Pub Date : 2024-10-01Epub Date: 2024-07-04DOI: 10.1097/QCO.0000000000001035
Eva H Clark, Caryn Bern
Purpose of review: To highlight recent advances in our understanding of Trypanosoma cruzi infection in immunocompromised individuals, a condition that is increasingly recognized as populations shift and use of immunosuppressive medications becomes more commonplace.
Recent findings: Chagas disease screening programs should include people at risk for both Chagas disease and immunocompromise, e.g. people who have resided for ≥6 months in endemic Latin America who have an immunocompromising condition such as HIV or who are planned to start an immunosuppressive medication regimen. The goal of identifying such individuals is to allow management strategies that will reduce their risk of T. cruzi reactivation disease. For people with HIV- T. cruzi coinfection, strict adherence to antiretroviral therapy is important and antitrypanosomal treatment is urgent in the setting of symptomatic reactivation. People at risk for T. cruzi reactivation due to immunosuppression caused by advanced hematologic conditions or postsolid organ transplantation should be monitored via T. cruzi qPCR and treated with preemptive antitrypanosomal therapy if rising parasite load on serial specimens indicates reactivation. Reduction of the immunosuppressive regimen, if possible, is important.
Summary: Chronic Chagas disease can lead to severe disease in immunocompromised individuals, particularly those with advanced HIV (CD4 + < 200 cells/mm 3 ) or peri-transplantation.
综述的目的:随着人口迁移和免疫抑制药物的使用越来越普遍,人们越来越认识到这种疾病:恰加斯病筛查计划应包括同时患有恰加斯病和免疫力低下的高危人群,例如,在拉丁美洲恰加斯病流行地区居住≥6 个月,患有艾滋病毒等免疫力低下疾病,或计划开始接受免疫抑制药物治疗的人群。识别这些人的目的是制定管理策略,降低他们罹患克鲁兹原虫再活化疾病的风险。对于同时感染艾滋病毒和克鲁兹绦虫的人来说,严格遵守抗逆转录病毒疗法非常重要,在出现症状性再活化的情况下,抗盘虫治疗是当务之急。对于因晚期血液病或实体器官移植后引起的免疫抑制而面临 T. cruzi 再激活风险的人群,应通过 T. cruzi qPCR 进行监测,如果连续标本中寄生虫量上升表明有再激活迹象,则应进行先期抗盘虫治疗。小结:慢性恰加斯病可导致免疫功能低下者,尤其是晚期艾滋病毒感染者(CD4+ < 200 cells/mm3)或移植前后的患者出现严重疾病。
{"title":"Chagas disease in the immunocompromised host.","authors":"Eva H Clark, Caryn Bern","doi":"10.1097/QCO.0000000000001035","DOIUrl":"10.1097/QCO.0000000000001035","url":null,"abstract":"<p><strong>Purpose of review: </strong>To highlight recent advances in our understanding of Trypanosoma cruzi infection in immunocompromised individuals, a condition that is increasingly recognized as populations shift and use of immunosuppressive medications becomes more commonplace.</p><p><strong>Recent findings: </strong>Chagas disease screening programs should include people at risk for both Chagas disease and immunocompromise, e.g. people who have resided for ≥6 months in endemic Latin America who have an immunocompromising condition such as HIV or who are planned to start an immunosuppressive medication regimen. The goal of identifying such individuals is to allow management strategies that will reduce their risk of T. cruzi reactivation disease. For people with HIV- T. cruzi coinfection, strict adherence to antiretroviral therapy is important and antitrypanosomal treatment is urgent in the setting of symptomatic reactivation. People at risk for T. cruzi reactivation due to immunosuppression caused by advanced hematologic conditions or postsolid organ transplantation should be monitored via T. cruzi qPCR and treated with preemptive antitrypanosomal therapy if rising parasite load on serial specimens indicates reactivation. Reduction of the immunosuppressive regimen, if possible, is important.</p><p><strong>Summary: </strong>Chronic Chagas disease can lead to severe disease in immunocompromised individuals, particularly those with advanced HIV (CD4 + < 200 cells/mm 3 ) or peri-transplantation.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"333-341"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1097/qco.0000000000001060
P Lewis White
PURPOSE OF REVIEWThis review describes the current status of diagnosing invasive mould disease and Pneumocystis pneumonia using nonconventional diagnostics methods.RECENT FINDINGSThere has been significant development in the range of nonculture mycological tests. Lateral flow tests (LFTs) for diagnosing aspergillosis complement galactomannan ELISA testing, and LFTs for other fungal diseases are in development. Rapid and low through-put B-D-Glucan assays increase access to testing and there has been significant progress in the standardization/development of molecular tests. Despite this, no single perfect test exists and combining tests (e.g., antigen and molecular testing) is likely required for the optimal diagnosis of most fungal diseases.SUMMARYBased on established clinical performance few mycological tests can be used alone for optimal diagnosis of fungal disease (FD) and combining tests, including classical approaches is the preferred route for confirming and excluding disease. Next-generation sequencing will likely play an increasing role in how we diagnose disease, but optimization, standardization and validation of the entire molecular process is needed and we must consider how host biomarkers can stratify risk. Given the burden of FD in low- and medium-income countries, improved access to novel but more so existing diagnostic testing is critical along with simplification of testing processes.
