RESUMEN
Antibiotic-induced loss of intestinal hypoxia boosts the growth of C. albicans in mice.
Asunto(s)
Candida albicans , Hipoxia , Animales , Ratones , Hipoxia/metabolismo , Candida albicans/metabolismo , Antibacterianos/farmacología , Candidiasis/microbiología , Candidiasis/prevención & control , Candidiasis/metabolismo , Intestinos/microbiología , HumanosRESUMEN
Epitopes from the Candida cell surface proteins Fba and Met6 are putative vaccine targets for invasive candidiasis. Here, we describe a Candida vaccine approach in which short peptides derived from Fba and Met6 are used in spontaneous nanoliposome antigen particle (SNAP) format. SNAP was enabled by the interaction of cobalt porphyrin phospholipid in liposomes with three histidine residues on the N-terminus of synthetic short peptide immunogens from Fba (F-SNAP), Met6 (M-SNAP), or bivalent Fba and Met6 (FM-SNAP). Liposomes were adjuvanted with synthetic monophosphoryl lipid and QS-21. In mice, immunization with F-SNAP, M-SNAP, or FM-SNAP induced antigen-specific IgG responses and mixed Th1/Th2 immunity. The duplex FM-SNAP vaccine elicited stronger antibody responses against each peptide, even at order-of-magnitude lower peptide dosing than a comparable adjuvanted, conjugate vaccine. Enzyme-linked immunosorbent spot analysis revealed the induction of antigen-specific, cytokine-producing T cells. Compared to F-SNAP or M-SNAP, higher production of TNFα, IL-2, and IFNγ was observed with re-stimulation of splenocytes from bivalent FM-SNAP-immunized mice. When vaccinated BALB/c mice were challenged with Candida auris, analysis of the fungal burden in the kidneys showed that SNAP vaccination protected from disseminated candidiasis. In a lethal fungal exposure model in A/J mice, F-SNAP, M-SNAP, and FM-SNAP vaccination protected mice from candidiasis challenge. Together, these results show that further investigation into the SNAP adjuvant platform is warranted using Fba and Met6 epitopes for a pan-Candida peptide vaccine that provides multifaceted protective immune responses. IMPORTANCE: This study introduces a promising vaccine strategy against invasive candidiasis, a severe fungal infection, by targeting specific peptides on the surface of Candida. Using a novel approach called spontaneous nanoliposome antigen particle (SNAP), we combined peptides from two key Candida proteins, Fba and Met6, into a vaccine. This vaccine induced robust immune responses in mice, including the production of protective antibodies and the activation of immune cells. Importantly, mice vaccinated with SNAP were shielded from disseminated candidiasis in experiments. These findings highlight a potential avenue for developing a broad-spectrum vaccine against Candida infections, which could significantly improve outcomes for patients at risk of these often deadly fungal diseases.
Asunto(s)
Anticuerpos Antifúngicos , Candidiasis , Vacunas Fúngicas , Liposomas , Ratones Endogámicos BALB C , Animales , Ratones , Vacunas Fúngicas/inmunología , Vacunas Fúngicas/administración & dosificación , Liposomas/inmunología , Candidiasis/prevención & control , Candidiasis/inmunología , Femenino , Anticuerpos Antifúngicos/inmunología , Antígenos Fúngicos/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Citocinas/inmunología , Vacunación , Proteínas Fúngicas/inmunología , Proteínas Fúngicas/administración & dosificación , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Candida albicans/inmunología , Candida/inmunología , Modelos Animales de EnfermedadRESUMEN
In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (â¼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.
Asunto(s)
Antifúngicos , Farmacorresistencia Fúngica , Pichia , Organización Mundial de la Salud , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Pichia/aislamiento & purificación , Pichia/efectos de los fármacos , Incidencia , Factores de Riesgo , Candidiasis/epidemiología , Candidiasis/microbiología , Candidiasis/prevención & controlRESUMEN
Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine is a priority. Here, we could for the first time successfully attenuate the virulence of Candida albicans by treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation of C. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell wall with elevated levels of mannan and ß-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected in Ca- vs CAET-challenged mice. While hyper-inflammation and immunosuppression caused the killing of Ca-challenged mice, a critical balance of pro- and anti-inflammatory cytokines-mediated immune responses are the likely reasons for the protective immunity in CAET-infected mice.
