Initiation Of Appropriate Antifungal Therapy Research Articles

Invasive Fungal Infections Associated with COVID-19.

The COVID-19 pandemic caused >6 million deaths worldwide, often from respiratory failure. Complications frequently occurred in hospitalized patients, particularly in the intensive care unit. Among these, fungal infections were a cause of high morbidity and mortality. Invasive aspergillosis, candidiasis and mucormycosis were the most serious of these infections. Risk factors included alterations in immune defense mechanisms by COVID-19 itself, as well as immunosuppression due to various therapies utilized in severely ill patients. Diagnosis was often challenging due to lack of sensitivity of current testing. Outcomes were generally poor, due to significant co-morbidities and delayed diagnosis, with mortality rates >50% in some studies. High index of clinical suspicion is needed to facilitate early diagnosis and initiation of appropriate antifungal therapy.

S2.3c High-resolution digital DNA melting: a breakthrough in diagnosing IMI?

S2.3 Novel diagnostic tools for invasive mold infection, September 21, 2022, 3:00 PM - 4:30 PMInvasive mold infections (IMIs) such as Aspergillosis, Mucormycosis, Fusariosis, and Lomentosporiosis have emerged as important pathogens in immunocompromised patients, with mortality rates as high as 50% to nearly 80% for these infections. Outcomes can be substantially improved with early initiation of appropriate antifungal therapy, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive microbiologic findings. Conventional fungal culture and PCR techniques are limited by low sensitivity, long turn-around time, and are insufficient for differentiating between infection and colonization. Other non-culture-based tests, such as the Galactomannan test, are available only for invasive aspergillosis and are limited by imperfect test performance. Better and more rapid diagnostics are needed to enable early diagnosis and targeted treatment of IMIs and improve survival. We have developed a new technology called digital high resolution melting analysis (dHRM) to enable a rapid and robust diagnosis of IMI. This technology accomplishes fast genotyping of fungal genomic sequences in clinical samples by: (1) conducting broad-based amplification of fungal genes in a digital PCR format, and (2) conducting high-resolution melting of the DNA amplicons in each digital reaction. High resolution melting measures the fluorescence of a saturating intercalating dye as dPCR-amplified fungal DNA fragments are rapidly heated and disassociated, producing sequence-defined melt curves in a closed reaction format. These melt curves serve as unique fungal ‘fingerprints’, which allows us to correctly identify disease-causing pathogen(s) with an accuracy of 99%-100% through the use of machine learning methods trained to tolerate variations in reaction conditions. This approach provides a simple, low-cost, fast, and robust method for pathogen identification. Here, we will present the performance of this new technology on clinical bronchoalveolar lavage (BAL) samples from patients with and without IMI. A total of 75 patient BAL samples were tested, coming from 30 patients with proven (n = 1), probable (n = 25), or putative (n = 4) invasive pulmonary aspergillosis (IPA) infections, and from 45 patients classified as not having IPA (n = 4 possible IPA and n = 41 no IPA). Our results show that dHRM was able to reliably differentiate between different Aspergillus spp. and was also able to identify Aspergillus spp. in BAL samples from patients with probable IPA where qPCR had resulted in negative. In a few instances, it also detected rare molds in culture-negative samples and multiple Aspergillus spp. within one BAL sample, a phenomenon that has been previously described in cultures. Interestingly, there was no clear correlation between dHRM results and BAL galactomannan levels, suggesting that dHRM may serve as an independent method allowing for a combined diagnostic approach. While further validation and optimization are needed, these results suggest that dHRM is a promising new diagnostic technology capable of providing clinically relevant information within 2-3 h.

"CAPA in Progress": A New Real-Life Approach for the Management of Critically Ill COVID-19 Patients.

