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Extracorporeal membrane oxygenation (ECMO) is a life-saving technique used in critical care medicine for patients with severe respiratory or cardiac failure. This review examines the treatment and prophylaxis of fungal infections in ECMO patients, proposing specific regimens based on available data for different antifungals (azoles, echinocandins, amphotericin B/liposomal amphotericin B) and invasive fungal infections. Currently, isavuconazole and posaconazole have the most supported data, while modified dosages of isavuconazole are recommended in ECMO. Echinocandins are preferred for invasive candidiasis. However, choosing echinocandins is challenging due to limited and varied data on concentration loss in the ECMO circuit. Caution is likewise advised when using liposomal amphotericin B due to uncertain concentrations and potential ECMO dysfunction based on scarce data. We further conclude with the importance of further research on the impact of ECMO on antifungal drug concentrations to optimize dosing regimens in critically ill patients.
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BACKGROUND: Serum galactomannan (GM) testing is essential for diagnosing invasive aspergillosis (IA), particularly in immunocompromised individuals. The global lack of on-site GM testing capacities necessitates cost-effective alternatives, such as .the clarus Aspergillus GM enzyme immunoassay prototype (clarus AGM prototype). METHODS: This single-centre, cross-sectional study compared the diagnostic performance of the clarus AGM prototype (IMMY, Norman, Oklahoma) with the serological gold standard (=Platelia AGM assay; Bio-Rad, Marnes-la-Cocquette, France). IA was classified according to modified 2020 EORTC/MSG consensus and 2024 FUNDICU criteria. In total, 300 prospectively (May-Dec 2023) and retrospectively (2012-2015) collected samples were included. RESULTS: Among 300 samples from 232 patients, 49 (16%) were classified as proven (n = 1) or probable IA (n = 48). In non-IA cases (n = 250), one patient was classified as possible IA. With the manufacturer recommended cut-off of ≥0.2, sensitivity and specificity of the clarus AGM prototype were 27% (13/49; 95% confidence interval [CI]: 15%-41%) and 99% (248/250; 95% CI: 97%-100%), respectively, while sensitivity and specificity were 78% and 79% when using the optimised Youden's cut-off of 0.0045 ODI. ROC curve analysis demonstrated an area under the curve (AUC) of 0.829 (95% CI: 0.760-0.898) for the clarus AGM prototype in distinguishing between proven/probable IA and non-IA. The AUC for the Platelia AGM was 0.951 (95% CI: 0.909-994). Spearman's correlation analysis showed a weak correlation between the two assays (0.382; p < .001). CONCLUSIONS: The weak correlation between the clarus AGM prototype and Platelia AGM highlights the need for further investigation into the clinical performance of the clarus AGM prototype, giving the different antigen epitopes addressed.
Subject(s)
Aspergillus , Galactose , Immunoenzyme Techniques , Invasive Pulmonary Aspergillosis , Mannans , Sensitivity and Specificity , Humans , Mannans/blood , Galactose/analogs & derivatives , Invasive Pulmonary Aspergillosis/diagnosis , Immunoenzyme Techniques/methods , Cross-Sectional Studies , Male , Middle Aged , Female , Aged , Retrospective Studies , Aspergillus/isolation & purification , Aspergillus/immunology , Adult , Prospective Studies , Antigens, Fungal/blood , Aged, 80 and over , Young Adult , ROC CurveABSTRACT
We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.
Subject(s)
Critical Illness , Hantavirus Infections , Invasive Pulmonary Aspergillosis , Humans , Austria/epidemiology , Hantavirus Infections/epidemiology , Hantavirus Infections/complications , Invasive Pulmonary Aspergillosis/epidemiology , Invasive Pulmonary Aspergillosis/drug therapy , OrthohantavirusABSTRACT
B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of patients with TB and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue. Flow cytometry and transcriptomics identify multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease. Additionally, TB lungs contain high levels of Mtb-reactive antibodies, specifically IgM, which promotes Mtb phagocytosis. Overall, these data reveal the presence of functionally diverse B cell subsets in the lungs of patients with TB and suggest several potential localized roles that may represent a target for interventions to promote immunity or mitigate immunopathology.