Asunto(s)
Candida albicans , Candidiasis , Animales , Candida albicans/inmunología , Ratones , Candidiasis/inmunología , Candidiasis/prevención & control , Vacunas Fúngicas/inmunología , Modelos Animales de Enfermedad , Virulencia , Femenino , Citocinas/metabolismo , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrolloRESUMEN
Disseminated fungal infections account for ~1.5 million deaths per year worldwide, and mortality may increase further due to a rise in the number of immunocompromised individuals and drug-resistance fungal species. Since an approved antifungal vaccine is yet to be available, this study explored the immunogenicity and vaccine efficacy of a DNA polymerase mutant strain of Candida albicans. CNA25 is a pol32ΔΔ strain that exhibits growth defects and does not cause systemic candidiasis in mice. Immunized mice with live CNA25 were fully protected against C. albicans and C. parapsilosis but partially against C. tropicalis and C. glabrata infections. CNA25 induced steady expression of TLR2 and Dectin-1 receptors leading to a faster recognition and clearance by the immune system associated with the activation of protective immune responses mostly mediated by neutrophils, macrophages, NK cells, B cells, and CD4+ and CD8+ T cells. Molecular blockade of Dectin-1, IL-17, IFNγ, and TNFα abolished resistance to reinfection. Altogether, this study suggested that CNA25 collectively activates innate, adaptive, and trained immunity to be a promising live whole-cell vaccine against systemic candidiasis.
Asunto(s)
Candida albicans , Candidiasis , Vacunas Fúngicas , Animales , Candidiasis/inmunología , Candidiasis/prevención & control , Candidiasis/microbiología , Vacunas Fúngicas/inmunología , Vacunas Fúngicas/administración & dosificación , Ratones , Candida albicans/inmunología , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Femenino , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/inmunología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
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.
Asunto(s)
Antifúngicos , COVID-19 , Candida auris , Candidiasis , Control de Infecciones , Humanos , Candidiasis/prevención & control , Candidiasis/epidemiología , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Control de Infecciones/métodos , Candida auris/efectos de los fármacos , COVID-19/prevención & control , COVID-19/epidemiología , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Inglaterra/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , SARS-CoV-2 , Farmacorresistencia Fúngica , Candida/efectos de los fármacos , Candida/clasificación , Candida/aislamiento & purificación , Brotes de Enfermedades/prevención & controlRESUMEN
Candida albicans can cause superficial or systemic infections in humans, particularly in immunocompromised individuals. Vaccination strategies targeting specific antigens of C. albicans have shown promise in providing protection against invasive candidiasis. This study aimed to evaluate the immuno-protective capacity of a KLH conjugated complex peptide, 3P-KLH, containing epitopes from C. albicans antigens Als3, Hwp1, and Met6 in a murine model of hematogenously induced candidiasis. Mice immunized with 3P-KLH raised a specific antibody response, and protection against C. albicans infection was assessed. Immunized mice exhibited significantly lower fungal load in their kidneys compared to the control group. Moreover, 37.5 % of immunized mice survived 21 days after the infection, while all control animals died within the first nine days. These findings suggest that the 3P-KLH complex peptide, targeting C. albicans key antigens, elicits a protective immune response and reduces the severity of systemic Candida infection. In addition, the high binding affinity of the selected epitopes with MHC II alleles further supports the potential immunogenicity of this peptide in humans. This research provides insights into the development of novel immunotherapeutic approaches against invasive candidiasis.
Asunto(s)
Anticuerpos Antifúngicos , Antígenos Fúngicos , Candida albicans , Candidiasis , Proteínas Fúngicas , Vacunas Fúngicas , Animales , Candida albicans/inmunología , Vacunas Fúngicas/inmunología , Vacunas Fúngicas/administración & dosificación , Antígenos Fúngicos/inmunología , Proteínas Fúngicas/inmunología , Proteínas Fúngicas/genética , Ratones , Candidiasis/prevención & control , Candidiasis/inmunología , Anticuerpos Antifúngicos/inmunología , Femenino , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Epítopos/inmunología , Péptidos/inmunología , Riñón/inmunología , Riñón/microbiología , Riñón/patologíaRESUMEN
We surveyed members of the Emerging Infections Network about Candida auris screening practices at US healthcare facilities. Only 37% of respondents reported conducting screening; among these, 75% reported detection of at least 1 C. auris case in the last year. Increased screening could improve C. auris detection and prevent spread.