{"title":"Progress on nonculture based diagnostic tests for invasive mould infection.","authors":"P Lewis White","doi":"10.1097/qco.0000000000001060","DOIUrl":"https://doi.org/10.1097/qco.0000000000001060","url":null,"abstract":"PURPOSE OF REVIEWThis review describes the current status of diagnosing invasive mould disease and Pneumocystis pneumonia using nonconventional diagnostics methods.RECENT FINDINGSThere has been significant development in the range of nonculture mycological tests. Lateral flow tests (LFTs) for diagnosing aspergillosis complement galactomannan ELISA testing, and LFTs for other fungal diseases are in development. Rapid and low through-put B-D-Glucan assays increase access to testing and there has been significant progress in the standardization/development of molecular tests. Despite this, no single perfect test exists and combining tests (e.g., antigen and molecular testing) is likely required for the optimal diagnosis of most fungal diseases.SUMMARYBased on established clinical performance few mycological tests can be used alone for optimal diagnosis of fungal disease (FD) and combining tests, including classical approaches is the preferred route for confirming and excluding disease. Next-generation sequencing will likely play an increasing role in how we diagnose disease, but optimization, standardization and validation of the entire molecular process is needed and we must consider how host biomarkers can stratify risk. Given the burden of FD in low- and medium-income countries, improved access to novel but more so existing diagnostic testing is critical along with simplification of testing processes.","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"20 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1097/qco.0000000000001063
Chin Fen Neoh,Monica A Slavin
PURPOSE OF REVIEWGiven the high mortality and morbidity associated with invasive fungal diseases (IFDs), the use of combination antifungal therapies is often considered despite the dearth of data. This review aims to summarize the current state of literature of combination antifungal therapies, discussing the potential roles of newer antifungal combinations and key considerations for their clinical use.RECENT FINDINGSIn infections other than cryptococcal meningitis or in the setting of empirical treatment for suspected azole-resistant Aspergillus infections, the utility of the combination antifungal approaches remains controversial given the paucity of well designed randomized controlled trials. Data on potential combined antifungal treatments have been primarily limited to in-vitro studies, animal models, case reports and/or observational studies. With availability of novel antifungal agents (e.g. ibrexafungerp, fosmanogepix), combination therapy to treat mould infections should be re-visited. A phase 2 clinical trial of ibrexafungerp combined with voriconazole to treat invasive pulmonary aspergillosis is on-going.SUMMARYThere is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting.
