Incidence of invasive fungal diseases in inflammatory bowel disease patients: A nationwide study in South Korea.

BACKGROUND: Limited reports exist regarding invasive fungal diseases (IFDs) in inflammatory bowel disease (IBD) patients. OBJECTIVES: This study aims to investigate the incidence and risk factors of IFDs, specifically invasive candidiasis, aspergillosis and pneumocystosis, in IBD patients in South Korea using nationwide data. PATIENTS/METHODS: A population-based retrospective cohort of 42,913 IBD patients between January 2010 and December 2018 was evaluated using the Health Insurance Review and Assessment database. The primary outcome was the incidence of IFDs, including invasive candidiasis, aspergillosis and pneumocystosis, while the secondary outcome involved analysing the risk factors associated with each specific infection. RESULTS: The study included a total of 42,913 IBD patients, with 29,909 (69.7%) diagnosed with ulcerative colitis (UC) and 13,004 (30.3%) diagnosed with Crohn's disease (CD). IFDs occurred in 166 IBD patients (0.4%), with 93 cases in UC patients and 73 cases in CD patients. The incidence rates of invasive candidiasis, aspergillosis and pneumocystosis in IBD patients were 0.71 per 1000 person-years (PYs), 0.15 per 1000 PYs and 0.12 per 1000 PYs, respectively. The cumulative incidence of invasive candidiasis (adjusted p-value <.001) and Pneumocystosis (adjusted p-value = .012) was found to be higher in CD patients than in UC patients. Each IFD had different risk factors, including IBD subtypes, age at diagnosis, anti-tumour necrotic factor agents or the Charlson comorbidity index. CONCLUSION: Based on nationwide data in South Korea, this study shows that IFDs occur consistently in patients with IBD, albeit with a low frequency.

Risk Factors for Early Fungal Disease in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND: Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. METHODS: We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. RESULTS: We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. CONCLUSIONS: Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

[Skin lesions associated with invasive candidiasis in a neutropenic patient with acute myeloid leukemia] / Lesiones cutáneas asociadas a candidiasis invasiva en un paciente neutropénico con leucemia mieloide aguda.

A 51-year-old male with profound and prolonged neutropenia 12 days after receiving chemotherapy for an acute myeloid leukemia developed a nodular, erythematous lesion with a necrotic center on the base of the neck, associated with fever, chills, and myalgia. An invasive fungal infection was diagnosed after growth of Candia tropicalis in blood cultures. He evolved with multiple reddish papular lesions concentrated mainly on the trunk, although they also spread to the extremities. The most common skin lesions of disseminated candidiasis are erythematous-violaceous papules with vesicular centers, which, in some cases, can progress to necrosis. Other forms of cutaneous presentation of invasive candidiasis are ecthyma gangrenosum-like lesions, hemorrhagic plaques or bullae, rash resembling folliculitis, and subcutaneous nodules.

Un varón de 51 años que se encontraba con neutropenia profunda y prolongada luego de 12 días del inicio de su quimioterapia por una leucemia mieloide aguda desarrolló una lesión nodular, eritematosa y con centro necrótico en la base del cuello, asociada a fiebre, escalofríos y mialgias. Se diagnosticó infección fúngica invasiva luego del desarrollo de Candia tropicalis en los hemocultivos. Evolucionó con múltiples lesiones papulares rojizas concentradas principalmente en el tronco, aunque también extendidas a las extremidades. Las lesiones cutáneas más frecuentes de la candidiasis diseminada son pápulas eritematosas-violáceas con centros vesiculares, que, en algunos casos, pueden evolucionar a necrosis. Otras formas de presentación cutánea de la candidiasis invasiva son lesiones similares a ectima gangrenoso, placas o bullas hemorrágicas, erupción que resembla foliculitis, y nódulos subcutáneos.

Sudden Esophageal Necrosis and Mediastinitis Associated with Invasive Candidiasis: A Case Report.

