Case of the month: patient with septic shock and massive intravascular haemolysis

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open Allur texti - Full tex

Fungemia and other invasive fungal infections in Icelandic children. A nationwide study

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenIntroduction: Invasive fungal infections are increasing in incidence. Among those who are at increased risk of fungal blood stream infections (fungemia) and disseminated fungal infections are premature infants and immunosuppressed children. These infections are associated with high morbidity and mortality. Invasive fungal infections have not yet been studied in Iceland. Material and methods: We studied all cases of fungemia and/or disseminated fungal infections in Icelandic children (16 years) during a 20 year period. Histopathology reports and autopsies were reviewed. Information on predisposing factors, symptoms, treatment and outcome was collected. All obtainable fungal blood stream isolates were subcultured and their susceptibility to common antifungals determined. Results: In the 20 year period from 1980-1999, 19 episodes of invasive fungal infections were diagnosed in 18 infants and children in Iceland. Twelve episodes of fungemia occured in 11 children and the nationwide annual incidence increased from 0.28 to 1.90 cases/100,000/year (p=0.037) during the study period. Half of the children were premature infants. All patients had a central venous catheter at the time of blood culture and most had received intravenous antibiotics or corticosteroids. Candida albicans was the most commonly isolated species (nine of 12 episodes, 75%). In addition to patients with fungemia, three children were diagnosed with disseminated fungal infection by histology or autopsy. Two cases of fungal meningitis, without fungemia, were identified. Furthermore, two children had invasive infections with Aspergillus fumigatus and both patients survived. Three children (3/16; 19%) with invasive Candida-infections died. Conclusions: In this study of invasive fungal infections among Icelandic children we demonstrate that the incidence of fungemia has risen significantly in the past 20 years. Diagnosis of invasive fungal infections can be complicated and negative blood cultures do not exclude disseminated infection. Given the high attributable mortality, timely diagnosis and aggressive treatment is extremely important.Inngangur: Tíðni ífarandi sveppasýkinga fer vaxandi víðast hvar í hinum vestræna heimi. Fyrirburar og ónæmisbæld börn eru í hættu á að fá blóðsýkingar af völdum sveppa og í kjölfarið dreifðar sýkingar. Sýkingar af þessum toga hafa í för með sér háa dánartíðni. Þær hafa ekki verið rannsakaðar hjá börnum hérlendis. Efniviður og aðferðir: Farið var yfir sjúkraskrár allra barna 16 ára og yngri á Íslandi er greindust með blóðsýkingar og/eða dreifðar sýkingar af völdum ger- og myglusveppa á árunum 1980-1999. Niðurstöður krufninga og vefjarannsókna voru einnig kannaðar. Skráðar voru upplýsingar um áhættuþætti, einkenni, meðferð og afdrif sjúklinga. Allir tiltækir sveppastofnar voru ræktaðir og næmi þeirra fyrir sveppalyfjum kannað. Niðurstöður: Alls greindust 18 börn með 19 ífarandi sveppasýkingar á þessu 20 ára tímabili. Tólf blóðsýkingar greindust hjá 11 börnum og jókst nýgengið marktækt á rannsóknartímabilinu úr 0,28 í 1,90 sýkingar á 100.000 börn á ári (p=0,037). Tæpur helmingur barna með blóðsýkingu voru fyrirburar. Öll börn með sannaða blóðsýkingu voru með djúpa æðaleggi og flest höfðu fengið næringu í æð, sýklalyf og barkstera. Candida albicans ræktaðist í níu tilvikum af 12 (75%). Þrjú börn af 11 fengu dreifða sýkingu. Til viðbótar greindust þrjú börn með dreifða Candida sýkingu við krufningu eða vefjarannsókn. Að auki fengu tvö börn heilahimnubólgu af völdum Candida albicans án sannaðrar blóðsýkingar. Tvö börn greindust með ífarandi sýkingar af völdum myglusveppsins Aspergillus fumigatus og læknuðust þau bæði. Þrjú börn af þeim 16 sem fengu ífarandi Candida sýkingar létust. Ályktanir: Þessi rannsókn á ífarandi sveppasýkingum hjá börnum er sú fyrsta er nær til heillar þjóðar. Veruleg hækkun hefur orðið á nýgengi sveppasýkinga í blóði hjá börnum hérlendis á síðastliðnum 20 árum. Greining alvarlegra sveppasýkinga er oft torveld og neikvæð blóðræktun útilokar ekki dreifða sýkingu. Í ljósi hækkandi nýgengis og hárrar dánartíðni er mikilvægt að hafa umræddar greiningar í huga hjá mikið veikum börnum

