Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.
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SUBMITTER: Giacobbe DR
PROVIDER: S-EPMC7997529 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:During recent years, a rising incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic critically ill patients has been reported. Critically ill patients are prone to develop disturbances in immunoregulation during their stay in the ICU, which render them more vulnerable for fungal infections. Risk factors such as chronic obstructive pulmonary disease (COPD), prolonged use of steroids, advanced liver disease, chronic renal replacement therapy, near-drowning and diabetes mellitus have been described. Diagnosis of IPA may be difficult and obtaining histo- or cytopathological demonstration of the fungus in order to meet the gold standard for IPA is not always feasible in these patients. Laboratory markers used as a non-invasive diagnostic tool, such as the galactomannan antigen test (GM), 1,3-beta-glucan, and Aspergillus PCR, show varying results. Antifungal therapy might be considered in patients with persistent pulmonary infection who exhibit risk factors together with positive cultures or sequentially positive GM and Aspergillus PCR in serum, in whom voriconazole is the drug of choice. The benefit of combination antifungal therapy lacks sufficient evidence so far, but this treatment might be considered in patients with breakthrough infections or refractory disease.
| S-EPMC2039828 | biostudies-other
Project description:The estimated attributable mortality rate for invasive candidiasis (IC) in the intensive care unit (ICU) setting varies from 30 to 40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin, and therefore, dosing adjustments might be mandatory. The objective of this study was to determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment. Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin. MIC values for Candida isolates were determined to assess the probability of target attainment for patients. Data from 19 patients with suspected or proven invasive candidiasis were available for analysis. The median area under the concentration-time curve from 0 to 24 h at steady state (AUC0-24) was 89.6 mg · h/liter (interquartile range [IQR], 75.4 to 113.6 mg · h/liter); this was significantly lower than the median micafungin AUC0-24 values of 152.0 mg · h/liter (IQR, 136.0 to 162.0 mg · h/liter) and 134.0 mg · h/liter (IQR, 118.0 to 148.6 mg · h/liter) in healthy volunteers (P = <0.0001 and P = <0.001, respectively). All Candida isolates were susceptible to micafungin, with a median MIC of 0.016 mg/liter (IQR, 0.012 to 0.023 mg/liter). The median AUC0-24/MIC ratio was 5,684 (IQR, 4,325 to 7,578), and 3 of the 17 evaluable patients (17.6%) diagnosed with proven invasive candidiasis did not meet the AUC/MIC ratio target of 5,000. Micafungin exposure was lower in critically ill patients than in healthy volunteers. The variability in micafungin exposure in this ICU population could be explained by the patients' body weight. Our findings suggest that healthier patients (sequential organ failure assessment [SOFA] score of <10) weighing more than 100 kg and receiving 100 mg micafungin daily are at risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT01716988.).
| S-EPMC5700342 | biostudies-literature
Project description:A prospective, multicentre, phase IIIb study with an exploratory, open-label design was conducted to evaluate efficacy and safety of anidulafungin for the treatment of candidaemia/invasive candidiasis (C/IC) in specific ICU patient populations. Adult ICU patients with confirmed C/IC meeting ? 1 of the following criteria were enrolled: post-abdominal surgery, solid tumour, renal/hepatic insufficiency, solid organ transplant, neutropaenia, and age ? 65 years. Patients received anidulafungin (200 mg on day 1, 100 mg/day thereafter) for 10-42 days, optionally followed by oral voriconazole/fluconazole. The primary efficacy endpoint was global (clinical and microbiological) response at the end of all therapy (EOT). Secondary endpoints included global response at the end of intravenous therapy (EOIVT) and at 2 and 6 weeks post-EOT, survival at day 90, and incidence of adverse events (AEs). The primary efficacy analysis was performed in the modified intent-to-treat (MITT) population, excluding unknown/missing responses. The safety and MITT populations consisted of 216 and 170 patients, respectively. The most common pathogens were Candida albicans (55.9%), C. glabrata (14.7%) and C. parapsilosis (10.0%). Global success was 69.5% (107/154; 95% CI, 61.6-76.6) at EOT, 70.7% (111/157) at EOIVT, 60.2% (77/128) at 2 weeks post-EOT, and 50.5% (55/109) at 6 weeks post-EOT. When unknown/missing responses were included as failures, the respective success rates were 62.9%, 65.3%, 45.3% and 32.4%. Survival at day 90 was 53.8%. Treatment-related AEs occurred in 33/216 (15.3%) patients, four (1.9%) of whom had serious AEs. Anidulafungin was effective, safe and well tolerated for the treatment of C/IC in selected groups of ICU patients.