Subject(s)
B-Lymphocytes , Humans , B-Lymphocytes/immunology , Lung/immunology , Lung/microbiology , Lung/pathology , Mycobacterium tuberculosis/immunology , Mycobacterium tuberculosis/physiology , Phenotype , Tuberculosis/immunology , Tuberculosis/microbiology , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/pathology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/genetics , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/metabolism , Male , Female , AdultABSTRACT
SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into "sequestered" sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), Pneumocystis jirovecii infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance.
Subject(s)
Antifungal Agents , Drug Resistance, Fungal , Invasive Fungal Infections , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacokinetics , Antifungal Agents/pharmacology , Humans , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Fungi/drug effects , Animals , Treatment OutcomeABSTRACT
BACKGROUND: Widespread inappropriate use of antimicrobial substances drives resistance development worldwide. In long-term care facilities (LTCF), antibiotics are among the most frequently prescribed medications. More than one third of antimicrobial agents prescribed in LTCFs are for urinary tract infections (UTI). We aimed to increase the number of appropriate antimicrobial treatments for UTIs in LTCFs using a multi-faceted antimicrobial stewardship intervention. METHODS: We performed a non-randomized cluster-controlled intervention study. Four LTCFs of the Geriatric Health Centers Graz were the intervention group, four LTCFs served as control group. The main components of the intervention were: voluntary continuing medical education for primary care physicians, distribution of a written guideline, implementation of the project homepage to distribute guidelines and videos and onsite training for nursing staff. Local nursing staff recorded data on UTI episodes in an online case report platform. Two blinded reviewers assessed whether treatments were adequate. RESULTS: 326 UTI episodes were recorded, 161 in the intervention group and 165 in the control group. During the intervention period, risk ratio for inadequate indication for treatment was 0.41 (95% CI 0.19-0.90), p = 0.025. In theintervention group, the proportion of adequate antibiotic choices increased from 42.1% in the pre-intervention period, to 45.9% during the intervention and to 51% in the post-intervention period (absolute increase of 8.9%). In the control group, the proportion was 36.4%, 33.3% and 33.3%, respectively. The numerical difference between intervention group and control group in the post-intervention period was 17.7% (difference did not reach statistical significance). There were no significant differences between the control group and intervention group in the safety outcomes (proportion of clinical failure, number of hospital admissions due to UTI and adverse events due to antimicrobial treatment). CONCLUSIONS: An antimicrobial stewardship program consisting of practice guidelines, local and web-based education for nursing staff and general practitioners resulted in a significant increase in adequate treatments (in terms of decision to treat the UTI) during the intervention period. However, this difference was not maintained in the post-intervention phase. Continued efforts to improve the quality of prescriptions further are necessary. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov NCT04798365.
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Anti-Infective Agents , Antimicrobial Stewardship , Urinary Tract Infections , Aged , Humans , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Long-Term Care/methods , Nursing Homes , Urinary Tract Infections/drug therapyABSTRACT
Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.
Subject(s)
Acceptance and Commitment Therapy , Depressive Disorder, Major , Hallucinogens , Humans , Psilocybin , Depressive Disorder, Major/drug therapy , Depression/drug therapyABSTRACT
NTRODUCTION: The last two decades have been leading to the development of several types of surgical techniques and procedures to manage the LHB lesions. This paper analyses and compares the difference in muscle strength pre- and post-operatively in two most commonly used surgical procedures - LHB tenotomy and tenodesis. METHOD: The study includes 68 patients who underwent surgery between 2016 and 2020. The patients who had met the prospective study inclusion criteria were divided into two groups based on type of surgery they had undergone (LHB tenotomy or tenodesis); each group consisted of 34. The muscle strength during elbow flexion was measured preoperatively and postoperatively using the Commander Echo Console ultrasound muscle testing device. All patients enrolled in the study had been assessed for elbow flexion strength preoperatively. The muscle strength was measured preoperatively and then 3 years postoperatively (12 to 60 months) on average. CONCLUSION: The study confirmed that the patients who had undergone LHB tenodesis show a significantly lower decrease in elbow flexion strength and a significantly lower incidence of "Popeye" deformity than the patients after LHB tenotomy. Moreover, in the tenodesis group, it was possible to initiate rehabilitation earlier. The incidence of postoperative complications was almost identical in both groups of patients (Tab. 10, Fig. 6, Ref. 40).