(1) Background: COVID-19-associated pulmonary aspergillosis (CAPA) has worsened the prognosis of patients with pneumonia and acute respiratory distress syndrome admitted to the intensive care unit (ICU). The lack of specific diagnosis criteria is an obstacle to the timely initiation of appropriate antifungal therapy. Tracheal aspirate (TA) has been employed under special pandemic conditions. Galactomannan (GM) antigens are released during active fungal growth. (2) Methods: We proposed the term “CAPA in progress” (CAPA-IP) for diagnosis at an earlier stage by GM testing on TA in a specific population admitted to ICU presenting with clinical deterioration. A GM threshold ≥0.5 was set as the mycological inclusion criterion. This was followed by a pre-emptive short-course antifungal. (3) Results: We prospectively enrolled 200 ICU patients with COVID-19. Of these, 164 patients (82%) initially required invasive mechanical ventilation and GM was tested in TA in 93 patients. A subset of 19 patients (11.5%) fulfilled the CAPA-IP criteria at a median of 9 days after ICU admittance. The median GM value was 3.25 ± 2.82. CAPA-IP cases showed significantly higher ICU mortality [52.6% (10/19) vs. 34.5% (50/145), p = 0.036], as well as a much longer median ICU stay than those with a normal GM index [27 (7–64) vs. 11 (9–81) days, p = 0.008]. All cases were treated with a pre-emptive systemic antifungal for a median time of 19 (3–39) days. (4) Conclusions: CAPA-IP highlights a new real-life early approach in the field of fungal stewardship in ICU programs.

COVID-19-Associated Pulmonary Aspergillosis in a Tertiary Hospital.

Our study aims to assess the prevalence of CAPA (COVID-19-associated pulmonary aspergillosis) and describe the associated risk factors and their impact on mortality. A prospective study was conducted. We included patients with COVID-19 disease who were admitted to the ICU with a diagnosis of respiratory failur. Mycological culture and other biomarkers (calcofluor staining, LFD, LFA, PCR, GM, and B-D-glucan) were performed. A total of 300 patients were included in the study. Thirty-five patients were diagnosed with CAPA (prevalence 11.7%). During admission, 57 patients died (19%), and, in the group of CAPA patients, mortality was 31.4%. In multivariate analysis, independent risk factors associated with CAPA diagnosis were age (OR: 1.05; 95% CI 1.01–1.09; p = 0.037), chronic lung disease (OR: 3.85; 95% CI 1.02–14.9; p = 0.049) and treatment with tocilizumab during admission (OR: 14.5; 95% 6.1–34.9; p = 0.001). Factors independently associated with mortality were age (OR: 1.06; 95% CI 1.01–1.11; p = 0.014) and CAPA diagnosis during admission (OR: 3.34; 95% CI 1.38–8.08; p = 0.007). CAPA is an infection that appears in many patients with COVID-19 disease. CAPA is associated with high mortality rates, which may be reduced by early diagnosis and initiation of appropriate antifungal therapy, so screening of COVID-19 ARDS (acute respiratory distress syndrome) patients for CAPA is essential.

“Mucormycosis” the Emerging Global Threat; Overview and Treatment Outcome Among Pediatric Cancer Patients in Egypt

