Early Antifungal Treatment Research Articles

Impact of Candidemia on Survival Rates in Major Burn Patients: A Retrospective Study from the South of Türkiye

Abstract Objective In severely burned patients, fungal infections are among the most devastating complications. Candidemia is an important cause of mortality with an increasing incidence despite advances in burn care management. Higher affected body surface area, long intensive care unit (ICU) stay, flame burn, third-degree burn, and previous bacterial infections were associated with the development of candidemia. Candidemia in patients with major burns admitted to an ICU of a tertiary burns center is investigated. Methods Patients hospitalized in the ICU of Adana City Training and Research Hospital from July 1, 2017, to November 10, 2020, were included. The demographic and clinical variables, the Candida species isolated from blood cultures and their antifungal susceptibilities, need for grafting, complications, and rate of mortality are evaluated retrospectively. Patients were grouped as “candidemia” or “noncandidemia” according to whether or not they experienced Candida bloodstream infection. Results A total of 371 patients were included; the mean age was 22.02 ± 20.9 years. Most patients were male (69.5%). The percentage of burned surface area was 25.93 ± 17.6. The mean ICU stay was 16.95 ± 16.3 days. There were 90 candidemia episodes in 69 patients. The most commonly isolated Candida species were C. parapsilosis, C. tropicalis, and C. albicans. The mortality rates in the candidemia and noncandidemia groups were 24.6 and 5.6%, respectively (p < 0.001). Conclusion Adhering to isolation rules, early wound debridement and closure, avoidance of catheters where possible, and avoidance of the early use of broad-spectrum antibiotics are important measures in reducing candidemia in patients with major burns. Candidemia was associated with greater burn surface areas, duration of hospital stay, and larger numbers of interventional procedures. However, previous bacterial infection receiving prolonged antibiotic therapy was the greatest risk factor of candidemia. Culture results are important to select the antifungal agent with high susceptibility, but results are not rapidly available. There is need for early clinical prediction measures to inform early and effective antifungal treatment.

Inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in susceptible pediatric patients: a case series

BackgroundPulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and timely treatment of pulmonary aspergillosis can play a crucial role in reducing mortality among children admitted with suspected infections.Case presentationThe present study reports three cases of inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in two Iranian pediatric patients under investigation and one Afghan patient. Unfortunately, two of them died. The cases involved patients aged 9, 1.5, and 3 years. They had been diagnosed with pulmonary disorders, presenting nonspecific clinical signs and radiographic images suggestive of pneumonia. The identification of A. flavus was confirmed through DNA sequencing of the calmodulin (CaM) region.ConclusionA. flavus was the most prevalent cause of pulmonary aspergillosis in pediatric patients. Early diagnosis and accurate antifungal treatment of pulmonary aspergillosis could be crucial in reducing the mortality rate and also have significant potential for preventing other complications among children. Moreover, antifungal prophylaxis seems to be essential for enhancing survival in these patients.

Invasive candidiasis.

Invasive candidiasis is an important fungal disease caused by Candida albicans and, increasingly, non-albicans Candida pathogens. Invasive Candida infections originate most frequently from endogenous human reservoirs and are triggered by impaired host defences. Signs and symptoms of invasive candidiasis are non-specific; candidaemia is the most diagnosed manifestation, with disseminated candidiasis affecting single or multiple organs. Diagnosis poses many challenges, and conventional culture techniques are frequently supplemented by non-culture-based assays. The attributable mortality from candidaemia and disseminated infections is ~30%. Fluconazole resistance is a concern for Nakaseomyces glabratus, Candida parapsilosis, and Candida auris and less so in Candida tropicalis infection; acquired echinocandin resistance remains uncommon. The epidemiology of invasive candidiasis varies in different geographical areas and within various patient populations. Risk factors include intensive care unit stay, central venous catheter use, broad-spectrum antibiotics use, abdominal surgery and immune suppression. Early antifungal treatment and central venous catheter removal form the cornerstones to decrease mortality. The landscape of novel therapeutics is growing; however, the application of new drugs requires careful selection of eligible patients as the spectrum of activity is limited to a few fungal species. Unanswered questions and knowledge gaps define future research priorities and a personalized approach to diagnosis and treatment of invasive candidiasis is of paramount importance.

