High Risk For Fungal Infections Research Articles

Mobile air-decontamination units: Can they be used for immunocompromised patients at high risk for fungal infections?

Immunocompromised patients in the hematology department are usually hospitalized in areas protected by the high-efficiency particulate air (HEPA) filtration system. Renovations may require moving these patients at risk for invasive fungal infection to areas without HEPA. Mobile air handling units may be a solution in these cases. For renovation purposes, we evaluated the efficiency of mobile air handling units called Plasmair® as well as their optimization, by comparing two generations of devices.Particle counts were performed to determine a particle cleanliness classification according to the ISO 14644–1 standard (high ISO classes correspond to a degraded particulate cleanliness). Mycological air samples were also taken to determine the percentage of positive samples and the median number of filamentous fungi colonies.Without air treatment, only 18 % (38/216) of particle counts were classified as ISO 6. With the use of mobile air treatment units, this proportion increased to 71 % (205/288). The positivity rate of mycological samples without air treatment was 86 % (31/36) with a median number of fungal colonies of 3 (1–5)/0.5m3. A significant decrease in fungal pressure was observed when using Plasmair®. Percentages of positive air samples and the median number of colonies found between the old generation Plasmair® (T2006) and the new generation Plasmair® (Guardian) were significantly different, respectively 55.6 % (20/36) versus 22.2 % (8/36) and 1(0–1) versus 0 (0–0).Finally, we confirm Plasmair® were effective in reducing airborne fungal pressure, the new generation especially. However, they were not effective enough to obtain negative mycological air samples as usually observed with the HEPA system, whatever the generation.

Advancing Vaccine Strategies against Candida Infections: Exploring New Frontiers.

Candida albicans, along with several non-albicans Candida species, comprise a prominent fungal pathogen in humans, leading to candidiasis in various organs. The global impact of candidiasis in terms of disease burden, suffering, and fatalities is alarmingly high, making it a pressing global healthcare concern. Current treatment options rely on antifungal drugs such as azoles, polyenes, and echinocandins but are delimited due to the emergence of drug-resistant strains and associated adverse effects. The current review highlights the striking absence of a licensed antifungal vaccine for human use and the urgent need to shift our focus toward developing an anti-Candida vaccine. A number of factors affect the development of vaccines against fungal infections, including the host, intraspecies and interspecies antigenic variations, and hence, a lack of commercial interest. In addition, individuals with a high risk of fungal infection tend to be immunocompromised, so they are less likely to respond to inactivated or subunit whole organisms. Therefore, it is pertinent to discover newer and novel alternative strategies to develop safe and effective vaccines against fungal infections. This review article provides an overview of current vaccination strategies (live attenuated, whole-cell killed, subunit, conjugate, and oral vaccine), including their preclinical and clinical data on efficacy and safety. We also discuss the mechanisms of immune protection against candidiasis, including the role of innate and adaptive immunity and potential biomarkers of protection. Challenges, solutions, and future directions in vaccine development, namely, exploring novel adjuvants, harnessing the trained immunity, and utilizing immunoinformatics approaches for vaccine design and development, are also discussed. This review concludes with a summary of key findings, their implications for clinical practice and public health, and a call to action for continued investment in candidiasis vaccine research.

MicroRNAs: Regulators of the host antifungal immune response

Fungi pose a severe threat to human health worldwide, especially to patients with weakened immune systems. Perioperative patients are at a high risk of fungal infection and death because of the immunosuppression caused by the surgery, as well as the use of surgical instruments. Perioperative patients in ICU are at greater risk of fungal infection. Fungal infections are often difficult to identify, and the treatment is particularly challenging. A well-functioning host immune and an appropriate level of inflammation is essential for controlling fungal infections. MicroRNAs (miRNAs) play critical roles in regulating host immune function, primarily through participating in the post-transcriptional regulation of target genes. After fungal infection, miRNAs are differentially expressed in various tissues, cells, and extracellular vesicles, promoting or inhibiting antifungal effects through different mechanisms to modulate the host immune response. In addition, differentially expressed miRNAs could serve as potential biological markers for the diagnosis and treatment of fungal infections. In this review, we discuss the role and significance of miRNAs in fungal infections.

