Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Raquel Sabino was not included as an author in the published article. It was corrected a posteriori.Erratum in - Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? [Front Microbiol. 2018] Front Microbiol. 2019 Jan 14;9:3245. doi: 10.3389/fmicb.2018.03245. eCollection 2018.Disponível em: https://www.frontiersin.org/articles/10.3389/fmicb.2018.03245/fullFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882871/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340063/Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.This work was supported by ECMM, ISHAM, and EFISG and in part by an unrestricted research grant through the Investigator Initiated Studies Programof Astellas, MSD, and Pfizer. This study was fundet by the Christian Doppler Laboratory for invasive fungal infections.info:eu-repo/semantics/publishedVersio

Plasmodium falciparum Malaria: Evaluation of Three Imported Cases

Among Plasmodium species the causative agent of malaria in Turkey is P.vivax, however the incidence of imported falciparum malaria cases is steadily increasing. P.falciparum may cause severe malaria with the involvement of central nervous system, acute renal failure, severe anemia or acute respiratory distress syndrome. Furhermore most of the casualties due to malaria are related with P.falciparum. There is recently, a considerable increase in malaria infections especially in tropical areas. In this report, three cases, who have admitted to our hospital with three different clinical presentations of falciparum malaria, and all shared common history of travelling to Africa were presented. First case was a 27 years old, male patient who returned from Malawi seven days ago where he stayed for two weeks. He admitted to our hospital with the complaints of sensation of cold, shivering and fever. In physical examination his body temperature was 37.9 degrees C, C-reactive protein level was high, and the other systemic results were normal. The second case was a 25 years old, male patient who returned from Gambia two weeks ago. He was suffering from fever, headache, shivering and unable to maintain his balance. The patient's body temperature was 38 degrees C. Laboratory tests revealed hyperbilirubinemia and thrombocytopenia. Parasitological examination of the Giemsa-stained peripheral blood smear of these two patients demonstrated ring forms compatible with P.falciparum. Treatment was commenced with arthemeter plus lumefantrine, resulting with complete cure. Third case was a 46 years old, male patient who had been working in Uganda, and returned to Turkey two weeks ago. He had sudden onset of fever, headache, nausea and vomiting and impaired consciousness. His peripheral blood smear revealed ring-formed trophozoites and banana-shaped gametocytes of P.falciparum. Arthemeter plus lumefantrine therapy was started, however, he developed severe thrombocytopenia and jaundice under treatment. His general condition was detoriated and the patient lost his consciousness. As the patient's clinical signs were compatible with sepsis ceftriaxone plus clindamycin were added to the antiparasitic treatment emprically. Due to the development of acute tubular necrosis, the patient have undergone hemodialysis. On the 9(th) day of therapy the complaints and laboratory findings of the patient have improved, so he was discharged. However, visual defects due to retinopathy and severe neurocognitive impairment that were thought to be the complications of malaria continued in his follow-ups. As a result, it should be keep in mind that both the African students who have come to our country for education from endemic regions and as well as the returned citizens of our country who have gone to work in endemic areas, are under risk of malaria and it is very important to consider malaria in the distinctive diagnosis of patients with the complaints of fever, headache, nausea, vomiting and muscle pain.WoSScopusTr-Dizi

A case of Legionnaires’ disease with severe rhabdomyolysis misdiagnosed as COVID-19

Background: COVID-19 case numbers have begun to rise with the recently reported Omicron variant. In the last two years, COVID-19 is the first diagnosis that comes to mind when a patient is admitted with respiratory symptoms and pulmonary ground-glass opacities. However, other causes should be kept in mind as well. Here we present a case of Legionnaires’ disease misdiagnosed as COVID-19. Case presentation: A 48-year-old male was admitted with complaints of dry cough and dyspnea. Chest computed-tomography revealed bilateral ground-glass opacities; therefore, a preliminary diagnosis of COVID-19 was made. However, two consecutive COVID PCR tests were negative and the patient deteriorated rapidly. As severe rhabdomyolysis and acute renal failure were present, Legionnaires’ disease was suspected. Urine antigen test for Legionella and Legionella pneumophila PCR turned out to be positive. The patient responded dramatically to intravenous levofloxacin and was discharged successfully. Discussion: Legionnaires’ disease and COVID-19 may present with similar signs and symptoms. They also share common risk factors and radiological findings. Conclusions: Shared clinical and radiological features between COVID-19 and other causes of acute respiratory failure pose a challenge in diagnosis. Other causes such as Legionnaires’ disease must be kept in mind and appropriate diagnostic tests should be performed accordingly

