Current Opinion in Infectious Diseases最新文献

Purpose of review: Urinary tract infections (UTIs) are a major source of morbidity in immunocompromised patients, including transplant recipients, individuals with hematologic malignancies, people living with HIV, and those receiving immunosuppressive therapies. This review provides a synthesis of recent evidence, highlighting challenges in diagnosis, management, and antimicrobial resistance in these high-risk populations.

Recent findings: Recent literature highlights the high burden of UTIs among immunocompromised patients. These infections are often caused by multidrug-resistant pathogens. Across these groups, common risk factors include immunosuppression, diabetes, urologic instrumentation, and catheterization. Diagnostic uncertainty - particularly distinguishing true infection from asymptomatic bacteriuria - frequently leads to overtreatment. Emerging stewardship tools, such as reflex urinalysis protocols and electronic phenotyping of antimicrobials (e.g. the use of the 'Acute Urinary Antibiotics' labelling), show promise for reducing inappropriate antibiotic use in outpatient settings.

Summary: UTIs in immunocompromised patients are increasingly complex due to atypical presentations and resistant pathogens. Clinical care must prioritize accurate diagnosis, judicious use of antibiotics, and implementation of stewardship interventions. Further research is needed to validate risk-based diagnostic tools and expand outpatient stewardship infrastructure in transplant and oncology settings.

Purpose of review: Tuberculosis disease (TBD) has high mortality in transplant recipients. This review evaluates the current evidence for latent tuberculosis infection (LTBI) screening and treatment in solid organ transplant (SOT) and hematopoietic stem cell transplant recipients (HCST).

Recent findings: Untreated LTBI still poses a significant risk in transplant recipients, with reactivation to TBD leading to high mortality rates. Currently available methods to test for LTBI (interferon-gamma release assays and tuberculin skin tests) can have low predictive value for determining who will progress from LTBI to TBD in transplant. Tuberculosis preventive therapy (TPT) is recommended for those with a positive LTBI screening test. Evidence indicates that short-course, rifamycin-based TPT regimens are associated with less hepatoxicity and improved treatment completion compared to isoniazid. In the transplant population, however, drug-drug interactions limit their use, so isoniazid preventive therapy remains the preferred regimen. Several recent studies have evaluated moxifloxacin as a potential TPT regimen in transplant, but this regimen has not yet been incorporated into guidelines. The timing of LTBI treatment can differ for SOT versus HSCT.

Summary: While comprehensive LTBI screening and TPT are critical for reducing the risk of TBD, future research should aim to optimize LTBI diagnostic tools and therapeutic regimens to enhance the efficacy of LTBI diagnostics and minimize TPT side effects and drug-drug interactions in the transplant population.

Purpose of review: We review recent advances in diagnosis and treatment of chronic meningitis, focusing on tuberculous meningitis (TBM), cryptococcal meningitis (CM), syphilitic meningitis, neuroborreliosis, and recurrent chronic meningitis. Noninfectious causes and unique challenges faced in resource-limited settings are also considered.

Recent findings: Novel biomarkers are being identified that may be useful for the diagnosis of TBM [i.e. monokine induced by interferon-γ (MIG), plasminogen binding proteins] and syphilitic meningitis (i.e. CXCL13, neurofilament light protein, etc.) but require more validation. Much progress has been made regarding diagnosis and treatment of CM, with a new semiquantitative lateral flow assay showing high diagnostic and prognostic utility and clinical trials demonstrating that regimens of oral lipid nanocrystal formulation and a single dose of liposomal formulation of amphotericin B maintain clinical efficacy with improved side effect profiles. An ongoing clinical trial of ceftriaxone for treatment of syphilitic meningitis and early stage studies of linezolid for TBM treatment may also lead to changes in recommended treatment regimens for these conditions in the near future.

Summary: Diagnosis and management of chronic meningitis remains a significant challenge, and further research is needed to improve our diagnostic and therapeutic armamentariums. However, emergence of potential new biomarkers for diagnosis and disease course is cause for optimism.