MEDIA ALTERNATIF EKSTRAK UBI JALAR SEBAGAI MEDIA TUMBUH JAMUR Aspergillus sp dan Candida sp PADA SERUMEN TELINGA PETANI DI KELURAHAN DORPEDU KOTA TERNATE

Fungal are plants that require habitat conditions and high humidity. So it is one of the causes of public health problems in Indonesia. Groups at high risk of fungal infection are farmers because one of them is in direct contact with warm and humid areas at work. Otomycosis is a fungal infection that often occurs in the outer ear. Predisposing factors that influence include high humidity, local trauma which is often caused by the habit of using cotton buds, iron hooks and hair strands, long-term use of steroids and a history of dermatomycosis. Otomycosis is one of the common symptoms that are often found in ENT clinics and its prevalence reaches 9% of all patients who show symptoms and signs of otitis externa with Candida Sp and Aspergillus as the fungal species obtained the most from the oscillates. This study aims to determine the presence of fungal growth in the ear serum of farmers in Dorpedu Village. The location of the sampling was conducted in the Dorpedu Village, Ternate City and the location of this research was carried out at the Integrated Laboratory of the Health Polytechnic of the Ministry of Health of Ternate, Department of Medical Laboratory Technology. The method used in this study is to examine the culture and followed by 10% KOH staining. This study used accidental sampling technique with a sample of 20 farmers' ear serumThe results obtained showed that from 20 samples of farmers' ear serum in Dorpedu Village examined, Candida albicans and Aspergillus sp.: Based on the results of the research conducted, it can be seen that from 20 samples of farmer ear serum in Dorpedu Village, it was found that in the sweet potato extract media there were 17 (85%) positive samples of C. albicans, 1 (5%)positive samples of Aspergillus sp. PDA 20 (100%) samples were positive for C. albicans, and 2 (10%) samples were negative on sweet potato extract media where no fungal colonies were found. Sweet potato extract media can be used as an alternative medium for fungal growth.Keywords: Fungal, ear cerumen swab, otomycosis

Dosage, Safety and Efficacy of Posaconazole As Primary Antifungal Prophylaxis in High-Risk Recipients of Allogeneic Stem Cell Transplantation