Determination of amphotericin B antifungal susceptibility in Candida strains using an inverted microscope.

Invasive Candida infections have recently shown a significant increase in prevalence and are associated with high mortality rates. Initiating early antifungal treatment in patients with candidemia is vital. The aim of our study was to compare the antifungal susceptibility results of a new method called Flat Plate Method modified from reference "Clinical and Laboratory Standards Institute (CLSI) microdilution method by us with Sensitititre Yeast One colorimetric method and the reference CLSI method. We tested 100 Candida isolates from blood cultures. We followed the CLSI M27-A3 (reference method for broth dilution antifungal susceptibility testing of yeasts; third edition) guidelines for testing in vitro susceptibility to amphotericin B. In the Flat Plate method, 96-well plates were used for evaluation with an inverted microscope. Minimum inhibitory concentration (MIC) values in the SYO method were measured following the manufacturer's instructions. The MIC values obtained by all three methods were considered compatible if they were within ± 2 dilution limits. The SYO method detected C. albicans and C. glabrata with 100% essential agreement, whereas there was 96.29% essential agreement in the case of C. parapsilosis. In the Flat Plate method, the essential agreement with amphotericin B was 91.42%, for C. albicans isolates and 89.47%.for C. glabrata strains. When determining early antifungal susceptibility using the Flat Plate method, the results are obtained quickly, with high accuracy, and without incurring additional costs. However, there is a need for comprehensive studies comparing different antifungals.

Spectrum and management of rare Candida/yeast infections in Kuwait in the Middle East.

Invasive fungal infections (IFIs) are associated with high mortality rates and mostly affect patients with compromised immunity. The incidence of IFIs is increasing worldwide with the expanding population of susceptible patients. Candida and other yeast infections represent a major component of IFIs. Rare Candida/yeast infections have also increased in recent years and pose considerable diagnostic and management challenges as they are not easily recognized by routine phenotypic characteristic-based diagnostic methods and/or by the automated yeast identification systems. Rare Candida/yeasts also exhibit reduced susceptibility to antifungal drugs making proper management of invasive infections challenging. Here, we review the diagnosis and management of 60 cases of rare Candida/yeast IFIs described so far in Kuwait, an Arabian Gulf country in the Middle East. Interestingly, majority (34 of 60, 56.7%) of these rare Candida/yeast invasive infections occurred among neonates or premature, very-low-birth-weight neonates, usually following prior bacteremia episodes. The clinical details, treatment given, and outcome were available for 28 of 34 neonates. The crude mortality rate among these neonates was 32.2% as 19 of 28 (67.8%) survived the infection and were discharged in healthy condition, likely due to accurate diagnosis and frequent use of combination therapy. Physicians treating patients with extended stay under intensive care, on mechanical ventilation, receiving broad spectrum antibiotics and with gastrointestinal surgery/complications should proactively investigate IFIs. Timely diagnosis and early antifungal treatment are essential to decrease mortality. Understanding the epidemiology and spectrum of rare Candida/yeast invasive infections in different geographical regions, their susceptibility profiles and management will help to devise novel diagnostic and treatment approaches and formulate guidelines for improved patient outcome.

Invasive Aspergillosis Mimicking Tolosa-Hunt Syndrome: A Case Report

Invasive fungal infection remains a major cause of morbidity and mortality in immunocompromised patients. Invasive fungal sinusitis can present as a Tolosa-Hunt syndrome (THS) or orbital apex, leading to frequent misdiagnosis. Accurate diagnosis of fungal infection invading the cavernous sinus or orbital apex is essential to reduce mortality through early antifungal treatment and reduce the risk of worsening with steroid treatment due to misdiagnosis of THS. Herein, we report a case of invasive fungal sinusitis mimicking THS.

Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality.