Purpose of review: This review summarizes available data for lenacapavir (LEN), a first-in-class agent that targets several functions of the HIV capsid in the viral cycle, including nuclear entry, viral assembly, and capsid formation.

Recent findings: LEN has been approved in the United States as both oral tablets and injectable solution for treatment in heavily treatment-experienced adults with multidrug-resistant HIV-1. The subcutaneous injections are administered every 26 weeks (6 months). In 2024, LEN was named the biggest science breakthrough for HIV prevention, and is currently under review at the FDA.

Summary: LEN is a novel agent that can be administered subcutaneously every 6 months. Approved for treatment-experienced adults with multidrug-resistant HIV, lenacapavir may have additional uses including for HIV prevention.

Purpose of review: This review focuses on the temporal relationship between the discontinuation of the global smallpox eradication effort with the rise of mpox in Africa and worldwide. It also discusses the global 2022 clade II mpox epidemic and the current 2024 clade I mpox outbreak. Newer findings on viral evolution and pathogenesis, plus current and future strategies for disease prevention, are reviewed.

Recent findings: The temporal association between the incidence of mpox and the World Health Organization's Global Smallpox Eradication Program (GSEP) is presented. The 2022 global mpox epidemic is discussed. Recent data show that clade IIb monkeypox virus (MPXV)-2022 has novel genetic features supporting a greater propensity for mutations that may be responsible for enhanced human-to-human transmissibility, increased disease severity and accelerated viral evolution. In 2023, another outbreak of mpox began in Africa, this time due to the potentially more virulent MPXV clade Ib strains. This outbreak remains ongoing in Africa, and clade Ib mpox cases have recently been reported elsewhere including the United States and Great Britain. The World Health Organization has deemed mpox to be a global public health emergency. Two smallpox vaccines are approved for mpox prevention in the United States; a third smallpox vaccine and an improved diagnostic test have recently received WHO Emergency Use authorization. Newer mRNA-based vaccines for evolving orthopoxvirus infections are discussed.

Summary: Vaccination to prevent smallpox provides immunologic cross-protection against infection with other members of genus Orthopoxvirus , including mpox. Discontinuation of the global smallpox eradication program in the 1980s and the subsequent waning of herd immunity contributed to the 2022 multinational epidemic of human clade IIb mpox infections. A second multinational outbreak with clade Ib MPXV is ongoing. Vaccination against smallpox remains the gold standard for mpox prevention, however newer multiepitope mRNA-based vaccines are in development and hold promise for prevention of mpox and other orthopoxvirus outbreaks.

Purpose of review: This review addresses the multifaceted nature of aseptic meningitis, a condition with diverse infectious and noninfectious etiologies. Despite its common presentation in clinical settings, over half of the cases remain without an identified cause, necessitating a comprehensive examination of diagnostic and management strategies. The increasing availability of advanced molecular diagnostics and the challenge of distinguishing bacterial from nonbacterial cases make this an opportune time to explore its implications for clinical practice.

Recent findings: The literature highlights the pivotal role of advanced molecular diagnostics, such as multiplex PCR and metagenomic sequencing, in improving the identification of pathogens in aseptic meningitis. Enteroviruses remain the leading cause, but pathogens like Herpesviridae, arboviruses, and nonviral agents such as fungi and spirochetes also contribute significantly. New diagnostic algorithms and clinical models are emerging to distinguish bacterial from viral meningitis, reducing unnecessary treatments.

Summary: Aseptic meningitis management is evolving with advancements in diagnostic technologies that allow for earlier pathogen identification, improving patient outcomes and minimizing healthcare costs. These findings underscore the importance of timely and accurate diagnostics and tailored therapeutic strategies in both clinical and research settings. Enhanced awareness of noninfectious causes is also crucial for comprehensive care.

Purpose of review: Viruses are frequent causes of central nervous system (CNS) infection. Lacking specific antiviral treatment or inadequate clinical response may lead to treatment with corticosteroids. This review describes the rationale for and clinical experience with the use of adjunctive corticosteroids for viral CNS infections.