Introduction: The use of anti-mold prophylaxis with anti-aspergillus activity is recommended for patients (pts) undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with high risk of fungal infection (Maertens, J Antimicrob Chemother 2018). Yet, few data are available regarding the use of posaconazole. Methods: This retrospective study included all Allo-HSCT adult recipients having benefited from posaconazole therapy in our center as a primary anti-fungal prophylaxis for high-risk of fungal infection. The latter was defined as use of i)an alternative donor, ii)sequential conditioning regimen, iii)a regimen associated with severe mucositis, iv) post-transplant cyclophosphamide (PT-Cy) or v) previous allo-HSCT. Posaconazole was programmed to be initiated at day (D) 0 or D5/6 (in case of PT-Cy) and administered up to day 100. We report here on the residual concentration of posaconazole during the neutropenic phase then on the tolerance and efficacy of such prophylaxis in this cohort. Results: Seventy high-risk pts (males 63.3%, median age 54 years old, range 20-73) received Allo-HSCT between April 2020 and December 2021 for a myeloid (n=51), lymphoid (n=17) or non-malignant hematological (n=2) disease and received posaconazole as a primary prophylaxis. The Sorror score at transplant time was ≥ 3 for 24 pts (33.8%). Twenty-two patients had already received posaconazole as a primary prophylaxis before Allo-SCT including 26 during the neutropenic phase of their induction for AML or MDS, 3 for prolonged neutropenia, 2 during treatment with alemtuzumab for T-cell leukemia/lymphoma, and 1 during a previous AlloHCST. Four patients had also received other antifungal agentsbefore Allo-SCT (caspofongine (n=1), voriconazole (n=1) or liposomal amphotericin B (n=2)) because of a suspected mold infection which has been finally excluded. All pts had at least one high-risk criterion of fungal infection. These included the use of an alternative donor in 42 pts (haplo-identical donor n= 41, umbilical cord blood n=1), sequential conditioning regimen in 9, with PT-Cy in 57, second or third allo-HSCT in 8 and conditioning regimen associated with severe mucositis in 11 (TBI 8-12gy n=3, thiotepa-based n=8). All but one pts received posaconazole using the gastroresistant tablet form at a dose of 300mg/day. One patient received the drinkable suspension form at a dose of 200mg 3 times a day. Following prophylaxis initiation, serum posaconazole concentrations were available in 51 and 16 patients at medians of 9 and 39 days, respectively. A protective residual level of posaconazole (> 0.5mg/L) was achieved in 57% of the patients (n=29) at first assessment and 87.5% (n=12) at second evaluation. Posaconazole was stopped early due to related-toxicity in 9 cases (12.6%), including liver toxicity in 7 pts, QT prolongation in 1 and skin hyperesthesia in 1. Treatment was restarted without recurrence of toxicity in 2 cases. Posaconazole was stopped early in 2 patients due to non-related toxicity, including one veno-occlusive disease and one hepatic acute GVHD. Posaconazole was temporary discontinued in 4 patients due to a suspected fungal infection before being restarted. Most patients (n=59/70, 84.2%) did not present fungal infections while being under posaconazole therapy. Only 11 cases were documented with this complication (Table 1), including 8 invasive pulmonary aspergillosis (IPA; possible n=3; probable n=5), one possible invasive fungal infection and 2 mucormycoses (1 with possible IPA). Fungal infections occurred despite documentation of a protective residual level of posaconazole (> 0.5mg/L) in 5 of 6 evaluable patients. Of note, 9/11 patients had received PTCY as GVHD prophylaxis. Posaconazole was stopped (before D7 in 3) and other antifungal drugs started (voriconazole or liposomal amphotericin B) allowing to fungal infection cure in 5 pts. However, 7 pts died including 2 of an uncontrolled fungal infection. Conclusion: Posaconazole is a well-tolerated and efficient primary prophylaxis in recipients of Allo-HSCT at high-risk of fungal infection. As some fungal infections occured very early after D0 while prophylaxis started only a D5/6 after PTCY, our results suggests to propose posaconazole as early as the beginning of the conditionning together with dose monitoring. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COVID-19-ассоциированный риноорбитальный мукормикоз

Relevance. Mucormycosis is a rare aggressive fungal infection that often affects people with weakened immune systems, in particular those suffering from diabetes mellitus. Since the emergence of the SARS-CoV-2 virus, a significant increase in cases of mucormycosis has been reported, especially in some hot countries, in particular India, as a rule, after suffering a new coronavirus infection COVID-19. Rhino-orbital mucormycosis (ROM), as a manifestation of the rhino-cerebral form of the disease, can initially be localized in the nose and paranasal sinuses, then quickly spread to the orbit and the cranial cavity. Purpose. To present case reports with covid-associated rhino-orbital mucormycosis. Material and methods. The study included 29 patients admitted to the hospital with ROM, which developed 20-40 days after a new coronavirus infection COVID-19. All patients underwent eye examination, which included visometry, biomicroscopy, ophthalmoscopy, pneumotonometry, and in some cases exophthalmometry. In addition, all patients underwent computer or magnetic resonance imaging of the brain, orbit and paranasal sinuses. Results. All the patients had a medical history of long-term antibacterial and steroid therapies. It should be noted that due to the pandemic, steroid and antibiotic therapies in 25 patients (86.2 %) was uncontrolled, since in most cases it was carried out on an outpatient basis. All the patients upon admission suffered from type 2 diabetes mellitus. Ocular and orbital signs of ROM were detected in all 29 patients which were manisfested by the following symptoms: fever, sinus pain, orbital cellulitis, with exophthalmos, permanent loss of vision, black necrosis of the palate, nasal sinuses, nasal septum. The mortality rate was 44.8 % (13 patients). Conclusion. Diabetes mellitus is one of the most important risk factors for the development of such a formidable fungal infection as mucormycosis, which developes in patients after moderate or severe COVID-19, as well as long-term and uncontrolled outpatient high doses of antibiotics and especially corticosteroids. In addition to intensive antifungal therapy, surgical treatment is indicated to all the patients with rhino-orbital mucormycosis, due to the high risk of fungal infection entering the cranial cavity and, therefore, the lethality of the disease. Keywords: COVID-19, rhinocerebral and rhinocerebral covid-associated mucormycosis, treatment with large doses of steroids and antibiotics, diabetes mellitus, clinical cases

