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OBJECTIVES: The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection.
DATA SOURCES: A systematic review and meta-analysis of randomized controlled trials comparing any antifungal use versus placebo to prevent candidiasis in ICU patients were performed.
STUDY SELECTION: Searches were performed on PubMed, Embase, Scopus, main conference proceedings, and ClinicalTrials.gov, as well as reference lists.
DATA EXTRACTION: The primary outcomes were mortality and invasive candidiasis. The secondary outcome was the rate of Candida albicans and nonalbicans strains after treatment. A random effect model was used, and sensitivity analysis was performed for both outcomes. Results are expressed as risk ratios and their 95% CIs.
DATA SYNTHESIS: Nineteen trials (10 with fluconazole, four with ketoconazole, one with itraconazole, three with micafungin, and one with caspofungin) including 2,792 patients were identified. No individual trial showed a decreased mortality rate. Combined analysis showed that preventive antifungal did not decrease mortality (risk ratio, 0.88; 95% CI, 0.74-1.04; p = 0.14) but significantly decreased secondary fungal infections by 50% (risk ratio, 0.49; 95% CI, 0.35-0.68; p = 0.0001). No shift across nonalbicans strains was observed during treatment (risk ratio, 0.62; 95% CI, 0.19-1.97; p = 0.42). However, publication biases preclude any definite conclusions for prevention of infection.
CONCLUSIONS: Antifungal prevention of systemic candidiasis in immunocompetent critically ill adults did not reduce mortality and may have decreased secondary fungal infection rates. However, significant publication bias was present.
Infectious Diseases (5) Candidiasis (5), Infections (4), more mentions
RATIONALE: Mucormycosis is a rare fungal infection but life-threatening, especially in lupus nephritis (LN). Mucormycosis may manifest as rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, renal, or disseminated forms.
PATIENT CONCERNS: We report a case of a 52-year-old woman with cutaneous mucormycosis infection who was admitted because of LN.
DIAGNOSES: Histopathological analysis of the lesion confirmed the Rhizopus microspores from the family Mucoraceae.
INTERVENTIONS AND OUTCOMES: The mortality of mucormycosis remains unacceptably high. Our patient died at last even with standard therapy (aggressive surgical debridement and anti-mucormycosis drugs).
LESSONS: It is difficult to diagnose because lacking of specific clinical features, it is necessary to identify the susceptible patients, and then make diagnosis rapidly through tissue biopsy. Despite the outcome is poor, aggressive surgical debridement and Amphotericin B/Posaconazole can be effective.
Immune System Diseases (3) Mucormycosis (7), Lupus Nephritis (3), Infections (2), more mentions
To identify the epidemiology, treatments, outcomes, and risk factors for patients with early- or late-onset invasive candidiasis (EOIC or LOIC) in intensive care units in China.Patients were classified as EOIC (≤10 days) or LOIC (>10 days) according to the time from hospital admission to IC onset to identify distinct clinical characteristics.There were 105 EOIC cases and 201 LOIC cases in this study. EOIC was related to more severe clinical conditions at ICU admission or prior to IC. Significantly, more cases of Candida parapsilosis infection were found in patients with LOIC than in those with EOIC. The mortality of EOIC was significantly lower than that for LOIC. Sequential Organ Failure Assessment (SOFA) score at ICI diagnosis in the EOIC group and the interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality. Susceptibility to the first-line agent was associated with a lower risk of mortality in the LOIC group.The mortality rate was significantly lower in the EOIC group, and there were more cases of non-albicans infection in the LOIC group. Susceptibility to the first-line agent was an important predictor of mortality in the LOIC group. SOFA score at ICI diagnosis in the EOIC group and interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality.
BACKGROUND: Honokiol, a compound extracted from Magnolia officinalis, has antifungal activities by inducing mitochondrial dysfunction and triggering apoptosis in Candida albicans. However, the mechanism of honokiol-induced oxidative stress is poorly understood. The present investigation was designed to determine the specific mitochondrial reactive oxygen species (ROS)-generation component.
METHODS/RESULTS: We found that honokiol induced mitochondrial ROS accumulation, mainly superoxide anions (O2•-) measured by fluorescent staining method. The mitochondrial respiratory chain complex I (C I) inhibitor rotenone completely blocked O2•- production and provided the protection from the killing action of honokiol. Moreover, respiratory activity and the C I enzyme activity was significantly reduced after honokiol treatment. The differential gene-expression profile also showed that genes involved in oxidoreductase activity, electron transport, and oxidative phosphorylation were upregulated.