Infections, including invasive fungal infections (IFIs), are among the leading causes of mortality in liver transplant recipients during the first year post-transplantation. To investigate the epidemiology, clinical manifestations, risk factors, treatment outcomes, and mortality rate of post-liver transplantation invasive aspergillosis (IA). In this case-control study, 22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran, Iran, between 2014 and 2019. The control group comprised 38 patients without IA infection matched for age and sex. The information obtained included the baseline characteristics of liver transplant patients, operative reports, post-transplantation characteristics of both groups and information about the fungal infection of the patient group. The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%. The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant, renal replacement therapy, antithymocyte globulin induction therapy, post-transplant bile leakage, post-transplant hepatic artery thrombosis, repeated surgery within 30 d after the transplant, bacterial pneumonia before the aspergillosis diagnosis, receiving systemic antibiotics before the aspergillus infection, cytomegalovirus infection, and duration of post-transplant hospitalization in the intensive care unit. The most prevalent form of infection was invasive pulmonary aspergillosis, and the most common chest computed tomography scan findings were nodules, pleural effusion, and the halo sign. In the case group, prophylactic antifungal therapy was administered more frequently than in the control group. The antifungal therapy response rate at 12 wk was 63.7%. The 3- and 12- mo mortality rates of the patients with IA were 36.4% and 45.4%, respectively (compared with the mortality rate of the control group in 12 mo, which was zero). In this study, the prevalence of IA among liver transplant recipients was relatively low. However, it was one of the leading causes of mortality following liver transplantation. Targeted antifungal therapy may be a factor in the low incidence of infections at our facility. Identifying the risk factors of IFIs, maintaining an elevated level of clinical suspicion, and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.

Development of a Corticosteroid-Immunosuppressed Mouse Model to Study the Pathogenesis and Therapy of Influenza-Associated Pulmonary Aspergillosis.

Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA.

Post Covid-19 Sinonasal Candidiasis: A Crisis Within the Pandemic.

The aim of this study was to find out the association of sinonasal candidiasis and Covid-19 infection. A prospective observational study was conducted at a tertiary care centre from April to September 2021, involving all patients with invasive candidiasis of the paranasal sinuses having a history of Covid-19 infection. A total of 18 patients of covid associated sinonasal candidiasis among the 475 cases of fungal rhinosinusitis were studied. All patients had involvement of nose and sinuses and 2 patients had orbital involvement with no loss of vision, while 3 had intracranial extensions and 1 had pulmonary involvement. Mandible was involved in 1 patient alone, while the maxilla and palate were involved in 5 patients. 15 patients were hypertensive, 12 diabetics and 1 had aplastic anaemia. Cultures showed that 8 patients had C. parapsilosis, 5 had C. albicans, 3 had C. tropicalis and 2 had mixed fungal infections. All patients underwent surgical debridement and antifungal administration. They were followed up for a minimum of 3 months. There was only one mortality (with aplastic anaemia), rest 17 were disease free at the time of writing this article. This is perhaps the first case series of post covid sinonasal candidiasis in the world. Invasive sinonasal candidiasis is a newer sequela of COVID-19 infection. Uncontrolled diabetes and over-zealous use of steroids at the time of Covid-19 are few of the known risk factors. Early surgical intervention and anti-fungal treatment should be sought for management.

Evaluation of Candida colonization index, molecular identification, and antifungal susceptibility pattern of Candida species isolated from critically ill pediatric patients: A single-center study in Iran.

Given the high mortality rate of invasive candidiasis in hospitalized pediatric patients, it is crucial to establish a predictive system to achieve early diagnosis and treatment of patients who are likely to benefit from early antifungal treatment. This study aimed to assess the Candida colonization index, species distribution, and antifungal susceptibility pattern of Candida strains isolated from pediatric patients with high Candida colonization index (CI). This study was carried out at the Children's Medical Center in Tehran-Iran. In total, 661 samples were collected from 83 patients. The Candida CI was calculated according to the descriptions of previous studies. The isolates were identified using polymerase chain reaction-based techniques. The Clinical and Laboratory Standard Institute protocol M60 was used to conduct the antifungal susceptibility test. A colonization index greater than 0.5 was confirmed in 29 cases (58% of positive samples) with two children developing candidemia. Candida albicans (n=53, 49.5%) was the most common Candida species in patients with CI > 0.5. Except for acute lymphoblastic leukemia, no risk factors were linked to a high index in colonized children (P > 0.05). Twelve isolates (7.01%) were multi-azole resistant with high MICs against both isavuconazole and ravuconazole and seven strains (4.09%) were echinocandins resistant. In pediatric intensive care units, patients are at risk of fungal infection, particularly candidemia. In this study, more than half of the children with positive yeast cultures had CI > 0.5, and 6.8% developed candidemia.