Prevalence and Types of Fungi in Kintamani Bali Dogs

Indonesia, located in the tropics with high humidity, is a suitable area for the growth of various types of fungi. Kintamani Bali dogs have thick and beautiful fur, so it is unfortunate to get a fungal infection. There is a high risk for fungal infection, and no research data for Kintamani Bali Dog make this research very important. Samples were taken randomly from Kintamani Bali dogs with fungal disease characteristics using the toothbrush technique. The samples were identified by colony identification and microscopic examination through slide culture using Methylene blue staining. The results showed that from 15 samples, identified 31 fungi. Among these, commonly found were Aspergillus sp. 54.84% and each of Curvularia sp. Trichophyton sp. Candida sp. 12.9% while Penicillium sp. 6.45%. Based on sex, generally, the female Kintamani had a higher (61.29%) fungal infection than male Kintamani Bali dogs (38.71%). In young age dogs, more infection was found (70.97%) than adult dogs (29.03%).

Rare cause of sepsis in an immunocompromised child with acute lymphocytic leukaemia - A Case Report

Haematological malignancies are at a high risk of fungal infection and subsequent high mortality. A patient with a relapsed acute lymphocytic leukaemia (ALL) and a rare fungal infection is presented. A four-year-old patient with ALL relapsed after 3 years of remission. He presented with a papular, erythematous rash mainly on the limbs and trunk, accompanied with high intermittent fever which did not respond to broad spectrum antibiotics. Histopathological examination of a skin biopsy revealed yeast cells. Trichosporon species was isolated on culture. Voriconazole was started according to sensitivity test results and a brief response was demonstrated. Clinical deterioration was seen with worsening of the underlying malignancy. Amphotericin B was added with poor response. Unfortunately, he succumbed to his disease process without recovery from fever, skin rash or the malignancy. Trichosporon species is a rare infection even in patients with haematological malignancies. Recovery from neutropenia is an important prognostic factor in the treatment of trichosporonosis.

Frontal Sinus Osteomyelitis: a late complication in Post COVID Mucormycosis

During the current pandemic of COVID-19, numerous manifestations and complications have developed. As seen after the Second wave patients with COVID-19 are at high risk of fungal infections, such as mucormycosis, that may result directly from COVID-19 infection and/or as a side effect of the drugs used in the COVID-19 treatment protocol. Rhino-orbito-cerebral mucormycosis is a fungal infection that can be fatal especially in immunocompromised patients. In this report, we described a series of 3 cases with frontal sinus osteomyelitis in post-COVID-19 diabetic patients diagnosed with mucormycosis.

Using Child-Pugh Class to Optimize Voriconazole Dosage Regimens and Improve Safety in Patients with Liver Cirrhosis: Insights from a Population Pharmacokinetic Model-based Analysis.

