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1.
Clin Microbiol Rev ; 37(2): e0000423, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38551323

RESUMO

SUMMARYAlthough Scedosporium species and Lomentospora prolificans are uncommon causes of invasive fungal diseases (IFDs), these infections are associated with high mortality and are costly to treat with a limited armamentarium of antifungal drugs. In light of recent advances, including in the area of new antifungals, the present review provides a timely and updated overview of these IFDs, with a focus on the taxonomy, clinical epidemiology, pathogenesis and host immune response, disease manifestations, diagnosis, antifungal susceptibility, and treatment. An expansion of hosts at risk for these difficult-to-treat infections has emerged over the last two decades given the increased use of, and broader population treated with, immunomodulatory and targeted molecular agents as well as wider adoption of antifungal prophylaxis. Clinical presentations differ not only between genera but also across the different Scedosporium species. L. prolificans is intrinsically resistant to most currently available antifungal agents, and the prognosis of immunocompromised patients with lomentosporiosis is poor. Development of, and improved access to, diagnostic modalities for early detection of these rare mold infections is paramount for timely targeted antifungal therapy and surgery if indicated. New antifungal agents (e.g., olorofim, fosmanogepix) with novel mechanisms of action and less cross-resistance to existing classes, availability of formulations for oral administration, and fewer drug-drug interactions are now in late-stage clinical trials, and soon, could extend options to treat scedosporiosis/lomentosporiosis. Much work remains to increase our understanding of these infections, especially in the pediatric setting. Knowledge gaps for future research are highlighted in the review.


Assuntos
Antifúngicos , Scedosporium , Humanos , Antifúngicos/uso terapêutico , Scedosporium/efeitos dos fármacos , Scedosporium/classificação , Farmacorresistência Fúngica , Micoses/tratamento farmacológico , Micoses/diagnóstico , Micoses/microbiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Ascomicetos/classificação , Ascomicetos/efeitos dos fármacos
2.
J Antimicrob Chemother ; 79(3): 632-640, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305582

RESUMO

BACKGROUND: Neutropenic fever (NF) is a common complication in patients receiving chemotherapy. Judicious antimicrobial use is paramount to minimize morbidity and mortality and to avoid antimicrobial-related harms. OBJECTIVES: To use an Australian national dataset of antimicrobial prescriptions for the treatment of NF to describe antimicrobial use, prescription guideline compliance and appropriateness; and to compare these findings across different healthcare settings and patient demographics. We also aimed to identify trends and practice changes over time. METHODS: Data were extracted from the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) database from August 2013 to May 2022. Antimicrobial prescriptions with a NF indication were analysed for antimicrobial use, guideline compliance and appropriateness according to the Hospital NAPS methodology. Demographic factors, hospital classifications and disease characteristics were compared. RESULTS: A total of 2887 (n = 2441 adults, n = 441 paediatric) NF prescriptions from 254 health facilities were included. Piperacillin-tazobactam was the most prescribed antimicrobial. Overall, 87.4% of prescriptions were appropriate. Piperacillin-tazobactam and cefepime had the highest appropriateness though incorrect piperacillin-tazobactam dosing was observed. Lower appropriateness was identified for meropenem, vancomycin, and gentamicin prescribing particularly in the private hospital and paediatric cohorts. The most common reasons for inappropriate prescribing were spectrum too broad, incorrect dosing or frequency, and incorrect duration. CONCLUSIONS: This study provides insights into antimicrobial prescribing practices for NF in Australia. We have identified three key areas for improvement: piperacillin-tazobactam dosing, paediatric NF prescribing and private hospital NF prescribing. Findings from this study will inform the updated Australian and New Zealand consensus guidelines for the management of neutropenic fever in patients with cancer.


Assuntos
Anti-Infecciosos , Hospitais , Adulto , Humanos , Criança , Austrália , Instalações de Saúde , Combinação Piperacilina e Tazobactam
3.
J Antimicrob Chemother ; 79(1): 46-54, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37944018

RESUMO

BACKGROUND: Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without haematological malignancy. This study investigated excess index hospitalization costs and cumulative costs of these infections. The predictors of excess cost and length of stay (LOS) of index hospitalization were determined. These estimates serve as valuable inputs for cost-effectiveness models of novel antifungal agents. METHODS: A retrospective case-control study was conducted at six Australian hospitals. Cases of proven/probable invasive Scedosporium/L. prolificans infections between 2011 and 2021 (n = 34) were matched with controls (n = 66) by predefined criteria. Cost data were retrieved from activity-based costing systems and analysis was performed from the Australian public hospital perspective. All costs were presented in 2022 Australian dollars (AUD). Median regression analysis was used to adjust excess costs of index hospitalization whereas cumulative costs up to 1.5 years follow-up were estimated using interval-partitioned survival probabilities. RESULTS: Invasive Scedosporium/L. prolificans infections were independently associated with an adjusted median excess cost of AUD36 422 (P = 0.003) and LOS of 16.27 days (P < 0.001) during index hospitalization. Inpatient stay was the major cost driver (42.7%), followed by pharmacy cost, of which antifungal agents comprised 23.8% of the total cost. Allogeneic haematopoietic stem cell transplant increased the excess cost (P = 0.013) and prolonged LOS (P < 0.001) whereas inpatient death within ≤28 days reduced both cost (P = 0.001) and LOS (P < 0.001). The median cumulative cost increased substantially to AUD203 292 over 1.5 years in cases with Scedosporium/L. prolificans infections. CONCLUSIONS: The economic burden associated with invasive Scedosporium/L. prolificans infections is substantial.


