schedules impedes drawing general conclusions on their <i>in vivo</i> PK/PD features. Additionally, the drawback of acquired bacteriophage resistance of MDR pathogens with clinical and environmental implications should be taken into consideration. Here, we provide an overview of the current state of the field of PK and PD of bacteriophage therapy with a focus on its application against MDR Gram-negative infections, highlighting the potential knowledge gaps and the challenges in translation from the bench to the bedside. After reviewing the <i>in vitro</i> PKs and PDs of bacteriophages against the four major MDR Gram-negative pathogens, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i> complex, <i>Pseudomonas aeruginosa</i>, and <i>Escherichia coli</i>, specific data on <i>in vivo</i> PKs (tissue distribution, route of administration, and basic PK parameters in animals and humans) and PDs (survival and reduction of bacterial burden in relation to the route of administration, timing of therapy, dosing regimens, and resistance) are summarized. Currently available data merit close scrutiny, and optimization of bacteriophage therapy in the context of a better understanding of the underlying PK/PD principles is urgent to improve its therapeutic effect and to minimize the occurrence of bacteriophage resistance.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0004424"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787398","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 : 2024-09-12Epub Date: 2024-07-30DOI: 10.1128/cmr.00006-24
Ferrin Antony, Divya Kinha, Anna Nowińska, Barry T Rouse, Amol Suryawanshi
SUMMARYHuman alphaherpesvirus 1 (HSV-1) is a highly successful neurotropic pathogen that primarily infects the epithelial cells lining the orofacial mucosa. After primary lytic replication in the oral, ocular, and nasal mucosal epithelial cells, HSV-1 establishes life-long latency in neurons within the trigeminal ganglion. Patients with compromised immune systems experience frequent reactivation of HSV-1 from latency, leading to virus entry in the sensory neurons, followed by anterograde transport and lytic replication at the innervated mucosal epithelial surface. Although recurrent infection of the corneal mucosal surface is rare, it can result in a chronic immuno-inflammatory condition called herpetic stromal keratitis (HSK). HSK leads to gradual vision loss and can cause permanent blindness in severe untreated cases. Currently, there is no cure or successful vaccine to prevent latent or recurrent HSV-1 infections, posing a significant clinical challenge to managing HSK and preventing vision loss. The conventional clinical management of HSK primarily relies on anti-virals to suppress HSV-1 replication, anti-inflammatory drugs (such as corticosteroids) to provide symptomatic relief from pain and inflammation, and surgical interventions in more severe cases to replace damaged cornea. However, each clinical treatment strategy has limitations, such as local and systemic drug toxicities and the emergence of anti-viral-resistant HSV-1 strains. In this review, we summarize the factors and immune cells involved in HSK pathogenesis and highlight alternate therapeutic strategies for successful clinical management of HSK. We also discuss the therapeutic potential of immunoregulatory cytokines and immunometabolism modulators as promising HSK therapies against emerging anti-viral-resistant HSV-1 strains.