BACKGROUND Esophageal necrosis is a rare entity characterized by the presence of extensive circumferential necrosis of the esophagus. It generally affects older adults who have associated chronic pathologies and has a reported mortality rate of approximately 32%. Most patients with esophageal necrosis have a complex clinical course. CASE REPORT We present the case of a 37-year-old man with idiopathic chronic renal failure who presented to the Emergency Department with sudden esophageal necrosis and mediastinitis, associated with invasive candidiasis. Diagnosis was challenging owing to the rarity of the condition. The patient required intensive care management and multiple surgical procedures. CONCLUSIONS Esophageal necrosis is an uncommon pathology that can be fatal because of associated complications. Its pathophysiology is unclear, and its treatment is based on the control of local injury and signs and symptoms. Acute esophageal necrosis associated with invasive Candida sp. infection is even more infrequent, with only a few cases reported in the literature.

Inborn Errors of Immunity in the Premature Infant: Challenges in Recognition and Diagnosis.

Due to heightened awareness and advanced genetic tools, inborn errors of immunity (IEI) are increasingly recognized in children. However, diagnosing of IEI in premature infants is challenging and, subsequently, reports of IEI in premature infants remain rare. This review focuses on how common disorders of prematurity, such as sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia, can clinically overlap with presenting signs of IEI. We present four recent cases from a single neonatal intensive care unit that highlight diagnostic dilemmas facing neonatologists and clinical immunologists when considering IEI in preterm infants. Finally, we present a conceptual framework for when to consider IEI in premature infants and a guide to initial workup of premature infants suspected of having IEI.

Candida colonization as a predictor of invasive candidiasis in non-neutropenic ICU patients with sepsis: A systematic review and meta-analysis.

BACKGROUND: Candida colonization is a risk factor for the development of invasive candidiasis. This study sought to estimate the magnitude of this association, and determine if this information can be used to guide empirical antifungal therapy initiation in critically ill septic patients. METHODS: PubMed/MEDLINE and Embase were systematically reviewed for all published studies evaluating predictors of invasive candidiasis in ICU patients with sepsis. Meta-analysis was used to determine the pooled odds ratio for invasive candidiasis among colonized versus non-colonized patients. Sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV), and positive and negative likelihood ratios (+LR, -LR) were then calculated by considering the presence/absence of Candida colonization as the diagnostic test, and the presence/absence of invasive candidiasis as the disease of interest. RESULTS: Out of 9825 patients in the 10 eligible studies, 3886 (40%) were colonized with Candida and 462 patients (4.7%) developed invasive candidiasis. Meta-analysis indicated that critically ill patients with sepsis who are colonized with candida are more likely to develop invasive candidiasis (odds ratio 3.32; 95% CI 1.68-6.58) compared with non-colonized patients. The pooled SN was 75.2% (95% CI 59.6-86.2%), while the pooled SP was 49.2% (95% CI 33.2-65.3%).The NPV of Candida colonization was high (96.9%; 95% CI 92.0-98.9%), but the PPV was low (9.1%; 95% CI 5.5-14.6%). CONCLUSION: Candida colonization is strongly associated with the likelihood of invasive candidiasis among ICU patients with sepsis. Available data argue against initiating empirical antifungal treatment in non-neutropenic septic patients without prior documented Candida colonization.

Fungal Co-infections Associated with Global COVID-19 Pandemic: A Clinical and Diagnostic Perspective from China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been sweeping across the globe. Based on a retrospective analysis of SARS and influenza data from China and worldwide, we surmise that the fungal co-infections associated with global COVID-19 might be missed or misdiagnosed. Although there are few publications, COVID-19 patients, especially severely ill or immunocompromised, have a higher probability of suffering from invasive mycoses. Aspergillus and Candida infections in COVID-19 patients will require early detection by a comprehensive diagnostic intervention (histopathology, direct microscopic examination, culture, (1,3)-ß-D-glucan, galactomannan, and PCR-based assays) to ensure effective treatments. We suggest it is prudent to assess the risk factors, the types of invasive mycosis, the strengths and limitations of diagnostic methods, clinical settings, and the need for standard or individualized treatment in COVID-19 patients. We provide a clinical flow diagram to assist the clinicians and laboratory experts in the management of aspergillosis, candidiasis, mucormycosis, or cryptococcosis as co-morbidities in COVID-19 patients.