COVID-19-Associated Rhino-Mucormycosis and Pulmonary Aspergillosis Infection

In the current pandemic, the incidence of fungal infections-associated COVID-19 is surging. Diabetes mellitus, overzealous steroid, and antibiotic use for COVID-19 management may cause or exacerbate the fungal disease. In paranasal sinus (PNS), ethmoids followed by the maxillary sinus are commonly involved with the risk of intra-orbital or/and intracranial involvement is quite common. In lungs, COVID-19 infection has higher mortality rate, if there is an associated fungal infection. Aspergillus fumigates is the most common fungus that cause lung infection and present as discrete lesion different from COVID-19 manifestation. Two cases of COVID-associated fungal infections, i.e., rhino-mucormycosis and pulmonary aspergillosis are described here. In the first case, computed tomography (CT) of PNS was done for the complaints of mild right-sided facial swelling and mild restriction of the eye globe on day 27 of illness. CT showed hyperdense content involving the right-sided nasal sinus with the remodeling of bones with erosion and thinning of the inferior and medial orbital wall with the extension of soft tissue into the extraorbital space. The patient was treated with Amphotericin B and posaconazole oral suspension as the first-line antifungal monotherapy. In the second case, on complaints of cough with expectoration on the 20th day of illness, X-ray chest and CT chest were done which confirmed a thick-walled cavity in the right lung and other post COVID features. The tracheal aspirate culture was suggestive of Aspergillus fumigatus and Aspergillus antigen galactomannan was found positive in the fluid. The patient was treated for the same with antifungal therapy. Hence it is important to pay attention to the high probability of fungal infections in COVID-19 patients. The association of coronavirus with mucormycosis of the PNSs and aspergillosis of the lung must be given outmost consideration. Noncontrast CT of the PNSs is usually the first investigation of choice for PNS involvement, and CT chest help in the diagnosis of pulmonary fungal infection. Uncontrolled diabetes and use of steroids are two of the main factors for aggravating factors. Both early surgical intervention and anti-fungal treatment should be sought for the management.

COVID-19-associated pulmonary aspergillosis: an underdiagnosed or overtreated infection?

Purpose of reviewCoronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) may concern up to one third of intensive care unit (ICU) patients. The purpose of this review is to discuss the diagnostic criteria, the pathogenesis, the risk factors, the incidence, the impact on outcome, and the diagnostic and therapeutic management of CAPA in critically ill patients.Recent findingsThe incidence of CAPA ranges 3--28% of critically ill patients, depending on the definition used, study design, and systematic or triggered screening. COVID-19 is associated with direct damage of the respiratory epithelium, immune dysregulation, and common use of immunosuppressive drugs which might promote Aspergillus respiratory tract colonization and invasion. Positive Aspergillus tests among COVID-19 critically patients might reflect colonization rather than invasive disease. CAPA usually appears during the second week after starting invasive mechanical ventilation and is independently associated with ICU mortality.SummaryFurther studies are needed to validate CAPA case definitions, to determine the accurate incidence of CAPA in comparison to adequate controls, and its evolution during the pandemic. A pro-active diagnostic strategy, based on risk stratification, clinical assessment, and bronchoalveolar lavage could be recommended to provide early antifungal treatment in patients with high probability of CAPA and clinical deterioration.

Section 2. Colombian consensus for prophylaxis, treatment and prevention of invasive aspergillosis in adult and pediatric patients

The invasive aspergillosis (IA) continues to be an important cause of morbidity and mortality, difficult to manage in severely immunocompromised patients, however, with its appearance in a heterogeneous group of patients (e.g., critical ICU patients, patients with human immunodeficiency virus [HIV/AIDS], etc.), who were not classically considered high risk, as well as more chronic forms of aspergillosis, (including those with a propensity for invasion), which have been better defined, different antifungal treatment modalities have been established for Aspergillus-associated infections according to the specific patient’s condition. The understanding of the different risk factors for the development of IFI/IA, which are constantly evolving, and which include, among others, the underlying malignancy, the associated condition and treatment, the presence of comorbidities, environmental exposure, and the presence of certain genetic polymorphisms in the patient, allows for a more precise risk stratification, which together with the use of diagnostic algorithms, would allow the characterization of patients who would benefit from the different early intervention strategies, and the optimization of management protocols. The evaluation of the clinical manifestations of the patient is an essential step, as it involves the site of infection, the severity and dynamic nature of immunosuppression, and the characteristics of the etiological agent involved, which with the use of imaging modalities (with an increasingly important role in diagnosis), and of novel and accessible diagnostic tools, useful for the detection and follow-up of the disease, allow the early recognition of the infection, the selection of an early antifungal treatment, the use of more effective antifungal drugs and the development of local clinical practice guidelines