{"title":"Reassessment of the role of combination antifungal therapy in the current era.","authors":"Chin Fen Neoh,Monica A Slavin","doi":"10.1097/qco.0000000000001063","DOIUrl":"https://doi.org/10.1097/qco.0000000000001063","url":null,"abstract":"PURPOSE OF REVIEWGiven the high mortality and morbidity associated with invasive fungal diseases (IFDs), the use of combination antifungal therapies is often considered despite the dearth of data. This review aims to summarize the current state of literature of combination antifungal therapies, discussing the potential roles of newer antifungal combinations and key considerations for their clinical use.RECENT FINDINGSIn infections other than cryptococcal meningitis or in the setting of empirical treatment for suspected azole-resistant Aspergillus infections, the utility of the combination antifungal approaches remains controversial given the paucity of well designed randomized controlled trials. Data on potential combined antifungal treatments have been primarily limited to in-vitro studies, animal models, case reports and/or observational studies. With availability of novel antifungal agents (e.g. ibrexafungerp, fosmanogepix), combination therapy to treat mould infections should be re-visited. A phase 2 clinical trial of ibrexafungerp combined with voriconazole to treat invasive pulmonary aspergillosis is on-going.SUMMARYThere is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting.","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"5 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1097/qco.0000000000001064
Kimberly Davis,Yara-Natalie Abo,Andrew C Steer,Joshua Osowicki
PURPOSE OF REVIEWWe describe the epidemiology of the recent global surge in invasive group A streptococcal (GAS) disease and consider its proximate and distal causes. We highlight important knowledge gaps regarding clinical management and discuss potential strategies for prevention.RECENT FINDINGSRates of invasive GAS (iGAS) disease were increasing globally prior to the COVID-19 pandemic. Since mid-2022, following the worst years of the pandemic in 2020 and 2021, many countries with systems to monitor GAS syndromes have reported surges in cases of iGAS concurrent with increased scarlet fever, pharyngitis, and viral co-infections. The emergence of the hypervirulent M1UK strain as a cause of iGAS, particularly in high income countries, is concerning. New data are emerging on the transmission dynamics of GAS. GAS remains universally susceptible to penicillin but there are increasing reports of macrolide and lincosamide resistance, particularly in invasive isolates, with uncertain clinical consequences. Intravenous immunoglobulin is used widely for streptococcal toxic shock syndrome and necrotizing soft tissue infections, although there is limited clinical evidence, and none from a completed randomized controlled trial. Intensive and expensive efforts at population-level control of GAS infections and postinfectious autoimmune complications have been only partially successful. The great hope for control of GAS diseases remains vaccine development. However, all modern vaccine candidates remain in the early development stage.SUMMARYIn many countries, iGAS rates surged from mid-2022 in the aftermath of pandemic control measures and physical distancing. The emergence of a dominant hypervirulent strain is an important but incomplete explanation for this phenomenon. Clinical management of iGAS remains highly empirical and new data has not emerged. A vaccine remains the most likely means of achieving a sustainable reduction in the burden of iGAS.
综述目的我们描述了近期全球侵袭性 A 组链球菌(GAS)疾病激增的流行病学情况,并考虑了其近端和远端原因。我们强调了临床管理方面的重要知识缺口,并讨论了潜在的预防策略。自 2022 年年中以来,在 2020 年和 2021 年疫情最严重的年份之后,许多有系统监测 GAS 综合征的国家报告 iGAS 病例激增,同时猩红热、咽炎和病毒合并感染也有所增加。高病毒性 M1UK 菌株成为 iGAS 的病因,尤其是在高收入国家,令人担忧。有关 GAS 传播动态的新数据不断涌现。GAS 仍普遍对青霉素敏感,但对大环内酯类和林可霉素类药物耐药的报道越来越多,尤其是在侵袭性分离株中,其临床后果尚不确定。静脉注射免疫球蛋白被广泛用于治疗链球菌中毒性休克综合征和坏死性软组织感染,但临床证据有限,而且没有一项已完成的随机对照试验。为在人群中控制 GAS 感染和感染后自身免疫并发症所做的大量工作耗资巨大,但只取得了部分成功。控制 GAS 疾病的最大希望仍然是开发疫苗。摘要在许多国家,大流行病控制措施和物理隔离之后,iGAS 的发病率从 2022 年年中开始激增。一种优势高病毒株的出现是这一现象的重要原因,但并不能完全解释这一现象。对 iGAS 的临床管理仍然是高度经验性的,尚未出现新的数据。疫苗仍是持续减少 iGAS 负担的最可能手段。
{"title":"Chains of misery: surging invasive group A streptococcal disease.","authors":"Kimberly Davis,Yara-Natalie Abo,Andrew C Steer,Joshua Osowicki","doi":"10.1097/qco.0000000000001064","DOIUrl":"https://doi.org/10.1097/qco.0000000000001064","url":null,"abstract":"PURPOSE OF REVIEWWe describe the epidemiology of the recent global surge in invasive group A streptococcal (GAS) disease and consider its proximate and distal causes. We highlight important knowledge gaps regarding clinical management and discuss potential strategies for prevention.RECENT FINDINGSRates of invasive GAS (iGAS) disease were increasing globally prior to the COVID-19 pandemic. Since mid-2022, following the worst years of the pandemic in 2020 and 2021, many countries with systems to monitor GAS syndromes have reported surges in cases of iGAS concurrent with increased scarlet fever, pharyngitis, and viral co-infections. The emergence of the hypervirulent M1UK strain as a cause of iGAS, particularly in high income countries, is concerning. New data are emerging on the transmission dynamics of GAS. GAS remains universally susceptible to penicillin but there are increasing reports of macrolide and lincosamide resistance, particularly in invasive isolates, with uncertain clinical consequences. Intravenous immunoglobulin is used widely for streptococcal toxic shock syndrome and necrotizing soft tissue infections, although there is limited clinical evidence, and none from a completed randomized controlled trial. Intensive and expensive efforts at population-level control of GAS infections and postinfectious autoimmune complications have been only partially successful. The great hope for control of GAS diseases remains vaccine development. However, all modern vaccine candidates remain in the early development stage.SUMMARYIn many countries, iGAS rates surged from mid-2022 in the aftermath of pandemic control measures and physical distancing. The emergence of a dominant hypervirulent strain is an important but incomplete explanation for this phenomenon. Clinical management of iGAS remains highly empirical and new data has not emerged. A vaccine remains the most likely means of achieving a sustainable reduction in the burden of iGAS.","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"269 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1097/qco.0000000000001061