| S-EPMC3510306 | biostudies-literature
Project description:Rabbits that had been infected intravenously with conidiospores of Aspergillus fumigatus were used as sources of antibody for screening a lambda phage cDNA expression library. The cDNA was derived from A. fumigatus mRNA that had been extracted from newly formed, germling hyphae. Thirty-six antigens were identified using antisera from six rabbits. Though many of these antigens were expected to be intracellular proteins because their genes did not encode a signal sequence, the antisera showed consistently a stronger immunoblot reaction with a cell fraction enriched for the fungal cell wall than with a fraction of predominantly intracellular components. Antibodies to eight antigens, including the glycosylhydrolase Asp f 16, were produced by more than one rabbit. In current vaccine studies, Asp f 16 is the only single antigen which has been reported to be capable of inducing protection against invasive aspergillosis in mice. Enolase and Aspergillus HSP90 were detected also; their homologues in Candida albicans have been tested as vaccines and have been reported to provide a partially protective response against invasive candidiasis in mice. The Aspergillus antigens reported here may have value both in diagnostic tests for different forms of aspergillosis and as vaccine candidates for protection against invasive disease.
| S-EPMC1201263 | biostudies-literature
Project description:IntroductionOver 5,000 cases of invasive Candida species infections occur in the United Kingdom each year, and around 40% of these cases occur in critical care units. Invasive fungal disease (IFD) in critically ill patients is associated with increased morbidity and mortality at a cost to both the individual and the National Health Service. In this paper, we report the results of a systematic review performed to identify and summarise the important risk factors derived from published multivariable analyses, risk prediction models and clinical decision rules for IFD in critically ill adult patients to inform the primary data collection for the Fungal Infection Risk Evaluation Study.MethodsAn internet search was performed to identify articles which investigated risk factors, risk prediction models or clinical decisions rules for IFD in critically ill adult patients. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of the eligible articles was assessed using a set of questions addressing both general and statistical methodologies.ResultsThirteen articles met the inclusion criteria, of which eight articles examined risk factors, four developed a risk prediction model or clinical decision rule and one evaluated a clinical decision rule. Studies varied in terms of objectives, risk factors, definitions and outcomes. The following risk factors were found in multiple studies to be significantly associated with IFD: surgery, total parenteral nutrition, fungal colonisation, renal replacement therapy, infection and/or sepsis, mechanical ventilation, diabetes, and Acute Physiology and Chronic Health Evaluation II (APACHE II) or APACHE III score. Several other risk factors were also found to be statistically significant in single studies only. Risk factor selection process and modelling strategy also varied across studies, and sample sizes were inadequate for obtaining reliable estimates.ConclusionsThis review shows a number of risk factors to be significantly associated with the development of IFD in critically ill adults. Methodological limitations were identified in the design and conduct of studies in this area, and caution should be used in their interpretation.