Management of Acute Invasive Fungal Sinusitis

Acute invasive fungal sinusitis (AIFS) is an uncommon and usually life-threatening clinical condition. Mortality in AIFS is very high. The colonization of the fungi at the sinonasal tract does not indicate the infection. The status of the immune condition of the patient plays an integral part in different manifestations of AIFS. AISF is an aggressive type of fungal infection and often leads to a fatal situation, particularly in patients who are immunocompromised. Diagnostic nasal endoscopy, as well as a computed tomography scan, is warranted in these patients. Magnetic resonance imaging improves diagnostic accuracy and assesses the spread of the disease into orbit and the brain. Histopathological and microbiological examinations confirm the diagnosis. To save lives, early diagnosis and treatment are essential. Therefore, clinicians need to have a high level of suspicion for this illness. Management of AIFS requires a multidisciplinary approach with significant predictors of survival being surgical debridement and antifungal treatment. Patients require urgent hospitalizations with intravenous antifungal therapy and surgical debridement. As soon as AIFS is identified, antifungal medication should begin. Higher survival rates are achieved with complete endoscopic resection of the disease than with incomplete resection. Liposomal amphotericin B has a more favorable outcome and fewer side effects than amphotericin B. The mainstays of AIFS management continue to be early surgical debridement and antifungal treatment. This review article discusses the epidemiology, etiopathogenesis, clinical features, investigations, and current treatment options of AIFS.

Republication de : Reducing mortality in mucormycosis of the head and neck in diabeticpatients: A CARE case series

Rhinocerebral mucormycosis is extremely fatal, with mortality rates ranging from 85-93% despite the best treatment in immunocompromised patients . We emphasize the importance of early diagnosis, repeated debridement , and aggressive antifungal treatment to reduce mortality. We report six cases (five male and one female), with a mean age of 51 years who were diagnosed to have mucormycosis from 2017 to 2019. All patients were diabetic. Intracranial involvement and orbital involvement were found in four cases. Facial nerve palsy was seen in two cases, one without any apparent otological involvement. Aggressive serial debridement and amphotericin B was started. Posaconazole was added subsequently to the treatment in two cases. One patient succumbed to the disease five months after discharge . The other five patients are on regular follow-up for a mean duration of 14 months at the end of which two had residual disease which was under control. Repeated surgical debridement with an early aggressive and combination antifungal therapy can result in good outcomes even in advanced mucormycosis. Concurrent management of the underlying pathology, monitoring of liver and kidney functions, and therapeutic drug monitoring are useful to ensure smooth and effective treatment.

Cutaneous Invasive Fungal Infections with Saksenaea Species in Immunocompetent Patients in Europe: A Systematic Review and Case Report.

Background:Invasive fungal infections from Saksenaea, a fungus belonging to the Mucorales, have been rarely reported in central European climate zones. This study aims to raise awareness of invasive cutaneous infections with Saksenaea species. The first case of a cutaneous infection was diagnosed in Switzerland in an immunocompetent 79-year-old patient. A minor skin trauma of her left lower leg led to a fulminant infection causing necrosis and extensive loss of tissue. The combination of surgical debridement and administration of antifungal agents averted a prolonged course with a possible worse outcome. A pedicled hemisoleus muscle flap was used to reconstruct the defect and treatment was continued for 63 days.Methods:A systematic review in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis guidelines was conducted to identify all European cases of infection with Saksenaea species in immunocompetent hosts. The epidemiology, clinical presentation, microbiological diagnosis, and management of cases reported in Europe were summarized and analyzed.Conclusions:The prognosis of soft tissue infections with Saksenaea species. depends on early diagnosis and appropriate antifungal and surgical treatment. Reconstruction can be successful under ongoing antifungal treatment.