Asunto(s)
Candida auris , Candidiasis , Instituciones de Salud , Tamizaje Masivo , Humanos , Estados Unidos , Candidiasis/diagnóstico , Candidiasis/prevención & control , Candidiasis/epidemiología , Tamizaje Masivo/métodos , Encuestas y Cuestionarios , Infección Hospitalaria/prevención & control , Infección Hospitalaria/diagnóstico , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/epidemiología , Candida/aislamiento & purificaciónRESUMEN
BACKGROUND: Candida auris (C auris) is a fungal pathogen that has the potential for environmental persistence leading to outbreaks in health care settings. There has been a worldwide surge in C auris outbreaks during the COVID-19 pandemic. In this report, we describe an outbreak of C auris, its control, patient outcomes, and lessons learned. METHODS: The outbreak occurred in a 600-bed adult academic tertiary care hospital. Contact tracing was initiated immediately after identification of the index case and surveillance testing for C auris was obtained from patients who were exposed to the index case. Infection prevention measures were closely followed. RESULTS: A total of 560 cultures were performed on 453 unique patients between August 2021 and December 2021. Of those, 31 cultures (5.5%) were positive for C auris; 27 (87.1%) were colonized with C auris, while 4 patients developed a clinical infection (12.9%). The secondary attack rate was 6.8% (31/453). The 30-day all-cause mortality rate for all patients who tested positive for C auris was 9.7%. DISCUSSION: C auris can cause protracted outbreaks that result in colonization and invasive infections. Multidisciplinary work to improve adherence to infection prevention measures as well as targeted admission screening are essential to limit outbreaks.
Asunto(s)
COVID-19 , Candida auris , Candidiasis , Brotes de Enfermedades , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , Centros de Atención Terciaria/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Anciano , Candidiasis/epidemiología , Candidiasis/microbiología , Candidiasis/prevención & control , Adulto , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/microbiología , Control de Infecciones/métodos , Trazado de Contacto , Anciano de 80 o más Años , Candidiasis InvasivaRESUMEN
ABSTRACT: Candida auris is a highly transmissible yeast that is capable of causing invasive and fatal infections, particularly among persons with underlying medical conditions. Its incidence is rising, especially among patients cared for in post-acute care facilities. Individuals colonized with the yeast may be cared for in inpatient rehabilitation settings, without heightened risk for invasive infection and/or transmission to others, as long as appropriate infection control measures are followed. This article reviews key information for rehabilitation nurses caring for persons with C. auris , including risk factors for infection, the need for contact precautions, appropriate disinfection practices for therapy and diagnostic equipment, and critical components of safe transitions in the care of these patients.
Asunto(s)
Candidiasis Invasiva , Candidiasis , Control de Infecciones , Enfermería en Rehabilitación , Humanos , Candidiasis/prevención & control , Control de Infecciones/métodos , Enfermería en Rehabilitación/métodos , Candida auris/fisiología , Factores de Riesgo , Infección Hospitalaria/prevención & controlRESUMEN
BACKGROUND: Ex situ normothermic liver perfusion (NMP) in a blood-based perfusate is associated with a risk of microbe growth, resulting in life-threatening posttransplant sepsis. Antibiotics are widely used, but the pharmacokinetics of these agents are unknown as is their efficacy. We wished to assess the perfusate concentrations of the meropenem and fluconazole that we use and to audit the incidence of infection with this antimicrobial therapy. METHODS: Fluconazole and meropenem (100 mg each) were added to the perfusate before NMP began, and serial samples were taken and assayed for drug concentrations. Perfusate cultures were available from 210 of the 242 perfusions performed between February 1, 2018, and April 6, 2023; these were reviewed. RESULTS: Following administration of 100 mg fluconazole, levels fell slightly from a median of 24.9 mg/L at 1 h to 22.6 mg/L at 10 h. In contrast, meropenem concentrations fell over time, from a median of 21.8 mg/L at 1 h to 9.4 mg/L at 10 h. There were 4 significant microorganisms grown in the perfusions, including 3 Candida species and an Enterococcus faecium . All the Candida -infected livers were transplanted with no adverse consequences, the recipients being treated with anidulafungin upon identification of the infecting organism; the Enterococcus -infected liver was not transplanted. CONCLUSIONS: Serious infection is a risk with NMP but appears to be mitigated with a protocol combining fluconazole and meropenem. This combination may not be appropriate in areas where resistance is prevalent. Routine culture of NMP perfusate is essential to identify breakthrough organisms early and enable recipient treatment.
