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Thorax Dec 2023Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk...
BACKGROUND
Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort.
METHODS
From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs). CAPA was defined using European Confederation for Medical Mycology and the International Society for Human and Animal Mycology criteria and fungal diagnostics performed on respiratory and serum samples.
RESULTS
Twenty-nine of 266 patients (10.9%) had probable CAPA, 14 (5.2%) possible CAPA and none proven CAPA. Probable CAPA was diagnosed a median of 9 (IQR 7-16) days after ICU admission. Factors associated with probable CAPA after multivariable logistic regression were cumulative steroid dose given within 28 days prior to ICU admission (adjusted OR (aOR) 1.16; 95% CI 1.01 to 1.43 per 100 mg prednisolone-equivalent), receipt of an interleukin (IL)-6 inhibitor (aOR 2.79; 95% CI 1.22 to 6.48) and chronic obstructive pulmonary disease (COPD) (aOR 4.78; 95% CI 1.13 to 18.13). Mortality in patients with probable CAPA was 55%, vs 46% in those without. After adjustment for immortal time bias, CAPA was associated with an increased risk of 90-day mortality (HR 1.85; 95% CI 1.07 to 3.19); however, this association did not remain statistically significant after further adjustment for confounders (adjusted HR 1.57; 95% CI 0.88 to 2.80). There was no difference in mortality between patients with CAPA prescribed antifungals (9 of 17; 53%) and those who were not (7 of 12; 58%) (p=0.77).
INTERPRETATION
In this first prospective UK study, probable CAPA was associated with corticosteroid use, receipt of IL-6 inhibitors and pre-existing COPD. CAPA did not impact mortality following adjustment for prognostic variables.
Topics: Adult; Animals; Humans; COVID-19; Prospective Studies; Respiration, Artificial; Pulmonary Aspergillosis; Pulmonary Disease, Chronic Obstructive; United Kingdom
PubMed: 37657925
DOI: 10.1136/thorax-2023-220002 -
Antibiotics (Basel, Switzerland) Jul 2023Nearly 10% of COVID-19 cases will require admission to the intensive care unit (ICU). Our aim was to assess the clinical and microbiological outcomes of secondary...
Clinical and Microbiological Outcomes and Follow-Up of Secondary Bacterial and Fungal Infections among Critically Ill COVID-19 Adult Patients Treated with and without Immunomodulation: A Prospective Cohort Study.
BACKGROUND
Nearly 10% of COVID-19 cases will require admission to the intensive care unit (ICU). Our aim was to assess the clinical and microbiological outcomes of secondary infections among critically ill COVID-19 adult patients treated with/without immunomodulation.
METHODS
A prospective observational cohort study was performed between 2020 and 2022 at a single ICU. The diagnosis and severity classification were established by the ECDC and WHO criteria, respectively. Eligible patients were included consecutively at admission, and followed for +30 days post-inclusion. Bloodstream-infections (BSIs), ventilator-associated bacterial pneumonia (VAP), and COVID-19-associated invasive pulmonary aspergillosis (CAPA) were defined according to international guidelines. Patient stratification was performed by immunomodulatory therapy administration (dexamethasone, tocilizumab, baricitinib/ruxolitinib). The primary outcome was any microbiologically confirmed major infectious complication, secondary outcomes were invasive mechanical ventilation (IMV) requirement and all-cause mortality.
RESULTS
Altogether, 379 adults were included. At baseline, 249/379 (65.7%) required IMV and 196/379 (51.7%) had a cytokine storm. At +30 days post-inclusion, the rate of any microbiologically confirmed major infectious complication was 151/379 (39.8%), IMV requirement and all-cause mortality were 303/379 (79.9%) and 203/379 (53.6%), respectively. There were no statistically significant outcome differences after stratification. BSI, VAP, and CAPA episodes were mostly caused by (27/124, 22.1%), (26/91, 28.6%), and (20/20, 100%), respectively. Concerning the primary outcome, Kaplan-Meier analysis showed similar probability distributions between the treatment subgroups (118/299, 39.5% vs. 33/80, 41.3%, log-rank = 0.22), and immunomodulation was not retained as its independent predictor in multivariate logistic regression.
CONCLUSIONS
Secondary infections among critically ill COVID-19 adult patients represent a relevant burden, probably irrespective of immunomodulatory treatment.
