Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006–2008)

Tortorano, Anna Maria; Dho, Giovanna; Prigitano, Anna; Breda, Giuseppe; Grancini, Anna; Emmi, V.; Cavanna, C.; Marino, Giovanni; Morero, Silvia; Ossi, C.; Delvecchio, G; Passera, Marco; Cusumano, Vitaliano; David, Antonio; Bonaccorso, G.; Corona, Alberto; Favaro, M.; Vismara, Chiara; Garau, Maria Graziella; Falchi, S; Tejada, M.

doi:10.1111/j.1439-0507.2011.02044.x

Cited by 106 publications

(88 citation statements)

References 21 publications

(71 reference statements)

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“…Among Candida species, Candida glabrata and Candida albicans account for about 20 and 60%, respectively, of Candida bloodstream infections (3)(4)(5). C. glabrata, a constituent of the normal human microflora, is emerging as a clinically important opportunistic fungal pathogen, as the mortality rate of up to 60% has been associated with C. glabrata infections (5)(6)(7).…”

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confidence: 99%

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

Sharma

Purushotham

Kaur

2016

Journal of Biological Chemistry

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Edited by James SiedowThe phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival, and virulence in the pathogenic yeast Candida glabrata. Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption. Consistently, the Cgvps34⌬ mutant displayed growth attenuation in low-and high-iron media, increased intracellular iron content, elevated mitochondrial aconitase activity, impaired biofilm formation, and extenuated mouse organ colonization potential. Furthermore, we demonstrate for the first time that C. glabrata cells respond to iron limitation by expressing the iron permease CgFtr1 primarily on the cell membrane, and to iron excess via internalization of the plasma membrane-localized CgFtr1 to the vacuole. Our data show that CgVps34 is essential for the latter process. We also report that macrophage-internalized C. glabrata cells express CgFtr1 on the cell membrane indicative of an iron-restricted macrophage internal milieu, and Cgvps34⌬ cells display better survival in iron-enriched medium-cultured macrophages. Overall, our data reveal the centrality of PI3K signaling in iron metabolism and host colonization.

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confidence: 99%

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

Sharma

Purushotham

Kaur

2016

Journal of Biological Chemistry

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“…In most previous studies, A. fumigatus was the predominant species of Aspergillus from patients with IA (10,21,33,37). In our previous environmental studies A. flavus also was the most distributed species among genus Aspergillus in indoor and outdoor environment (16,17).…”

Section: Discussionmentioning

confidence: 66%

“…The mortality percentage among IA patients was 61.5%. The previous studies have shown a diverse incidence of IA in ICU patients (10,24,37). Meersseman et al (24) in a review paper presented an incidence of IA from 0.33% to 19% among ICU patients.…”

Section: Discussionmentioning

confidence: 97%

“…Meersseman et al (24) in a review paper presented an incidence of IA from 0.33% to 19% among ICU patients. Recently, Tortorano et al (37) in a prospective survey in 38 ICUs of 27 Italian hospitals reported the median rate of 6.31 per 1000 admissions (range 1.26-28.64) for Aspergillus infection. This diversity may be due to difference in design of study, duration of study, type of underlying or immunosuppressive conditions and diagnosis methods.…”

Section: Discussionmentioning

confidence: 99%

“…These data are concordant with other previous studies (10)(11)(12)24) however Meersseman et al (25) reported a mortality rate for IA in ICU patients up to 97%. It should also be indicated that aspergillosis is more severe than candidiasis as the most prevalent fungal infections among ICU patients (37).…”

Section: Discussionmentioning

confidence: 99%

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Invasive Aspergillosis in Intensive Care Unit Patients in Iran