Opportunistic pathogenic fungal co-infections are prevalent in critically ill COVID-19 patients: Are they risk factors for disease severity?

Fungal co-infections, especially with Aspergillus and Candida species, are prevalent in hospitalised COVID-19 patients, and could influence patient outcomes and hamper treatment efforts. However, information about and elucidation of the causal relationship between fungal co-infections and COVID-19 disease outcomes or severity in patients are still lacking. Such information, if and when available, will help facilitate appropriate case management.

Hyperpigmentation as a cutaneous manifestation of fungal sepsis in neonates: Case series report.

With improved and prolonged survival of very and extremely low birth weight infants, invasive fungal infection has emerged as an important concern in the neonatal intensive care units. Candidiasis is the third leading cause of late onset sepsis in these neonates and is associated with 20-30% mortality. Extreme prematurity, central venous catheters, prolonged antibiotic exposure, parenteral nutrition are important risk factors. Various forms of cutaneous manifestations of candidiasis have been described ranging from local diaper dermatitis and oral thrush to widespread erosive and ulcerative lesions with extensive crusting in invasive fungal dermatitis. We report a series of four cases with cutaneous hyperpigmentation as manifestation of systemic candidiasis.

Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project.

BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Epidemiology and treatment approaches in management of invasive fungal infections in hematological malignancies: Results from a single-centre study.

Invasive fungal infections (IFIs) are a leading cause of morbidity and attributable mortality in oncohematologic patients. Timely diagnosis is essential but challenging. Herein we retrospectively describe 221 cases of antifungal treatments (AFT) administered in a monocentric real-life cohort of hematological malignancies. Between January 2010 and July 2017, 196 oncohematologic patients were treated with AFT at our Hematology Department. Diagnosis of IFIs was carried out according to EORTC/MSG-2008 guidelines.The most represented disease was acute myeloid leukemia (104 patients). Median age was 61 years; at fever onset 177 (80%) patients had a neutrophil count<0.5x109/L. Twenty-nine (13%) patients were receiving antifungal prophylaxis (26 posaconazole, 2 fluconazole, 1 itraconazole). The incidence of AFT was 13%. Serum galactomannan antigen (GM) was positive in 20% of the tested cases, while 85% of the patients had a CT scan suggestive for IFI. Twenty-one percent of these cases had a GM positive. Sixty-five out of 196 patients (33%) showed positive culture results, in particular Candida spp. were identified in 45 isolates, while Aspergillus spp. in 16 cases. Fourteen patients presented multiple positivity. Twenty-two (10%) cases were classified as proven IFIs, 61 (28%) as probable and 81 (37%) as possible, but 57 (26%) cases could not be classified. Fifty-nine percent of the patients received single agent AFT, 37% sequential AFT, 8% a combination regimen. Liposomal-amphotericin-B was the most used AFT. IFIs attributable mortality was 20%. This epidemiologic survey underlined a persistent significant use of AFT and a high mortality rate of IFIs. We suggest that further powerful diagnostic approaches should be investigated to improve the diagnostic accuracy and potential therapeutic implication.

ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients.

INTRODUCTION: The term invasive candidiasis (IC) refers to both bloodstream and deep-seated invasive infections, such as peritonitis, caused by Candida species. Several guidelines on the management of candidemia and invasive infection due to Candida species have recently been published, but none of them focuses specifically on critically ill patients admitted to intensive care units (ICUs). MATERIAL AND METHODS: In the absence of available scientific evidence, the resulting recommendations are based solely on epidemiological and clinical evidence in conjunction with expert opinion. The task force used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the recommendations and assign levels of evidence. The recommendations and their strength were decided by consensus and, if necessary, by vote (modified Delphi process). Descriptive statistics were used to analyze the results of the Delphi process. Statements obtaining > 80% agreement were considered to have achieved consensus. CONCLUSIONS: The heterogeneity of this patient population necessitated the creation of a mixed working group comprising experts in clinical microbiology, infectious diseases and intensive care medicine, all chosen on the basis of their expertise in the management of IC and/or research methodology. The working group's main goal was to provide clinicians with clear and practical recommendations to optimize microbiological diagnosis and treatment of IC. The Systemic Inflammation and Sepsis and Infection sections of the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) therefore decided to develop a set of recommendations for application in non-immunocompromised critically ill patients.