CONCLUSIONS: The present work shows that honokiol may bind to mitochondrial respiratory chain C I, leading to mitochondrial dysfunction, accompanied by increased cellular superoxide anion and oxidative stress.
GENERAL SIGNIFICANCE: This work not only provides insights on the mechanism by which honokiol interferes with fungal cell, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of M. officinalis as a Chinese medicine due to the toxic for mitochondria and suggests the possibility of using honokiol as chemosensitizer.
BACKGROUND: Candidiasis and certain types of cancer are related to immunocompromised status. This study aimed to evaluate whether Candida infection (CI) is associated with subsequent cancer risk in Taiwan.
METHODS: Data from the National Health Insurance system of Taiwan were used to evaluate the association between CI and cancer risk. The CI cohort comprised 34,829 patients. Each patient was randomly frequency matched with one person from the general population without CI on the basis of age, sex, year of index date of CI diagnosis, and other characteristics to generate the control group. We used Cox's proportional hazard regression analysis to estimate the effects of CI on subsequent cancer risk.
RESULTS: Compared with the control group, patients with CI had a significantly higher risk of overall cancer (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09-1.30). For subsite analysis, the risks of hematologic malignancy and head and neck, pancreatic, skin, and thyroid cancers were significantly higher in the CI group. Stratified analyses by sex, age, and follow-up time revealed different patterns.
CONCLUSION: Our study suggested that CI can significantly increase overall and some individual cancer risks, which is partially compatible with previous findings.
BACKGROUND: Sporotrichosis is an implantation mycosis caused by Sporothrix species prevalent worldwide, which occasionally can also result in intraocular infection presenting as an exogenous or endogenous infection (disseminated sporotrichosis). Knowledge in its clinical recognition and management is limited.
AIMS: To systematically review and analyse data from published literature with a view to comparing clinical outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix.
METHODS: Case reports of intraocular sporotrichosis, published from 1960 to 2016, were retrieved from MEDLINE, Embase, Cochrane, LILACS and SciELO databases. The entire data set was divided into two patient groups: (1) exogenous endophthalmitis and (2) endogenous endophthalmitis. Primary outcomes were differences in ocular findings and clinical ocular outcomes between the two groups.
RESULTS: From 16 publications retrieved, a total of 8 eyes of 8 patients with exogenous endophthalmitis and 13 eyes of 10 patients with endogenous endophthalmitis were identified. Compared with exogenous endophthalmitis, endogenous endophthalmitis was more common in patients infected with HIV (p=0.001) and those from hyperendemic areas (p=0.036). Anterior uveitis (p=0.015) and posterior uveitis (p=0.04) were more common in the exogenous and endogenous endophthalmitis groups, respectively. The majority of patients with endogenous endophthalmitis had partial or full clinical resolution of ocular lesions with systemic amphotericin B alone or in combination with an oral antifungal, whereas patients with exogenous endophthalmitis had poor outcomes with irreversible vision loss, enucleation and evisceration.
CONCLUSIONS: Anterior uveitis is more common in exogenous endophthalmitis with worse overall outcomes and complications, compared with endogenous endophthalmitis where posterior uveitis is the most common clinical manifestation, especially in patients infected with HIV and those from hyperendemic areas. Sporothrix infection should be included in the differential diagnosis for ocular inflammation, regardless of the presence or absence of autoimmune comorbidities and whether the patient resides in an endemic area or not. Ophthalmologists should consider intravitreal and systemic antifungal therapy for exogenous and endogenous endophthalmitis caused by Sporothrix.
