Salvage Treatment for Invasive Aspergillosis and Mucormycosis: Challenges, Recommendations and Future Considerations

Infection and Drug Resistance, Journal Year: 2023, Volume and Issue: Volume 16, P. 2167 - 2178

Published: April 1, 2023

Invasive mold diseases are devastating systemic infections which demand meticulous care in selection, dosing, and therapy monitoring of antifungal drugs. Various circumstances regarding PK/PD properties the applied drug, resistance/tolerance causative pathogen or host intolerability can lead to failure initial therapy. This necessitates treatment adaption sense switching drug class potentially adding another for a combination approach. In current state drastically limited options classes remains challenging. Current guidelines provide restricted recommendations only emphasize individual approaches. However, novel antifungals, incorporating innovative mechanisms action, show promising results late stage clinical development. These will expand salvage future as monotherapy with conventional other antifungals. We outline including considerations well elucidate possible invasive aspergillosis mucormycosis.

Language: Английский

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Predictors for Prolonged Hospital Stay Solely to Complete Intravenous Antifungal Treatment in Patients with Candidemia: Results from the ECMM Candida III Multinational European Observational Cohort Study

Mycopathologia, Journal Year: 2023, Volume and Issue: 188(6), P. 983 - 994

Published: Aug. 11, 2023

To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates azole resistance among non-albicans spp. continue to increase. The objective this sub-analysis European multicenter observational cohort study III was describe demographical and clinical characteristics requiring prolonged hospitalization solely complete intravenous (iv) antifungal (AF Tx).Each participating hospital (number eligible hospitals per country determined by population size) included first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, treating physicians answered question on whether stay completion therapy. Descriptive analyses as well binary logistic regression used assess predictors iv AF Tx.Hospital Tx in 16% (100/621) a median 16 days (IQR 8 - 28). In multivariable model, initial echinocandin positive predictor (aOR 2.87, 95% CI 1.55 5.32, p < 0.001), (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, total parenteral nutrition, (v) C. parapsilosis causative pathogen were found be negative 0.22 0.45; 0.03).Hospital stays due need patients with candidemia. Those more likely receive echinocandins less severely ill infected parapsilosis.

Language: Английский

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COVID-19 associated Pulmonary Aspergillosis in Patients Admitted to the Intensive Care Unit: Impact of Antifungal Prophylaxis

Mycopathologia, Journal Year: 2024, Volume and Issue: 189(1)

Published: Jan. 13, 2024

Abstract Early after the beginning of coronavirus disease 2019 (COVID-19)-pandemic, it was observed that critically ill patients in intensive care unit (ICU) were susceptible to developing secondary fungal infections, particularly COVID-19 associated pulmonary aspergillosis (CAPA). Here we report our local experience on impact mold active antifungal prophylaxis CAPA occurrence patients. This is a monocentric, prospective cohort study including all consecutive with acute respiratory failure who admitted medical ICU. Based treating physician’s discretion, may have received or not. All retrospectively characterized as having according 2020 ECMM/ISHAM consensus definitions. Seventy-seven ICU during April and May 2021 included study. The majority invasive-mechanical ventilation (61%). Fifty-three (68.8%) posaconazole prophylaxis. Six cases probable diagnosed within clinical routine management. six non-prophylaxis group. incidence overall 0.57 events per 100 days 2.20 No difference cumulative 84-days survival could be between two groups ( p = 0.115). In this monocentric cohort, application did significantly reduce rate CAPA.

Language: Английский

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Clinical evaluation of a multiplex droplet digital PCR for diagnosing suspected bloodstream infections: a prospective study