Subject(s)
Rotator Cuff Injuries , Tenodesis , Humans , Tenodesis/methods , Tenotomy/methods , Elbow/surgery , Prospective Studies , Rotator Cuff Injuries/surgery , Arthroscopy/methodsABSTRACT
OBJECTIVES: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality and frequently leads to ICU admission. Overall survival in adults with sHLH remains poor, especially in those requiring intensive care. Classical chemotherapeutic treatment exhibits myelosuppression and toxicity. Recently, inhibition of Janus kinase signaling by ruxolitinib has shown efficacy in pediatric HLH. We therefore aimed to determine the activity and safety of a ruxolitinib-based regimen, in critically ill adults with sHLH. DESIGN: Observational pilot study. SETTING: Single-center tertiary academic ICU. PATIENTS: Nine adults (≥ 18 yr) who fulfilled at least five of the eight HLH-2004 criteria. INTERVENTION: Triplet regimen combining: 1) ruxolitinib, 2) polyvalent human IV immunoglobulins (IVIG) at a dose of 1 g/kg bodyweight for 5 days, and 3) high-dose corticosteroids (CSs, dexamethasone 10 mg/m² body surface area, or methylprednisolone equivalent) with subsequent tapering according to the HLH-2004 protocol. MEASUREMENT AND MAIN RESULTS: Nine patients (median age: 42 yr [25th-75th percentile: 32-54]; male: n = 6 males, median H-score: 299 [255-304]) were treated with the triplet regimen. The median Sequential Organ Failure Assessment score at HLH diagnosis was 9 (median; 25th-75th percentile: 7-12), indicating multiple-organ dysfunction in all patients. Within 10 days a significant decrease of the inflammatory parameters soluble interleukin-2 receptor and ferritin as well as a stabilization of the blood count could be shown. All patients were alive at ICU discharge (100% ICU survival), 1 patient died after ICU discharge because of traumatic intracerebral hemorrhage that might be related to HLH or treatment, corresponding to an overall survival of 86% in a 6 months follow-up period. CONCLUSION: In this small case series, a triplet regimen of ruxolitinib in combination with IVIG and CS was highly effective and save for treating critically ill adults with sHLH.
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BACKGROUND: Yet often overlooked in public health discourse, fungal infections pose a crucial global disease burden associated with annual mortality rates approximately equal to tuberculosis and HIV. In response, the WHO published its first global priority list of fungal pathogens in 2022 assigning Aspergillus fumigatus, Candida albicans, Candida auris, and Cryptococcus neoformans to the critical group. OBJECTIVES: This review provides succinct insights into novel antifungals in development, aiming to contribute valuable information and perspectives with a focus on recent clinical findings and new treatment approaches for critical members of the WHO fungal pathogen priority list. SOURCES: PubMed literature search using 'Aspergillus fumigatus', 'Cryptococcus neoformans', 'Candida auris', and 'Candida albicans', along with the names of novel antifungal substances, including 'fosmanogepix', 'ibrexafungerp', 'opelconazole', 'oteseconazole', 'MAT2203', 'olorofim', and 'rezafungin' was conducted. CONTENT: For each critical pathogen, current issues and global clinical data from recent trials are covered. The remarkable development of three new antifungal therapeutics recently receiving Food and Drug Administration approval (ibrexafungerp-June 2021, oteseconazole -April 2022, and rezafungin-March 2023) is outlined, with two more exciting new antifungal substances, namely, olorofim and fosmanogepix expecting approval within the next years. Ibrexafungerp, fosmanogepix, and rezafungin have additionally been granted orphan drug status by the European Medicines Agency in Europe (ibrexafungerp-November 2021, fosmanogepix-July 2022, and rezafungin-January 2024). IMPLICATIONS: Although the limited number of targets and the emergence of resistance have posed challenges to antifungal treatment, new drugs such as ibrexafungerp, rezafungin, fosmanogepix, or olorofim have shown promising clinical efficacy. These drugs not only provide alternative options for invasive fungal infections but also alleviate treatment in outpatient settings. More clinical data, implementation of stewardship programmes, and surveillance, including utilization of drugs in agriculture, are necessary to prevent resistance development and to ensure the safety and efficacy of these new agents.
