Candida auris is an emerging species of yeast characterized by colonization of skin, persistence in the healthcare environment, and antifungal resistance. C. auris was first described in 2009 from a ...single isolate but has since been reported in more than 25 countries worldwide. Resistance to fluconazole and amphotericin B is common, and resistance to the echinocandins is emerging in some countries. Antifungal resistance has been shown to be acquired rather than intrinsic and the primary mechanisms of resistance to the echinocandins and azoles have been determined. There are a number of new antifungal agents in phase 2 and phase 3 clinical trials and many have activity against C. auris. This review will discuss what is currently known about antifungal resistance in C. auris, limitations to antifungal susceptibility testing, the mechanisms of resistance, and the new antifungals that are on the horizon.
Although not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST ...is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for
Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of
data.
The epidemiology of invasive candidiasis has evolved in recent years, warranting a review of the changes and the implications for current and future diagnosis and treatment. The overall burden of ...invasive candidiasis remains high, particularly in the expanding populations of patients at risk of opportunistic infection, such as the elderly or immunosuppressed. Progressive shifts from Candida albicans to non-albicans Candida spp. have been observed globally. The recent emergence of novel, multiresistant species, such as Candida auris, amplifies the call for vigilance in detection and advances in treatment. Among the current treatment options, fluconazole is still widely used throughout the world. Increased resistance to fluconazole, both acquired and naturally emerging, has been observed. Resistance to echinocandins is presently low but this may change with increased use. Improvement of diagnostic techniques and strategies, development of international surveillance networks and implementation of antifungal stewardship programmes represent major challenges for a better epidemiological control of invasive candidiasis.
Recent reports have demonstrated a decline in bacterial bloodstream infections (BSIs) following adherence to central line insertion practices; however, declines have been less evident for BSIs due to ...Candida species.
We conducted active, population-based laboratory surveillance for candidemia in metropolitan Atlanta, GA and Baltimore, MD over a 5-year period. We calculated annual candidemia incidence and antifungal drug resistance rates.
We identified 3,848 candidemia cases from 2008-2013. Compared with 2008, candidemia incidence per 100,000 person-years decreased significantly by 2013 in both locations (GA: 14.1 to 9.5, p<0.001; MD: 30.9 to 14.4, p<0.001). A total of 3,255 cases (85%) had a central venous catheter (CVC) in place within 2 days before the BSI culture date. In both locations, the number of CVC-associated cases declined (GA: 473 to 294; MD: 384 to 151). Candida albicans (CA, 36%) and Candida glabrata (CG, 27%) were the most common species recovered. In both locations, the proportion of cases with fluconazole resistance decreased (GA: 8.0% to 7.1%, -10%; MD: 6.6% to 4.9%, -25%), while the proportion of cases with an isolate resistant to an echinocandin increased (GA: 1.2% to 2.9%, +147%; MD: 2.0% to 3.5%, +77%). Most (74%) echinocandin-resistant isolates were CG; 17 (<1%) isolates were resistant to both drug categories (multidrug resistant MDR, 16/17 were CG). The proportion of CG cases with MDR Candida increased from 1.8% to 2.6%.
We observed a significant decline in the incidence of candidemia over a five-year period, and increases in echinocandin-resistant and MDR Candida. Efforts to strengthen infection control practices may be preventing candidemia among high-risk patients. Further surveillance for resistant Candida is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fungal infections throughout the world appear to be increasing. This may in part be due to the increase in the population of patients that are susceptible to otherwise rare fungal infections ...resulting from the use of immune modulating procedures such as hematopoietic stem cell transplants and drugs like tissue necrosis factor antagonists. Histoplasma capsulatum, an endemic fungus throughout North and South America, is reemerging among HIV+ patients in Central and South America and among patients taking tissue necrosis factor antagonists and other biologics in North America. Fusarium species, a relatively rare fungal infection, is reemerging worldwide in the immunocompromised populations, especially those who are neutropenic like hematopoietic stem cell transplant recipients. A new yeast species is currently emerging worldwide: Candida auris, unknown just a decade ago. It is causing large healthcare-associated outbreaks on four continents and is spreading throughout the world through patient travel. In this review the epidemiology, pathology, detection and treatment of these three emerging and reemerging fungi will be discussed.
is an emerging multidrug-resistant fungal pathogen causing nosocomial and invasive infections associated with high mortality.
is commonly misidentified as several different yeast species by ...commercially available phenotypic identification platforms. Thus, there is an urgent need for a reliable diagnostic method. In this paper, we present fast, robust, easy-to-perform and interpret PCR and real-time PCR assays to identify
and related species:
,
, and
Targeting rDNA region nucleotide sequences, primers specific for
only or
and related species were designed. A panel of 140 clinical fungal isolates was used in both PCR and real-time PCR assays followed by electrophoresis or melting temperature analysis, respectively. The identification results from the assays were 100% concordant with DNA sequencing results. These molecular assays overcome the deficiencies of existing phenotypic tests to identify
and related species.
and the emerging non-
spp. have significant clinical relevance among many patient populations. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of ...these infections, but it is only fungistatic against
spp. and both inherent and acquired resistance to fluconazole have been reported. Such mechanisms of resistance include increased drug efflux, alteration or increase in the drug target, and development of compensatory pathways for producing the target sterol, ergosterol. While many mechanisms of resistance observed in
are also found in the non-
species, there are also important and unexpected differences between species. Furthermore, mechanisms of fluconazole resistance in emerging
spp., including the global health threat
, are largely unknown. In order to preserve the utility of one of our fundamental antifungal drugs, fluconazole, it is essential that we fully appreciate the manner by which
spp. manifest resistance to it.
Candida auris is an emerging, multi-drug resistant, health care-associated fungal pathogen. Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize ...the skin, or persist in an environment outside the host-a trait unique from other Candida species. Besides being associated globally with life-threatening disseminated infections, C. auris also poses significant clinical challenges due to its ability to adhere to polymeric surfaces and form highly drug-resistant biofilms. Here, we performed bioinformatic studies to identify the presence of adhesin proteins in C. auris, with sequence as well as 3-D structural homologies to the major adhesin/invasin of C. albicans, Als3. Anti-Als3p antibodies generated by vaccinating mice with NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) recognized C. auris in vitro, blocked its ability to form biofilms and enhanced macrophage-mediated killing of the fungus. Furthermore, NDV-3A vaccination induced significant levels of C. auris cross-reactive humoral and cellular immune responses, and protected immunosuppressed mice from lethal C. auris disseminated infection, compared to the control alum-vaccinated mice. The mechanism of protection is attributed to anti-Als3p antibodies and CD4+ T helper cells activating tissue macrophages. Finally, NDV-3A potentiated the protective efficacy of the antifungal drug micafungin, against C. auris candidemia. Identification of Als3-like adhesins in C. auris makes it a target for immunotherapeutic strategies using NDV-3A, a vaccine with known efficacy against other Candida species and safety as well as efficacy in clinical trials. Considering that C. auris can be resistant to almost all classes of antifungal drugs, such an approach has profound clinical relevance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated ...infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis.
Methods
We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention’s Emerging Infections Program during April–August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher’s exact tests.
Results
Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit–level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%).
Conclusions
One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.
We used surveillance data to assess differences in candidemia patients with and without a prior COVID-19 diagnosis. Patients with COVID-19 and candidemia lacked established underlying conditions associated with candidemia but had twice the mortality rate versus candidemia patients without COVID-19.
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