| S-EPMC3388661 | biostudies-literature
Project description:IntroductionCritically ill patients with chronic obstructive respiratory diseases (CORD) who require intensive care unit (ICU) admission are at particular risk for invasive bronchial-pulmonary aspergillosis (IBPA). The purpose of this study is to investigate clinical features for rapid recognition of IBPA in critically ill patients with CORD.MethodsWe included 55 consecutive CORD patients in a respiratory ICU in a prospective, single-center, cohort study. In this study, IBPA combined two entities: ATB and IPA.ResultsThirteen of 55 patients were diagnosed with IBPA. Before ICU admission, three variables were independent predictors of IBPA with statistical significance: more than three kinds of antibiotics used before the ICU admission, accumulated doses of corticosteroids (>350 mg) received before the ICU admission, and APACHE II scores >18 (OR, 1.208; P = 0.022; OR, 8.661; P = 0.038; and OR, 19.488; P = 0.008, respectively). After ICU admission, more IBPA patients had a high fever (>38.5 °C) (46.2% versus 11.9%; P = 0.021), wheeze without exertion (84.6% versus 50.0%; P = 0.027), dry rales (84.6% versus 40.4%; P = 0.005), higher white blood cell counts (21 × 109/L versus 9.4 × 109/L; P = 0.012), lower mean arterial pressures (77.9 mm Hg versus 90.5 mm Hg; P = 0.019), and serum creatinine clearances (36.2 ml/min versus 68.8 ml/min; P < 0.001), and liver-function and coagulation abnormalities. Bronchospasm, sputum ropiness, and plaque formation were more common for IBPA patients during bronchoscopy (66.7% versus 14.3%; P = 0.082; 18% versus 0; P = 0.169; and 73% versus 13%; P = 0.003, respectively). More IBPA patients had nodules and patchiness on chest radiograph on day 1 of admission, which rapidly progressed to consolidation on day 7. IBPA mortality was higher than that of non-IBPA patients (69.2% versus 16.7%; P = 0.001).ConclusionsIBPA may be suspected in critically ill CORD patients with respiratory failure and clinical and bronchoscopic manifestations of severe infection, bronchospasm, and rapid progression of radiologic lesions that are irresponsive to steroids and antibiotics. To avoid misdiagnosis and establish the microbiologic etiology, early bronchoscopy and tight radiologic follow-up should be performed.
| S-EPMC3222032 | biostudies-literature
Project description:Severe coronavirus disease 2019 pneumonia can lead to acute respiratory distress syndrome. Recently, several publications reported on coronavirus disease 2019-associated pulmonary aspergillosis. However, risk factors remain unclear. We retrospectively collected all the cases of coronavirus disease 2019 acute respiratory distress syndrome patients (n = 46) admitted to our 34-bed ICU between March 24, 2020, and May 25, 2020, and identified six patients that met the diagnosis of invasive pulmonary aspergillosis according to previously established definitions. This population exhibited higher severity scores at admission and less hospital discharge compared with noninvasive pulmonary aspergillosis patients. Chronic obstructive pulmonary disease, malnutrition, and systemic corticosteroid use were identified as risk factors for invasive pulmonary aspergillosis in coronavirus disease 2019-induced acute respiratory distress syndrome patients. Coronavirus disease 2019-associated pulmonary aspergillosis may be a serious concern regarding corticosteroids use to control the inflammatory response of coronavirus disease 2019-induced acute respiratory distress syndrome.
| S-EPMC7665250 | biostudies-literature
Project description:BackgroundSuperinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.MethodsWe prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.FindingsCAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.InterpretationCAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.
| S-EPMC7968651 | biostudies-literature
Project description:Influenza was recently reported as a risk factor for invasive aspergillosis (IA). We aimed to describe prognostic factors for influenza-associated IA (IAA) and poor outcome and mortality in critically ill patients in Switzerland. All adults with confirmed influenza admitted to the ICU at two Swiss tertiary care centres during the 2017/2018 influenza season were retrospectively evaluated. IAA was defined by clinical, mycological and radiological criteria: a positive galactomannan in bronchoalveolar lavage or histopathological or cultural evidence in respiratory specimens of Aspergillus spp., any radiological infiltrate and a compatible clinical presentation. Poor outcome was defined as a composite of in-hospital mortality, ICU length of stay (LOS), invasive ventilation for > 7 days or extracorporeal membrane oxygenation. Of 81 patients with influenza in the ICU, 9 (11%) were diagnosed with IAA. All patients with IAA had poor outcome compared to 26 (36%) patients without IAA (p < 0.001). Median ICU-LOS and mortality were 17 vs. 3 days (p < 0.01) and 3/9 (33%) vs. 13/72 (18%; p = 0.37) in patients with vs. without IAA, respectively. Patients with IAA had significantly longer durations of antibiotic therapy, vasoactive support and mechanical ventilation. Aspergillus was the most common respiratory co-pathogen (9/40, 22%) followed by classical bacterial co-pathogens. IAA was not associated with classical risk factors. Aspergillus is a common superinfection in critically ill influenza patients associated with poor outcome and longer duration of organ supportive therapies. Given the absence of classical risk factors for aspergillosis, greater awareness is necessary, particularly in those requiring organ supportive therapies.
| S-EPMC7266735 | biostudies-literature
Project description:Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-?-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe.
| S-EPMC5008300 | biostudies-literature