PubMed: 37508292
DOI: 10.3390/antibiotics12071196 -
Clinical Drug Investigation Sep 2023A double-blind phase 3 study was conducted to compare posaconazole 300 mg intravenously (IV)/300 mg orally once daily (twice daily day 1) with voriconazole 4 mg/kg IV... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
A double-blind phase 3 study was conducted to compare posaconazole 300 mg intravenously (IV)/300 mg orally once daily (twice daily day 1) with voriconazole 4 mg/kg IV twice daily/200 mg orally twice daily (6 mg/kg day 1) for treatment of invasive aspergillosis. This analysis was conducted to summarize the pharmacokinetics and exposure-response relationships of posaconazole and voriconazole using plasma trough concentration (C) as a surrogate for exposure from the double-blind phase 3 study.
METHODS
The pharmacokinetic evaluable population included all intention-to-treat (ITT) participants with at least one plasma concentration during the treatment period. Treatment blinding was maintained without therapeutic drug monitoring. C sampling occurred throughout treatment; efficacy and safety were evaluated using quartiles determined by mean C concentrations. Exposure efficacy variables included day 42 all-cause mortality (primary study endpoint) and global clinical response. Exposure safety variables included all adverse events and treatment-related adverse events.
RESULTS
The pharmacokinetic analysis population included 506 of 575 ITT participants (437 with C concentrations: 228 posaconazole, 209 voriconazole). No trend was seen across quartiles of posaconazole C for the key efficacy endpoint of all-cause mortality through day 42. Participants in the highest quartile of voriconazole C had higher all-cause mortality through day 42 than participants in the lower three quartiles of voriconazole C. Similar findings were observed for global clinical response and C. No clear exposure safety trend by quartile was seen for posaconazole or voriconazole.
CONCLUSIONS
A strong exposure-response relationship was not observed across the range of exposure from the administered doses and formulations for posaconazole or voriconazole.
TRIAL REGISTRATION
NCT01782131; registered January 30, 2013.
Topics: Humans; Voriconazole; Triazoles; Aspergillosis; Double-Blind Method
PubMed: 37676612
DOI: 10.1007/s40261-023-01282-7 -
Journal of Feline Medicine and Surgery Jan 2024In contrast to superficial fungal infections, such as dermatophytosis, invasive fungal infections (IFIs) are characterised by penetration of tissues by fungal elements.... (Review)
Review
CLINICAL RELEVANCE
In contrast to superficial fungal infections, such as dermatophytosis, invasive fungal infections (IFIs) are characterised by penetration of tissues by fungal elements. Disease can spread locally within a region or can disseminate haematogenously or via the lymphatics. The environment is the most common reservoir of infection. Since fungal spores are airborne, indoor cats are also susceptible to IFIs. Some environmental fungi are ubiquitous and present globally, while others are endemic or hyperendemic within specific geographic regions. Zoonotic pathogens include and
AIM
In the first of a two-part article series, the approach to the investigation of feline IFIs and oomycoses is reviewed. As well as tips for diagnosis, and information on the ecological niche and distribution of fungal pathogens, the review covers clinical presentation of the most common IFIs, including cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis, phaeohyphomycosis, aspergillosis and dermatophytic pseudomycetoma, as well as the oomycoses pythiosis, lagenidiosis and paralagenidiosis. In Part 2, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties and adverse effects of antifungal drugs are reviewed, and the treatment and prognosis for specific IFIs and oomycoses are discussed.
EVIDENCE BASE
The review draws on published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology.
Topics: Cats; Animals; Invasive Fungal Infections; Antifungal Agents; Coccidioidomycosis; Dermatomycoses; Histoplasmosis; Cat Diseases
PubMed: 38189288
DOI: 10.1177/1098612X231219696 -
International Journal of Molecular... Dec 2023Anticytokine autoantibodies (ACAAs) are a fascinating group of antibodies that have gained more and more attention in the field of autoimmunity and secondary... (Review)
Review
Anticytokine autoantibodies (ACAAs) are a fascinating group of antibodies that have gained more and more attention in the field of autoimmunity and secondary immunodeficiencies over the years. Some of these antibodies are characterized by their ability to target and neutralize specific cytokines. ACAAs can play a role in the susceptibility to several infectious diseases, and their infectious manifestations depending on which specific immunological pathway is affected. In this review, we will give an outline per infection in which ACAAs might play a role and whether additional immunomodulatory treatment next to antimicrobial treatment can be considered. Finally, we describe the areas for future research on ACAAs.