{"title":"The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis.","authors":"Ferrin Antony, Divya Kinha, Anna Nowińska, Barry T Rouse, Amol Suryawanshi","doi":"10.1128/cmr.00006-24","DOIUrl":"10.1128/cmr.00006-24","url":null,"abstract":"<p><p>SUMMARYHuman alphaherpesvirus 1 (HSV-1) is a highly successful neurotropic pathogen that primarily infects the epithelial cells lining the orofacial mucosa. After primary lytic replication in the oral, ocular, and nasal mucosal epithelial cells, HSV-1 establishes life-long latency in neurons within the trigeminal ganglion. Patients with compromised immune systems experience frequent reactivation of HSV-1 from latency, leading to virus entry in the sensory neurons, followed by anterograde transport and lytic replication at the innervated mucosal epithelial surface. Although recurrent infection of the corneal mucosal surface is rare, it can result in a chronic immuno-inflammatory condition called herpetic stromal keratitis (HSK). HSK leads to gradual vision loss and can cause permanent blindness in severe untreated cases. Currently, there is no cure or successful vaccine to prevent latent or recurrent HSV-1 infections, posing a significant clinical challenge to managing HSK and preventing vision loss. The conventional clinical management of HSK primarily relies on anti-virals to suppress HSV-1 replication, anti-inflammatory drugs (such as corticosteroids) to provide symptomatic relief from pain and inflammation, and surgical interventions in more severe cases to replace damaged cornea. However, each clinical treatment strategy has limitations, such as local and systemic drug toxicities and the emergence of anti-viral-resistant HSV-1 strains. In this review, we summarize the factors and immune cells involved in HSK pathogenesis and highlight alternate therapeutic strategies for successful clinical management of HSK. We also discuss the therapeutic potential of immunoregulatory cytokines and immunometabolism modulators as promising HSK therapies against emerging anti-viral-resistant HSV-1 strains.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0000624"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792086","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 : 2024-09-12Epub Date: 2024-06-10DOI: 10.1128/cmr.00175-23
Ouli Xie, Mark R Davies, Steven Y C Tong
SUMMARYStreptococcus dysgalactiae subsp. equisimilis (SDSE) is an increasingly recognized cause of disease in humans. Disease manifestations range from non-invasive superficial skin and soft tissue infections to life-threatening streptococcal toxic shock syndrome and necrotizing fasciitis. Invasive disease is usually associated with co-morbidities, immunosuppression, and advancing age. The crude incidence of invasive disease approaches that of the closely related pathogen, Streptococcus pyogenes. Genomic epidemiology using whole-genome sequencing has revealed important insights into global SDSE population dynamics including emerging lineages and spread of anti-microbial resistance. It has also complemented observations of overlapping pathobiology between SDSE and S. pyogenes, including shared virulence factors and mobile gene content, potentially underlying shared pathogen phenotypes. This review provides an overview of the clinical and genomic epidemiology, disease manifestations, treatment, and virulence determinants of human infections with SDSE with a particular focus on its overlap with S. pyogenes. In doing so, we highlight the importance of understanding the overlap of SDSE and S. pyogenes to inform surveillance and disease control strategies.
{"title":"<i>Streptococcus dysgalactiae</i> subsp. <i>equisimilis</i> infection and its intersection with <i>Streptococcus pyogenes</i>.","authors":"Ouli Xie, Mark R Davies, Steven Y C Tong","doi":"10.1128/cmr.00175-23","DOIUrl":"10.1128/cmr.00175-23","url":null,"abstract":"<p><p>SUMMARY<i>Streptococcus dysgalactiae</i> subsp. <i>equisimilis</i> (SDSE) is an increasingly recognized cause of disease in humans. Disease manifestations range from non-invasive superficial skin and soft tissue infections to life-threatening streptococcal toxic shock syndrome and necrotizing fasciitis. Invasive disease is usually associated with co-morbidities, immunosuppression, and advancing age. The crude incidence of invasive disease approaches that of the closely related pathogen, <i>Streptococcus pyogenes</i>. Genomic epidemiology using whole-genome sequencing has revealed important insights into global SDSE population dynamics including emerging lineages and spread of anti-microbial resistance. It has also complemented observations of overlapping pathobiology between SDSE and <i>S. pyogenes</i>, including shared virulence factors and mobile gene content, potentially underlying shared pathogen phenotypes. This review provides an overview of the clinical and genomic epidemiology, disease manifestations, treatment, and virulence determinants of human infections with SDSE with a particular focus on its overlap with <i>S. pyogenes</i>. In doing so, we highlight the importance of understanding the overlap of SDSE and <i>S. pyogenes</i> to inform surveillance and disease control strategies.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0017523"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295698","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 : 2024-09-12Epub Date: 2024-06-20DOI: 10.1128/cmr.00022-23
Kathryn A Lurain, Ramya Ramaswami, Laurie T Krug, Denise Whitby, Joseph M Ziegelbauer, Hao-Wei Wang, Robert Yarchoan
SUMMARYWithin weeks of the first report of acquired immunodeficiency syndrome (AIDS) in 1981, it was observed that these patients often had Kaposi sarcoma (KS), a hitherto rarely seen skin tumor in the USA. It soon became apparent that AIDS was also associated with an increased incidence of high-grade lymphomas caused by Epstein-Barr virus (EBV). The association of AIDS with KS remained a mystery for more than a decade until Kaposi sarcoma-associated herpesvirus (KSHV) was discovered and found to be the cause of KS. KSHV was subsequently found to cause several other diseases associated with AIDS and human immunodeficiency virus (HIV) infection. People living with HIV/AIDS continue to have an increased incidence of certain cancers, and many of these cancers are caused by EBV and/or KSHV. In this review, we discuss the epidemiology, virology, pathogenesis, clinical manifestations, and treatment of cancers caused by EBV and KSHV in persons living with HIV.