Cirrhotic patients are at a high risk of fungal infections. Voriconazole is widely used as prophylaxis and in the treatment of invasive fungal disease. However, the safety, pharmacokinetics, and optimal regimens of voriconazole are currently not well defined in cirrhotic patients. Retrospective pharmacokinetics study. Two large, academic, tertiary-care medical center. Two hundred nineteen plasma trough concentrations (Cmin ) from 120 cirrhotic patients and 83 plasma concentrations from 11 non-cirrhotic patients were included. Data pertaining to voriconazole were collected retrospectively. A population pharmacokinetics analysis was performed and model-based simulation was used to optimize voriconazole dosage regimens. Voriconazole-related adverse events (AEs) developed in 29 cirrhotic patients, and the threshold Cmin for AE was 5.12mg/L. A two-compartment model with first-order elimination adequately described the data. The Child-Pugh class and body weight were the significant covariates in the final model. Voriconazole clearance in non-cirrhotic, Child-Pugh class A and B cirrhotic (CP-A/B) and Child-Pugh class C cirrhotic (CP-C) patients was 7.59, 1.86, and 0.93L/hour, respectively. The central distribution volume and peripheral distribution volume was 100.8 and 55.2 L, respectively. The oral bioavailability was 91.6%. Model-based simulations showed that a loading dose regimen of 200mg/12hours intravenously or orally led to 65.0-75.7% of voriconazole Cmin in therapeutic range on day 1, and the appropriate maintenance dosage regimens were 75mg/12hours and 150mg/24hours intravenously or orally for CP-A/B patients, and 50mg/12hours and 100mg/24hours intravenously or orally for CP-C patients. The predicted probability of achieving the therapeutic target concentration for optimized regimens at steady-state was 66.8-72.3% for CP-A/B patients and 70.3-74.0% for CP-C patients. These results recommended that the halved loading dose regimens should be used, and voriconazole maintenance doses in cirrhotic patients should be reduced to one-fourth for CP-C patients and to one-third for CP-A/B patients compared to that for patients with normal liver function.

Diagnosis of Pneumocystis jirovecii Pneumonia in Pediatric Patients in Serbia, Greece, and Romania. Current Status and Challenges for Collaboration.

Pneumocystis jirovecii can cause fatal Pneumocystis pneumonia (PcP). Many children have been exposed to the fungus and are colonized in early age, while some individuals at high risk for fungal infections may develop PcP, a disease that is difficult to diagnose. Insufficient laboratory availability, lack of knowledge, and local epidemiology gaps make the problem more serious. Traditionally, the diagnosis is based on microscopic visualization of Pneumocystis in respiratory specimens. The molecular diagnosis is important but not widely used. The aim of this study was to collect initial indicative data from Serbia, Greece, and Romania concerning pediatric patients with suspected PcP in order to: find the key underlying diseases, determine current clinical and laboratory practices, and try to propose an integrative future molecular perspective based on regional collaboration. Data were collected by the search of literature and the use of an online questionnaire, filled by relevant scientists specialized in the field. All three countries presented similar clinical practices in terms of PcP prophylaxis and clinical suspicion. In Serbia and Greece the hematology/oncology diseases are the main risks, while in Romania HIV infection is an additional risk. Molecular diagnosis is available only in Greece. PcP seems to be under-diagnosed and regional collaboration in the field of laboratory diagnosis with an emphasis on molecular approaches may help to cover the gaps and improve the practices.

Invasive fungal infections amongst patients with acute-on-chronic liver failure at high risk for fungal infections.

To study the prevalence, risk factors, role of serum biomarkers for diagnosis and impact of invasive fungal infections (IFIs) in patients with acute-on-chronic liver failure (ACLF). An analysis of IFI in patients with ACLF (EASL criteria) was conducted retrospectively. The diagnosis of IFI in clinically suspected patients was based on EORTC/MSG criteria. The demographical, clinical, laboratory details and outcomes were analysed. Out of 264 patients with ACLF, 54 (20.4%) patients with suspicion of IFI were evaluated and IFI was diagnosed in 39 (14.7%). Invasive candidiasis was documented in 25 (64.1%) and invasive aspergillosis in 14 (35.8%). The most common source of infection was respiratory (n=13) followed by renal (n=7) and spontaneous fungal peritonitis (n=6). On univariate analysis, diabetes mellitus, hemodialysis, prior antibiotic use, cerebral and respiratory organ failures, Chronic Liver Failure Consortium (CLIF-OF and CLIF-C ACLF) scores were predictors for development of IFI (P<0.05). On multivariate analysis, hemodialysis and prior antibiotics use predicted the development of IFI (P<0.05). Non-survivors were more likely to have IFI (P=0.029), high CLIF-OF and CLIF-C ACLF scores (P<0.001; for both) and higher 1,3-β D Glucan (BDG) levels (P=0.009). The sensitivity, specificity, and AUROC of BDG (80pg/mL) and Galactomannan index (GMI [0.5]) for diagnosing IFI were 97.4%, 60%, 0.770% and 43.6%, 100%, 0.745 respectively. Invasive fungal infections constitutes an important cause of mortality in ACLF patients. BDG and GMI can be useful markers to guide antifungal therapy in patients at high risk for IFI.