Paula Beltran-Reyes,Luis Ostrosky-Zeichner,Maria F Gonzalez-Lara
PURPOSE OF REVIEWRecently, fungal meningitis outbreaks have occurred in association with neuraxial and epidural anesthesia in immunocompetent patients. Herein, we describe the course of those outbreaks, their diagnosis, treatment, prognosis, and lessons learned.RECENT FINDINGSTwo outbreaks of Fusarium solani meningitis during 2022-2023 were associated with epidural anesthesia in two distant cities in Mexico (Durango and Matamoros). The initial etiological agent identification was delayed due to insensitivity of cultures. A Fusarium solani qPCR was validated and positive in 38% cerebrospinal fluid (CSF) samples from Durango, while BD-Glucan allowed early diagnosis of the index case in Matamoros. Antifungal treatment with voriconazole and liposomal amphotericin B (L-AmB) was recommended. Overall mortality was 51%. Once the cause was confirmed, some patients received fosmanogepix.SUMMARYFungal meningitis outbreaks due to filamentous fungi are usually associated with direct epidural inoculation. They result in severe presentations and high mortality. Early diagnosis should be suspected, BD-Glucan CSF testing screening is recommended. Aggressive antifungal treatment based on antifungal susceptibility testing should be administered as early as possible. The advent of molecular diagnostic methods and new antifungal drugs may allow for timely diagnosis and treatment, increasing the chances of survival.
{"title":"Update on diagnosis and treatment of fungal meningitis: lessons from recent outbreaks.","authors":"Paula Beltran-Reyes,Luis Ostrosky-Zeichner,Maria F Gonzalez-Lara","doi":"10.1097/qco.0000000000001061","DOIUrl":"https://doi.org/10.1097/qco.0000000000001061","url":null,"abstract":"PURPOSE OF REVIEWRecently, fungal meningitis outbreaks have occurred in association with neuraxial and epidural anesthesia in immunocompetent patients. Herein, we describe the course of those outbreaks, their diagnosis, treatment, prognosis, and lessons learned.RECENT FINDINGSTwo outbreaks of Fusarium solani meningitis during 2022-2023 were associated with epidural anesthesia in two distant cities in Mexico (Durango and Matamoros). The initial etiological agent identification was delayed due to insensitivity of cultures. A Fusarium solani qPCR was validated and positive in 38% cerebrospinal fluid (CSF) samples from Durango, while BD-Glucan allowed early diagnosis of the index case in Matamoros. Antifungal treatment with voriconazole and liposomal amphotericin B (L-AmB) was recommended. Overall mortality was 51%. Once the cause was confirmed, some patients received fosmanogepix.SUMMARYFungal meningitis outbreaks due to filamentous fungi are usually associated with direct epidural inoculation. They result in severe presentations and high mortality. Early diagnosis should be suspected, BD-Glucan CSF testing screening is recommended. Aggressive antifungal treatment based on antifungal susceptibility testing should be administered as early as possible. The advent of molecular diagnostic methods and new antifungal drugs may allow for timely diagnosis and treatment, increasing the chances of survival.","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"9 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PURPOSE OF REVIEWWe review the clinical presentations of invasive fungal infections in a selection of inborn errors of immunity. In addition, we review the particularities of their management, including antifungal therapy, prophylaxis, and immunomodulatory treatments.RECENT FINDINGSPatients with chronic granulomatous disease and with signal transducer and activator of transcription 3 (STAT3) deficiency are particularly prone to aspergillosis. Mold-active antifungal prophylaxis should be prescribed to all patients with chronic granulomatous disease, and in patients with STAT3 deficiency and underlying parenchymal lung disease. Invasive fungal infections are rare in patients with STAT1 gain-of-function mutations, while the clinical phenotype of caspase-associated recruitment domain-containing protein 9 deficiency encompasses a wide range of superficial and invasive fungal infections. Most patients with inborn errors of immunity and invasive fungal infections require prolonged durations of antifungals. Hematopoietic stem cell transplantation should be considered early for patients with chronic granulomatous disease, but results have been more mixed for other inborn errors of immunity with active invasive fungal infections.SUMMARYInborn errors of immunity can confer increased susceptibility to a variety of invasive fungal infections, which can present with specific clinical and radiological features. Management of fungal infections in these patients is often challenging, and relies on a combination of antimicrobial prophylaxis, antifungal treatments, and immunomodulation.