{"title":"HIV-associated cancers and lymphoproliferative disorders caused by Kaposi sarcoma herpesvirus and Epstein-Barr virus.","authors":"Kathryn A Lurain, Ramya Ramaswami, Laurie T Krug, Denise Whitby, Joseph M Ziegelbauer, Hao-Wei Wang, Robert Yarchoan","doi":"10.1128/cmr.00022-23","DOIUrl":"10.1128/cmr.00022-23","url":null,"abstract":"<p><p>SUMMARYWithin weeks of the first report of acquired immunodeficiency syndrome (AIDS) in 1981, it was observed that these patients often had Kaposi sarcoma (KS), a hitherto rarely seen skin tumor in the USA. It soon became apparent that AIDS was also associated with an increased incidence of high-grade lymphomas caused by Epstein-Barr virus (EBV). The association of AIDS with KS remained a mystery for more than a decade until Kaposi sarcoma-associated herpesvirus (KSHV) was discovered and found to be the cause of KS. KSHV was subsequently found to cause several other diseases associated with AIDS and human immunodeficiency virus (HIV) infection. People living with HIV/AIDS continue to have an increased incidence of certain cancers, and many of these cancers are caused by EBV and/or KSHV. In this review, we discuss the epidemiology, virology, pathogenesis, clinical manifestations, and treatment of cancers caused by EBV and KSHV in persons living with HIV.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0002223"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426485","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 : 2024-09-12Epub Date: 2024-08-13DOI: 10.1128/cmr.00163-22
Sofia Etlin, Julianna Rose, Luca Bielski, Claire Walter, Ashley S Kleinman, Christopher E Mason
SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.
摘要人体微生物群包括居住在人体各部位(如皮肤、鼻腔和胃肠道)内、上和周围的各种微生物群落。尽管研究仍在继续,但微生物群通过产生和改变代谢物和小分子对人体产生重大影响的观点已得到公认。微生物群组成的紊乱--菌群失调--也与各种不良健康后果有关。随着人类开始执行更长时间的太空任务,了解太空旅行的条件如何影响微生物群,进而影响宇航员的健康非常重要。本文将首先描述人类肠道微生物群的主要分类群及其相关代谢物的特征,然后讨论潜在的菌群失调和对健康的负面影响。文章还将详细介绍宇航员在太空飞行期间观察到的微生物变化,重点是肠道微生物群的组成以及致病菌的毒力和存活率。然后将分析如何通过饮食、运动和抗生素保护宇航员的健康免受不利微生物变化的影响,最后讨论航天器微生物群和太空微生物培养方法。这篇综述的影响至关重要,尤其是美国国家航空航天局正在实施的 "从月球到火星架构"(Moon to Mars Architecture),其中将包括数周或数月的太空生活和新的栖息地。
{"title":"The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies.","authors":"Sofia Etlin, Julianna Rose, Luca Bielski, Claire Walter, Ashley S Kleinman, Christopher E Mason","doi":"10.1128/cmr.00163-22","DOIUrl":"10.1128/cmr.00163-22","url":null,"abstract":"<p><p>SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0016322"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970798","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 : 2024-09-12Epub Date: 2024-07-17DOI: 10.1128/cmr.00041-24
Shamim Ahmed, Alon Herschhorn
SUMMARYThe success of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA vaccines to lessen/prevent severe COVID-19 opened new opportunities to develop RNA vaccines to fight other infectious agents. HIV-1 is a lentivirus that integrates into the host cell genome and persists for the lifetime of infected cells. Multiple mechanisms of immune evasion have posed significant obstacles to the development of an effective HIV-1 vaccine over the last four decades since the identification of HIV-1. Recently, attempts to address some of these challenges have led to multiple studies that manufactured, optimized, and tested, in different animal models, mRNA-based HIV-1 vaccines. Several clinical trials have also been initiated or are planned to start soon. Here, we review the current strategies applied to HIV-1 mRNA vaccines, discuss different targeting approaches, summarize the latest findings, and offer insights into the challenges and future of HIV-1 mRNA vaccines.