Background: Mucormycosis is a serious emerging fungal infection. Unlike invasive aspergillosis, the prognosis and outcome of hematologic malignancy patients who develop invasive Mucormycosis have not significantly improved over the past decade.The aim of the study was to evaluate clinical characteristics and treatment outcome in pediatric oncology patients with Mucormycosis in children cancer hospital 57357, Cairo, Egypt. Patients and Methods: A retrospective study during the period from 2007 to 2016. Data collected included patients' demographics, diagnosis, risk factors, diagnostic work up, antifungal treatment given and treatment outcome. Diagnosis was made according to the EORTC/MSG modified criteria (2008). Results: During the study period, 45 patients developed proven Mucormycosis. Mean age was 8 years (range 2-17). Male to female ratio 1:1. Diagnosis of Mucormycosis was highest among patients with hematological malignancies (90%). Twenty-two cases of acute myeloid leukemia (49%), 17 cases acute lymphoblastic leukemia (37%), and 1 case of CML post-transplant. The other 10% were having solid malignancies. Sinus involvement has been documented in (55.5%) representing the sole localization in 16 cases. The other 9 patients had secondary localizations; 2 central nervous system (Rhino-cerebral) and 7 lung (Sino-pulmonary) cases. Other primary sites of infection were: Pulmonary, Cutaneous and Gastrointestinal in (13.3%), (8.8%) and (11%) respectively. Disseminated disease was seen in 5 cases (11%). All patients had infection documented by histopathology or/and culture. Diagnosis was reported by histopathology in 38 patients (84%), blood culture in 2 patients (4 %) and both culture and histopathology in 5 patients (12%). At time of diagnosis, 15 patients (33%) were on Voriconazole prophylaxis (n =13) or Micafungin (n= 2). Liposomal Amphotercin -B 5mg/kg/day was the mainstay of treatment with duration ranging from 3 to 4 weeks. Posaconazole was used as secondary prophylaxis in 35 % of cases mainly for patients with hematological malignancies. Combination of liposomal amphotericin B with caspofungin was used in 3 cases with progressive Mucormycosis. Surgical intervention was achievable in 50 % of cases; sinus debridement in 11 cases, lung lobectomy in 3 cases, intestinal resection anastomosis in 5 cases and debridement of necrotic lesion in 4 cases. Therapy was successful in 30 patients (66%). Co-Morbidities related to Mucormycosis was seen in 5 cases with disfigurement, and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in 1 case. Mucormycosis was the primary cause of death in 15 cases (34%). Gastrointestinal and disseminated Mucormycosis was independent risk factors for mortality. Conclusion: Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, are the back bone of decreasing Mucormycosis-related mortality and morbidity among pediatric cancer patients. Disseminated and gastrointestinal Mucormycosis had higher risk for mortality. DisclosuresNo relevant conflicts of interest to declare.

Fungal Infection in Burn Patents: A Review of 36 Case Reports.

The aims of this study were to review recent fungal infection case reports published, evaluate the treatment regimens and clinical outcomes, and provide recommendations for future management. A review of case reports published over the last decade was conducted. PubMed was searched to collect the relevant citations using a combination of the key words ("burn," "burned," "burns," "fungal," "fungi," and "fungus") in title or abstract. Case series, reviews, guidelines, and experimental and non-English studies were excluded. Statistical analyses were performed using Microsoft Excel 2019. A total of 36 case reports encompassing a total of 44 burn patients with fungal infection were included in the final analysis. Ablative surgeries, including surgical excision, debridement, skin graft, vitrectomy, teeth extraction, valve replacement, or amputation, were performed in 38 cases after the suspicion or identification of fungal infection. Twenty-nine of them were eventually discharged, yielding a survival rate of 76.3%. In the remaining 6 cases, ablative surgery was not mentioned and 3 of them eventually died, yielding a survival rate of 50%. The total mortality was 27.27%. Among the 12 death cases, 1 was infected with Candida albicans, 1 with non-albicans Candida, 2 with Aspergillus spp, 2 with Fusarium spp, 4 with Zygomycetes, and 2 with other fungal species. The overall mortality of fungal wound infection is still high in burn patients around the world, especially those infected with non-Candida species. Early diagnosis of fungal infection, early initiation of appropriate antifungal therapy, and effective surgical intervention are key measures to improve the treatment effect and reduce the mortality of fungal infection in burn patients.

Molecular Methods for the Diagnosis of Invasive Candidiasis.

Invasive infections caused by members of the genus Candida are on the rise. Especially patients in intensive care units, immunocompromised patients, and those recovering from abdominal surgery are at risk for the development of candidemia or deep-seated candidiasis. Rapid initiation of appropriate antifungal therapy can increase survival rates significantly. In the past, most of these infections were caused by C. albicans, a species that typically is very susceptible to antifungals. However, in recent years a shift towards infections caused by non-albicans species displaying various susceptibly patterns has been observed and the prompt diagnosis of the underlying species has become an essential factor determining the therapeutic outcome. The gold standard for diagnosing invasive candidiasis is blood culture, even though its sensitivity is low and the time required for species identification usually exceeds 48 h. To overcome these issues, blood culture can be combined with other methods, and a large number of tests have been developed for this purpose. The aim of this review was to give an overview on strengths and limitations of currently available molecular methods for the diagnosis of invasive candidiasis.

Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia.

We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia (AML). We performed a retrospective analysis of all adult patients admitted to the University of Michigan Health System for AML over a 3-year period from 2010 to 2013. We determined comorbidities, hematopoietic cell transplant (HCT) status, antifungal prophylaxis, proven and probable IFI, and outcomes at 12weeks after initiation of appropriate antifungal therapy. Of 333 patients in our cohort, 116 of whom had received a HCT, 98 (29%) developed an IFI. Of the 30 (9%) patients who had a proven or probable IFI, 18 had breakthrough infection while on micafungin (n = 5), voriconazole (n = 4), posaconazole (n = 5), or fluconazole (n = 4). Breakthrough IFIs were due to Aspergillus species (n = 11), other molds (n = 4), and Candida species (n = 3). Factors associated with breakthrough IFI were prolonged severe neutropenia (p = .05) and having received tacrolimus (p = .04). Antifungal therapy was successful in 7 of the 18 (39%) patients with breakthrough IFI and 8 of the 12 (67%) patients with non-breakthrough IFI, p = .13. Mortality at 12weeks was 27%, 5 with breakthrough IFI and 3 with non-breakthrough IFI and was associated with prolonged severe neutropenia, p = .04. Patients with AML remain at risk for IFI despite the use of several different antifungal agents for prophylaxis. Mortality remains high in patients with AML who develop IFI.

Antifungals patterns in critical patients with candidiasis in the intensive care units at Sanglah General Hospital 2019

Abstract
 Introduction: The prompt initiation of appropriate antifungal therapy is essential in controlling invasive candidiasis and improving the prognosis in critical patients undergoing treatment in the Intensive Care Unit. Candida Score can assess patients at risk of candidiasis and is expected to assist clinicians in starting antifungal therapy in patients suspected Candidiasis. The purpose of this study was to determine the pattern of antifungal administration in critically ill patients with candidiasis in the Intensive Care Unit at Sanglah General Hospital.
 Patients and Methods: The design of this study is a cross-sectional descriptive study involving critically ill patients who were under treatment in Intensive Care Unit of Sanglah General Hospital from Januari to June 2019. The patients included in this study were patients who were ≥ 18 years old and under treatment in ICU for at least 7 days.
 Results: There are 64 patients undergoing treatment in the Intensive Care Unit. From 64 patients, 6 pasien had CS = 0, 29 patients had CS = 1, 13 patients had CS = 2, 11 patients had CS = 3, 5 patients had CS = 4, and no patients had CS = 5. Eleven patients received empirical antifungal therapy. All empirical antifungal therapies use the Triazole group.
 Conclusion: In this study was found that 11 of 16 patients with a CS value of ≥ 2.5 were given empirical antifungal therapy, while 48 patients with a CS value of <2.5 were not given empirical antifungal therapy.
 Keywords: Invasive Candidiasis, Candida Score, Empirical Antifungal Therapy.