综述目的我们综述了部分先天性免疫错误患者侵袭性真菌感染的临床表现。此外,我们还回顾了其治疗的特殊性,包括抗真菌治疗、预防性治疗和免疫调节治疗。所有慢性肉芽肿疾病患者、STAT3 缺乏症患者以及患有潜在肺实质疾病的患者都应进行霉菌活性抗真菌预防。STAT1 功能增益突变患者很少发生侵袭性真菌感染,而 Caspase-associated recruitment domain-containing protein 9 缺乏症的临床表型则包括各种浅表性和侵袭性真菌感染。大多数先天性免疫错误和侵袭性真菌感染患者需要长期服用抗真菌药物。慢性肉芽肿病患者应及早考虑造血干细胞移植,但其他先天性免疫缺陷并伴有活动性侵袭性真菌感染的患者则结果不一。对这些患者真菌感染的治疗通常具有挑战性,需要结合抗菌药预防、抗真菌治疗和免疫调节。
{"title":"Inborn errors of immunity and invasive fungal infections: presentation and management.","authors":"Olivier Paccoud,Adilia Warris,Anne Puel,Fanny Lanternier","doi":"10.1097/qco.0000000000001062","DOIUrl":"https://doi.org/10.1097/qco.0000000000001062","url":null,"abstract":"PURPOSE OF REVIEWWe review the clinical presentations of invasive fungal infections in a selection of inborn errors of immunity. In addition, we review the particularities of their management, including antifungal therapy, prophylaxis, and immunomodulatory treatments.RECENT FINDINGSPatients with chronic granulomatous disease and with signal transducer and activator of transcription 3 (STAT3) deficiency are particularly prone to aspergillosis. Mold-active antifungal prophylaxis should be prescribed to all patients with chronic granulomatous disease, and in patients with STAT3 deficiency and underlying parenchymal lung disease. Invasive fungal infections are rare in patients with STAT1 gain-of-function mutations, while the clinical phenotype of caspase-associated recruitment domain-containing protein 9 deficiency encompasses a wide range of superficial and invasive fungal infections. Most patients with inborn errors of immunity and invasive fungal infections require prolonged durations of antifungals. Hematopoietic stem cell transplantation should be considered early for patients with chronic granulomatous disease, but results have been more mixed for other inborn errors of immunity with active invasive fungal infections.SUMMARYInborn errors of immunity can confer increased susceptibility to a variety of invasive fungal infections, which can present with specific clinical and radiological features. Management of fungal infections in these patients is often challenging, and relies on a combination of antimicrobial prophylaxis, antifungal treatments, and immunomodulation.","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"58 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-27DOI: 10.1097/qco.0000000000001055
Almudena Burillo,Emilio Bouza
PURPOSE OF REVIEWInfections caused by nonprimarily pathogenic Gram-negative bacilli (GNB) have been increasingly reported from the second half of the 20th century to the present. This phenomenon has expanded during the antibiotic era and in the presence of immunodeficiency.Before the discovery of sulphonamides and penicillin G, infections caused by GNB were rare compared to Gram-positive infections. The advent of anticancer therapy, the expansion of surgical procedures, the use of corticosteroids, and the implantation of prosthetic materials, along with better control of Gram-positive infections, have promoted the current increase in GNB infections.GNB have similar antimicrobial targets to Gram-positive bacteria. However, only antibiotics that can penetrate the double membrane of GNB and remain in them for a sufficient duration have antibacterial activity against them.RECENT FINDINGSSulphonamides and early penicillins had limited activity against GNB. Ampicillin and subsequent beta-lactams expanded their spectrum to treat GNB. Aminoglycosides may re-surge with less toxic drugs, as highly resistant to beta-lactams GNB rise. Polymyxins, tetracyclines, and fluoroquinolones are also used for GNB. Combinations with other agents may be needed in specific cases, such as in the central nervous system and prostate, where beta-lactams may have difficulty reaching the infection site.Alternatives to current treatments must be sought in the discovery of new drug families and therapies such as phage therapy combined with antibiotics.SUMMARYNarrower-spectrum immunosuppressive therapies and antibiotics, antimicrobials that minimally intervene with the human microbiota, and instant diagnostic methods are necessary to imagine a future where currently dominant bacteria in infectious pathology lose their preeminence.