{"title":"mRNA-based HIV-1 vaccines.","authors":"Shamim Ahmed, Alon Herschhorn","doi":"10.1128/cmr.00041-24","DOIUrl":"10.1128/cmr.00041-24","url":null,"abstract":"<p><p>SUMMARYThe success of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA vaccines to lessen/prevent severe COVID-19 opened new opportunities to develop RNA vaccines to fight other infectious agents. HIV-1 is a lentivirus that integrates into the host cell genome and persists for the lifetime of infected cells. Multiple mechanisms of immune evasion have posed significant obstacles to the development of an effective HIV-1 vaccine over the last four decades since the identification of HIV-1. Recently, attempts to address some of these challenges have led to multiple studies that manufactured, optimized, and tested, in different animal models, mRNA-based HIV-1 vaccines. Several clinical trials have also been initiated or are planned to start soon. Here, we review the current strategies applied to HIV-1 mRNA vaccines, discuss different targeting approaches, summarize the latest findings, and offer insights into the challenges and future of HIV-1 mRNA vaccines.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0004124"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626134","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 : 2024-09-12Epub Date: 2024-06-20DOI: 10.1128/cmr.00118-23
Deborah M Crepin, Marie Chavignon, Paul O Verhoeven, Frédéric Laurent, Jérôme Josse, Marine Butin
SUMMARYStaphylococcus capitis is divided into two subspecies, S. capitis subsp. ureolyticus (renamed urealyticus in 1992; ATCC 49326) and S. capitis subsp. capitis (ATCC 27840), and fits with the archetype of clinically relevant coagulase-negative staphylococci (CoNS). S. capitis is a commensal bacterium of the skin in humans, which must be considered an opportunistic pathogen of interest particularly as soon as it is identified in a clinically relevant specimen from an immunocompromised patient. Several studies have highlighted the potential determinants underlying S. capitis pathogenicity, resistance profiles, and virulence factors. In addition, mobile genetic element acquisitions and mutations contribute to S. capitis genome adaptation to its environment. Over the past decades, antibiotic resistance has been identified for S. capitis in almost all the families of the currently available antibiotics and is related to the emergence of multidrug-resistant clones of high clinical significance. The present review summarizes the current knowledge concerning the taxonomic position of S. capitis among staphylococci, the involvement of this species in human colonization and diseases, the virulence factors supporting its pathogenicity, and the phenotypic and genomic antimicrobial resistance profiles of this species.