1981. Implementation of an Antifungal Stewardship Bundle Focused on Candidemia in an Indian Hospital

BackgroundIn India, Candida bloodstream infections have a reported incidence of 1–12 per 1,000 admissions and a mortality rate of up to 60%. Antimicrobial stewardship programs (ASP) can improve quality of care and clinical outcomes. This study evaluates the impact of a comprehensive candidemia ASP bundle in a hospital in southern India with an established stewardship program.MethodsA single-center, pre-post quasi-experimental study was conducted at a tertiary-care center in southern India to analyze the impact of an ASP care bundle for the management of adults with candidemia. During the intervention period (October 2017–December 2018), the ASP provided recommendations to providers in accordance with the 2016 IDSA Guidelines for the Management of Candidemia, which included the following bundle: (1) appropriate selection and dosing of antifungal therapy; (2) repeat blood cultures every 48 hours until clearance; (3) removal of central venous catheters and other potential removable foci of infection; (4) echocardiogram; (5) ophthalmologic evaluation; and (6) appropriate duration of therapy. The primary outcome was initiation of appropriate antifungal therapy. Additional clinical outcomes were also compared with a historical cohort.ResultsOne hundred and four patients with candidemia were included: 52 in the pre-intervention and 52 in the post-intervention group. Overall, baseline demographics were similar between the two groups (Table 1). Candida tropicalis (26.9%) and Candida parapsilosis (29.8%) were the most common causes of candidemia in the cohort. Following intervention, administration of appropriate antifungal therapy improved by 40.4% (28.8% pre vs. 69.2% post, P < 0.01). Average time to effective treatment initiation following culture positivity decreased from 57.6 hours to 12 hours in the post-intervention group (P < 0.01). Thirty-day all-cause mortality was similar between the two groups (34.6% 38.4%, P = 0.84).ConclusionImplementation of a comprehensive candidemia care bundle by the ASP significantly improved the use and timing of initiation of appropriate antifungal therapy. Disclosures All authors: No reported disclosures.

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt.

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

369. Using Hybrid Models and Blockchain Technology as a Means to Develop a Novel Propensity Score for Candidemia and Invasive Candidiasis

BackgroundEarly initiation of empiric antifungal therapy has been shown to decrease morbidity and mortality among patients with candidemia/invasive candidiasis (C/IC). However, the initiation of appropriate antifungal therapy is frequently delayed due to the severe limitations in early diagnosis. The goal of this study is to develop a high-risk scoring system to identify patients who may be eligible for preemptive antifungal therapy. The proposed new methodology combines hybrid modeling and blockchain technology.MethodsOur approach is novel and using expert physicians’ perception of C/IC risk factors with those described in the hospitals through a set of models (hybrid model building from primary and secondary data). The goal is to improve the early detection of C/IC and initiate antifungal therapy. Once candidate hybrid models are derived, blockchain technology will be utilized. The methodology is based on vectors consisting of the ranking of candidiasis risk factors. These vectors will be constructed based on expert clinicians rank scores of known risk factors. Such methods are different than the usual statistical rank correlation computations, such as Spearman’s rank correlation, etcResultsPreliminary analysis suggests threepotential models. Model 1: uses the following order of variables, by their relative importance: (1) major surgery within 0–3 days, (2)TPN-7–3 days, (3) steroids 0–3 days, (4) ECMO, (5) hemodialysis 0–3 days, (6) diabetes mellitus. Model 2 includes: (1)multifocal Candida colonization, 2.) central venous catheter 0–3 days, (3) LVAD, (4) medical ICU, (5) APACHE score > 20, (6) mechanical ventilation. Model 3 includes (1) pancreatitis –710 days, (2) diabetes mellitus, (3) hemodialysis 0–3 days, (4) central venous catheter 0–3 days, (5) TPN-7–3 days, 6.) APACHE score > 20.Conclusion Blockchain methods we propose are some of the first of their kind used in health research and are very suitable for the early detection of C/IC and other diseases where preemptive therapy is necessary. The following step will be to verify and use these models in the clinical realm and verify their effects on outcomes. Second we need to develop and evaluate our proposed methodology in building hybrid models, followed by algorithms for the early detection of diseases. These concepts still need to be fully evaluated on large population studies.Disclosures All authors: No reported disclosures.

Serum cryptococcal antigen titre as a diagnostic tool and a predictor of mortality in HIV-infected patients with cryptococcal meningitis.