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 16, 2025

Though droplet digital PCR (ddPCR) has emerged as a promising tool for early pathogen detection in bloodstream infections (BSIs), more studies are needed to support its clinical application widely due different ddPCR platforms with discrepant diagnostic performance. Additionally, there is still lack of data reveal the association between loads detected by and corresponding BSIs. In this prospective study, 173 patients suspected BSIs were enrolled. A multiplex assay was used detect 18 pathogens. The results testing evaluated comparison blood cultures (BCs) diagnosis. Taking BC gold standard, receiver operating characteristic curve Cohen's kappa agreement investigate whether load could predict culture-proven BSI top five microorganisms ddPCR. Of samples collected, positive 48 (27.7%) 92 (53.2%) cases, respectively. Compared BC, aggregate sensitivity specificity 81.3% 63.2%, After adjudication, increased 88.8% 86.0%, There 143 DNA these ranged from 30.0 3.2×105 copies/mL (median level: 158.0 copies/mL), 72.7% (104/143) which below 1,000 copies/mL. Further, statistical analysis showed Escherichia coli (AUC: 0.954, 95% CI: 0.898-1.000, κ=0.731, cut-off values: 93.0 copies/mL) Klebsiella pneumoniae 0.994, 0.986-1.000, κ=0.834, 196.5 excellent predictors Pseudomonas aeruginosa 0.816, 0.560-1.000, κ=0.167), Acinetobacter baumannii 0.728, 0.195-1.000), Enterococcus spp. 0.282, 0.000-0.778) had little predictive value Our indicate that platform complementary add-on conventional BC. E. K. present Further research explore potential other microorganisms.

Language: Английский

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Mycobacterium haemophilum diagnosed via Karius test in a heart transplant recipient: A case report

Transplant Immunology, Journal Year: 2025, Volume and Issue: 90, P. 102221 - 102221

Published: March 17, 2025

Language: Английский

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Impact of physician awareness and microbiological examination on incidence of COVID-19-associated pulmonary aspergillosis: a retrospective study

BMC Pulmonary Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 25, 2025

The reported incidence of aspergillosis among COVID-19 patients has varied significantly, which can be partly attributed to differences in diagnostic approaches and levels physicians' proficiency diagnosing COVID-19-associated pulmonary (CAPA). Consequently, we conducted a retrospective study investigate the potential reasons for these discrepancies analyzed risk factors with COVID-19. Data were retrospectively collected from December 1, 2022, September 30, 2023, who admitted First Affiliated Hospital Wenzhou Medical University. research platform was used screen discharge diagnoses pneumonia. CAPA defined according 2020 ECMM/ISHAM criteria Chinese expert consensus. Clinical data that included about underlying diseases, laboratory examinations microbiological detection. Analyses R software, continuous variables t-tests, categorical chi-square tests, logistic regression ROC curves assess CAPA. 13.4% general ward, 30.8% RICU, 6.8% other ICUs. average time diagnosis 5.6 days wards, 3.7 7.4 Diagnostic testing revealed following sensitivities: 78% BALF galactomannan (GM), 48% serum GM, 52% culture 71% mNGS. Risk chronic respiratory disease, renal insufficiency, diabetes. primary Aspergillus species identified A. fumigatus, followed by flavus. Differences may arise varying physician awareness, influence rate at GM samples are submitted testing. sensitivity is higher than GM. Furthermore, mNGS enhance clinical detection include diabetes, aid identifying at-risk patients. flavus, providing reference empirical treatment. Not applicable.

Language: Английский

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Diagnostic efficacy of metagenomic next generation sequencing in bronchoalveolar lavage fluid for proven invasive pulmonary aspergillosis

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Aug. 24, 2023

To assess the diagnostic efficacy of metagenomic next generation sequencing (mNGS) for proven invasive pulmonary aspergillosis (IPA).A total 190 patients including 53 who had been diagnosed with IPA were retrospectively analyzed. Using pathological results tissue biopsy specimens as gold standard, we ploted receiver operating characteristic (ROC) curve to determine optimal cut-off value mNGS species-specific read number (SSRN) Aspergillus in bronchoalveolar lavage fluid (BALF)for IPA. Furthermore, evaluated SSRN different populations.The BALF diagnosis was 2.5 whole suspected population, and 1 4.5 immunocompromised diabetic patients, respectively. The accuracy 80.5%, 73.7% 85.3% respectively.The has a high IPA, superioring culture sputum GM test blood BALF. However, should be adjusted when population.

