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BACKGROUND: Invasive fungal disease (IFD) causes morbidity and mortality in immunocompromised hosts (ICH). Based on increasing recognition of the impact of IFD on human disease, a recent WHO priority list identified key areas of need. OBJECTIVES: This review examines changes in epidemiology of IFD, in particular emergence of antifungal resistant pathogens and current availability of rapid diagnostic tests and antifungal treatment options. SOURCES: Literature between 2000 and January 2024 regarding fungal epidemiology, diagnostic test, antifungal resistance, emerging fungal pathogens and novel antifungal agents in both adult and pediatric immunocompromised hosts (ICH) was reviewed. CONTENT: We describe the changing epidemiology and continued burden and mortality of IFD in ICH. Further we discuss the emergence of antifungal resistant organisms driven by new immunosuppressed populations, climate change and antifungal exposure in the individual and environment. We highlight novel antifungal agents and how they will address current unmet needs. IMPLICATIONS: The changing epidemiology and increased population at risk for IFD, lack of recognition of or quantification of risks for IFD with new therapies, current gaps in the availability of rapid diagnostic tests and the imminent availability of novel antifungals with distinct spectra of activity argue for improved availability of and access to rapid diagnostics, antifungal stewardship programs and global of access to antifungal agents.
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Febrile neutropenia is the most common potential emergency situation in children and adolescents with cancer. The host response of these patients is severely compromised by treatment-induced immunosuppression resulting in a lack of important defence mechanisms, so that bacterial infections and in certain risk groups also fungal infections can be life threatening. As the clinical course of these infectious complications may be rapid and fatal, early antibiotic treatment can save lives. This article aims to raise awareness to this emergency situation and gives an overview of the management of pediatric cancer patients with febrile neutropenia.
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SCOPE: Presenting symptoms, distributions and patterns of diseases and vulnerability to invasive aspergillosis (IA) are similar between children and adults. However, differences exist in the epidemiology and underlying conditions, the usefulness of newer diagnostic tools, the pharmacology of antifungal agents and in the evidence from interventional phase 3 clinical trials. Therefore, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) have developed a paediatric-specific guideline for the diagnosis and management of IA in neonates and children. METHODS: Review and discussion of the scientific literature and grading of the available quality of evidence was performed by the paediatric subgroup of the ESCMID-ECMM-European Respiratory Society (ERS) Aspergillus disease guideline working group, which was assigned the mandate for the development of neonatal- and paediatric-specific recommendations. QUESTIONS: Questions addressed by the guideline included the epidemiology of IA in neonates and children; which paediatric patients may benefit from antifungal prophylaxis; how to diagnose IA in neonates and children; which antifungal agents are available for use in neonates and children; which antifungal agents are suitable for prophylaxis and treatment of IA in neonates and children; what is the role of therapeutic drug monitoring of azole antifungals; and which management strategies are suitable to be used in paediatric patients. This guideline provides recommendations for the diagnosis, prevention and treatment of IA in the paediatric population, including neonates. The aim of this guideline is to facilitate optimal management of neonates and children at risk for or diagnosed with IA.
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Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/normas , Aspergillus/efeitos dos fármacos , Criança , Gerenciamento Clínico , Monitoramento de Medicamentos , Humanos , Recém-NascidoRESUMO
Coprinopsis cinerea is an environmental fungus which can cause disseminated infections in immunocompromised patients, often leading to death. Here we report the case of a paediatric patient with an invasive wound infection due to C. cinerea, which was successfully treated with surgical debridement and oral posaconazole.
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The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.
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Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Gerenciamento Clínico , Anticorpos Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/complicações , Aspergilose/imunologia , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Biópsia/métodos , Lavagem Broncoalveolar , Diagnóstico Precoce , Flucitosina/farmacologia , Flucitosina/uso terapêutico , Galactose/análogos & derivados , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Imageamento por Ressonância Magnética , Mananas/análise , Testes de Sensibilidade Microbiana , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêuticoRESUMO
BACKGROUND: Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. METHODS: Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. RESULTS: One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. CONCLUSION: Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. KEY POINTS: ⢠CT evaluation offers good prediction of outcome for invasive pulmonary aspergillosis. ⢠Predictive capability exceeds galactomannan, blood counts, and lesion count. ⢠Any progression between day 7 and day 14 constitutes a high-risk scenario.