{"title":"The evolution of knowledge for treating Gram-negative bacterial infections.","authors":"Almudena Burillo,Emilio Bouza","doi":"10.1097/qco.0000000000001055","DOIUrl":"https://doi.org/10.1097/qco.0000000000001055","url":null,"abstract":"PURPOSE OF REVIEWInfections caused by nonprimarily pathogenic Gram-negative bacilli (GNB) have been increasingly reported from the second half of the 20th century to the present. This phenomenon has expanded during the antibiotic era and in the presence of immunodeficiency.Before the discovery of sulphonamides and penicillin G, infections caused by GNB were rare compared to Gram-positive infections. The advent of anticancer therapy, the expansion of surgical procedures, the use of corticosteroids, and the implantation of prosthetic materials, along with better control of Gram-positive infections, have promoted the current increase in GNB infections.GNB have similar antimicrobial targets to Gram-positive bacteria. However, only antibiotics that can penetrate the double membrane of GNB and remain in them for a sufficient duration have antibacterial activity against them.RECENT FINDINGSSulphonamides and early penicillins had limited activity against GNB. Ampicillin and subsequent beta-lactams expanded their spectrum to treat GNB. Aminoglycosides may re-surge with less toxic drugs, as highly resistant to beta-lactams GNB rise. Polymyxins, tetracyclines, and fluoroquinolones are also used for GNB. Combinations with other agents may be needed in specific cases, such as in the central nervous system and prostate, where beta-lactams may have difficulty reaching the infection site.Alternatives to current treatments must be sought in the discovery of new drug families and therapies such as phage therapy combined with antibiotics.SUMMARYNarrower-spectrum immunosuppressive therapies and antibiotics, antimicrobials that minimally intervene with the human microbiota, and instant diagnostic methods are necessary to imagine a future where currently dominant bacteria in infectious pathology lose their preeminence.","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PURPOSE OF REVIEWInfections caused by multidrug-resistant Acinetobacter baumannii present a significant global health challenge. Available treatment options are limited and frequently constrained by unfavourable safety and pharmacokinetic profiles. Sulbactam-durlobactam is a novel β-lactamase inhibitors combination specifically developed to target A. baumannii, including carbapenem-resistant strains. The purpose of this review is to assess the current evidence supporting the role of sulbactam-durlobactam in the management of A. baumannii infections.RECENT FINDINGSWe summarize the available evidence regarding the pharmacokinetic and pharmacodynamic profiles of sulbactam-durlobactam from key in-vitro and in-vivo studies. Additionally, efficacy results from the Phase III randomized controlled trial and real-world data on sulbactam-durlobactam's use against severe A. baumannii infections are also discussed.SUMMARYSulbactam-durlobactam is a promising addition to the treatment options for carbapenem-resistant A. baumannii infections. Ongoing research and vigilance are essential to monitor the development of in-vivo resistance, assess effectiveness across diverse patient populations, and explore potential synergistic combinations with other antimicrobials. Careful stewardship and comprehensive clinician education will be crucial to optimizing the clinical use of sulbactam-durlobactam.