Diagnostic performance and longitudinal analysis of fungal biomarkers in COVID-19 associated pulmonary aspergillosis

Objectives: Galactomannan lateral flow assay (GM-LFA) is a reliable test for COVID-19 associated pulmonary aspergillosis (CAPA) diagnosis. We aimed to assess the diagnostic performance of GM-LFA with different case definitions, the association between the longitudinal measurements of serum GM-ELISA, GM-LFA, and the risk of death. Methods: Serum and nondirected bronchial lavage (NBL) samples were periodically collected. The sensitivity and specificity analysis for GM-LFA was done in different time periods. Longitudinal analysis was done with the joint model framework. Results: A total of 207 patients were evaluated. On the day of CAPA diagnosis, serum GM-LFA had a sensitivity of 42 % (95 % CI: 23–63) and specificity of 82 % (95 % CI: 78–84), while NBL GM-LFA had a sensitivity of 73 % (95 % CI: 45–92), specificity of 85 % (95 % CI: 76–91) for CAPA. Sensitivity decreased through the following days in both samples. Univariate joint model analysis showed that increasing GM-LFA and GM-ELISA levels were associated with increased mortality, and that effect remained same with serum GM-ELISA in multivariate joint model analysis. Conclusion: GM-LFA, particularly in NBL samples, seems to be a reliable method for CAPA diagnosis. For detecting patients with higher risk of mortality, longitudinal measurement of serum GM-ELISA can be useful

Carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates from Turkey with OXA-48-like carbapenemases and outer membrane protein loss

Treatment options are limited in infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, with carbapenems generally preferred. Disturbingly, however, carbapenem-resistant strains are emerging worldwide. Here we report two clinical isolates, one Escherichia coli and one Klebsiella pneumoniae, each with high-level carbapenem resistance (imipenem minimum inhibitory concentration of 32 microg/mL). They were isolated following imipenem therapy from two hospital patients who had received imipenem therapy in different regions of Turkey. Both isolates produced OXA-48-like carbapenemases, enzymes so far reported only from Turkey. Both isolates also had group 1 CTX-M-type ESBLs and had lost major outer membrane proteins. OXA-48-like carbapenemases appear to be scattered in Turkey and surveillance to determine their prevalence is warranted

Relative Vaccine Effectiveness of the Third Dose of CoronaVac or BNT162b2 Following a Two-Dose CoronaVac Regimen: A Prospective Observational Cohort Study from an Adult Vaccine Center in Turkey

Coronavirus disease 2019 (COVID-19) continues to pose a threat to public health with the potential for the emergence of new variants. Vaccines are the milestones to control and slow down the damage of the pandemic. As of January 2021, a two-dose regimen with CoronaVac was authorized in Turkey. Due to the waning seroprevalence rate of SARS-CoV-2 over time, BNT162b2 or CoronaVac has been administered as the third dose following a two-dose CoronaVac regimen as a national vaccination policy. As of 14 January 2021, 5243 volunteers who received two doses of the CoronaVac vaccine at Hacettepe University Adult Vaccine Center were followed prospectively. In our study, relative vaccine effectiveness (VEff) for the third dose of the CoronaVac was 58.24% and 87.27% for BNT162b2 in preventing symptomatic COVID-19 cases. There were no hospitalizations, intensive care unit admissions, or deaths in third-dose booster groups with either BNT162b2 or CoronaVac, yielding 100% effectiveness. Both homologous or heterologous third-dose boosters provided further protection against severe COVID-19 and should be prioritized as an effective strategy to combat the COVID-19 pandemic

Risk Factors and Predictors of Outcome in Patients with Cancer and Breakthrough Candidemia

Hematogenous candidiasis adds substantially to the morbidity and mortality rates of patients with cancer. Little is known about the risk factors and outcome in patients with breakthrough (BT) candidemia while on systemic antifungal therapy. All 479 episodes of candidemia in 474 consecutive patients with candidemia that was diagnosed at M. D. Anderson Cancer Center from 1988 through 1992 were studied retrospectively. A total of 49 patients had BT candidemia, defined as candidemia that developed after at least 5 days of systemic antifungal therapy. Risk factors for BT candidemia and predictors of mortality were investigated. Multivariate analysis revealed that intensive care unit stay, neutropenia, use of corticosteroids, and duration of neutropenia as significant risk factors for BT candidemia. Seventy-six percent of patients with BT candidemia died, compared with 50% of patients with non-BT infection. In multivariate analysis, intensive care unit stay, being and remaining neutropenic, APACHE III score, and disseminated disease were independent prognostic factors. In conclusion, identification of risk factors and predictors of a poor outcome in patients with cancer with BT candidemia may have important implications in early diagnosis and appropriate therapy of these patients.WoSScopu