Asunto(s)
Fluconazol , Trasplante de Hígado , Meropenem , Perfusión , Humanos , Meropenem/farmacocinética , Meropenem/administración & dosificación , Trasplante de Hígado/efectos adversos , Fluconazol/farmacocinética , Fluconazol/administración & dosificación , Incidencia , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Preservación de Órganos/métodos , Profilaxis Antibiótica/métodos , Estudios Retrospectivos , Hígado/metabolismo , Hígado/microbiología , Hígado/efectos de los fármacos , Candidiasis/epidemiología , Candidiasis/prevención & control , Candidiasis/tratamiento farmacológico , Candidiasis/diagnósticoRESUMEN
Candida auris is a multidrug-resistant fungus that has led to health care-associated outbreaks globally. Contact investigations for new cases of Candida auris are a recommended infection prevention practice; however, there is limited knowledge and experience with such investigations. We describe our institution's experience from June 2018 through January 2019.
Asunto(s)
Candida , Candidiasis , Humanos , Candidiasis/epidemiología , Candidiasis/prevención & control , Candidiasis/tratamiento farmacológico , Candida auris , Trazado de Contacto , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Ciudad de Nueva York/epidemiología , Hospitales Urbanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Health care-associated infections, particularly those caused by multidrug-resistant organisms (MDROs), pose significant challenges to patient safety. Candida auris (C auris), an emerging MDRO fungus, has been acknowledged as an urgent threat by the Centers for Disease Control and Prevention due to its high mortality and difficulty in prevention, diagnosis, and treatment. In this study, we investigated the efficacy of 254 nm ultraviolet-C light (UV-C) in inactivating C auris on hard surfaces. A mobile UV-C tower equipped with high-performance bulbs was used, and within 7 minutes of continuous exposure, ≥99.97% (≥3.86 log10) inactivation of C auris was achieved in a patient-room-sized test chamber. Our findings suggest that UV-C can serve as an adjunct infection control measure for preventing C auris and other MDRO Health care-associated infections in health care settings. Implementation of UV-C disinfection protocols can contribute to enhanced patient safety and combat the growing threat of MDRO pathogens.
Asunto(s)
Candidiasis , Infección Hospitalaria , Humanos , Candida/fisiología , Candidiasis/prevención & control , Candidiasis/microbiología , Candida auris , Control de Infecciones/métodos , Infección Hospitalaria/prevención & control , Infección Hospitalaria/microbiología , AntifúngicosRESUMEN
Candida auris, an emerging fungal pathogen with significant morbidity and mortality, can be difficult for health care facilities to identify, isolate, and control. We present our identification and infection control response to Candida auris at a 695-bed academic level I trauma center in Florida.
Asunto(s)
Candida , Candidiasis , Humanos , Candidiasis/epidemiología , Candidiasis/prevención & control , Candidiasis/tratamiento farmacológico , Candida auris , Centros Traumatológicos , Control de Infecciones , Antifúngicos/farmacología , Antifúngicos/uso terapéuticoRESUMEN
Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP's therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 µg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 µg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.
Asunto(s)
Candidiasis Vulvovaginal , Candidiasis , Femenino , Ratones , Humanos , Animales , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/prevención & control , Candidiasis Vulvovaginal/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Especies Reactivas de Oxígeno/farmacología , Cremas, Espumas y Geles Vaginales/farmacología , Candida , Candidiasis/tratamiento farmacológico , Candidiasis/prevención & control , Candida glabrata , Candida tropicalis , Ergosterol/farmacología , Candida albicans , Pruebas de Sensibilidad MicrobianaRESUMEN
Importance: To date, only 1 statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the US, and no statewide prevalence survey has been performed for Candida auris, making the current burden of these emerging pathogens unknown. Objective: To determine the prevalence of A baumannii and C auris among patients receiving mechanical ventilation in Maryland. Design, Setting, and Participants: The Maryland Multi-Drug Resistant Organism Prevention Collaborative performed a statewide cross-sectional point prevalence of patients receiving mechanical ventilation admitted to acute care hospitals (n = 33) and long-term care facilities (n = 18) between March 7, 2023, and June 8, 2023. Surveillance cultures (sputum, perianal, arm/leg, and axilla/groin) were obtained from all patients receiving mechanical ventilation. Sputum, perianal, and arm/leg cultures were tested for A baumannii and antibiotic susceptibility testing was performed. Axilla/groin cultures were tested by polymerase chain reaction for C