{"title":"<i>Staphylococcus capitis</i>: insights into epidemiology, virulence, and antimicrobial resistance of a clinically relevant bacterial species.","authors":"Deborah M Crepin, Marie Chavignon, Paul O Verhoeven, Frédéric Laurent, Jérôme Josse, Marine Butin","doi":"10.1128/cmr.00118-23","DOIUrl":"10.1128/cmr.00118-23","url":null,"abstract":"<p><p>SUMMARY<i>Staphylococcus capitis</i> is divided into two subspecies, <i>S. capitis</i> subsp. <i>ureolyticus</i> (renamed <i>urealyticus</i> in 1992; ATCC 49326) and <i>S. capitis</i> subsp. <i>capitis</i> (ATCC 27840), and fits with the archetype of clinically relevant coagulase-negative staphylococci (CoNS). <i>S. capitis</i> is a commensal bacterium of the skin in humans, which must be considered an opportunistic pathogen of interest particularly as soon as it is identified in a clinically relevant specimen from an immunocompromised patient. Several studies have highlighted the potential determinants underlying <i>S. capitis</i> pathogenicity, resistance profiles, and virulence factors. In addition, mobile genetic element acquisitions and mutations contribute to <i>S. capitis</i> genome adaptation to its environment. Over the past decades, antibiotic resistance has been identified for <i>S. capitis</i> in almost all the families of the currently available antibiotics and is related to the emergence of multidrug-resistant clones of high clinical significance. The present review summarizes the current knowledge concerning the taxonomic position of <i>S. capitis</i> among staphylococci, the involvement of this species in human colonization and diseases, the virulence factors supporting its pathogenicity, and the phenotypic and genomic antimicrobial resistance profiles of this species.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0011823"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426484","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 : 2024-09-12Epub Date: 2024-08-09DOI: 10.1128/cmr.00160-22
Léo Sauvat, Paul O Verhoeven, Julie Gagnaire, Philippe Berthelot, Stéphane Paul, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon
SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridioides difficile, are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens. It is undeniable that complementary to infection prevention and control measures, prophylactic approaches by active or passive immunization are needed. Specific groups at-risk (elderly people, chronic condition as immunocompromised) and also healthcare workers are key targets. Medical procedures and specific interventions are known to be at risk of HAIs, in addition to hospital environmental exposure. Vaccines or monoclonal antibodies can be seen as attractive preventive approaches for HAIs. In this review, we present an overview of the vaccines and monoclonal antibodies in clinical development for prevention of the major bacterial HAIs pathogens. Based on the current state of knowledge, we look at the challenges and future perspectives to improve prevention by these means.
{"title":"Vaccines and monoclonal antibodies to prevent healthcare-associated bacterial infections.","authors":"Léo Sauvat, Paul O Verhoeven, Julie Gagnaire, Philippe Berthelot, Stéphane Paul, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon","doi":"10.1128/cmr.00160-22","DOIUrl":"10.1128/cmr.00160-22","url":null,"abstract":"<p><p>SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens (<i><u>E</u>nterococcus faecium, <u>S</u>taphylococcus aureus, <u>K</u>lebsiella pneumoniae, <u>A</u>cinetobacter baumannii, <u>P</u>seudomonas aeruginosa,</i> and <i><u>E</u>nterobacter species</i>) and <i>Clostridioides difficile</i>, are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens. It is undeniable that complementary to infection prevention and control measures, prophylactic approaches by active or passive immunization are needed. Specific groups at-risk (elderly people, chronic condition as immunocompromised) and also healthcare workers are key targets. Medical procedures and specific interventions are known to be at risk of HAIs, in addition to hospital environmental exposure. Vaccines or monoclonal antibodies can be seen as attractive preventive approaches for HAIs. In this review, we present an overview of the vaccines and monoclonal antibodies in clinical development for prevention of the major bacterial HAIs pathogens. Based on the current state of knowledge, we look at the challenges and future perspectives to improve prevention by these means.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0016022"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906092","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 : 2024-09-12Epub Date: 2024-08-19DOI: 10.1128/cmr.00215-21
Lisa Saiman, Valerie Waters, John J LiPuma, Lucas R Hoffman, Kevin Alby, Sean X Zhang, Yvonne C Yau, Damian G Downey, Isabelle Sermet-Gaudelus, Jean-Philippe Bouchara, Timothy J Kidd, Scott C Bell, A Whitney Brown
SUMMARYThis guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Burkholderia cepacia complex; other less common non-lactose fermenting Gram-negative bacilli, e.g., Stenotrophomonas maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of S. aureus, although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g., S. maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices.