The aim was to determine the effectiveness of the serum cryptococcal antigen (CrAg) test in the diagnosis of concurrent cryptococcal meningitis (CM) and as a predictor of mortality in HIV-infected patients. In this retrospective study, all HIV-infected patients admitted to Shanghai Public Health Clinical Center from 1 January 2014 to 31 August 2016 were screened for serum CrAg using the latex agglutination test. Serum CrAg-positive patients underwent lumbar puncture to confirm CM prior to the initiation of appropriate antifungal therapy and were followed up for at least 6months. One hundred and four (7.1%) of the total of 1474 HIV-infected patients screened were serum CrAg-positive. CM was diagnosed in the majority of serum CrAg-positive patients (71.3%; 67 of 94) and was confirmed in all (46 of 46) of the patients with headache or coma and in 43.8% (21 of 48) of patients without neurological symptoms. CrAg titres ≥1:1024 showed a sensitivity of 82.5% and a specificity of 86.7% for the diagnosis of concurrent CM (P<0.001). The positive predictive value for CM in this population was 94.3%. A total of 13 serum CrAg-positive patients [13.8%; 95% confidence interval (CI) 7.5-22.4%] died (11 as a result of CM and two others as a result of bacterial pneumonia) despite early antifungal treatment initiation. Serum CrAg titres ≥1:1024 predicted all-cause mortality (hazard ratio3.69; P=0.03). Serum CrAg titres ≥1:1024 not only were associated with concurrent CM but also predicted mortality. HIV-infected patients with a positive serum CrAg test during screening should receive lumbar punctures regardless of symptoms to rule out CM and patients with serum CrAg titres ≥1:1024 should be offered immediate care.

Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study.

Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%-100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking. A 5-year retrospective cohort study (2011-2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated. Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), despite switching to appropriate antifungal therapy after a median of 10 days. Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality.

Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO).

Invasive fungal diseases (IFD) are a primary cause of morbidity and mortality in patients with haematological malignancies. These infections are mostly life-threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other Non-Aspergillus moulds are increasingly identified in case of documented IFD. For definite diagnosis of IFD, a combination of diagnostic tools have to be applied, including conventional mycological culture and non-conventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. Although varying widely in cancer patients, the risk of invasive fungal infection is highest in those with allogeneic stem cell transplantation and those with acute leukaemia and markedly lower in patients with solid cancer. Since the last edition of Diagnosis of Invasive Fungal Diseases recommendations of the German Society for Hematology and Oncology in 2012, integrated care pathways have been proposed for the management and therapy of IFDs with either a diagnostic driven strategy as opposed to a clinical or empirical driven strategy. This update discusses the impact of this additional evidence and effective revisions.

Prevalence of candidemia and associated candida subtypes following severe sepsis in non-neutropenic critically ill patients.

Background: Invasive candidiasis management through the rapid initiation of appropriate antifungal therapy has been shown to be associated with the better prognosis, improved clinical outcome and reduced mortality in critically ill patients. Therefore, selection of an appropriate antifungal therapy should be based on the distribution of candida species and the pattern of antifungal resistance. This study aimed to assess the prevalence of candidemia and associated subtypes following severe sepsis in non-neutropenic critically ill patients. Methods: This study was a cross-sectional study that was conducted on severe sepsis patients stayed at least seven days in intensive care unit. Patients less than 18 years old, pregnant and breastfeeding patients, immunocompromised patients, neutropenic patients, patients with concurrent use of antifungal medicines and cytotoxic agents were excluded.To asses the candidemia, one mililiter of patients’ blood sample was collected. Sample analysis was performed by Real-Time PCR and high resolution melting curve analysis method. Results: Thirty-one critically ill patients were recruited in this study over 12-month period. Candidemia with a detection limit of 100 pg per 0.2 ml blood sample was not recognized in any of the included patients. Conclusion: The present result indicates low incidence of candidemia in the targeted intensive care units, but other factors such as small sample size, exclusion of patients with compromised immune system and the low fungal load at the time of sampling may also account for our observation. (www.actabiomedica.it)

Application of a standardized screening protocol for diagnosis of invasive mold infections in children with hematologic malignancies.