Topics: Humans; Autoantibodies; Autoimmunity; Cytokines; Immunomodulation; Communicable Diseases
PubMed: 38203686
DOI: 10.3390/ijms25010515 -
Pathogens (Basel, Switzerland) Oct 2023Infections due to the species constitute an important challenge for human health. Invasive aspergillosis represents a life-threatening disease, mostly in patients with... (Review)
Review
Infections due to the species constitute an important challenge for human health. Invasive aspergillosis represents a life-threatening disease, mostly in patients with immune defects. Drugs used for fungal infections comprise amphotericin B, triazoles, and echinocandins. However, in the last decade, an increased emergence of azole-resistant strains has been reported, principally belonging to species. Therefore, both the early diagnosis of aspergillosis and its epidemiological surveillance are very important to establish the correct antifungal therapy and to ensure a successful patient outcome. In this paper, a literature review is performed to analyze the prevalence of antifungal resistance in European countries. Amphotericin B resistance is observed in 2.6% and 10.8% of isolates in Denmark and Greece, respectively. A prevalence of 84% of amphotericin B-resistant isolates is reported in France, followed by 49.4%, 35.1%, 21.7%, and 20% in Spain, Portugal, Greece, and amphotericin B resistance of isolates is observed in Greece and Belgium with a prevalence of 75% and 12.8%, respectively. The prevalence of triazole resistance of isolates, the most studied mold obtained from the included studies, is 0.3% in Austria, 1% in Greece, 1.2% in Switzerland, 2.1% in France, 3.9% in Portugal, 4.9% in Italy, 5.3% in Germany, 6.1% in Denmark, 7.4% in Spain, 8.3% in Belgium, 11% in the Netherlands, and 13.2% in the United Kingdom. The mechanism of resistance is mainly driven by the TR/L98H mutation. In Europe, no in vivo resistance is reported for echinocandins. Future studies are needed to implement the knowledge on the spread of drug-resistant spp. with the aim of defining optimal treatment strategies.
PubMed: 38003770
DOI: 10.3390/pathogens12111305 -
Journal de Mycologie Medicale Jun 2024With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections... (Review)
Review
With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections in Tunisia. We have estimated the incidence and prevalence of the most serious fungal diseases in Tunisia for the first time. Using published literature from Tunisia, or if absent other countries, we have estimated the burden of life-threatening fungal infections and those causing significant morbidity, using deterministic modeling, based on populations at greatest risk. An estimated 250,494 (2.12% of the Tunisian population) are affected by a serious fungal disease annually. Invasive and chronic pulmonary aspergillosis are relatively common with 708 and 2090 patients affected, partly linked to the prevalence of chronic obstructive pulmonary disease (COPD). Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization) have an estimated prevalence of 38,264 (5.8% of the adult asthma population). Fungal keratitis probably affects 1,761 eyes annually, often leading to uniocular blindness. Candidaemia and Candida peritonitis probably affect at least 680 people annually, with a high mortality. Recurrent vulvovaginal candidiasis probably affects over 200,000 women. While fungal diseases are regularly diagnosed in Tunisia, epidemiological studies with denominators are uncommon. Some fungal diseases are poorly addressed with the current diagnostic portfolio, and surveillance is lacking. Studies on these diseases and the implementation of a national program of surveillance are required.
Topics: Humans; Tunisia; Prevalence; Incidence; Female; Mycoses; Male; Adult; Asthma; Middle Aged; Pulmonary Disease, Chronic Obstructive; Adolescent; Aged; Candidiasis, Vulvovaginal; Young Adult; Child; Keratitis; Aspergillosis, Allergic Bronchopulmonary; Candidemia; Pulmonary Aspergillosis; Child, Preschool
PubMed: 38604083
DOI: 10.1016/j.mycmed.2024.101479 -
Indian Journal of Pathology &... Mar 2024Numerous pathogens (bacteria, viruses, or fungi) can cause childhood pneumonia. The clinical presentations of viral and bacterial pneumonia can be similar. Though...
CONTEXT
Numerous pathogens (bacteria, viruses, or fungi) can cause childhood pneumonia. The clinical presentations of viral and bacterial pneumonia can be similar. Though viruses are a more common cause as compared to bacteria, antibiotics remain the first line of treatment for pneumonia.
