Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a ...clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.
In patients with AIDS, tuberculosis is a leading cause of death.1 In the past two decades, diagnosis of tuberculosis has improved markedly, with tests such as interferon-γ release assays, GeneXpert ...MTB/RIF, and lateral flow urine lipoarabinomannan assay. Post-mortem examination finally detected disseminated histoplasmosis in many of these patients.4 In addition to a poor disease awareness, the late diagnosis and the limited access to less toxic antifungal drugs, such as liposomal amphotericin B (L-AmB), help to explain why the mortality of disseminated histoplasmosis is about three-times higher in Latin America than in the USA. ...is to have better drugs in place, particularly L-AmB, which in a randomised double-blind trial5 had superiority over deoxycholate amphotericin B, with a survival benefit.
Neglected endemic mycoses Queiroz-Telles, Flavio; Fahal, Ahmed Hassan; Falci, Diego R ...
The Lancet infectious diseases,
November 2017, 2017-11-00, 20171101, Letnik:
17, Številka:
11
Journal Article
Recenzirano
Fungi often infect mammalian hosts via the respiratory route, but traumatic transcutaneous implantation is also an important source of infections. Environmental exposure to spores of pathogenic fungi ...can result in subclinical and unrecognised syndromes, allergic manifestations, and even overt disease. After traumatic cutaneous inoculation, several fungi can cause neglected mycoses such as sporotrichosis, chromoblastomycosis, mycetoma, entomophthoramycosis, and lacaziosis. Most of these diseases have a subacute to chronic course and they can become recalcitrant to therapy and lead to physical disabilities, including inability to work, physical deformities, and amputations. For many years, paracoccidioidomycosis was considered the most prevalent endemic systemic mycosis in the Americas, but this situation might be changing with recognition of the worldwide presence of Histoplasma capsulatum. Both paracoccidioidomycosis and histoplasmosis can mimic several infectious and non-infectious medical conditions and lead to death if not recognised early and treated. Cutaneous implantation and systemic mycoses are neglected diseases that affect millions of individuals worldwide, especially in low-income countries where their management is suboptimum because challenges in diagnosis and therapeutic options are substantial issues.
Corticosteroids have potent anti-inflammatory and immunosuppressive effects. Recently, these medications have gained importance in the treatment of severe COVID-19. Here we present data demonstrating ...a marked (10-fold) increase in frequency of candidemia in hospitalized patients with COVID-19 receiving corticosteroids in Brazil. Overall mortality was 72.7%, despite antifungal therapy. Physicians should be aware of the potential risk for candidemia among severely ill COVID-19 patients receiving high-doses of corticosteroids.
Endemic mycoses are difficult-to-diagnose conditions that may mimic several other diseases, particularly tuberculosis, community-acquired pneumonia, and cancer ...
Most of the information available about Aspergillus infections has originated from the study of A. fumigatus, the most frequent species in the genus. This review aims to compare the pathogenicity and ...clinical aspects of Aspergillosis caused by A. fumigatus an A. flavus. Experimental data suggests that A. flavus is more virulent than A. fumigatus. However, these were mostly models of disseminated Aspergillus infection which do not properly mimic the physiopathology of invasive aspergillosis, a condition that is usually acquired by inhalation. In addition, no conclusive virulence factor has been identified for Aspergillus species. A. flavus is a common cause of fungal sinusitis and cutaneous infections. Chronic conditions such as chronic cavitary pulmonary aspergillosis and sinuses fungal balls have rarely been associated with A. flavus. The bigger size of A. flavus spores, in comparison to those of A. fumigatus spores, may favour their deposit in the upper respiratory tract. Differences between these species justify the need for a better understanding of A. flavus infections.
Summary
Despite the existence of endemic mycoses in Latin America and the Caribbean, in addition to a large population of patients at risk for invasive mycoses, the capability of medical centres to ...perform a proper diagnosis in mycology has not been studied in the region. Moreover, availability of antifungal drugs in the region is unknown. Here, we report the results of a survey involving 129 centres in 24 countries. Only 9% of centres would have the potential to apply for the minimum standards in mycology, as determined by the European Confederation of Medical Mycology. There is an urgent need to improve diagnostic conditions in Latin America and the Caribbean, as well as providing access to safer and more efficacious antifungal drugs.
Aspergillosis is an infection or allergic response caused by the fungus Aspergillus. Aspergillus conidia are widely dispersed in the environment and can easily reach human lungs and/or paranasal ...sinuses: most people inhale Aspergillosis spores every day! The label Aspergillosis is used for several diverse clinical conditions. For instance, invasive Aspergillosis typically affects severely immunocompromised patients such as those with prolonged neutropenia or receiving therapy with steroids. On the other hand, allergic forms of Aspergillosis cause exuberant clinical syndromes that mostly affect patients with asthma and cystic fibrosis. Slowly destructive lung diseases may also occur in the apparently immunocompentent host, especially in the context of previous damage to the lung architecture. These are difficult-to-diagnose infections, and diagnostic tests perform differently depending on the specific scenario. This book summarizes the current knowledge about Aspergillosis, covering: Epidemiology Pathogenesis Clinical manifestations Diagnosis Treatment Prevention Written by internationally respected authors, the information presented in this book adds for a better understanding of Aspergillosis by providing a comprehensive and clear overview of all aspects associated with this complex disease.
Purpose
To describe temporal trends in the epidemiology, clinical management and outcome of candidemia in intensive care unit (ICU) patients.
Methods
This study was a retrospective analysis of 1,392 ...episodes of candidemia in 647 adult ICU patients from 22 Brazilian hospitals. The characteristics of candidemia in these ICU patients were compared in two periods (2003–2007, period 1; 2008–2012, period 2), and the predictors of 30-day mortality were assessed.
Results
The proportion of patients who developed candidemia while in the ICU increased from 44 % in period 1 to 50.9 % in period 2 (
p
= 0.01). Prior exposure to fluconazole before candidemia (22.3 vs. 11.6 %,
p
< 0.001) and fungemia due to
Candida glabrata
(13.1 vs. 7.8 %,
p
= 0.03) were more frequent in period 2, as was the proportion of patients receiving an echinocandin as primary therapy (18.0 vs. 5.9 %,
p
< 0.001). The 30-day mortality rate decreased from 76.4 % in period 1 to 60.8 % in period 2 (
p
< 0.001). Predictors of 30-day mortality by multivariate analysis were older age, period 1, treatment with corticosteroids and higher APACHE II score, while treatment with an echinocandin were associated with a higher probability of survival.
Conclusions
We found a clear change in the epidemiology and clinical management of candidemia in ICU patients over the 9-year period of the study. The use of echinocandins as primary therapy for candidemia appears to be associated with better outcomes.
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