Immune System Diseases (1) Endophthalmitis (14), Sporotrichosis (3), Infections (3), more mentions
Patient adherence is a key consideration in the choice of a topical regimen for the treatment of onychomycosis. The objective of this study was to investigate patient-reported outcomes (treatment utilisation, adherence and satisfaction) in onychomycosis treated with once-weekly amorolfine 5% nail lacquer versus once-daily ciclopirox 8% nail lacquer (Study A) or once-daily urea 40% ointment/bifonazole 1% cream combination regimen (Study B). Study A: Subjects received amorolfine and ciclopirox on opposite feet for 12 weeks. Study B: Subjects received amorolfine and urea/bifonazole on opposite feet for 6-7 weeks. Assessments included subject adherence as per label, treatment preference and questionnaire. Study A: More subjects adhered to amorolfine (85%) than to ciclopirox (60%) (P = .025). Overall, subjects were satisfied (95% vs 100%, respectively) and the treatments were balanced in terms of preference (50% vs 45%) at week 12. Study B: More subjects adhered to amorolfine dosage (81.8%) than to the dosage of the urea/bifonazole combination regimen (59.1%) (P = .096). At the end of study, 85.7% of subjects preferred amorolfine versus 14.3% for urea/bifonazole. Fewer subjects experienced local side effects with amorolfine (4.5%) compared to urea (27.3%) and bifonazole (15%). Amorolfine 5% nail lacquer offers a simple and convenient treatment option, which may result in improved patient adherence and consequently lead to improved efficacy and patient satisfaction.
Candida albicans is the most common fungal microorganism in healthy individuals, as well as the cause of high mortality infections in high-risk hosts such as immunocompromised patients. Antifungal vaccines and monoclonal antibodies useful for active or passive immunizations have recently generated considerable excitement for the treatment of fungal infections. The cell wall proteins of C. albicans, which are crucial for virulence and pathogenicity, are attractive target antigens. Als3p, a member of the C. albicans agglutinin-like sequence (ALS) family, is a hyphal-specific glycophosphatidylinositol cell wall protein that plays a key role in the interaction with host cells. The abundance of Als3p on the hyphal surface makes it an attractive target. For example, the NDV-3 vaccine, targeted at the N-terminus of Als3p, has entered a preparation of Phase 2 clinical trial. The Als3p-specific antibodies include monoclonal antibodies (MAbs) 3-A5, MAb 113, and scFv3. In addition, MAb C7, MAb 3D9.3 and MAb 2G8, which were supposed to be identifying other targets, have also provided good protection by recognizing Als3p. In this review, we summarize the functions of Als3p and highlight the development of the vaccines and the antibodies that are associated, directly or indirectly, with this protein.
BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is acommon opportunistic, mucosal fungal infection, predominantly caused by the fungus Candida albicans.Mannose-binding lectin (MBL) is an acute-phase protein that plays a key role in the innate immunity defense against infectious disease.
OBJECTIVES: The present study was conducted to evaluate the relationship between the MBL serum level and the relative expression of MBL mRNA in RVVC using real-time PCR for the first time.
PATIENTS/METHODS: The case-control study included 40 female participants suffering from RVVC and 40 healthy individuals. The MBL serum level was measured using a commercial ELISA kit. The relative mRNA expression of the MBL gene was quantified using real-time PCR. Data analysis was done by SPSS software.
RESULTS: The MBL concentration was significantly higher in the participants suffering from RVVC compared to the control group (0.330 ng/ml versus 0.253 ng/ml). The prognostic value (P<0.001) for RVVC diagnosis has been calculated. Quantitative RT-PCR results from 35 samples showed a low to significant values for mRNA levels corresponding to MBL gene expression (1-352 folds) (P<0.001).
CONCLUSION: The results of this study suggest that MBL plays a main role in the innate immunity and it is also affected by environmental factors and other genetic variations. Therefore, the MBL gene expression profile does not reflect precise phenotypic levels in the serum. This article is protected by copyright. All rights reserved.
OBJECTIVE: Severe dermatophytosis is described in immunocompromised patients with defective cellular immunity. We report here a large series and a literature review of severe dermatophytosis in solid organ transplant (SOT) recipients.