auris. Main Outcomes and Measures: Prevalence of A baumannii, carbapenem-resistant A baumannii (CRAB), and C auris. Prevalence was stratified by type of facility. Results: All 51 eligible health care facilities (100%) participated in the survey. A total of 482 patients receiving mechanical ventilation were screened for A baumannii and 470 were screened for C auris. Among the 482 patients who had samples collected, 30.7% (148/482) grew A baumannii, 88 of the 148 (59.5%) of these A baumannii were CRAB, and C auris was identified in 31 of 470 (6.6%). Patients in long-term care facilities were more likely to be colonized with A baumannii (relative risk [RR], 7.66 [95% CI, 5.11-11.50], P < .001), CRAB (RR, 5.48 [95% CI, 3.38-8.91], P < .001), and C auris (RR, 1.97 [95% CI, 0.99-3.92], P = .05) compared with patients in acute care hospitals. Nine patients (29.0%) with cultures positive for C auris were previously unreported to the Maryland Department of Health. Conclusions: A baumannii, carbapenem-resistant A baumannii, and C auris were common among patients receiving mechanical ventilation in both acute care hospitals and long-term care facilities. Both pathogens were significantly more common in long-term care facilities than in acute care hospitals. Patients receiving mechanical ventilation in long-term care facilities are a high-risk population for emerging pathogens, and surveillance and prevention efforts should be targeted to these facilities.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Candida auris , Candidiasis , Instituciones de Salud , Respiración Artificial , Humanos , Acinetobacter baumannii/aislamiento & purificación , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/prevención & control , Candida auris/aislamiento & purificación , Carbapenémicos/uso terapéutico , Estudios Transversales , Pruebas de Sensibilidad Microbiana , Prevalencia , Respiración Artificial/efectos adversos , Respiración Artificial/estadística & datos numéricos , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Candidiasis/microbiología , Candidiasis/prevención & control , Maryland/epidemiología , Instituciones de Salud/estadística & datos numéricos , Vigilancia de la Población , Farmacorresistencia MicrobianaRESUMEN
Protection against lethal Candida albicans (Ca)/Staphylococcus aureus (Sa) intra-abdominal infection (IAI)-mediated sepsis can be achieved by a novel form of trained innate immunity (TII) involving Gr-1+ myeloid-derived suppressor cells (MDSCs) that are induced by inoculation (immunization) with low virulence Candida species [i.e., Candida dubliniensis (Cd)] that infiltrate the bone marrow (BM). In contrast, more virulent Candida species (i.e., C. albicans), even at sub-lethal inocula, fail to induce similar levels of protection. The purpose of the present study was to test the hypothesis that the level of TII-mediated protection induced by Ca strains inversely correlates with damage in the BM as a reflection of virulence. Mice were immunized by intraperitoneal inoculation with several parental and mutant strains of C. albicans deficient in virulence factors (hyphal formation and candidalysin production), followed by an intraperitoneal Ca/Sa challenge 14 d later and monitored for sepsis and mortality. Whole femur bones were collected 24 h and 13 d after immunization and assessed for BM tissue/cellular damage via ferroptosis and histology. While immunization with standard but not sub-lethal inocula of most wild-type C. albicans strains resulted in considerable mortality, protection against lethal Ca/Sa IAI challenge varied by strain was usually less than that for C. dubliniensis, with no differences observed between parental and corresponding mutants. Finally, levels of protection afforded by the Ca strains were inversely correlated with BM tissue damage (R 2 = -0.773). TII-mediated protection against lethal Ca/Sa sepsis induced by Candida strain immunization inversely correlates with BM tissue/cellular damage as a reflection of localized virulence.
Asunto(s)
Candidiasis , Sepsis , Ratones , Animales , Médula Ósea , Candida , Candida albicans , Candidiasis/prevención & control , Sepsis/prevención & control , InmunizaciónRESUMEN
ß-(1,2)-Mannan antigens incorporated into vaccines candidates for immunization studies, showed that antibodies raised against ß-(1,2)-mannotriose antigens can protect against disseminated candidiasis. Until recently, ß-(1,2)- mannans could only be obtained by isolation from microbial cultures, or by lengthy synthetic strategies involving protecting group manipulation. The discovery of two ß-(1,2)-mannoside phosphorylases, Teth514_1788 and Teth514_1789, allowed efficient access to these compounds. In this work, Teth514_1788 was utilised to generate ß-(1,2)-mannan antigens, tri- and tetra-saccharides, decorated with a conjugation tether at the reducing end, suitable to be incorporated on a carrier en-route to novel vaccine candidates, illustrated here by conjugation of the trisaccharide to BSA.