Hedayati

Khodavaisy

Amini

et al. 2013

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary:We assessed the intensive care unit (ICU) patients for Invasive aspergillosis (IA) with culture and non-culture based diagnostic methods from Iran. Thirty-six ICU patients with underlying predisposing conditions for IA were enrolled in the study. Sixty eight Bronchoalveolar lavage (BAL) samples were collected by bronchoscope twice a weekly. BAL samples were analyzed by microscopic examination, fungal culture and galactomannan (GM) detection. The Platelia Aspergillus GM EIA was used to quantify GM indices. Samples with a BAL GM index ≥1 were considered as positive for GM. Patients were classified as having probable or possible IA. Out of 36 suspected patients to IA, 36.1% of cases showed IA which were categorized as: 4 cases of possible IA and 9 of probable IA. 76.2% of BAL samples were positive for GM. From 13 patients with IA, 11 (84.6%) had at least one positive BAL GM index. Of these patients, 9 (81.8%) showed probable IA. The main underlying predisposing conditions were neutropenia (53.8%) and COPD (30.8%). Our study has indicated that COPD must be considered as one of the main predisposing condition for occurrence of aspergillosis in ICU patients. Our data have also revealed that GM detection in BAL samples play a significant role to IA diagnosis.

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The Changing Epidemiology of Invasive Fungal Infections

Enoch

Yang

Aliyu

et al. 2016

Methods in Molecular Biology

285

208

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Invasive fungal infections (IFI) are an emerging problem worldwide with invasive candidiasis and candidemia responsible for the majority of cases. This is predominantly driven by the widespread adoption of aggressive immunosuppressive therapy among certain patient populations (e.g., chemotherapy, transplants) and the increasing use of invasive devices such as central venous catheters (CVCs). The use of new immune modifying drugs has also opened up an entirely new spectrum of patients at risk of IFIs. While the epidemiology of candida infections has changed in the last decade, with a gradual shift from C. albicans to non-albicans candida (NAC) strains which may be less susceptible to azoles, these changes vary between hospitals and regions depending on the type of population risk factors and antifungal use. In certain parts of the world, the incidence of IFI is strongly linked to the prevalence of other disease conditions and the ecological niche for the organism; for instance cryptococcal and pneumocystis infections are particularly common in areas with a high prevalence of HIV disease. Poorly controlled diabetes is a major risk factor for invasive mould infections. Environmental factors and trauma also play a unique role in the epidemiology of mould infections, with well-described hospital outbreaks linked to the use of contaminated instruments and devices. Blastomycosis is associated with occupational exposure (e.g., forest rangers) and recreational activities (e.g., camping and fishing).The true burden of IFI is probably an underestimate because of the absence of reliable diagnostics and lack of universal application. For example, the sensitivity of most blood culture systems for detecting candida is typically 50 %. The advent of new technology including molecular techniques such as 18S ribosomal RNA PCR and genome sequencing is leading to an improved understanding of the epidemiology of the less common mould and dimorphic fungal infections. Molecular techniques are also providing a platform for improved diagnosis and management of IFI.Many factors affect mortality in IFI, not least the underlying medical condition, choice of therapy, and the ability to achieve early source control. For instance, mortality due to pneumocystis pneumonia in HIV-seronegative individuals is now higher than in seropositive patients. Of significant concern is the progressive increase in resistance to azoles and echinocandins among candida isolates, which appears to worsen the already significant mortality associated with invasive candidiasis. Mortality with mould infections approaches 50 % in most studies and varies depending on the site, underlying disease and the use of antifungal agents such as echinocandins and voriconazole. Nevertheless, mortality for most IFIs has generally fallen with advances in medical technology, improved care of CVCs, improved diagnostics, and more effective preemptive therapy and prophylaxis.

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Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006–2008)

Cited by 106 publications

References 21 publications

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

The Phosphoinositide 3-Kinase Regulates Retrograde Trafficking of the Iron Permease CgFtr1 and Iron Homeostasis in Candida glabrata

Invasive Aspergillosis in Intensive Care Unit Patients in Iran

The Changing Epidemiology of Invasive Fungal Infections

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