METHOD: The data main source was a national French retrospective study of severe dermatophytosis in SOT recipients between 2010 and 2016. Inclusion criteria were the presence of dermatophytes in skin culture and one severity criteria: dermal invasion by dermatophytes (invasive dermatophytosis) or involvement of at least two body sites or >10% of body surface area (extensive dermatophytosis) RESULTS: Twelve patients were included (8 men, median age of 56 years [range: 33-71]). Ten were kidney transplant. The median time from transplantation to severe dermatophytosis diagnosis was 16 months [range: 2-94]. Clinical signs of superficial dermatophytosis were present in 8/12 patients before the emergence of severe dermatophytosis. Nine patients had invasive forms and three extensive ones and nodules of the lower extremities were found in eight. Trichophyton rubrum was isolated in 11 cases. First line treatment was terbinafine (7/12), posaconazole (3/12) or topical treatment alone (2/12). Immunosuppressive therapy was reduced in three patients because of associated infections. Complete response was obtained for 3/3 and 5/9 patients with extensive or invasive forms, respectively after a median treatment's duration of 2.5 [range: 1.5-5] months and 7.5 months [range: 4-12]. Unrelated deaths (n = 2) and graft function impairment (n = 3) occurred.
CONCLUSION: Severe dermatophytosis is a late complication in SOT recipients presenting with lower limb nodules, which might be prevented by prompt treatment of superficial dermatophytosis. This article is protected by copyright. All rights reserved.
PURPOSE: IL-17 antagonists are effective for psoriasis in clinical trials, but long-term safety is not fully characterized. Since chronic mucocutaneous candidiasis (CMC) is caused by defects in the IL-17 pathway, CMC risk data has been touted as providing reassurance about the safety of IL-17 antagonism.
METHODS: We performed a literature review to identify patients with CMC and compared the prevalence of cancer in these patients to the reported 5-year prevalence.
RESULTS: There was a higher prevalence of oropharyngeal (2.5% vs. 0.028%; p < 0.0001) and esophageal cancer (1.9% vs 0.013%; p < 0.0001) in patients with CMC. There were no reports of cancer in 31 patients with CMC caused by an isolated IL-17 deficiency (IL-17F, IL-17RA, IL17RC); however, a study would need over 1,000 patients to detect even a 10-fold increase of the most common malignancy of CMC patients.
CONCLUSIONS: There is evidence that some forms of CMC are associated with an increase in cancer. While CMC is heterogeneous, our findings suggest that we cannot use CMC data to reassure patients on the long-term safety of IL-17 antagonists beyond the safety results from clinical trials, and perhaps caution should be taken with the development of candidiasis in patients taking these medications.
CARD9 deficiency (CANDF2; OMIM# 212050) is an autosomal-recessive monogenic inborn error of immunity conferring susceptibility to invasive fungal diseases, including the very distinct syndrome of spontaneous central nervous system candidiasis, in which opportunistic yeast of the genus Candida infect the central nervous system (either brain parenchyma and/or meninges) in the absence of trauma, chemotherapy or underlying systemic disease. We present a patient with spontaneous endophthalmitis of the right eye due to Candida albicans; further investigations revealed concomitant cerebral abscess. She had a history of left endophthalmitis due to the dematiaceous mould, Aureobasidium pullulans, 15 years earlier. Targeted sequencing of the CARD9 gene revealed 2 novel variants (c.184G>A and c.288C>T). Analysis in silico predicted each variant altered splicing, which was confirmed by sequencing of cDNA from proband and carrier offsprings: c.184G>A results in a 4-base pair frameshift deletion with loss of allelic expression; c.288C>T results in an in-frame 36-bp pair deletion with detectable protein. CARD9 deficiency can present with a phenotype of spontaneous candidal endophthalmitis. We report 2 novel mutations in CARD9, both affecting splicing, expanding the range of morbid variants causing CARD9 deficiency, emphasising the importance of both genomic and cDNA sequencing for this condition.
Nail psoriasis and onychomycosis can often be hard to differentiate clinically and may coexist, complicating each other's course. The aim of this study was to determine the prevalence of onychomycosis among patients with nail psoriasis not being treated with immunosuppressive agents, which constitute an independent risk factor for fungal infections. A cross-sectional study was performed. All adult patients with nail psoriasis who were not receiving antifungal and/or immunosuppressive treatment were recruited at the 2nd University Dermatology Department of Aristotle University of Thessaloniki from 10/2016 till 02/2017. If onychomycosis was clinically suspected, nail samples were collected and direct microscopy with 15% KOH solution and culture were performed. Target-NAPSI and DLQI score were also calculated. Of the 23 patients recruited, 20 were men and 3 were women, with a mean age of 53.43 years (48.25, 58.62), a mean target-NAPSI score of 10.72 (9.62, 11.77) and a mean DLQI score of 10.17 (7.46, 12.89). A total of 34.78% of patients tested positive for onychomycosis. Yeast were isolated in 37.50% of cases, non-dermatophyte filamentous fungi in 37.50% and T. rubrum in 12.50%. The prevalence of onychomycosis among nail psoriasis patients is higher than that among the general population of Greece (15%-20%). Yeast and moulds predominate in infection cases of nail psoriasis patients.