{"title":"Practical Guidance for Clinical Microbiology Laboratories: Updated guidance for processing respiratory tract samples from people with cystic fibrosis.","authors":"Lisa Saiman, Valerie Waters, John J LiPuma, Lucas R Hoffman, Kevin Alby, Sean X Zhang, Yvonne C Yau, Damian G Downey, Isabelle Sermet-Gaudelus, Jean-Philippe Bouchara, Timothy J Kidd, Scott C Bell, A Whitney Brown","doi":"10.1128/cmr.00215-21","DOIUrl":"10.1128/cmr.00215-21","url":null,"abstract":"<p><p>SUMMARYThis guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, <i>Haemophilus influenzae</i>, and <i>Burkholderia cepacia</i> complex; other less common non-lactose fermenting Gram-negative bacilli, e.g., <i>Stenotrophomonas maltophilia</i>, <i>Inquilinus</i>, <i>Achromobacter</i>, <i>Ralstonia</i>, and <i>Pandoraea</i> species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of <i>S. aureus</i>, although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g., <i>S. maltophilia</i>, <i>Inquilinus</i>, <i>Achromobacter</i>, <i>Ralstonia</i>, and <i>Pandoraea</i> species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0021521"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999506","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}
Jaclyn A Cusumano, Andreas P Kalogeropoulos, Mathieu Le Provost, Nicolas R Gallo, Steven M Levine, Thomas Inzana, Aikaterini Papamanoli
SUMMARYInfective endocarditis (IE) is a life-threatening infection that has nearly doubled in prevalence over the last two decades due to the increase in implantable cardiac devices. Transcatheter aortic valve implantation (TAVI) is currently one of the most common cardiac procedures. TAVI usage continues to exponentially rise, inevitability increasing TAVI-IE. Patients with TAVI are frequently nonsurgical candidates, and TAVI-IE 1-year mortality rates can be as high as 74% without valve or bacterial biofilm removal. Enterococcus faecalis, a historically less common IE pathogen, is the primary cause of TAVI-IE. Treatment options are limited due to enterococcal intrinsic resistance and biofilm formation. Novel approaches are warranted to tackle current therapeutic gaps. We describe the existing challenges in treating TAVI-IE and how available treatment discovery approaches can be combined with an in silico "Living Heart" model to create solutions for the future.
{"title":"The emerging challenge of <i>Enterococcus faecalis</i> endocarditis after transcatheter aortic valve implantation: time for innovative treatment approaches.","authors":"Jaclyn A Cusumano, Andreas P Kalogeropoulos, Mathieu Le Provost, Nicolas R Gallo, Steven M Levine, Thomas Inzana, Aikaterini Papamanoli","doi":"10.1128/cmr.00168-23","DOIUrl":"10.1128/cmr.00168-23","url":null,"abstract":"<p><p>SUMMARYInfective endocarditis (IE) is a life-threatening infection that has nearly doubled in prevalence over the last two decades due to the increase in implantable cardiac devices. Transcatheter aortic valve implantation (TAVI) is currently one of the most common cardiac procedures. TAVI usage continues to exponentially rise, inevitability increasing TAVI-IE. Patients with TAVI are frequently nonsurgical candidates, and TAVI-IE 1-year mortality rates can be as high as 74% without valve or bacterial biofilm removal. <i>Enterococcus faecalis,</i> a historically less common IE pathogen, is the primary cause of TAVI-IE. Treatment options are limited due to enterococcal intrinsic resistance and biofilm formation. Novel approaches are warranted to tackle current therapeutic gaps. We describe the existing challenges in treating TAVI-IE and how available treatment discovery approaches can be combined with an <i>in silico</i> \"Living Heart\" model to create solutions for the future.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0016823"},"PeriodicalIF":19.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132040","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}