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Centre for Genomic Pathogen Surveillance and the Euro-GASP study group: Sonja Pleininger, Alexander Indra, Irith De Baetselier, Wim Vanden Berghe, Blaženka Hunjak, Tatjana Nemeth Blažić, Panayiota Maikanti-Charalambous, Despo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Lasse Jessen Schwartz, Rita Peetso, Jevgenia Epstein, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Cécile Bébéar, Florence Lot, Susanne Buder, Klaus Jansen, Vivi Miriagou, Georgios Rigakos, Vasilios Raftopoulos, Eszter Balla, Mária Dudás, Lena Rós Ásmundsdóttir, Guðrún Sigmundsdóttir, Guðrún Svanborg Hauksdóttir, Thorolfur Gudnason, Aoife Colgan, Brendan Crowley, Sinéad Saab, Paola Stefanelli, Anna Carannante, Patrizia Parodi, Gatis Pakarna, Raina Nikiforova, Antra Bormane, Elina Dimina, Monique Perrin, Tamir Abdelrahman, Joël Mossong, Jean-Claude Schmit, Friedrich Mühlschlegel, Christopher Barbara, Francesca Mifsud, Alje Van Dam, Birgit Van Benthem, Maartje Visser, Ineke Linde, Hilde Kløvstad, Dominique Caugant, Beata Młynarczyk-Bonikowska, Jacinta Azevedo, Maria-José Borrego, Marina Lurdes Ramos Nascimento, Peter Pavlik, Irena Klavs, Andreja Murnik, Samo Jeverica, Tanja Kustec, Julio Vázquez Moreno, Asuncion Diaz, Raquel Abad, Inga Velicko, Magnus Unemo, Helen Fifer, Jill Shepherd, Lynsey PattersonBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.This study was supported by the European Centre for Disease Prevention and Control, the Centre for Genomic Pathogen Surveillance, the Li Ka Shing Foundation (Big Data Institute, University of Oxford), the Wellcome Genome Campus, the Foundation for Medical Research at Örebro University Hospital, and grants from Wellcome (098051 and 099202). LSB was funded by Conselleria de Sanitat Universal i Salut Pública, Generalitat Valenciana (Plan GenT CDEI-06/20-B), Valencia, Spain, and Ministry of Science, Innovation and Universities (PID2020–120113RA-I00), Spain, at the time of analysing and writing this manuscript.info:eu-repo/semantics/publishedVersio

Candidemia and invasive candidiasis: pathogenesis, molecular epidemiology, and predictors of outcome. A population-based study

The incidence of serious fungal infections has increased substantially in the past decades, incident to increased prevalence of susceptible hosts. Candidemia, in particular, is associated with high morbidity and mortality. This thesis outlines results from a nationwide study, conducted in Iceland from 1980 to 2006, of the incidence of candidemia. In addition, antifungal susceptibility of the pathogens was studied, as well as national consumption of antifungal agents. The clinical characteristics of candidemic patients (n=165; 172 episodes) from 1980 through 1999 are described, as well as predisposing conditions and their association with outcome. Furthermore, we studied the genetic relatedness of all available Candida bloodstream isolates (BSIs) in the country during a 15-year period. Finally, the virulence of Candida albicans and Candida dubliniensis were compared in a murine model of bloodstream infections. The annual incidence of candidemia in Iceland increased from 1.4 cases/100,000 inhabitants/year during 1980-1984 to 5.3 cases/100,000 inhabitants/year during 2000-2006 (p60 years). C. albicans was the predominant species responsible (61.6%). The national import of fluconazole increased approximately 5.5-fold from 1991 through 2006, but increased resistance to this agent was not observed. Most cases occurred in intensive care units (35.8%) and surgical wards (30.1%). In multivariate analysis, prompt removal of central venous catheters (odds ratio [OR], for death, 0.22) and septic shock (OR for death, 8.01) were the strongest independent predictors of outcome. PCR fingerprinting of Candida BSIs (n=219) from 94.4% of cases during 1991-2006 revealed temporo-spatial associations between 18.7-39.9% of all infections, suggestive of nosocomial clustering. When the virulence of C. albicans and C. dubliniensis was compared in a murine model, similar 7-day mortality was observed, with greater strain variation noted within species than between the two species. C. dubliniensis produced significantly lower levels of hyphae in kidneys than C. albicans (p<0.001). Increasing tissue burden of both hyphal forms (OR, 2.27) and yeasts (OR, 2.06) were independently associated with death, whereas greater infiltration of mononuclear cells was protective (OR, 0.02). These results confirm that invasive candidiasis has emerged as a serious threat to hospitalized patients in recent decades. They also highlight the importance of aggressive treatment. In an unselected hospital population, as many as one-third of all cases of candidemia may be attributable to nosocomial clusters, and the risk is highest in wards providing intensive care. Our results suggest a great overlap between the virulence properties of C. dubliniensis and C. albicans. In virulence studies, the source of fungal isolates may be a neglected confounding factor. Further studies of the virulence mechanisms of different Candida species and modes of transmission of infecting strains in the hospital environment are warranted in order to improve treatment and develop effective prevention strategies.The Eimskip Fund of The University of Iceland, The Icelandic Research Fund (grant 050431031), The Icelandic Research Fund for Graduate Students (grant 050750005), The University of Iceland Research Fund, The Landspitali University Hospital Research Fund, The Kristín Björnsdóttir Memorial Fund

Increasing Incidence of Candidemia: Results from a 20-Year Nationwide Study in Iceland