Internal transcribed spacer for identification of yeast species isolated from cancer patients at the Isotope and Radiation Center, Khartoum, Sudan: A cross-sectional, case-control study

Background:Cancer patients have a high risk of fungal infections, especially by Candida species.Non-C. albicans Candidainfections and less common yeast infections have been increasing in recent years. Identification by conventional methods can be difficult and sometimes inconclusive. This study aimed to detect the prevalence of oral yeast species isolated from cancer patients, from oral swab, sputum and urine, using Internal Transcribed Spacer (ITS) sequence analysis, since little is known about this problem in Sudan.Methods:The study involved 333 cancer patients (168 patients under treatment [study group] and 165 patients before treatment [control group]). Oral swabs were collected from all patients. Urine or sputum specimens were collected from patients under treatment showing clinical features of UTI or lower respiratory tract infection, respectively. ITS1 and ITS2 region of isolated yeast were amplified by PCR and sequenced. The obtained sequences were compared to reference sequence available in the GenBank database using BLAST.Results:Culture results showed oral yeastspecies were isolated from 69/168 (41.1%) and 74/165 (44.8%) of patients among study and control groups, respectively (P value &gt; 0.05). 2/9 (22.2%) patients were urine growth positive and 8/14 (57.1%) patients were sputum culture positive. Sequence analysis showed,C. albicanswas the most prevalent organism (93; 52.5%) followed byC. tropicalis(29; 16.4%), andC. glabrata(24; 13.6%). Non-C. albicans Candidaand uncommon rare yeast were found to be associated with oral infections and colonization among the study and control groups, whereasC.albicans was the most common species (66.7%) associated with oral candidiasis among the treated patients. Conclusion:Cancer patients were highly colonized with different oral yeast species, which indicates that ITS sequence analysis is an accurate method for identification. This will aid effective management to prevent dissemination of disease especially among those who are under chemo and/or radiotherapy treatment.

Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High Risk for Fungal Infections.

The purpose of our study was to determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed-release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs) and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels. A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that had received PCZ and obtained PCZ serum levels for either treatment or prophylaxis between 1 August 2014 and 31 August 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell transplantation (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 μg/liter and ≥1,000 μg/liter were considered appropriate for prophylaxis and treatment, respectively. The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients had PCZ serum levels of ≥700 μg/liter regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels of ≥1,000 μg/liter. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight of ≥90 kg, a diarrhea grade of ≥2, a mucositis grade of ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment than in those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough IFIs, one of which had a subtherapeutic level. We concluded that the use of PCZ DRT provided adequate concentrations in only 70% of our patients and that recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.

ID: 1046 Antifungal prophylaxis in hematopoietic stem cell transplantation recipients: drug use evaluation at Vietnam National Institute of Hemotology and Blood transfusion

