Invasive fungal infections in patients with cancer in the Intensive Care Unit
Infectious Diseases Unit, Pathophysiology Department, Laikon General Hospital and Medical School, National and Kapodistrian University of Athens, Athens, Greece. International journal of antimicrobial agents
(Impact Factor: 4.3).
02/2012; 39(6):464-71. DOI: 10.1016/j.ijantimicag.2011.11.017
Invasive fungal infections (IFIs) have emerged as a major cause of morbidity and mortality amongst critically ill patients. Cancer patients admitted to the Intensive Care Unit (ICU) have multiple risk factors for IFIs. The vast majority of IFIs in the ICU are due to Candida spp. The incidence of invasive candidiasis (IC) has increased over recent decades, especially in the ICU. A shift in the distribution of Candida spp. from Candida albicans to non-albicans Candida spp. has been observed both in ICUs and oncology units in the last two decades. Timely diagnosis of IC remains a challenge despite the introduction of new microbiology techniques. Delayed initiation of antifungal therapy is associated with increased mortality. Therefore, prediction rules have been developed and validated prospectively in order to identify those ICU patients at high risk for IC and likely to benefit from early treatment. These rules, however, have not been validated in cancer patients. Similarly, major clinical studies on the efficacy of newer antifungals typically do not include cancer patients. Despite the introduction of more potent and less toxic antifungals, mortality from IFIs amongst cancer patients remains high. In recent years, aspergillosis and mucormycosis have also emerged as significant causes of morbidity and mortality amongst ICU patients with haematological cancer.
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- "albicans spp. have been detected more commonly in candidemia [7,8]. Both C. albicans and non-C. "
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ABSTRACT: Invasive candidiasis is an important nosocomial infection associated with high mortality among immunosuppressive or critically ill patients. We described the incidence of invasive candidiasis in our hospital over 6 years and showed the antifungal susceptibility and genotypes of the isolated yeast.
The yeast species were isolated on CHROMagar Candida medium and identified using an yeast identification card, followed by analysis of the D1/D2 domain of 26S rDNA. The susceptibilities of the isolates to flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole were tested using the ATB FUNGUS 3 system, and that to caspofungin was tested using E-test strips. C. albicans was genotyped using single-strand conformation polymorphism of CAI (Candida albicans I) microsatellite DNA combined with GeneScan data.
From January 2006 to December 2011, a total of 259 isolates of invasive Candida spp. were obtained from 253 patients, among them 6 patients had multiple positive samples. Ninety-one stains were from blood and 168 from sterile fluids, accounting for 6.07% of all pathogens isolated in our hospital. Most of these strains were C. albicans (41.29% in blood/59.06% in sterile body fluids), followed by C. tropicalis (18.06%/25.72%), C. parapsilosis (17.42%/5.43%), C. glabrata (11.61%/3.99%) and other Candida spp. (11.61%/5.80%). Most Candida spp. were isolated from the ICU. The new species-specific CLSI candida MIC breakpoints were applied to these date. Resistance to fluconazole occurred in 6.6% of C. albicans isolates, 10.6% of C. tropicalis isolates and 15.0% of C.glabrata isolates. For the 136 C. albicans isolates, 54 CAI patterns were recognized. The C. albicans strains from blood or sterile body fluids showed no predominant CAI genotypes. C. albicans isolates from different samples from the same patient had the same genotype.
Invasive candidiasis has been commonly encountered in our hospital in the past 6 years, with increasing frequency of non-C. albicans. Resistance to fluconazole was highly predictive of resistance to voriconazole. CAI SSCP genotyping showed that all C. albicans strains were polymorphic. Invasive candidiasis were commonly endogenous infection.
Available from: jpet.aspetjournals.org
- "Hence, there is a need to develop alternative antimycotics, in particular those with novel mechanisms. Patients with cancer are particularly vulnerable to IFIs, which represent a major cause of morbidity and mortality (Sipsas and Kontoyiannis, 2012). Aspergillus is one of the main causes of IFIs in the intensive-care unit, causing 25% morbidity and 70% mortality (Andes et al., 2012). "
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ABSTRACT: We found that amiodarone has potent antifungal activity against a broad range of fungi, potentially defining a new class of antimycotics. Investigations into its molecular mechanisms showed amiodarone mobilized intracellular Ca(2+), which is thought to be an important antifungal characteristic of its fungicidal activity. Amiodarone is a synthetic drug based on the benzofuran ring system, which is contained in numerous compounds that are both synthetic and isolated from natural sources with antifungal activity. To define the structural components responsible for antifungal activity, we synthesized a series of benzofuran derivatives and tested them for the inhibition of growth of two pathogenic fungi, Cryptococcus neoformans and Aspergillus fumigatus, to find new compounds with antifungal activity. We found several derivatives that inhibited fungal growth, two of which had significant antifungal activity. We were surprised to find that calcium fluxes in cells treated with these derivatives did not correlate directly with their antifungal effects; however, the derivatives did augment the amiodarone-elicited calcium flux into the cytoplasm. We conclude that antifungal activity of these new compounds includes changes in cytoplasmic calcium concentration. Analyses of these benzofuran derivatives suggest that certain structural features are important for antifungal activity. Antifungal activity drastically increased on converting methyl 7-acetyl-6-hydroxy-3-methyl-2-benzofurancarboxylate (2b) into its dibromo derivative, methyl 7-acetyl-5-bromo-6-hydroxy-3-bromomethyl-2-benzofurancarboxylate (4).
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ABSTRACT: Invasive fungal infections (IFI) are catastrophic diseases associated with a high mortality. Relatively few cases of IFI have been described in systemic lupus erythematosus (SLE) and their related factors have not been completely explored. We evaluated factors associated with IFI in patients with SLE.
All patients with both IFI and SLE admitted to our hospital in the last 7 years were evaluated and each was compared with 5 hospitalized patients with SLE (controls). Demographic factors, duration of SLE, and treatment in the previous month were compared.
Sixty patients with SLE were evaluated (10 with IFI and 50 controls). Median age was 29 years. High C-reactive protein levels were associated with IFI, along with other factors such as high disease activity, mechanical ventilation, treatment with antibiotics, hemodialysis, high doses of glucocorticoids (GC), and treatment with mycophenolate mofetil. Mortality was 4 times more frequent in patients with IFI than in SLE patients without the deep fungal infection.
IFI is a rare infection observed in patients with rheumatic diseases. We describe factors associated with IFI in patients with SLE. IFI is associated with elevated morbidity and mortality. Early diagnosis and treatment are desirable.
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