耐多药鲍曼不动杆菌引起的感染是全球健康面临的重大挑战。现有的治疗方案十分有限,而且经常受到安全性和药代动力学特征不佳的限制。舒巴坦-杜鲁巴坦是一种新型β-内酰胺酶抑制剂复方制剂,专门针对鲍曼不动杆菌(包括耐碳青霉烯菌株)开发。本综述旨在评估支持舒巴坦-杜鲁巴坦在治疗鲍曼尼氏菌感染中发挥作用的现有证据。我们总结了主要体外和体内研究中有关舒巴坦-杜鲁巴坦药代动力学和药效学特征的现有证据。此外,还讨论了 III 期随机对照试验的疗效结果以及舒巴坦-杜鲁巴坦用于治疗严重鲍曼不动杆菌感染的实际数据。持续的研究和警惕对于监测体内耐药性的发展、评估不同患者群体的疗效以及探索与其他抗菌药物的潜在协同组合至关重要。谨慎管理和全面的临床医生教育对于优化舒巴坦-杜鲁巴坦的临床应用至关重要。
{"title":"The role of sulbactam-durlobactam in treating carbapenem-resistant Acinetobacter infections.","authors":"Matteo Bassetti,Daniele Roberto Giacobbe,Nadia Castaldo,Antonio Vena","doi":"10.1097/qco.0000000000001059","DOIUrl":"https://doi.org/10.1097/qco.0000000000001059","url":null,"abstract":"PURPOSE OF REVIEWInfections caused by multidrug-resistant Acinetobacter baumannii present a significant global health challenge. Available treatment options are limited and frequently constrained by unfavourable safety and pharmacokinetic profiles. Sulbactam-durlobactam is a novel β-lactamase inhibitors combination specifically developed to target A. baumannii, including carbapenem-resistant strains. The purpose of this review is to assess the current evidence supporting the role of sulbactam-durlobactam in the management of A. baumannii infections.RECENT FINDINGSWe summarize the available evidence regarding the pharmacokinetic and pharmacodynamic profiles of sulbactam-durlobactam from key in-vitro and in-vivo studies. Additionally, efficacy results from the Phase III randomized controlled trial and real-world data on sulbactam-durlobactam's use against severe A. baumannii infections are also discussed.SUMMARYSulbactam-durlobactam is a promising addition to the treatment options for carbapenem-resistant A. baumannii infections. Ongoing research and vigilance are essential to monitor the development of in-vivo resistance, assess effectiveness across diverse patient populations, and explore potential synergistic combinations with other antimicrobials. Careful stewardship and comprehensive clinician education will be crucial to optimizing the clinical use of sulbactam-durlobactam.","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-23DOI: 10.1097/QCO.0000000000001024
Matteo Bassetti, Massimo Andreoni, Pierachille Santus, Francesco Scaglione
Purpose of review: To review the rationale for and the potential clinical benefits of an early approach to viral acute respiratory infections with NSAIDs to switch off the inflammatory cascade before the inflammatory process becomes complicated.
Recent findings: It has been shown that in COVID-19 as in other viral respiratory infections proinflammatory cytokines are produced, which are responsible of respiratory and systemic symptoms. There have been concerns that NSAIDs could increase susceptibility to SARS-CoV-2 infection or aggravate COVID-19. However, recent articles reviewing experimental research, observational clinical studies, randomized clinical trials, and meta-analyses conclude that there is no basis to limit the use of NSAIDs, which may instead represent effective self-care measures to control symptoms.
Summary: The inflammatory response plays a pivotal role in the early phase of acute respiratory tract infections (ARTIs); a correct diagnosis of the cause and a prompt therapeutic approach with NSAIDs may have the potential to control the pathophysiological mechanisms that can complicate the condition, while reducing symptoms to the benefit of the patient. A timely treatment with NSAIDs may limit the inappropriate use of other categories of drugs, such as antibiotics, which are useless when viral cause is confirmed and whose inappropriate use is responsible for the development of resistance.