This study describes a standardized screening protocol for diagnosis of invasive mold infections in pediatric oncology patients with neutropenia and prolonged or recurrent fever. A retrospective chart review was performed of children receiving intensive chemotherapy for hematologic malignancies who developed invasive mold infections from 2004 to 2011. Characteristics and outcomes were compared before and after implementation of the screening protocol in November 2006. The screen includes direct nasal endoscopy performed at the bedside by an otorhinolaryngologist, noncontrast computed tomography (CT) of the chest, and abdominal ultrasound in patients with neutropenia and prolonged or recurrent fever. Fifty patients had proven, probable, or possible invasive mold infections. Before routine use of direct nasal endoscopy, invasive nasosinal disease was detected in 5 of 19 patients (26%) and all had a compatible clinical presentation. Thirteen of 31 patients (42%) in the post-screen group had nasosinal disease, and fever was the only sign for 8 patients (62%). Twenty-four patients with nasosinal disease had a sinus CT, and radiologic findings of bony erosion or peri-sinus invasion were never detected. Eight of 19 patients in the pre-screen group died from mold infection (42.1%) versus 4 of 31 (12.9%) in the post-screen group (p=0.04). A screening protocol including direct nasal endoscopy, noncontrast chest CT, and abdominal ultrasound was effective in detecting invasive mold infections in at-risk patients. Nasosinal involvement often occurs before specific symptoms develop, and sinus CTs are insensitive and nonspecific. Bedside nasal endoscopy precludes radiation exposure associated with sinus CT and was associated with decrease in mold-related mortality, likely due to earlier diagnosis and initiation of appropriate antifungal therapy.

Healthcare‐associated outbreaks due to Mucorales and other uncommon fungi

Healthcare-associated outbreaks of fungal infections, especially with uncommon and emerging fungi, have become more frequent in the past decade. Here, we reviewed the history and definition of healthcare-associated outbreaks of uncommon fungal infections and discussed the principles of investigating, containing and treatment of these outbreaks. In case of these uncommon diseases, occurrence of two or more cases in a short period is considered as an outbreak. Contaminated medical devices and hospital environment are the major sources of these outbreaks. Care must be taken to differentiate a real infection from colonization or contamination. Defining and identifying cases, describing epidemiologic feature of cases, finding and controlling the source of the outbreak, treating patients, and managing asymptomatic exposed patients are main steps for outbreak elimination. These fungal outbreaks are not only difficult to detect but also hard to treat. Early initiation of appropriate antifungal therapy is strongly associated with improved outcomes in infected patients. Choice of antifungal drugs should be made based on spectrum, pharmacodynamic and pharmacokinetic characteristics and adverse effects of available drugs. Combination antifungal therapy and surgical intervention may be also helpful in selected cases. A multidisciplinary approach and close collaboration between all key partners are necessary for successful control of fungal outbreaks.

Prospective assessment of FilmArray® technology for the rapid identification of yeast isolated from blood cultures

We prospectively assessed the ability of FilmArray® device to identify fungal species involved in bloodstream infections. It succeeded in identifying 85.7% of isolates. The automated readout of results enabled the rapid initiation of appropriate antifungal therapy. Thus, FilmArray® appeared as a reliable alternative diagnostic method for the most common yeast-like species.

Candida Sepsis: a New Entity?

Despite progress in the field of biological sciences, a definitive diagnosis of Candida sepsis remains an elusive target. Candida, which is frequently found in non-immunocompromised patients in intensive care units, causes severe sepsis, septic shock, and multiple-organ failure in a similar fashion as bacteria. Despite its imprecision, the blood and/or sterile-site culture is still the gold standard for diagnosis, although new biological markers are becoming available for earlier and more accurate diagnosis of invasive candidiasis. Mortality remains high due to a number of factors, and early initiation of appropriate antifungal therapy is a critical factor in positive outcomes. Echinocandins are the drug of choice for severe Candida infections in hospitalized patients. Antifungal stewardship programs may decrease the likelihood of resistance strains, and preventive measures are becoming available to lower the rate of fungal infections in intensive care units.