&#x0D; &#x0D; &#x0D; &#x0D; *For correspondence:&#x0D; tungson94@gmail.com&#x0D; &#x0D; Competing interests: The authors declare that no competing interests exist.&#x0D; Received: 2017-07-13 &#x0D; Accepted: 2017-08-04&#x0D; Published: 2017-09-05&#x0D; &#x0D; Copyright The Author(s) 2017. This article is published with open access by BioMedPress (BMP).&#x0D; This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Background: Hematopoietic stem cell transplantation (HSCT) recipients were known to be in high risk of fungal infection. However, not all HSCT patients need antifungal prophylaxis. The aim of this study was to describe the characteristics of the use of antifungal prophylaxis in hematopoietic stem cell transplantation recipients and to evaluate the appropriateness of use.&#x0D; Methods: In this observational prospective study, adult hematopoietic stem cell transplantation recipients without using antifungal treatment were recruited from start of stem cell transfusion in Vietnam National Institute of Hematology and Blood Transfusion (from April to December 2016) to end of antifungal prophylaxis or start of antifungal treatment. Appropriateness was defined based on National Comprehensive Cancer Network (NCCN) guidelines. Clinically significant Drug-drug interactions related to antifungals were defined based on Hansten and Horn’s Drug interaction and management 2013.&#x0D; Results: 38 patients (mean age: 35.7 ± 12.0; 57.9% male) were admitted, included 21 autologous and 17 allogeneic HSCT recipients. After HSCT, 3 deaths, 1 to ICU, 1 IFI. Azoles prophylaxis was given to 100% of patients with median 17.5 days (13 - 47.5). Fluconazole was the most used antifungal agents, in 94.7% of patients and 74.5% of episodes. 10 patients had been changed antifungal agents. Indication was appropriate in 44.7%, 0% in autologous and 100% in allogeneic group. In patients with appropriate indication, choice of antifungal agents was 100% appropriate. 100% of patients used inappropriate dosage, mostly lower than recommeded dosage with azoles. 12.7% had appropriate prophylactic time. Potential drug-drug interactions were identified in 92.1% of patients. Most frequent interactions involved azoles-diazepam (80.4% of episodes) and azoles-immunosuppressive drugs (49% of episodes).&#x0D; Conclusion: Our evaluation revealed a high proportion of inappropriate of antifungal prophylaxis. An antifungal stewardship programme is needed to strengthen rational use of antifungal in this specific circumstance.

Non-Invasive Methods to Diagnose Fungal Infections in Pediatric Patients with Hematologic Disorders.

BackgroundInvasive fungal infection (IFIs) is a major infectious complication in immunocompromised patients. Early diagnosis and initiation of antifungal therapy is important to achieve the best outcome.ObjectivesThe current study aimed to investigate the incidence of IFIs and evaluate the diagnostic performance of non-invasive laboratory tests: serologic (β-D-glucan, galactomannan) and molecular (nested polymerase chain reaction) tests to diagnose fungal infections in hematologic pediatric patients.Patients and MethodsIn a cross-sectional study from October 2014 to January 2015, 321 blood samples of 62 pediatric patients with hematologic disorders and at high risk for fungal infections were analyzed. Non-invasive tests including the Platelia Aspergillus enzyme immunoassay (EIA) to detect galactomannan antigen, Glucatell for β–D–glucan and nested PCR to detect Candida and Aspergillus species-specific DNA were used in a weekly screening strategy.ResultsTwenty six patients (42%) were considered as proven and probable IFIs, including 3 (5%) proven and 23 (37%) probable cases. Eighteen patients (29%) were considered as possible cases. The sensitivity, specificity, positive and negative predictive values for galactomannan test in 26 patients with proven and probable fungal infections were 94.4%, 100%, 100% and 94.7%; for β-D-glucan test 92.3%, 77.7%, 85%, 87.5% and for nested-PCR were 84.6%, 88.8%, 91.7% and 80%, respectively.ConclusionsThe rate of IFIs in pediatric patients with hematologic disorders is high, and sample collection from the sterile sites cannot be performed in immunocompromised patients. Detection of circulating fungal cell wall components and DNA in the blood using non-invasive methods can offer diagnostic help in patients with suspected IFIs. Their results should be interpreted in combination with clinical, radiological and microbiological findings.

Profil Candida Penyebab Kandidemia dan Pola Kepekaan terhadap Anti Jamur pada Pasien Sakit Kritis di Rumah Sakit Cipto Mangunkusuno

Candida spesies is important cause of nosocomial infection that lead to death and prolonged hospital stay. Guideline management of candidiasis by Infectious Diseases Society of America (IDSA) in 2009 proposed early antifungal therapy in critical patient with the risk of invasive candidiasis. Early identification of sepsis patien with high risk of fungal infection is challenging because long and low result from blood culture. Antifungal usage without appropriate indication can cause resistance to antifungal. The aim of the study is obtain data candida species that caused candidemia in Cipto Mangunkusuno hospital (RSCM) and sensitivity pattern to antifungal . This retrospective study used patient medical record from 2011-2014. This study had 117 candidemia case in RSCM during 2011-2014. Every year candidemia was dominated by Candida tropicalis, Candida albicans, and Candida parapsilosis with trend the increase number of Candida tropicalis since 2013. Susceptibility pattern of C andida that cause candidemia in RSCM from 71 isolat tested the result was86% spesies Candida flukonazol sensitive, 99% vorikonazol sensitive, 97% amfoterisin B sensitive and 100% flusitosin sensitive.

