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1.
ACS Infect Dis ; 10(8): 2615-2622, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39012184

RESUMO

Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([68Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [68Ga]Ga-SKN by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and S. epidermidis, but no uptake by Candida glabrata, C. albicans, or Aspergillus fumigatus, demonstrated its specificity to bacterial species. Whole-body [68Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent ex vivo biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [68Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.


Assuntos
Infecções Bacterianas , Radioisótopos de Gálio , Compostos Radiofarmacêuticos , Animais , Radioisótopos de Gálio/química , Camundongos , Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/microbiologia , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Distribuição Tecidual , Tomografia por Emissão de Pósitrons/métodos , Feminino , Bactérias , Proteínas Ribossômicas
2.
J Med Microbiol ; 73(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38771623

RESUMO

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.


Assuntos
Antifúngicos , COVID-19 , Candida auris , Candidíase , Controle de Infecções , Humanos , Candidíase/prevenção & controle , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Controle de Infecções/métodos , Candida auris/efeitos dos fármacos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Inglaterra/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , SARS-CoV-2 , Farmacorresistência Fúngica , Candida/efeitos dos fármacos , Candida/classificação , Candida/isolamento & purificação , Surtos de Doenças/prevenção & controle
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