AIMS
This study was planned to describe the pulmonary histopathological patterns in cases of pediatric pneumonia (age <12 years) at autopsy and aimed to identify the probable etiology and correlate with clinical presentations.
MATERIAL AND METHODS
This is a single-center 3-year retrospective descriptive autopsy study. Relevant clinical data was correlated with the postmortem findings. The cases were assigned to one of the following categories based on probable etiology: viral, bacterial, mixed, or others.
RESULTS
There were 89 cases with a postmortem diagnosis of pneumonia among 262 autopsied children (34%). Most patients had histological patterns that suggested viral and bacterial etiology in 46 (51.7%) and 27 (30.3%), respectively. A total of 35 out of 46 patients received antibiotics. Twelve cases had mixed viral and bacterial patterns. Antibiotics were also given in the remaining four children (4.5%) with a similar clinical presentation, where a diagnosis of tuberculosis (03 cases) and invasive aspergillosis (01) was made at autopsy.
CONCLUSION
Neither clinical features nor investigations reliably differentiate between viral and bacterial pneumonia. Autopsy has an important role in providing insights into the pathogenesis of pneumonia and suggests inappropriate antibiotic exposure. No prior Indian studies have been performed to compare the clinical and postmortem findings of pneumonia in children.
PubMed: 38563703
DOI: 10.4103/ijpm.ijpm_700_23 -
Biomedica : Revista Del Instituto... Aug 2023The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.
INTRODUCTION
The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.
OBJECTIVE
To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis.
MATERIALS AND METHODS
The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 °C ± 1 °C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after , 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors.
RESULTS
Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time.
CONCLUSION
The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.
Topics: Humans; Paracoccidioides; Cost-Benefit Analysis; Paracoccidioidomycosis; Reproducibility of Results; Blood Group Antigens; Antibodies
PubMed: 37721912
DOI: 10.7705/biomedica.6874 -
Therapeutic Advances in Urology 2023Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes... (Review)
Review
BACKGROUND
Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes of patients with isolated renal and genito-urinary tract aspergillosis.
METHODS
We systematically searched Medline, CINAHL, Embase, African Journal Online, Google Scholar, and the Cochrane Library, covering the period from inception to August 2023 using the key terms 'renal' OR 'kidney*' OR 'prostate' OR 'urinary bladder' OR 'urinary tract*AND 'aspergillosis' OR 'aspergillus' OR 'aspergilloma' OR 'mycetoma'. We included single case reports or case series. Review articles, guidelines, meta-analyses, animal studies, protocols, and cases of genitourinary and /or renal aspergillosis occurring as a part of disseminated disease were excluded.
RESULTS
We identified 91 renal and urinary aspergillosis cases extracted from 76 publications spanning 1925-2023. Among the participants, 79 (86.8%) were male, with a median age of 46 years. Predominantly, presentations consisted of isolated renal infections (74 instances, 81.3%), followed by prostate (5 cases, 5.5%), and bladder (7 cases, 7.7%) involvement. (42.9%), (9.9%), and (1.1% each) were isolated. Underlying risk factors included diabetes mellitus (29.7%), HIV (12.1%), haematological malignancies (11%), and liver cirrhosis (8.8%), while common symptoms encompassed flank pain (36.3%), fever (33%), and lower urinary tract symptoms (20.9%). An autopsy was conducted in 8.8% of cases. Diagnostic work-up involved histopathology (70.5%), renal CT scans and urine microscopy and culture (52.6% each), and abdominal ultrasound (17.9%). Treatments included amphotericin B (34 cases, 37.4%) and azole-based regimens (29 cases, 31.9%). Nephrectomy was performed in 16 of 78 renal cases (20.5%). All-cause mortality was 24.4% (19 cases). No significant mortality rate difference was observed among antifungal regimens ( = 0.739) or nephrectomy status ( = 0.8).
CONCLUSION
Renal and urinary aspergillosis is an important cause of morbidity and mortality, particularly in immunocompromised and people with diabetes mellitus. While varied treatment strategies were observed, mortality rates showed no significant differences based on treatments or nephrectomy status. Further research is needed to refine diagnostics, optimize treatments, and enhance awareness among clinicians for early detection and management.
PROSPERO REGISTRATION NUMBER
CRD42023430959.
PubMed: 38130371
DOI: 10.1177/17562872231218621