{"title":"NSAIDs for early management of acute respiratory infections.","authors":"Matteo Bassetti, Massimo Andreoni, Pierachille Santus, Francesco Scaglione","doi":"10.1097/QCO.0000000000001024","DOIUrl":"10.1097/QCO.0000000000001024","url":null,"abstract":"<p><strong>Purpose of review: </strong>To review the rationale for and the potential clinical benefits of an early approach to viral acute respiratory infections with NSAIDs to switch off the inflammatory cascade before the inflammatory process becomes complicated.</p><p><strong>Recent findings: </strong>It has been shown that in COVID-19 as in other viral respiratory infections proinflammatory cytokines are produced, which are responsible of respiratory and systemic symptoms. There have been concerns that NSAIDs could increase susceptibility to SARS-CoV-2 infection or aggravate COVID-19. However, recent articles reviewing experimental research, observational clinical studies, randomized clinical trials, and meta-analyses conclude that there is no basis to limit the use of NSAIDs, which may instead represent effective self-care measures to control symptoms.</p><p><strong>Summary: </strong>The inflammatory response plays a pivotal role in the early phase of acute respiratory tract infections (ARTIs); a correct diagnosis of the cause and a prompt therapeutic approach with NSAIDs may have the potential to control the pathophysiological mechanisms that can complicate the condition, while reducing symptoms to the benefit of the patient. A timely treatment with NSAIDs may limit the inappropriate use of other categories of drugs, such as antibiotics, which are useless when viral cause is confirmed and whose inappropriate use is responsible for the development of resistance.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"304-311"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-06DOI: 10.1097/QCO.0000000000001020
Eleftheria Kampouri, Jessica S Little, Roberto Crocchiolo, Joshua A Hill
Purpose of review: Viral infections continue to burden allogeneic hematopoietic cell transplant (HCT) recipients. We review the epidemiology, diagnosis, and management of human herpesvirus (HHV)-6, HHV-8 and parvovirus B19 following HCT.
Recent findings: Advances in HCT practices significantly improved outcomes but impact viral epidemiology: post-transplant cyclophosphamide for graft-versus-host disease prevention increases HHV-6 reactivation risk while the impact of letermovir for CMV prophylaxis - and resulting decrease in broad-spectrum antivirals - is more complex. Beyond the well established HHV-6 encephalitis, recent evidence implicates HHV-6 in pneumonitis. Novel less toxic therapeutic approaches (brincidofovir, virus-specific T-cells) may enable preventive strategies in the future. HHV-8 is the causal agent of Kaposi's sarcoma, which is only sporadically reported after HCT, but other manifestations are possible and not well elucidated. Parvovirus B19 can cause severe disease post-HCT, frequently manifesting with anemia, but can also be easily overlooked due to lack of routine screening and ambiguity of manifestations.
Summary: Studies should establish the contemporary epidemiology of HHV-6, and other more insidious viruses, such as HHV-8 and parvovirus B19 following HCT and should encompass novel cellular therapies. Standardized and readily available diagnostic methods are key to elucidate epidemiology and optimize preventive and therapeutic strategies to mitigate the burden of infection.
{"title":"Human herpesvirus-6, HHV-8 and parvovirus B19 after allogeneic hematopoietic cell transplant: the lesser-known viral complications.","authors":"Eleftheria Kampouri, Jessica S Little, Roberto Crocchiolo, Joshua A Hill","doi":"10.1097/QCO.0000000000001020","DOIUrl":"10.1097/QCO.0000000000001020","url":null,"abstract":"<p><strong>Purpose of review: </strong>Viral infections continue to burden allogeneic hematopoietic cell transplant (HCT) recipients. We review the epidemiology, diagnosis, and management of human herpesvirus (HHV)-6, HHV-8 and parvovirus B19 following HCT.</p><p><strong>Recent findings: </strong>Advances in HCT practices significantly improved outcomes but impact viral epidemiology: post-transplant cyclophosphamide for graft-versus-host disease prevention increases HHV-6 reactivation risk while the impact of letermovir for CMV prophylaxis - and resulting decrease in broad-spectrum antivirals - is more complex. Beyond the well established HHV-6 encephalitis, recent evidence implicates HHV-6 in pneumonitis. Novel less toxic therapeutic approaches (brincidofovir, virus-specific T-cells) may enable preventive strategies in the future. HHV-8 is the causal agent of Kaposi's sarcoma, which is only sporadically reported after HCT, but other manifestations are possible and not well elucidated. Parvovirus B19 can cause severe disease post-HCT, frequently manifesting with anemia, but can also be easily overlooked due to lack of routine screening and ambiguity of manifestations.</p><p><strong>Summary: </strong>Studies should establish the contemporary epidemiology of HHV-6, and other more insidious viruses, such as HHV-8 and parvovirus B19 following HCT and should encompass novel cellular therapies. Standardized and readily available diagnostic methods are key to elucidate epidemiology and optimize preventive and therapeutic strategies to mitigate the burden of infection.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"245-253"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}