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Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Progressão da Doença , Feminino , Galactose/análogos & derivados , Humanos , Interpretação de Imagem Assistida por Computador , Aspergilose Pulmonar Invasiva/mortalidade , Masculino , Mananas/metabolismo , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Valor Preditivo dos Testes , Análise de Sobrevida , Tomografia Computadorizada por Raios X/estatística & dados numéricosRESUMO
BACKGROUND: Current guidelines recommend antifungal prophylaxis for children at high risk for invasive fungal disease (IFD), but the use of polyenes and triazoles may not be feasible in some patients due to toxicities and drug-drug interactions. Micafungin is well tolerated, with intravenous daily dosing being the current standard. Recent reports indicate safety and efficacy of intermittent dosing of micafungin. METHODS: We analysed safety, efficacy and micafungin serum concentrations of children at high risk for IFD receiving prophylactic micafungin between 3 and 4 mg/kg twice weekly. All children were intolerant or had contraindications to polyenes and triazoles. RESULTS: A total of 21 children (median ageâ=â9 years) at high risk for IFD were included in the analysis. No significant clinical adverse event occurred, and end of treatment values of parameters of renal and hepatic function in serum were not different from baseline. Proven or probable breakthrough IFD did not occur in any of the patients. In 9 out of 11 patients in whom plasma micafungin concentrations were assessed, the first trough concentration exceeded 150 ng/mL, a concentration proposed to be effective for prophylaxis. CONCLUSIONS: Our data indicate that micafungin administered twice weekly at a dosage of 3-4 mg/kg of bodyweight could be a convenient, safe and efficient alternative for antifungal prophylaxis in children at high risk for IFD.
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Antifúngicos/administração & dosagem , Quimioprevenção/métodos , Equinocandinas/administração & dosagem , Fungemia/prevenção & controle , Lipopeptídeos/administração & dosagem , Adolescente , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Criança , Pré-Escolar , Equinocandinas/efeitos adversos , Equinocandinas/farmacocinética , Feminino , Humanos , Lactente , Testes de Função Renal , Lipopeptídeos/efeitos adversos , Lipopeptídeos/farmacocinética , Testes de Função Hepática , Masculino , Micafungina , Resultado do TratamentoRESUMO
Toxoplasmosis is a rare opportunistic infection in pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients and associated with severe T-cell deficiency. Here, we report the successful management of cerebral toxoplasmosis in a 15-year-old adolescent 4 months post allo-HSCT for non-Hodgkin lymphoma through rapid invasive diagnostics, long-term antiprotozoal chemotherapy, and an hematopoietic stem cell boost for persistently poor graft function. While supportive care and antiprotozoal chemotherapy achieved stabilization, definite improvement only occurred following recovery of CD4(+) T lymphocytes to >100 cells/µL. At 5 years after the diagnosis of toxoplasmosis, the patient is in continuing remission with normalized clinical and imaging findings.
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Antiprotozoários/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma não Hodgkin/cirurgia , Toxoplasma/efeitos dos fármacos , Toxoplasmose Cerebral/tratamento farmacológico , Adolescente , Linfócitos T CD4-Positivos , Humanos , Hospedeiro Imunocomprometido , Infecções Oportunistas/tratamento farmacológico , Transplante Homólogo , Resultado do TratamentoRESUMO
Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised patients, because diagnostic EORTC/MSG criteria are often not met. As biomarkers might elucidate the pathogen, we analysed the performance of an Aspergillus PCR assay in blood for diagnosis of IA in immunocompromised paediatric patients with suspected infections. Ninety-five haemato-oncological paediatric patients were included over a period of 3 years, the underlying diseases consisting of acute leukaemia, solid tumours, non-malignant immunocompromising disorders and haematopoietic stem cell transplantation recipients. We retrospectively analysed 253 consecutive episodes of suspected infections. Thirty-eight patients had possible IA, none of the patients fulfilled EORTC/MSG criteria of probable/proven IA. PCR positivity was observed in 97/967 analyses. Sensitivity, specificity, positive and negative predictive value of the PCR per episode were 34%, 78%, 31% and 81% using possible IA as endpoint. Taken together, an undirected blood screening by Aspergillus-specific PCR is of little diagnostic value in a heterogenous paediatric patient cohort. Harnessing PCR for diagnosis of IA should thus be focused on blood analyses of more homogenous high-risk patients and/or analyses of bronchoalveolar lavage, tissue or cerebrospinal fluid specimens.
