The most enigmatic aspect of the rise of
as a human pathogen is that it emerged simultaneously on three continents, with each clade being genetically distinct. Although new pathogenic fungal species ...are described regularly, these are mostly species associated with single cases in individuals who are immunosuppressed. In this study, we used phylogenetic analysis to compare the temperature susceptibility of
with those of its close relatives and to use these results to argue that it may be the first example of a new fungal disease emerging from climate change, with the caveat that many other factors may have contributed.
Mucormycoses Farmakiotis, Dimitrios; Kontoyiannis, Dimitrios P
Infectious disease clinics of North America,
03/2016, Volume:
30, Issue:
1
Journal Article
Peer reviewed
Life-threatening infections from virulent, angioinvasive molds of the order Mucorales are being recognized with increasing frequency in immunosuppressed hosts. Advances in the understanding of ...pathogenesis, early diagnosis, and the recent availability of active, nontoxic drugs have improved the prospects for effective control and even cure of this devastating infection. However, rates of delayed diagnosis and mortality are still high, partially because of the low yield and complexity of culture-based and molecular diagnostic methods. Therefore, there is an urgent need for novel diagnostic modalities and effective therapeutic approaches.
Mucormycosis (MCR) has been increasingly described in patients with coronavirus disease 2019 (COVID-19) but the epidemiological factors, presentation, diagnostic certainty, and outcome of such ...patients are not well described. We review the published COVID-19-associated mucormycosis (CAMCR) cases (total 41) to identify risk factors, clinical features, and outcomes. CAMCR was typically seen in patients with diabetes mellitus (DM) (94%) especially the ones with poorly controlled DM (67%) and severe or critical COVID-19 (95%). Its presentation was typical of MCR seen in diabetic patients (mostly rhino-orbital and rhino-orbital-cerebral presentation). In sharp contrast to reported COVID-associated aspergillosis (CAPA) cases, nearly all CAMCR infections were proven (93%). Treating physicians should have a high suspicion for CAMCR in patients with uncontrolled diabetes mellitus and severe COVID-19 presenting with rhino-orbital or rhino-cerebral syndromes. CAMR is the convergence of two storms, one of DM and the other of COVID-19.
While
spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as
,
, and
spp. are increasingly encountered in ...an expanding population of patients with severe and prolonged immunosuppression. High potential for tissue invasion and dissemination, resistance to multiple antifungals and high mortality rates are hallmarks of these non-
invasive mold infections (NAIMIs). Assessment of drug efficacy is particularly difficult in the complex treatment scenarios of NAIMIs. Specifically, correlation between
susceptibility and
responses to antifungals is hard to assess, in view of the multiple, frequently interrelated factors influencing outcomes, such as pharmacokinetic/pharmacodynamic parameters determining drug availability at the site of infection, the net state of immune suppression, delay in diagnosis, or surgical debulking of infectious foci. Our current therapeutic approach of NAIMIs should evolve toward a better integration of the dynamic interactions between the pathogen, the drug and the host. Innovative concepts of experimental research may consist in manipulating the host immune system to induce a specific antifungal response or targeted drug delivery. In this review, we discuss the challenges in the management of NAIMIs and provide an update about the latest advances in diagnostic and therapeutic approaches.
Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers ...historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients.
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BFBNIB, NUK, PNG, UL, UM, UPUK
How I treat mucormycosis Kontoyiannis, Dimitrios P.; Lewis, Russell E.
Blood,
08/2011, Volume:
118, Issue:
5
Journal Article
Peer reviewed
Open access
Unlike invasive aspergillosis, the prognosis and outcome of hematologic malignancy patients who develop invasive mucormycosis have not significantly improved over the past decade as a majority of ...patients who develop the infection still die 12 weeks after diagnosis. However, early recognition and treatment of invasive mucormycosis syndromes, as well as individualized approaches to treatment and secondary prophylaxis, could improve the odds of survival, even in the most persistently immunosuppressed patient receiving chemotherapy and/or of stem cell transplantation. Herein, we describe the subtle clinical and radiographic clues that should alert the hematologist to the possibility of mucormycosis, and aggressive and timely treatment approaches that may limit the spread of infection before it becomes fatal. Hematology patients with this opportunistic infection require integrated care across several disciplines and frequently highly individualized and complex sequence of decision-making. We also offer perspectives for the use of 2 antifungals, amphotericin B products and posaconazole, with activity against Mucorales. The availability of posaconazole in an oral formulation that can be administered safely for prolonged periods makes it an attractive agent for long-term primary and secondary prophylaxis. However, serum drug concentration monitoring may be required to minimize breakthrough infection or relapsing mucormycosis associated with inadequate blood concentrations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer patients are at risk for candidemia, and increasing Candida spp. resistance poses an emerging threat. We determined rates of antifungal drug resistance, identified factors associated with ...resistance, and investigated the correlation between resistance and all-cause mortality rates among cancer patients with ≥1 C. glabrata-positive blood culture at MD Anderson Cancer Center, Houston, Texas, USA, during March 2005-September 2013. Of 146 isolates, 30 (20.5%) were resistant to fluconazole, 15 (10.3%) to caspofungin, and 10 (6.8%) to multiple drugs (9 caspofungin-resistant isolates were also resistant to fluconazole, 1 to amphotericin B). Independently associated with fluconazole resistance were azole preexposure, hematologic malignancy, and mechanical ventilation. Independently associated with caspofungin resistance were echinocandin preexposure, monocytopenia, and total parenteral nutrition. Fluconazole resistance was highly associated with caspofungin resistance, independent of prior azole or echinocandin use. Caspofungin resistance was associated with increased 28-day all-cause mortality rates. These findings highlight the need for good stewardship of antifungal drugs.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Global warming was proposed to be a contributing cause for the nearly simultaneous emergence of different clades of
as a nosocomial pathogen in different continents. The global warming emergence ...hypothesis posits that
existed in the environment prior to its clinical recognition and became pathogenic for humans because of thermal adaptation in response to climate change. The isolation of
from two sites in the remote Andaman Islands establishes it as an environmental organism, a necessary condition for the hypothesis. The observation that one environmental isolate grew slower at mammalian temperatures than clinical strains is consistent with the notion that their ancestor recently adapted to higher temperatures. The knowledge that
can be recovered from the environment should prompt additional searches to define its ecological niches, and the analysis of future environmental isolates will provide evidence for validating or refuting the global warming emergence hypothesis.
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