Evaluation of Posaconazole for Primary Prophylaxis of IFI in Acute Myeloid Leukemia under Intensive Induction Chemotherapy. Comparative Real Life Study with Fluconazole in two Hematological Centers in Algeri

Introduction: Acute myeloid leukemia (AML) is a hematological malignancy with a poor prognosis. The early consequences of induction chemotherapy are represented by pancytopenia with severe immunosuppression, which favors the emergence of so-called “opportunistic” infections and in particular invasive fungal infections (IFI) such as invasive aspergillosis (IA). This justifies the implementation of early, empirical, pre-emptive or prophylactic antifungal treatment. The objective of this study is the evaluation of a comparative study before and after the use of primary prevention with posaconazole versus fluconazole, in terms of incidence and mortality of invasive fungal infections (IFIs) during AML inductions, in real life in Algeria. Patients and methods: This study was performed in two periods in the 2 centers concerning the same AML patients receiving the same induction chemotherapy (daunorubicin 60 mg/m2 for 3 days and cytarabine 100 mg/m2 for 7 days) but with a different type of hospitalization with common rooms for Tlemcen and protected single rooms for Oran. Period 1: The retrospective study was performed from 2014 to 2016 and involved 188 patients. 70 patients were hospitalized in a common room (Tlemcen) and 118 patients in a protected single room (Oran). All patients received as primary IFI prophylaxis fluconazole 400 mg/day. Period 2: The prospective study was conducted from April 2017 to September 2018 and involved 55 patients. Fourteen patients were hospitalized in Tlemcen and 41 patients in an Oran. These patients received posaconazole prophylaxis at a dose of 200 mgx3/day. The evaluation and comparison of descriptive and incidence data was performed using Chi2 statistical tests using SPSS version 19 software. Overall survival (OS) were calculated using the Kaplan-Meier estimate and were compared using the log-rank test with a significance level α of 0.05. Results: Period 1: The incidence rate of IFI: 34% at the Oran hospital versus 49% at the Tlemcen hospital (p=0.049). Among the 74 patients who presented with IFI, 39 (53%) died from IFI as the main cause of death, among these deaths, 16 (40%) were recorded at Oran and 23 (68%) at Tlemcen (p=0.011). Period 2: The IFI rate with fluconazole was 39% and that observed with posaconazole 22% (p=0.001) and the cumulative incidence was 39% at 21 days versus 10% at 15 days (p=0.046) with a highly significant decrease in IFI-related deaths: 53% versus 25% (p=0.004). Conclusion: This work has demonstrated the interest in terms of IFI incidence (17% versus 33%, p=0.04) and IFI-related mortality of posaconazole prophylaxis (25% versus 53%, p=0.004) used during AML in the context of hospitalization in common rooms. Furthermore, this work highlights that the combination of posaconazole prophylaxis and hospitalization in a protected single room allows an optimization of the management of this type of patients.
 
 

Intensive Care Antifungal Stewardship Programme Based on T2Candida PCR and Candida Mannan Antigen: A Prospective Study.

Non-culture-based biomarkers may improve diagnosis and antifungal treatment (AFT) of invasive candidiasis (IC). We evaluated an antifungal stewardship programme (AFSP) in a prospective intensive care unit (ICU) study, which included T2Candida and Candida mannan antigen (MAg) screening of patients with sepsis and a high risk of IC. Patients with non-neutropenic sepsis and a high risk of IC from two large tertiary ICUs were prospectively included, during a one-year period. IC was classified as proven, likely, possible or unlikely. The AFSP, diagnostic values of T2Candida and MAg, and the consumption of antifungals were evaluated. An amount of 219 patients with 504 T2Candida/MAg samples were included. IC was classified as proven in 29 (13.2%), likely in 7 (3.2%) and possible in 10 (5.5%) patients. Sensitivity/specificity/PPV/NPV values, comparing proven/likely versus unlikely IC, were 47%/100%/94%/90% for BC alone, 50%/97%/75%/90% for T2Candida alone, and 39%/96%/67%/88% for MAg alone. For the combination of T2Candida/MAg taken ≤3 days after AFT initiation, sensitivity/specificity/PPV/NPV was 70%/90%/63%/93%. T2Candida/MAg contributed to early (<3 days) AFT initiation in 13%, early AFT discontinuation in 25% and abstaining from AFT in 24% of patients. No reduction in overall use of AFT during the study period compared with the previous year was observed. An AFSP based on T2Candida and MAg screening contributed to a reduction of unnecessary treatment, but not overall AFT use. The diagnostic performance of T2Candida was lower than previously reported, but increased if T2Candida was combined with MAg.