Role of Candida Albicans Germ Tube Antibody in Diagnosis of Invasive Candidiasis in End Stage Liver Disease Patients.

Candida species are the leading cause of invasive fungal infections and a common cause of hospital-acquired bloodstream infections. Invasive candidiasisis a highly lethal infection associated with mortality rates between 40 and 60 %. This study was conducted with aim of assessing the role of Candida albicans germ tube antibody (CAGTA) level in the early diagnosis of invasive candidiasis and in monitoring the efficacy of antifungal drugs in patients with end stage liver disease. Sixty two end stage liver disease patients were included in this study. Candida albicans germ tube antibody (CAGTA) test was done for all cases by indirect immunofluorescence technique, and it was positive with (titre ≥ 1/160) in 18 cases including the 10 blood culture positive cases. Compared to positive blood culture, the sensitivity, specificity, negative predictive value, positive predictive value and accuracy of CAGTA test were 100%, 84.6 %, 55.6 %, 100 % and 73.3 % respectively. Candida albicans germ tube antibody (CAGTA) test is sensitive and specific test, that can be used for early diagnosis of invasive candidiasis and in monitoring the effect of treatment with antifungal drugs in end stage liver disease patients.

Breakthrough Candida guilliermondii (Meyerozyma guilliermondii) fungemia after cord blood transplantation for extranodal NK-cell lymphoma with azole prophylaxis.

Fluconazole (FLCZ) is an azole antifungal agent and it has shown excellent clinical activities in suppressing fungemia with Candida albicans after hematopoietic stem cell transplantation. Increased administration of prophylactic FLCZ seems to have given rise to the relatively higher incidence of more resistant Candida non-albicans infection. We present a case with a rare breakthrough fungemia with C. guilliermondii after cord blood transplantation for Extranodal NK cell Lymphoma, nasal type (ENKL), during antifungal prophylaxis with FLCZ. High level of caution is needed for the breakthrough, especially after long-term azole administration.

Efficacy of micafungin for the treatment of invasive candidiasis and candidaemia in patients with neutropenia.

Neutropenia is linked to the development of invasive candidiasis/candidaemia, for which micafungin has demonstrated efficacy, but evidence in patients with neutropenia is limited. The aim of this study was to evaluate the efficacy of micafungin for the treatment of invasive candidiasis/candidaemia in patients with neutropenia (<500 neutrophils/µL) and without neutropenia. This pooled, post hoc analysis of 2 Phase 3 trials compared micafungin 100 mg/d (adults) and 2 mg/kg/d (paediatrics) with L-AmB 3 mg/kg/d (NCT00106288) and micafungin 100 mg/d and 150 mg/d with caspofungin 70 mg/d followed by 50 mg/d (adults) (NCT00105144); treatment duration 2-4 weeks (≤8 weeks for chronic disseminated candidiasis). Effects of neutropenia duration and Candida spp. on efficacy outcomes (treatment success, clinical and mycological response) were examined. Of 685 patients, 77 had neutropenia. The most common infection in patients with/without neutropenia was due to C. tropicalis (31/77) and C. albicans (295/608) respectively. Overall success was numerically lower in patients with vs without neutropenia (63.6% vs 72.9%). Clinical and mycological response was similar between groups. Neutropenia duration or Candida spp. did not impact micafungin's overall success rate. This analysis supports evidence that micafungin is effective against invasive candidiasis/candidaemia in patients with neutropenia, irrespective of neutropenia duration or Candida spp., although overall success may be lower than in patients without neutropenia.

Antifungal Susceptibility and Clinical Outcome in Neonatal Candidiasis.

BACKGROUND: Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI. METHODS: This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18-22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III). RESULTS: Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed. CONCLUSIONS: Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.