Language: Английский

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Plasma Microbial Cell-Free DNA Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections

Journal of the Pediatric Infectious Diseases Society, Journal Year: 2024, Volume and Issue: 13(3), P. 211 - 219

Published: Feb. 8, 2024

Abstract Background Nearly half of all pediatric musculoskeletal infections (MSKIs) are culture negative. Plasma microbial cell-free DNA (mcfDNA) sequencing is noninvasive and not prone to the barriers culture. We evaluated performance plasma mcfDNA in identifying a pathogen, examined duration pathogen detection children with MSKIs. Methods conducted prospective study children, aged 6 months 18 years, hospitalized from July 2019 May 2022 MSKIs, whom we obtained serial samples compared results cultures. Results A was recovered by 23 34 (68%) participants, initial 25 31 (81%) participants. Multiple pathogens were detected majority (56%) positive samples. Complete concordance (all organisms accounted for both methods) 32%, partial (at least one same organism(s) identified 36%, discordance 32%. more likely show (complete or partial) if prior surgical procedure (82%), after (20%), (RR 4.12 [95% CI 1.25, 22.93], p = .02). There no difference based on timing antibiotics (presample 60% vs 75%, RR 0.8 0.40, 1.46], .65]). 67% culture-negative longer interval than blood (median 2 days [IQR 1, days] 1 day [1, day], &lt; .01). Conclusions may be useful MSKIs sample surgery. However, must interpreted appropriate clinical context as multiple frequently supporting need diagnostic stewardship.

Language: Английский

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Clinical performance of metagenomic next-generation sequencing for diagnosis of pulmonary Aspergillus infection and colonization

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: March 28, 2024

Background Investigations assessing the value of metagenomic next-generation sequencing (mNGS) for distinguish Aspergillus infection from colonization are currently insufficient. Methods The performance mNGS in distinguishing colonization, along with differences patients’ characteristics, antibiotic adjustment, and lung microbiota, were analyzed. Results abundance significantly differed between patients (n=36) (n=32) ( P &lt; 0.0001). Receiver operating characteristic (ROC) curve result bronchoalveolar lavage fluid (BALF) indicated an area under 0.894 (95%CI: 0.811-0.976), optimal threshold 23 discriminating colonization. group exhibited a higher proportion adjustments comparison to (50% vs. 12.5%, = 0.001), escalation being more dominant. Age, length hospital stay, hemoglobin, cough chest distress positively correlated infection. A. fumigatus Epstein-Barr virus (EBV) increased group, whereas niger . Conclusion BALF is valuable tool differentiating Variations age, observable

Language: Английский

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Risk factors and the value of microbiological examinations of COVID-19 associated pulmonary aspergillosis in critically ill patients in intensive care unit: the appropriate microbiological examinations are crucial for the timely diagnosis of CAPA

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 21, 2023

Introduction During the Omicron pandemic in China, a significant proportion of patients with Coronavirus Disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) necessitated admission to intensive care unit (ICU) and experienced high mortality. To explore clinical risk factors application/indication microbiological examinations CAPA ICU for timely diagnosis are very important. Methods This prospective study included COVID-19 admitted between December 1, 2022, February 28, 2023. The data influenza-associated (IAPA) from past five consecutive influenza seasons (November 2017, March 31, 2022) were collected comparison. types specimens methods used also recorded efficacy early diagnosis. Results Among 123 patients, 36 (29.3%) diagnosed probable CAPA. more immunosuppressed, serious condition, required advanced respiratory support had other organ comorbidities. Solid transplantation, APACHEII score ≥20 points, 5 points ≤SOFA &lt;10 independent Qualified lower tract obtained all 84/123 (68.3%) underwent bronchoscopy obtain bronchoalveolar lavage fluid (BALF) specimens. All patients’ fungal smear culture; 79/123 (64.2%) 69/123 (56.1%) BALF galactomannan (GM) serum GM detection, respectively; metagenomic next-generation sequencing (mNGS) was performed 62/123 (50.4%) patients. highest diagnostic sensitivity (84.9%), area under curve mNGS (0.812). Conclusion incidence extremely ICU. mainly depends on evidence owing non-specific manifestations, routine laboratory examinations, CT findings. should be as soon possible. most suitable Due accuracy result mNGS, it could assist might an option critically ill

Language: Английский

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