A prospective international Aspergillus terreus survey: An EFISG, ISHAM and ECMM joint study

Objectives: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. Methods: A total of 370 cases from 21 countries were evaluated. Results: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). Conclusions: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.Fil: Risslegger, Brigitte. Universidad de Innsbruck; AustriaFil: Zoran, Tamara. Universidad de Innsbruck; AustriaFil: Lackner, Michaela. Universidad de Innsbruck; AustriaFil: Aigner, María. Universidad de Innsbruck; AustriaFil: Sanchez Reus, Ferrán. Hospital de la Santa Creu I Sant Pau; EspañaFil: Rezusta, Antonio. Universidad de Zaragoza; EspañaFil: Chowdhary, Anuradha. University of Delhi; IndiaFil: Alcacer Sanchez, Juan Manuel. Hospital de la Santa Creu I Sant Pau;Fil: Taj Aldeen, Saad Jaber. Hamad Medical Corporation; QatarFil: Arendrup, Maiken C.. Universidad de Copenhagen; DinamarcaFil: Oliveri, Salvatore. Università degli Studi di Catania; ItaliaFil: Kontoyiannis, Dimitrios P.. The University of Texas MD Anderson Cancer Center; Estados UnidosFil: Alastruey Izquierdo, Ana. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Lagrou, Katrien. Katholikie Universiteit Leuven; BélgicaFil: Lo Cascio, Giuliana. Azienda Ospedaliera Universitaria Integrata; ItaliaFil: Meis, Jacques F.. Canisius Wilhelmina Hospital; Países BajosFil: Buzina, Walter. Medical University of Graz; AustriaFil: Farina, Claudio. ASST Papa Giovanni XXIII. Microbiology Institute; ItaliaFil: Drogari Apiranthitou, Miranda. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Grancini, Anna. Cà Granda Ospedale Maggiore Policlinico; ItaliaFil: Tortorano, Anna Maria. Università degli Studi di Milano; ItaliaFil: Willinger, Birgit. Universidad de Viena; AustriaFil: Hamprecht, Axel. Universitat Zu Köln; AlemaniaFil: Johnson, Elizabeth. Public Health England. Mycology Reference Laboratory; Reino UnidoFil: Klingspor, Lena. Karolinska Huddinge Hospital; SueciaFil: Arsic Arsenijevic, Valentina. University of Belgrade; SerbiaFil: Cornely, Oliver A.. Universitat Zu Köln; AlemaniaFil: Meletiadis, Joseph. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Prammer, Wolfgang. Klinikum Wels-Grieskirchen; AustriaFil: Tullio, Vivian. Università di Torino; ItaliaFil: Vehreschild, Jörg Janne. Universitat Bonn; Alemania. Universitat Zu Köln; AlemaniaFil: Trovato, Laura. Università degli Studi di Catania; ItaliaFil: Lewis, Russell E.. Universidad de Bologna; ItaliaFil: Segal, Esther. Tel Aviv University; IsraelFil: Rath, Peter Michael. Universitat Essen; AlemaniaFil: Hamal, Petr. Universtity Hospital Olomouc; República Checa. Palacky University Olomouc; República ChecaFil: Rodríguez Iglesias, Manuel. Universidad de Cádiz; EspañaFil: Roilides, Emmanuel. Aristotle University School of Health Sciences; GreciaFil: Arikan Akdagli, Sevtap. Hacettepe University; TurquíaFil: Chakrabarti, Arunaloke. Postgraduate Institute of Medical Education and Research; IndiaFil: Colombo, Arnaldo L.. Universidade Federal de Sao Paulo; BrasilFil: Fernández, Mariana Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martin Gomez, M. Teresa. Vall d’Hebron University Hospital; EspañaFil: Badali, Hamid. Mazandaran University of Medical Sciences; IránFil: Petrikkos, Georgios. European University Cyprus; ChipreFil: Klimko, Nikolai. North Western State Medical University; RusiaFil: Heimann, Sebastian M.. Universitat Zu Köln; AlemaniaFil: Houbraken, Jos. Fungal Biodiversity Centre; Países BajosFil: Uzun, Omrum. Hacettepe University Medical School; TurquíaFil: Edlinger, Michael. Universidad de Innsbruck; AustriaFil: de la Fuente, Sonia. Hospital Ernest Lluch Martin; EspañaFil: Lass Flörl, Cornelia. Universidad de Innsbruck; Austri