Recent findings: Corticosteroids display anti-inflammatory, immunosuppressive, antiproliferative, and vasoconstrictive effects by genomic and nongenomic regulation of human cells. Recent population-based studies consistently show that empiric dexamethasone during diagnostic work-up for meningitis has neither been associated with improved outcome nor adverse effects in viral meningitis. Myelitis is most often due to noninfectious causes and standard empiric treatment includes high-dose methylprednisolone. There are no convincing data on viral myelitis to support a change of this approach. Corticosteroids have occasionally been employed in different types of viral encephalitis. Observational data and a few randomized clinical trials have not documented any substantial beneficial effects of adjunctive corticosteroids in viral encephalitis. Risks of harm with current treatment regimens remained low in published studies.

Summary: Except for myelitis, there are no data to support routine use of corticosteroids for viral CNS infections. Large, multidisciplinary syndromic platform trials of all-cause encephalitis may be a viable way to inform treatment guidelines.

Purpose of review: The recent uptick in outbreaks of infectious diseases once firmly under control in North America and the UK (including measles, tuberculosis, scarlet fever, and whooping cough) concerns public health professionals in light of increasing vaccine skepticism. Because disease prevention and cure have evolved slowly, the general public may misunderstand the potential impact of rejecting vaccines and need stories that will clarify the risks.

Recent findings: Studying history and literature reveals that modern citizens of wealthy, industrialized nations have forgotten the emotional cost of widespread child mortality. Examples from nineteenth-century novels offer vivid reminders of the agonies created by communicable diseases in an age before vaccines and antibiotics. Better understanding both the causes of child mortality - which hovered near 50% in North America and the UK in the 1840s - and the shared cultural grief such losses produced is a powerful reminder of why no one would want to return to that public health moment.

Summary: Medical health professionals might usefully complement their scientific understanding with history, in order to be better equipped to reach those who are vaccine hesitant.

Purpose of review: This review highlights the complex pathophysiology of myocardial dysfunction in septic shock and emphasizes the need for early and repeated hemodynamic assessments to improve outcome.

Recent findings: Septic cardiomyopathy is a complex, dynamic process driven by multiple mechanisms such as direct myocardial depression induced by host immune mediators (e.g., cytokines, nitric oxide) and/or bacterial toxins, and mitochondrial metabolic dysfunction. Recent echocardiography studies have described multiple unique hemodynamic clusters (phenotypes) that correlated with clinical outcomes. Similarly, serial echocardiography findings and mean arterial pressure abnormalities in patients with Streptococcal Toxic Shock Syndrome (StrepTSS) yielded three distinct hemodynamic groups that predicted mortality and morbidity. Because excessive use of fluids and/or vasopressors can be detrimental, especially in patients with microvascular injury or cardiomyopathy, application of the cardiovascular performance criteria of these different phenotypes could better inform management decisions in real time and improve outcome.

Summary: Septic cardiomyopathy is a dynamic, multidimensional response of the myocardium to infection involving both normal and dysregulated immune responses in which the measurable changes in myocardial function predict outcomes. This current paradigm mandates that functional parameters of cardiac performance be measured early and repeatedly throughout the disease course using echocardiography to guide treatment and improve outcome.

Purpose of review: Cases of whooping cough (pertussis) have rebounded strongly from the very low incidence observed during the pandemic. This re-emergence is characterized by changes in epidemiology. Here we describe the importance of genomics to monitor and understand the drivers to these changes.

Recent findings: Changes in the genotype of strains isolated during recent outbreaks suggests that the pandemic disturbed the global Bordetella pertussis population structure. The emergence of dominant and antibiotic-resistant clones in China is of concern even though the source of antibiotic selection pressure on B. pertussis is unclear. A recent study illustrates how to use genomic data to go beyond just surveillance, inferring the relative fitness of genotypes and the identification of specific mutations distinguishing such lineages. Such approaches are required to understand the forces driving adaptation.

Summary: Pertussis is resurgent in many countries, involving changes in epidemiology and strong suggestions of strain adaptation. The continued use of vaccination, and design of new interventions, to control pertussis requires an understanding of these changes. Genomic analyses will be key to this, involving integration of more complete host and pathogen parameters than have been used to date.