Clinical Microbiology Reviews最新文献

SUMMARYStaphylococcus aureus is a major human pathogen. It can cause many types of infections, in particular bacteremia, which frequently leads to infective endocarditis, osteomyelitis, sepsis, and other debilitating diseases. The development of secondary infections is based on the bacterium's ability to associate with endothelial cells lining blood vessels. The success of endothelial colonization and infection by S. aureus relies on its ability to express a wide array of cell wall-anchored and secreted virulence factors. Establishment of endothelial infection by the pathogen is a multistep process involving adhesion, invasion, extravasation, and dissemination of the bacterium into surrounding tissues. The process is dependent on the type of endothelium in different organs (tissues) and pathogenetic potential of the individual strains. In this review, we report an update on the organization of the endothelium in the vessels, the structure and function of the virulence factors of S. aureus, and the several aspects of bacteria-endothelial cell interactions. After these sections, we will discuss recent advances in understanding the specific mechanisms of infections that develop in the heart, bone and joints, lung, and brain. Finally, we describe how neutrophils bind to endothelial cells, migrate to the site of infection to kill bacteria in the tissues, and how staphylococci counteract neutrophils' actions. Knowledge of the molecular details of S. aureus-endothelial cell interactions will promote the development of new therapeutic strategies and tools to combat this formidable pathogen.

SUMMARYSporotrichosis is a subacute-to-chronic infection endemic to tropical and subtropical regions. It usually involves subcutaneous tissue but can occasionally cause extracutaneous infections, especially in hyperendemic areas. Extracutaneous infections are classified based on the anatomic location of the lesion and the route of infection (primary or multifocal). The clinical forms are as follows: (i) pulmonary (primary or multifocal); (ii) osteoarticular (primary or multifocal); (iii) ocular (ocular adnexal lesions including eyelid lesions, conjunctivitis and dacryocystitis, and intraocular infections); (iv) central nervous system; and (v) mucosal (primary or disseminated). Multifocal clinical presentations are observed mainly in immunocompromised individuals. The diagnosis must be confirmed in the laboratory by mycological examination of the clinical samples. Itraconazole and amphotericin B are the most commonly used antifungal agents for treating pulmonary, osteoarticular, ocular, and mucosal forms. Treatment may include surgical excision of the initial lesions in pulmonary and osteoarticular forms. The treatment of neurological involvement is far from optimal and is associated with a high mortality rate despite long treatment periods.

SUMMARYHenipaviruses were first identified 30 years ago and have since been associated with over 30 outbreaks of disease in humans. Highly pathogenic henipaviruses include Hendra virus (HeV) and Nipah virus (NiV), classified as biosafety level 4 pathogens. In addition, NiV has been listed as a priority pathogen by the World Health Organization (WHO), the Coalition for Epidemic Preparedness Innovations (CEPI), and the UK Vaccines Research and Development Network (UKVN). Here, we re-examine epidemiological, ecological, clinical, and pathobiological studies of HeV and NiV to provide a comprehensive guide of the current knowledge and application to identify and evaluate countermeasures. We also discuss therapeutic and vaccine development efforts. Furthermore, with case identification, prevention, and treatment in mind, we highlight limitations in research and recognize gaps necessitating additional studies.

SUMMARYLyme borreliosis or Lyme disease is the most frequently reported tick-borne disease in the Northern Hemisphere. In countries of the Southern Hemisphere, such as Brazil, since the early 1990s, some researchers have argued for the existence of an autochthonous Lyme-like borreliosis, known locally as the Baggio-Yoshinari syndrome (BYS), an alleged "Brazilian borreliosis" supposedly caused by a different strain of Borrelia burgdorferi and transmitted by hard ticks. Currently, the existence of BYS in Brazil is still accepted by a large part of the human health care workers, scientists, medical societies, and patients. In fact, this alleged "Brazilian borreliosis" has been the tick-borne zoonotic disease with the greatest number of reported cases and published studies in Brazil during this century, second only to Brazilian spotted fever. In this manuscript, we reviewed all manuscripts directly related to BYS that have been published in Brazil during the last 35 years. This analysis included 199 individual human cases that have been reported in Brazil since 1989, plus multiple studies on ticks, domestic, and wild animals. Our revision aimed to provide a critical opinion on whether the current published works allow healthcare workers, public health agencies, and patients to accept the existence of Lyme disease, BYS, or other Lyme borreliosis-related disease in Brazil. For this purpose, we evaluated the strengths and weaknesses of each published study, considering the diagnostic methods used, such as serological, microbiological, and molecular analyses. Based on these evaluations, we conclude that there is not enough evidence to support the occurrence of Lyme borreliosis in Brazil or that BYS (Brazilian Lyme-like disease) is caused by a bacterium of the genus Borrelia. This assumption is based on the inaccuracy, unreliability, and misinterpretation of the different diagnostic methods that have been used in Brazil. Recognizing the lack of technical evidence for the occurrence of Lyme borreliosis in Brazil has highly relevant implications. For example, it becomes imperative to raise awareness among the country's medical profession, as they have adopted unnecessary and extreme therapies recommended for patients with a supposed borrelial infection, including BYS, in Brazil. Finally, the technical analyses carried out in this study could be applied to other countries in the Southern Hemisphere (e.g., Argentina, South Africa, Australia), where cases classified and alleged as Lyme disease have been reported.

SUMMARYIn the United Kingdom (UK) in 2022/23, influenza virus infections returned to the levels recorded before the COVID-19 pandemic, exerting a substantial burden on an already stretched National Health Service (NHS) through increased primary and emergency care visits and subsequent hospitalizations. Population groups ≤4 years and ≥65 years of age, and those with underlying health conditions, are at the greatest risk of influenza-related hospitalization. Recent advances in influenza virus vaccine technologies may help to mitigate this burden. This review aims to summarize advances in the influenza virus vaccine landscape by describing the different technologies that are currently in use in the UK and more widely. The review also describes vaccine technologies that are under development, including mRNA, and universal influenza virus vaccines which aim to provide broader or increased protection. This is an exciting and important era for influenza virus vaccinations, and advances are critical to protect against a disease that still exerts a substantial burden across all populations and disproportionately impacts the most vulnerable, despite it being over 80 years since the first influenza virus vaccines were deployed.

SUMMARYAntibiotic treatment failures in the absence of resistance are not uncommon. Recently, attention has grown around the phenomenon of antibiotic tolerance, an underappreciated contributor to recalcitrant infections first detected in the 1970s. Tolerance describes the ability of a bacterial population to survive transient exposure to an otherwise lethal concentration of antibiotic without exhibiting resistance. With advances in genomics, we are gaining a better understanding of the molecular mechanisms behind tolerance, and several studies have sought to examine the clinical prevalence of tolerance. Attempts have also been made to assess the clinical significance of tolerance through in vivo infection models and prospective/retrospective clinical studies. Here, we review the data available on the molecular mechanisms, detection, prevalence, and clinical significance of genotypic tolerance that span ~50 years. We discuss the need for standardized methodology and interpretation criteria for tolerance detection and the impact that methodological inconsistencies have on our ability to accurately assess the scale of the problem. In terms of the clinical significance of tolerance, studies suggest that tolerance contributes to worse outcomes for patients (e.g., higher mortality, prolonged hospitalization), but historical data from animal models are varied. Furthermore, we lack the necessary information to effectively treat tolerant infections. Overall, while the tolerance field is gaining much-needed traction, the underlying clinical significance of tolerance that underpins all tolerance research is still far from clear and requires attention.

SUMMARYThe opportunistic pathogen Mycobacterium abscessus (Mab) causes fatal lung infections that bear similarities-and notable differences-with tuberculosis (TB) pulmonary disease. In contrast to TB, no antibiotic is formally approved to treat Mab disease, there is no reliable cure, and the discovery and development pipeline is incredibly thin. Here, we discuss the factors behind the unsatisfactory cure rates of Mab disease, namely intrinsic resistance and persistence of the pathogen, and the use of underperforming, often parenteral and toxic, repurposed drugs. We propose preclinical strategies to build injectable-free sterilizing and safe regimens: (i) prioritize oral bactericidal antibiotic classes, with an initial focus on approved agents or advanced clinical candidates to provide immediate options for desperate patients, (ii) test drug combinations early, (iii) optimize novel leads specifically for M. abscessus, and (iv) consider pharmacokinetic-pharmacodynamic targets at the site of disease, the lung lesions in which drug tolerant bacterial populations reside. Knowledge and tool gaps in the preclinical drug discovery process are identified, including validated mouse models and computational platforms to enable in vitro mouse-human translation. We briefly discuss recent advances in clinical development, the need for readouts and biomarkers that correlate with cure, and clinical trial concepts adapted to the uniqueness of Mab patient populations for new regimen development. In an era when most pharmaceutical firms have withdrawn from antimicrobial drug discovery, the breakthroughs needed to fill the regimen development pipeline will likely come from partnerships between academia, biotech, pharma, non-profit organizations, and governments, with incentives that reward cooperation.

SUMMARYInfections due to Acinetobacter spp. are among the most difficult to treat. Most are resistant to standard antibiotics, and there is difficulty in distinguishing colonizers from pathogens. This mini-review examines the available antibiotics that exhibit activity against these organisms and provides guidance as to which cultures are relevant and how to treat active infections. Antibiograms describing resistance mechanisms and the minimum inhibitory concentration (MIC) are essential to determine which agent or combination of agents should be used after confirmation of infection, utilizing clinical parameters and biomarkers such as procalcitonin. Directed therapy should be prompt as despite its reputation as a colonizer, the attributable mortality is high. However, although combination therapy is advised, no specific combination has definite evidence of superiority.