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Aspergillus/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aspergilose Pulmonar Invasiva/diagnóstico , Programas de Rastreamento/métodos , Técnicas de Diagnóstico Molecular/métodos , Neoplasias/complicações , Reação em Cadeia da Polimerase/métodos , Adolescente , Aspergillus/genética , Sangue/microbiologia , Criança , Pré-Escolar , DNA Fúngico/sangue , DNA Fúngico/química , DNA Fúngico/genética , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Dados de Sequência Molecular , Sensibilidade e Especificidade , Análise de Sequência de DNA , Adulto JovemRESUMO
Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in hyalohyphomycosis is increasing and the most clinically important species belong to the genera Fusarium, Scedosporium, Acremonium, Scopulariopsis, Purpureocillium and Paecilomyces. Severely immunocompromised patients are particularly vulnerable to infection, and clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Diagnosis usually requires isolation and identification of the infecting pathogen. A poor prognosis is associated with fusariosis and early therapy of localized disease is important to prevent progression to a more aggressive or disseminated infection. Therapy should include voriconazole and surgical debridement where possible or posaconazole as salvage treatment. Voriconazole represents the first-line treatment of infections due to members of the genus Scedosporium. For Acremonium spp., Scopulariopsis spp., Purpureocillium spp. and Paecilomyces spp. the optimal antifungal treatment has not been established. Management usually consists of surgery and antifungal treatment, depending on the clinical presentation.
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Fusarium/isolamento & purificação , Hialoifomicose/diagnóstico , Hialoifomicose/tratamento farmacológico , Scedosporium/isolamento & purificação , Antifúngicos/uso terapêutico , HumanosRESUMO
The aetiological agents of many invasive fungal infections are saprobes and opportunistic pathogens. Some of these fungi are darkly pigmented due to melanin production and traditionally have been named 'dematiaceous'. The melanized fungi cause a wide array of clinical syndromes ranging from superficial to deep-seated infections. Diagnosis relies on histopathological examination of clinical specimens and on examination of cultures. Sequencing is recommended for accurate species identification, especially for unusual or newly described pathogens. In cases of mycetoma and chromoblastomycosis, pathognomonic histological findings are useful and the Fontana-Masson stain, specific for melanin, usually confirms the diagnosis. There are no standardized therapies but voriconazole, posaconazole and itraconazole demonstrate the most consistent in vitro activity against this group of fungi. Oral itraconazole has been considered the drug of choice, given the extensive clinical experience with this drug. However, voriconazole may presumably be superior for central nervous system infections because of its ability to achieve good levels in the cerebrospinal fluid. Posaconazole is a well-tolerated alternative drug, backed by less clinical experience but with excellent salvage treatment results after failure of other antifungals. Amphotericin B has been useful as alternative therapy in some cases. Combination antifungal therapy is recommended for cerebral abscesses when surgery is not possible and for disseminated infections in immunocompromised patients.
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Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Antifúngicos/uso terapêutico , Humanos , Feoifomicose/microbiologiaRESUMO
These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4×200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors.