Dermatology (9) Psoriasis (8), Onychomycosis (7), Infections (2), more mentions
Invasive Candida infection is the fourth most common bloodstream infection. Blood cultures are the current gold standard diagnostic method, however false negatives remain a clinical challenge. We developed a new technique measuring Candida reactive T cells as diagnostic read-out for invasive Candida infection. In a pilot study, we followed the treatment course of a patient with an invasive Candida infection of the lumbar vertebral spine. We present the case of the 56 year old patient with HIV-associated Burkitt lymphoma who developed septic shock during chemotherapy induced neutropenia. For the first time, we provide flow cytometry based diagnostics with Candida reactive T cells for invasive candidiasis with comprehensive MRI imaging. The Candida reactive T cell assay has potential to complement current diagnostic assays for invasive Candida infection and thus to support targeted treatment. This article is protected by copyright. All rights reserved.
Oral infections caused by Candida species, the most commonly isolated human fungal pathogen, are frequently associated with biofilms. Although Candida albicans is the predominant organism found in patients with oral thrush, a biofilm infection, there is an increasing incidence of oral colonization and infections caused by non- albicans Candida species, including C. glabrata, C. dubliniensis, and C. tropicalis, which are frequently more resistant to antifungal treatment. While single-species Candida biofilms have been well studied, considerably less is known about the dynamics of mixed- Candida species biofilms and how these dynamics are altered by antifungal treatment. To address these questions, we developed a quantitative polymerase chain reaction-based approach to determine the precise species composition of mixed- Candida species biofilms formed by clinical isolates and laboratory strains in the presence and absence of clinically relevant concentrations of 3 commonly used antifungals: fluconazole, caspofungin, and amphotericin B. In monospecies biofilms, fluconazole exposure favored growth of C. glabrata and C. tropicalis, while caspofungin generally favored significant growth of all species to a varying degree. Fluconazole was not effective against preformed mixed- Candida species biofilms while amphotericin B was potent. As a general trend, in mixed- Candida species biofilms, C. albicans lost dominance in the presence of antifungals. Interestingly, presence in mixed versus monospecies biofilms reduced susceptibility to amphotericin B for C. tropicalis and C. glabrata. Overall, our data suggest that antifungal treatment favors the growth of specific non- albicans Candida species in mixed- Candida species biofilms.
BACKGROUND: Neutropenic patients developing acute disseminated candidiasis may present with skin lesions.
AIMS: To evaluate the epidemiology of acute disseminated candidiasis with skin lesions in neutropenic patients, taking into consideration changes caused by different prophylactic strategies.
SOURCES: A systematic review of English articles using PubMed (1963-2016) was performed. We asked the following questions: (1) What Candida species are more frequently involved in this syndrome? (2) Has antifungal prophylaxis changed the species causing skin lesions? (3) What are the typical patterns of skin lesions? (4) What is the frequency of skin lesions in neutropenic patients with candidemia or acute disseminated candidiasis? (5) Has antifungal prophylaxis decreased the incidence of acute disseminated candidiasis with skin lesions?
CONTENT: Among 183 studies, 33 were selected, reporting 100 cases of acute disseminated candidiasis with skin lesions in neutropenic patients. It occurred more frequently in the setting of induction therapy for de novo or relapsed acute leukemia, and the most frequent species were C. tropicalis (68%) and C. krusei (15%). Diffuse maculopapular lesions predominated in cases caused by C. tropicalis and nodular and papular lesions in cases caused by C. krusei. Prophylaxis with fluconazole was reported in six cases; C. krusei in five, and C. ciferri in one. The death rate was 46.3%.
IMPLICATIONS: Two patterns were recognized: disseminated maculopapular lesions caused by C. tropicalis in patients not receiving fluconazole prophylaxis, occurring in 39-44% of neutropenic patients with acute disseminated candidiasis, and nodular lesions caused by C. krusei in patients on fluconazole prophylaxis, occurring less frequently.