Coping with stress and the emergence of multidrug resistance in fungi.

The incidence of invasive fungal infections poses a serious global health threat, killing nearly 1.4 million people a year—a number comparable to deaths from tuberculosis. Factors that contribute to this disease burden and high mortality include insufficient diagnostics and treatment, and the increasing numbers of individuals with immune system defects who are particularly susceptible to fungal pathogens [1]. Because of the high risk of fungal infections in immunocompromised individuals—e.g., low–birth-weight neonates or patients undergoing organ transplantation or chemotherapy—it has become common medical practice to utilize antifungal prophylaxis in these patients during immunosuppression [2–4]. However, the expanding use of antifungal drugs has been associated with increasing incidence of antifungal drug resistance resulting from inherently less sensitive species and/or acquisition of drug class–specific resistance mechanisms [5]. Most alarming in recent years, multidrug-resistant strains of certain Candida species have emerged that are resistant to azoles and echinocandins, the two most widely used classes of antifungal drugs [6,7]. In this article we explore the notion that frequent and prolonged exposures of fungal cells to antifungal drugs activate fungal stress responses, which both support the short-term cellular adaptation to the drugs [8,9] and promote genetic instability to facilitate the emergence of stable drug resistant mutants refractory to therapy [9,10], including multidrug-resistant (MDR) strains (Fig. 1). Antifungal drug-induced stress has been associated with genetic instability in such distantly related fungi as Candida and Cryptococcus [11,12], suggesting that it is a broadly conserved phenomenon. In this article, we focus on drug resistance in Candida spp. because of its clinical significance, especially with the development of emerging multidrug resistance, and because mechanisms of drug resistance and stress-associated genetic instability are best studied in Candida, both in the clinic and in the lab. Fig 1 A model for the formation of multidrug-resistant strains of C. glabrata.

PCR-based methods for the detection of fungal DNA in patients with chronic liver disease

Objective: Patients with end-stage liver disease are at high risk for fungal infections and candida species are the most frequently detected pathogens causing serious infections in this patient group. However, due to limited sensitivity of culture-based standard diagnostic procedures we applied a culture-independent PCR assay targeting the 18S rRNA gene for the detection of fungal DNA in sterile and colonised material such as whole blood, ascites, intestinal fluid and bile fluid.

Biomodification and biodeterioration of carbon coatings by fungal strains

Over the past years, surface protection by hard carbon coatings has been increasingly applied in many fields. This study aimed to characterize changes in the properties of carbon coatings brought about by the growth of fungi (the first report about these processes was published by Kaczorowska et al., Nanodiam, PWN, 2006, 99–116). Alterations in the structure of diamond-like carbon (DLC) and nanocrystalline diamond (NCD) coatings, examined by Raman spectroscopy, XRD, XPS, and FTIR, were found to be caused by the processes of oxidation (incorporation of oxygen atoms) and reduction (hydrogenation) occurring within graphite carbon and amorphous carbon domains (components of the surface layer of the tested coatings along with the diamond domain). Determination of the activity of selected enzymes synthesized by the studied strains of filamentous fungi revealed that the observed biomodification and biodeterioration processes involved, among others, laccase, Mn-dependent peroxidase, two catechol dioxygenases, and esterases. The biosynthesis of these enzymes by fungi was enhanced when graphite was added to their culture media. Because of the high risk of fungal infections, the quality of carbon coatings should be routinely controlled by standard microbiological tests employing suitable strains of filamentous fungi (e.g., Aspergillus niger) and yeasts synthesizing enzymes that attack carbon materials.