A nationwide study on candidemia was conducted in Iceland from 1980 to 1999. The annual incidence increased from 1.4 cases/100,000 inhabitants/year between 1980 and 1984 to 4.9 cases/100,000 inhabitants/year between 1995 and 1999 (P < 0.0001). Candidemia episodes at university hospitals increased from 0.15/1,000 admissions to 0.55/1,000 admissions (P < 0.0001). Candida albicans was the predominant species responsible (64.4%). The national import of fluconazole increased approximately fourfold during the second half of the study, but increased resistance to this agent was not observed

Case of the month: patient with septic shock and massive intravascular haemolysis

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open Allur texti - Full tex

Fungemia and other invasive fungal infections in Icelandic children. A nationwide study

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenIntroduction: Invasive fungal infections are increasing in incidence. Among those who are at increased risk of fungal blood stream infections (fungemia) and disseminated fungal infections are premature infants and immunosuppressed children. These infections are associated with high morbidity and mortality. Invasive fungal infections have not yet been studied in Iceland. Material and methods: We studied all cases of fungemia and/or disseminated fungal infections in Icelandic children (16 years) during a 20 year period. Histopathology reports and autopsies were reviewed. Information on predisposing factors, symptoms, treatment and outcome was collected. All obtainable fungal blood stream isolates were subcultured and their susceptibility to common antifungals determined. Results: In the 20 year period from 1980-1999, 19 episodes of invasive fungal infections were diagnosed in 18 infants and children in Iceland. Twelve episodes of fungemia occured in 11 children and the nationwide annual incidence increased from 0.28 to 1.90 cases/100,000/year (p=0.037) during the study period. Half of the children were premature infants. All patients had a central venous catheter at the time of blood culture and most had received intravenous antibiotics or corticosteroids. Candida albicans was the most commonly isolated species (nine of 12 episodes, 75%). In addition to patients with fungemia, three children were diagnosed with disseminated fungal infection by histology or autopsy. Two cases of fungal meningitis, without fungemia, were identified. Furthermore, two children had invasive infections with Aspergillus fumigatus and both patients survived. Three children (3/16; 19%) with invasive Candida-infections died. Conclusions: In this study of invasive fungal infections among Icelandic children we demonstrate that the incidence of fungemia has risen significantly in the past 20 years. Diagnosis of invasive fungal infections can be complicated and negative blood cultures do not exclude disseminated infection. Given the high attributable mortality, timely diagnosis and aggressive treatment is extremely important.Inngangur: Tíðni ífarandi sveppasýkinga fer vaxandi víðast hvar í hinum vestræna heimi. Fyrirburar og ónæmisbæld börn eru í hættu á að fá blóðsýkingar af völdum sveppa og í kjölfarið dreifðar sýkingar. Sýkingar af þessum toga hafa í för með sér háa dánartíðni. Þær hafa ekki verið rannsakaðar hjá börnum hérlendis. Efniviður og aðferðir: Farið var yfir sjúkraskrár allra barna 16 ára og yngri á Íslandi er greindust með blóðsýkingar og/eða dreifðar sýkingar af völdum ger- og myglusveppa á árunum 1980-1999. Niðurstöður krufninga og vefjarannsókna voru einnig kannaðar. Skráðar voru upplýsingar um áhættuþætti, einkenni, meðferð og afdrif sjúklinga. Allir tiltækir sveppastofnar voru ræktaðir og næmi þeirra fyrir sveppalyfjum kannað. Niðurstöður: Alls greindust 18 börn með 19 ífarandi sveppasýkingar á þessu 20 ára tímabili. Tólf blóðsýkingar greindust hjá 11 börnum og jókst nýgengið marktækt á rannsóknartímabilinu úr 0,28 í 1,90 sýkingar á 100.000 börn á ári (p=0,037). Tæpur helmingur barna með blóðsýkingu voru fyrirburar. Öll börn með sannaða blóðsýkingu voru með djúpa æðaleggi og flest höfðu fengið næringu í æð, sýklalyf og barkstera. Candida albicans ræktaðist í níu tilvikum af 12 (75%). Þrjú börn af 11 fengu dreifða sýkingu. Til viðbótar greindust þrjú börn með dreifða Candida sýkingu við krufningu eða vefjarannsókn. Að auki fengu tvö börn heilahimnubólgu af völdum Candida albicans án sannaðrar blóðsýkingar. Tvö börn greindust með ífarandi sýkingar af völdum myglusveppsins Aspergillus fumigatus og læknuðust þau bæði. Þrjú börn af þeim 16 sem fengu ífarandi Candida sýkingar létust. Ályktanir: Þessi rannsókn á ífarandi sveppasýkingum hjá börnum er sú fyrsta er nær til heillar þjóðar. Veruleg hækkun hefur orðið á nýgengi sveppasýkinga í blóði hjá börnum hérlendis á síðastliðnum 20 árum. Greining alvarlegra sveppasýkinga er oft torveld og neikvæð blóðræktun útilokar ekki dreifða sýkingu. Í ljósi hækkandi nýgengis og hárrar dánartíðni er mikilvægt að hafa umræddar greiningar í huga hjá mikið veikum börnum