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AIMS: Mucormycosis is a fast-progressing disease with a high mortality rate. The most important factor determining survival of patients is early and accurate diagnosis. Although histopathology often recognises invasive mould infections at first, histomorphology alone is insufficient in providing an accurate diagnosis. Unbiased molecular methods to detect and identify fungi are promising, yet their role in complementing routine histopathological workflows has not been studied sufficiently. METHODS AND RESULTS: We performed a retrospective single-centre study examining the clinical value of complementing histopathology with internal transcribed spacer (ITS) sequencing of fungal DNA in the routine diagnosis of mucormycosis. At our academic centre, we identified 14 consecutive mucormycosis cases diagnosed by histopathology and subsequent ITS sequencing. Using histomorphological examination, fungal hyphae could be detected in all cases; however, morphological features were unreliable regarding specifying the taxa. Subsequent ITS sequencing identified a remarkable phylogenetic diversity among Mucorales: the most common species was Rhizopus microsporus (six of 14; 42.9%), followed by Lichtheimia corymbifera (three of 14, 21.4%) and single detections of Rhizopus oryzae, Actinomucor elegans, Mucor circinelloides, Rhizomucor pusillus and Rhizomucor miehei (one of 14; 7.1%, respectively). In one case, we additionally detected Pneumocystis jirovecii in the same lung tissue specimen, suggesting a clinically relevant co-infection. Fungal culture was performed in 10 cases but yielded positive results in only two of 10 (20%), revealing its limited value in the diagnosis of mucormycosis. CONCLUSIONS: Our study demonstrates that a combination of histopathology and ITS sequencing is a practically feasible approach that outperforms fungal culture in detecting Mucorales in tissue-associated infections. Therefore, pathologists might adapt diagnostic workflows accordingly when mucormycosis is suspected.
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Mucormycosis , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiology , Mucormycosis/pathology , Retrospective Studies , PhylogenySubject(s)
Brain Abscess , Adult , Child , Humans , Brain Abscess/diagnosis , Brain Abscess/drug therapy , Practice Guidelines as TopicABSTRACT
INTRODUCTION: Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID-19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We estimated the risk of COVID-19 deaths and SARS-CoV-2 infections according to vaccination status in previously infected individuals in Austria. METHODS: This is a nationwide retrospective observational study. We calculated age and gender adjusted Cox proportional hazard ratios (HRs) of COVID-19 deaths (primary outcome) and SARS-CoV-2 infections (secondary outcome) from 1 November to 31 December 2022, primarily comparing individuals with four versus three vaccine doses. Relative vaccine effectiveness (rVE) was calculated as (1-HR) X 100. RESULTS: Among 3,986,312 previously infected individuals, 281,291 (7,1%) had four and 1,545,242 (38.8%) had three vaccinations at baseline. We recorded 69 COVID-19 deaths and 89,056 SARS-CoV-2 infections. rVE for four versus three vaccine doses was -24% (95% CI: -120 to 30) against COVID-19 deaths, and 17% (95% CI: 14-19) against SARS-CoV-2 infections. This latter effect rapidly diminished over time and infection risk with four vaccinations was higher compared to less vaccinated individuals during extended follow-up until June 2023. Adjusted HR (95% CI) for all-cause mortality for four versus three vaccinations was 0.79 (0.74-0.85). DISCUSSION: In previously infected individuals, a fourth vaccination was not associated with COVID-19 death risk, but with transiently reduced risk of SARS-CoV-2 infections and reversal of this effect in longer follow-up. All-cause mortality data suggest healthy vaccinee bias.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Austria/epidemiology , SARS-CoV-2 , VaccinationABSTRACT
INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is a biologically active protein and increased levels are associated with worse outcomes in critically ill patients. suPAR in bronchoalveolar fluid (BALF) may be helpful to differentiate between types of acute respiratory distress syndrome (ARDS) and may have potential for early detection of fungal infection. METHODS: We prospectively investigated levels of suPAR in BALF and serum in critically ill patients who underwent bronchoscopy for any reason at the ICU of the Department of Internal Medicine, Medical University of Graz, Graz, Austria. RESULTS: Seventy-five patients were available for analyses. Median age was 60 [25th-75th percentile: 50-69] years, 27% were female, and median SOFA score was 12 [11-14] points. Serum suPAR levels were significantly associated with ICU mortality in univariable logistic regression analysis. There was no correlation between BALF and serum suPAR. Serum suPAR was higher in ARDS patients at 11.2 [8.0-17.2] ng/mL compared to those without ARDS at 7.1 [3.7-10.1] (p < 0.001). BALF-suPAR was significantly higher in patients with evidence of fungal lung infection compared to patients without fungal infection both in the general cohort (7.6 [3.2-9.4] vs 2.5 [1.1-5.3], p = 0.013) and in the subgroup of ARDS (7.2 [3.1-39.2] vs 2.5 [1.0-5.2], p = 0.022). All patients were classified as putative/probable invasive aspergillosis. CONCLUSION: We found significant higher levels of serum suPAR in ARDS patients compared to those not fulfilling ARDS criteria. Serum and BALF-suPAR were significantly higher in those patients with evidence for invasive pulmonary aspergillosis. These findings may suggest testing this biomarker for early diagnosis of fungal infection in a greater cohort.
Subject(s)
Aspergillosis , Receptors, Urokinase Plasminogen Activator , Respiratory Distress Syndrome , Female , Humans , Male , Middle Aged , Biomarkers , Critical Illness , Prognosis , Prospective Studies , Receptors, Urokinase Plasminogen Activator/blood , Receptors, Urokinase Plasminogen Activator/chemistry , Respiratory Distress Syndrome/diagnosisABSTRACT
(1) Background: Long COVID syndrome (LCS) is a heterogeneous long-standing condition following COVID-19 infection. Treatment options are limited to symptomatic measures, and no specific medication has been established. Hyperbaric oxygenation (HBO) has been found to have a positive impact on the treatment of COVID-19 infection. This study evaluates both the feasibility and outcome of supportive HBO in patients with LCS. (2) Methods: Within 17 months, 70 patients with proven LCS were prospectively included. Each patient underwent a cycle of 10 subsequent HBO treatment sessions administered for 75 min at 2.2 atmospheres. Evaluation of the patients was performed before the first and after the last HBO session and 3 months afterwards. Statistical evaluation was based on an intention-to-treat analysis using Fisher's exact test and Student's t-test for paired samples. (3) Results: In total, 59 patients (33 females, 26 males; mean age: 43.9 years; range: 23-74 years; median: 45.0) were evaluable. After HBO, a statistically significant improvement of physical functioning (p < 0.001), physical role (p = 0.01), energy (p < 0.001), emotional well-being (p < 0.001), social functioning (p < 0.001), pain (p = 0.01) and reduced limitation of activities (p < 0.001) was confirmed. (4) Conclusions: Physical functioning and both the physical and emotional role improved significantly and sustainably, suggesting HBO as a promising supportive therapeutic tool for the treatment of LCS.