COVID-19-Associated Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Case Series in a Portuguese Hospital.

Invasive pulmonary aspergillosis (IPA) has become a recognizable complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs). Alveolar damage in the context of acute respiratory distress syndrome (ARDS) appears to be the culprit in facilitating fungal invasion in COVID-19 patients, leading to a COVID-19-associated pulmonary aspergillosis (CAPA) phenomenon. From November 2020 to 15 February 2021, 248 COVID-19 patients were admitted to our ICUs, of whom ten patients (4% incidence) were classified as either probable (six) or possible (four) CAPA cases. Seven patients had positive cultural results: Aspergillus fumigatus sensu stricto (five), A. terreus sensu stricto (one), and A. welwitschiae (one). Five patients had positive bronchoalveolar lavage (BAL) and galactomannan (GM), and two patients had both positive cultural and GM criteria. All but two patients received voriconazole. Mortality rate was 30%. Strict interpretation of classic IPA definition would have resulted in eight overlooked CAPA cases. Broader diagnostic criteria are essential in this context, even though differentiation between Aspergillus colonization and invasive disease might be more challenging. Herein, we aim to raise awareness of CAPA in view of its potential detrimental outcome, emphasizing the relevance of a low threshold for screening and early antifungal treatment in ARDS patients.

S2858 An Unusual Case of Donor-related Disseminated Histoplasmosis with Systemic Complications Due to Patient Noncompliance

Introduction: Disseminated histoplasmosis is a mycosis that often occurs in immunosuppressed settings, such as following solid organ transplants. We present the case of a 61-year-old man with a history of liver transplantation resulting in donor-related disseminated histoplasmosis complicated by Cytomegalovirus viremia and C-difficile infection. This case was also complicated by the patient’s voluntary discontinuation of prophylactic therapy, precipitating disseminated histoplasmosis. Case Description/Methods: A 61-year-old man with a history of liver cirrhosis secondary to non-alcoholic steatohepatitis received a deceased-donor liver transplant. He was given induction immunosuppression with thymoglobulin and subsequently initiated on tacrolimus, prednisone, and mycophenolate. Following the transplant, pathologic evidence of histoplasmosis was identified on the donor spleen. The recipient was placed on prophylactic itraconazole with monthly Histoplasmosis Antigen (Histo Ag) checks. The patient voluntarily discontinued itraconazole after 3 months due to headaches, while still monitoring Histo Ag levels. Three months later, he presented with right lower quadrant abdominal pain, fever, and diarrhea. AST levels were elevated at 240 IU/L ( > 35 IU/L) and ALT levels at 261 IU/L ( > 78 IU/L). A liver biopsy showed granulomatous hepatitis suggestive of histoplasmosis. A CT guided biopsy of a subpleural lung nodule showed similar granulomas. Urine Histo Ag was positive at 13.9 ng/mL (negative: < 0.10 ng/mL). The patient was also found to have cytomegalovirus (CMV) viremia despite taking prophylactic ganciclovir. He concurrently developed C. difficile colitis which resolved with vancomycin. The patient was reinitiated on itraconazole with successful suppression of Histo Ag levels, along with CMV viral load and liver enzymes. He remained on itraconazole for the following 4 years with continued stability. Discussion: Immunodeficient hosts, such as those on post-transplant immunosuppressive therapy, are at an increased risk of developing disseminated histoplasmosis when infected with Histoplasma capsulatum, as with this case. Here, we recognize the value of frequent Histo Ag monitoring and the rapid histoplasmosis progression that can occur if prophylaxis is discontinued. While early monitoring and antifungal treatment can improve outcomes, it is also important to manage treatment noncompliance. This case emphasizes the need for early discussions with patients about prophylactic therapy compliance to avoid complications.