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Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Antifúngicos/uso terapêutico , HumanosRESUMO
Respiratory viruses are an important yet underestimated cause of infectious morbidity and mortality in immunocompromised children and adolescents. Here, we report the occurrence of fatal lower respiratory tract disease associated with human metapneumovirus (HMPV) infection in a 10-year-old girl with chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (HSCT) for secondary chronic myeloid leukemia. Symptoms occurred 8 months after HSCT while on immunosuppression with 0.2 mg/kg/day of prednisone, and presented as dry cough, bilateral pneumonitis, and progressive respiratory distress. Non-invasive and invasive microbiological investigations revealed HMPV type B as the sole pathogen. Histopathological findings showed interstitial and intra-alveolar pneumonitis with profound alveolar cell damage. The patient was treated with intravenous and oral ribavirin and polyvalent immunoglobulins, but ultimately died from respiratory failure. The case reflects the potentially fatal impact of infections by respiratory viruses in immunocompromised patients and the need for effective approaches to their prevention and treatment.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/virologia , Infecções Respiratórias/virologia , Criança , Evolução Fatal , Feminino , Doença Enxerto-Hospedeiro/complicações , Humanos , Hospedeiro Imunocomprometido , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Infecções por Paramyxoviridae/complicações , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/patologia , Infecções Respiratórias/complicações , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/patologia , Transplante Homólogo/efeitos adversosRESUMO
To develop an evidence-based guideline for the empiric management of pediatric fever and neutropenia (FN). The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group composed of experts in pediatric oncology and infectious disease as well as a patient advocate. The Panel was convened for the purpose of creating this guideline. We followed previously validated procedures for creating evidence-based guidelines. Working groups focused on initial presentation, ongoing management, and empiric antifungal therapy. Each working group developed key clinical questions, conducted systematic reviews of the published literature, and compiled evidence summaries. The Grades of Recommendation Assessment, Development, and Evaluation approach was used to generate summaries, and evidence was classified as high, moderate, low, or very low based on methodologic considerations. Recommendations were made related to initial presentation (risk stratification, initial evaluation, and treatment), ongoing management (modification and cessation of empiric antibiotics), and empiric antifungal treatment (risk stratification, evaluation, and treatment) of pediatric FN. For each recommendation, the strength of the recommendation and level of evidence are presented. This guideline represents an evidence-based approach to FN specific to children with cancer. Although some recommendations are similar to adult-based guidelines, there are key distinctions in multiple areas. Implementation will require adaptation to the local context.
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Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Febre/diagnóstico , Neutropenia/diagnóstico , Neoplasias/complicações , Neoplasias/terapiaRESUMO
The process to develop a guideline in a European setting remains a challenge. The ESCMID Fungal Infection Study Group (EFISG) successfully achieved this endeavour. After two face-to-face meetings, numerous telephone conferences, and email correspondence, an ESCMID task force (basically composed of members of the Society's Fungal Infection Study Group, EFISG) finalized the ESCMID diagnostic and management/therapeutic guideline for Candida diseases. By appreciating various patient populations at risk for Candida diseases, four subgroups were predefined, mainly ICU patients, paediatric, HIV/AIDS and patients with malignancies including haematopoietic stem cell transplantation. Besides treatment recommendations, the ESCMID guidelines provide guidance for diagnostic procedures. For the guidelines, questions were formulated to phrase the intention of a given recommendation, for example, outcome. The recommendation was the clinical intervention, which was graded by a score of A-D for the 'Strength of a recommendation'. The 'level of evidence' received a score of I-III. The author panel was approved by ESCMID, European Organisation for Research and Treatment of Cancer, European Group for Blood and Marrow Transplantation, European Society of Intensive Care Medicine and the European Confederation of Medical Mycology. The guidelines followed the framework of GRADE and Appraisal of Guidelines, Research, and Evaluation. The drafted guideline was presented at ECCMID 2011 and points of discussion occurring during that meeting were incorporated into the manuscripts. These ESCMID guidelines for the diagnosis and management of Candida diseases provide guidance for clinicians in their daily decision-making process.
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Candidíase/diagnóstico , Medicina Baseada em Evidências/normas , Guias de Prática Clínica como Assunto , Candidíase/complicações , Europa (Continente) , Prova Pericial , HumanosRESUMO
As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made.
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Antifúngicos/farmacologia , Candida/isolamento & purificação , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Antifúngicos/uso terapêutico , Biomarcadores/análise , Candida/efeitos dos fármacos , Medicina Baseada em Evidências , Humanos , Testes de Sensibilidade MicrobianaRESUMO
This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be summarized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastrointestinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconazole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of 14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treatment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifungal regimen of choice is liposomal amphotericin B +/- flucytosine. In ocular candidiasis, liposomal amphotericin B +/- flucytosine is recommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives. Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
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Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Adulto , Antifúngicos/efeitos adversos , Candida/isolamento & purificação , Candidíase/diagnóstico , Candidíase/prevenção & controle , Medicina Baseada em Evidências , HumanosRESUMO
Invasive candidiasis (IC) is a relatively common syndrome in neonates and children and is associated with significant morbidity and mortality. These guidelines provide recommendations for the prevention and treatment of IC in neonates and children. Appropriate agents for the prevention of IC in neonates at high risk include fluconazole (A-I), nystatin (B-II) or lactoferrin ± Lactobacillus (B-II). The treatment of IC in neonates is complicated by the high likelihood of disseminated disease, including the possibility of infection within the central nervous system. Amphotericin B deoxycholate (B-II), liposomal amphotericin B (B-II), amphotericin B lipid complex (ABLC) (C-II), fluconazole (B-II), micafungin (B-II) and caspofungin (C-II) can all be potentially used. Recommendations for the prevention of IC in children are largely extrapolated from studies performed in adults with concomitant pharmacokinetic data and models in children. For allogeneic HSCT recipients, fluconazole (A-I), voriconazole (A-I), micafungin (A-I), itraconazole (B-II) and posaconazole (B-II) can all be used. Similar recommendations are made for the prevention of IC in children in other risk groups. With several exceptions, recommendations for the treatment of IC in children are extrapolated from adult studies, with concomitant pharmacokinetic studies. Amphotericin B deoxycholate (C-I), liposomal amphotericin B (A-I), ABLC (B-II), micafungin (A-I), caspofungin (A-I), anidulafungin (B-II), fluconazole (B-I) and voriconazole (B-I) can all be used.
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Antifúngicos/uso terapêutico , Candida/isolamento & purificação , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/prevenção & controle , Adolescente , Candida/efeitos dos fármacos , Candidíase Invasiva/microbiologia , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , PediatriaRESUMO
Fungal diseases still play a major role in morbidity and mortality in patients with haematological malignancies, including those undergoing haematopoietic stem cell transplantation. Although Aspergillus and other filamentous fungal diseases remain a major concern, Candida infections are still a major cause of mortality. This part of the ESCMID guidelines focuses on this patient population and reviews pertaining to prophylaxis, empirical/pre-emptive and targeted therapy of Candida diseases. Anti-Candida prophylaxis is only recommended for patients receiving allogeneic stem cell transplantation. The authors recognize that the recommendations would have most likely been different if the purpose would have been prevention of all fungal infections (e.g. aspergillosis). In targeted treatment of candidaemia, recommendations for treatment are available for all echinocandins, that is anidulafungin (AI), caspofungin (AI) and micafungin (AI), although a warning for resistance is expressed. Liposomal amphotericin B received a BI recommendation due to higher number of reported adverse events in the trials. Amphotericin B deoxycholate should not be used (DII); and fluconazole was rated CI because of a change in epidemiology in some areas in Europe. Removal of central venous catheters is recommended during candidaemia but if catheter retention is a clinical necessity, treatment with an echinocandin is an option (CII(t) ). In chronic disseminated candidiasis therapy, recommendations are liposomal amphotericin B for 8 weeks (AIII), fluconazole for >3 months or other azoles (BIII). Granulocyte transfusions are only an option in desperate cases of patients with Candida disease and neutropenia (CIII).
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Antifúngicos/uso terapêutico , Candidíase/prevenção & controle , Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas , Adulto , Candidíase/complicações , Candidíase/diagnóstico , Candidíase/terapia , Cateterismo Venoso Central/efeitos adversos , Medicina Baseada em Evidências/normas , Humanos , Neutropenia/complicaçõesRESUMO
Mucosal candidiasis is frequent in immunocompromised HIV-infected highly active antiretroviral (HAART) naive patients or those who have failed therapy. Mucosal candidiasis is a marker of progressive immune deficiency. Because of the frequently marked and prompt immune reconstitution induced by HAART, there is no recommendation for primary antifungal prophylaxis of mucosal candidiasis in the HIV setting in Europe, although it has been evidenced as effective in the pre-HAART era. Fluconazole remains the first line of therapy for both oropharyngeal candidiasis and oesophageal candidiasis and should be preferred to itraconazole oral solution (or capsules when not available) due to fewer side effects. For patients who still present with fluconazole-refractory mucosal candidiasis, oral treatment with any other azole should be preferred based on precise Candida species identification and susceptibility testing results in addition to the optimization of HAART when feasible. For vaginal candidiasis, topical therapy is preferred.