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BACKGROUND: In critically ill patients with extracorporeal membrane oxygenation (ECMO) attainment of target concentration of isavuconazole is delayed using the routine loading dose. OBJECTIVES: We investigated the influence of increasing the first loading dose of isavuconazole on plasma concentrations in critically ill patients treated with ECMO. METHODS: Fifteen patients were included in this study, and isavuconazole concentrations were measured at several timepoints starting 2 h after the first isavuconazole dose up to 168 h. By interim analysis of isavuconazole concentrations and meticulous screening for adverse events, the first loading dose was stepwise increased from 200 to 300 mg, and finally to 400 mg. RESULTS: Seven of 15 patients (47%) received standard isavuconazole loading dosage with 200 mg as the first dose, 3/15 (20%) received 300 mg, and 5/15 (33%) received 400 mg isavuconazole as the first dose, followed by subsequent standard dosing in all patients. In patients receiving 400 mg as the first dose all isavuconazole concentrations were significantly higher at timepoints up to the first 24 h, resulting in higher proportions of isavuconazole concentrations ≥1 mg/L compared with patients with other loading dosages. In timepoints ≥24 h after isavuconazole initiation all patient groups reached comparable plasma concentrations, regardless of the first loading dose regimen. We did not observe concentrations above ≥5 mg/L or any adverse events related to isavuconazole administration. CONCLUSIONS: In critically ill patients with ECMO the 400 mg loading dose of isavuconazole resulted in immediate median isavuconazole plasma concentrations ≥1 mg/L and remained constant above this threshold after the first loading dose.
Subject(s)
Extracorporeal Membrane Oxygenation , Humans , Extracorporeal Membrane Oxygenation/methods , Critical Illness/therapy , Nitriles , PyridinesABSTRACT
A previously healthy man in Austria had tularemia epididymo-orchitis develop, leading to unilateral orchiectomy. Francisella tularensis subspecies holartica was detected by 16S rRNA gene sequencing analysis of inflamed granulomatous testicular tissue. Clinicians should suspect F. tularensis as a rare etiologic microorganism in epididymo-orchitis patients with relevant risk factors.
Subject(s)
Francisella tularensis , Orchitis , Tularemia , Male , Humans , Austria/epidemiology , Francisella tularensis/genetics , RNA, Ribosomal, 16S/genetics , Tularemia/diagnosis , Tularemia/epidemiologyABSTRACT
The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included â¼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25-33%) while Italy and Turkey had the highest C. parapsilosis proportions (24-26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.
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INTRODUCTION: Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria. METHODS: Between October and November 2021, hospitals were contacted to participate in our online survey: www.clinicalsurveys.net/uc/IFI_management_capacity/. Centres were required to provide information on their institutional profile; self-assessment of burden of invasive fungal infections; access to microscopy, culture, serology, antigen detection and molecular testing; and availability of antifungal agents and therapeutic drug monitoring. RESULTS: Responses were collected from university hospitals and laboratories in Graz, Innsbruck, Linz and Vienna. The four hospitals can provide tertiary care and were highly specialised, including management of patients with severe immunosuppression. All sites consider the incidence of invasive fungal infections to be moderate. Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory. The maximum capacity to identify fungi varies from institution to institution. All currently marketed antifungal agents are available at the four sites. CONCLUSION: Austria is currently well equipped to deal with the emerging threat of invasive fungal infections. However, hospitals may consider preparing for the potential endemicity of certain infections in the near future.
Subject(s)
Antifungal Agents , Invasive Fungal Infections , Humans , Antifungal Agents/therapeutic use , Austria/epidemiology , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/epidemiology , Fungi , Health Services AccessibilityABSTRACT
BACKGROUND: To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). METHODS: Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. FINDINGS: Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 - 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 - 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 - 0.45; p < 0.03). INTERPRETATION: Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis.