Clinical Microbiology Reviews最新文献

SUMMARYXenotransplantation, the transplantation of living organs, tissues, or cells between species, carries the potential to address the global shortage of human organs for patients with end-stage organ failure. Recent advances in genetic engineering have improved prospects for clinical xenotransplantation by reducing immune and inflammatory responses to grafts, controlling coagulation on endothelial surfaces, and modifying viral risks, including the porcine endogenous retrovirus (PERV). Management of infectious risks posed by clinical xenotransplantation requires meticulous attention to the biosecure breeding and microbiological surveillance of source animals and recipients and consideration of novel infection control requirements. Infectious risks in xenotransplantation stem from both known human pathogens in immunosuppressed transplant recipients and from porcine organisms for which the clinical manifestations, microbial assays, and therapies are generally limited. Both known and unknown zoonoses may be transmitted from pigs to humans. Some pig-specific pathogens do not infect human cells but have systemic manifestations when active within the xenograft, including porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV), which contributes to graft rejection and consumptive coagulopathy. The role of porcine endogenous retrovirus (PERV) in humans remains uncertain despite the absence of documented transmissions and the availability of swine with inactivated genomic PERV. New technologies, such as metagenomic sequencing and multi-omics approaches, will be essential for detection of novel infections and for understanding interactions between the xenograft, the host's immune system, and potential pathogens. These approaches will allow development of infection control protocols, pathogen surveillance requirements, and tailored antimicrobial therapies to enhance the safety and success of clinical xenotransplantation.

SUMMARYThe human pathogen Neisseria meningitidis (Nm) is the causative agent of invasive meningococcal disease (IMD), usually presenting as meningitis, bacteremia, or sepsis. Unlike Neisseria gonorrhoeae, antibiotic resistance in Nm has developed slowly. However, in the last two decades and with the reemergence of IMD following the COVID-19 pandemic, antibiotic-resistant Nm isolates, especially to penicillin and fluoroquinolones, have progressively increased. Recent worldwide studies of penicillin intermediate and resistant Nm isolates and the PubMLST global database reveal a notable increase in fully penicillin-resistant isolates since 2016, mediated by mosaic penA alleles or the β-lactamase genes bla_ROB-1 and bla_TEM-1. Fluoroquinolone-resistant isolates, mediated by gyrA mutations, have increased since 2005. Also, while still exceptionally rare, four Nm isolates have been identified with third-generation cephalosporin-resistance since 2011. We review the emergence of antibiotic resistance determinants and lineages in Nm, the resistance to agents previously or currently used in treatment or chemoprophylaxis, and summarize updated treatment and prevention guidelines for IMD. Special populations (e.g., individuals on complement inhibitors) and antibiotic resistance in Nm urethritis isolates are also reviewed. The increasing number of resistant Nm isolates worldwide affects chemoprophylaxis and treatment options for IMD and emphasizes the need for enhanced global surveillance of antibiotic resistance in Nm.

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.