Assuntos
Antifúngicos , Scedosporium , Humanos , Antifúngicos/uso terapêutico , Estudos de Casos e Controles , Estudos Retrospectivos , Austrália/epidemiologia
4.
Transpl Infect Dis ; : e14273, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695847

RESUMO

This case involves a 53-year-old female with concurrent acute myeloid leukemia (AML) and multiple myeloma. She underwent cytarabine and daunorubicin (7+3) induction chemotherapy followed by cytarabine (HiDAC) consolidation, with an early AML relapse requiring azacitidine and venetoclax therapy. She achieved complete remission and incomplete count recovery. Following fludarabine, melphalan, and thymoglobulin induction chemotherapy, she underwent an allogeneic stem cell transplant with failure to engraft, requiring autologous stem cell rescue, buffy coat, and granulocyte transfusions, eventually presenting with a diffuse skin rash consistent with Steven-Johnson syndrome and toxic epidermal necrolysis, persistent neutropenic fevers and positive blood cultures.

5.
Transpl Infect Dis ; 26(3): e14301, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38809102

RESUMO

Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS-CoV-2 infection in immunocompromised patients, particularly in the management of persistent SARS-CoV-2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti-CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS-CoV-2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Humanos , Antivirais/uso terapêutico , SARS-CoV-2/imunologia , COVID-19/imunologia , Quimioterapia Combinada , Anticorpos Neutralizantes/uso terapêutico
6.
Clin Infect Dis ; 77(7): 976-986, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37235212

RESUMO

BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.


Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Infecções por HIV , Meningite , Humanos , HIV , Estudos Retrospectivos , Nova Zelândia/epidemiologia , Austrália/epidemiologia , Criptococose/diagnóstico , Criptococose/epidemiologia , Hospitais , Antígenos de Fungos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia
7.
Med Mycol ; 61(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37019819

RESUMO

Time-to-positivity (TTP) may assist in predicting the outcome of candidaemia. We analysed a candidaemia dataset collected prospectively in Australia over 1 year (2014-2015). TTP was defined as the period from blood culture sampling to the blood culture flagging positive. Of 415 candidaemia episodes, overall, 30-day mortality was 29% (120/415); mortality with Candida albicans was 35% (59/169), C. glabrata complex, 37% (43/115), C. tropicalis, 43% (10/23), Pichia kudriavzevii 25% (3/12), and C. parapsilosis complex 7% (5/71). Each day of increased TTP multiplied the odds ratio (OR) of survival at 30 days by a factor of 1.32 [95% confidence interval (CI) 1.06-1.69]. Shorter TTP was associated with increased mortality, with 1-day TTP associated with 30-day mortality 37% (41/112) (95%CI: 28%-46%) and 5-day TTP 11% (2/18) (95%CI: 2%-36%).


Time-to-positivity is a measure that is available to clinicians when patients are identified as having candida in their bloodstream. Our data support the association of a shorter time to positivity with higher mortality.


Assuntos
Candida , Candidemia , Animais , Prognóstico , Candidemia/tratamento farmacológico , Candidemia/veterinária , Candida glabrata , Candida albicans , Candida tropicalis , Candida parapsilosis , Antifúngicos/uso terapêutico
8.
Pediatr Blood Cancer ; 70(11): e30633, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37592047

RESUMO

BACKGROUND: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking. METHODS: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs. RESULTS: The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193-$18,461) compared to low-risk ($10,574, 95% CI: $9818-$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis. CONCLUSION: The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.


Assuntos
Antineoplásicos , Neutropenia Febril , Neoplasias , Idoso , Criança , Humanos , Austrália , Programas Nacionais de Saúde , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neutropenia Febril/tratamento farmacológico
9.
Transpl Infect Dis ; 25 Suppl 1: e14171, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37864299

RESUMO

The preferred strategy for preventing CMV in at-risk populations in alloHCT has undergone a significant practice shift in recent years where the pendulum has swung from a pre-emptive approach to now offering letermovir prophylaxis to all CMV seropositive recipients. Letermovir prophylaxis has resulted in significant reductions in post-transplant clinically significant CMV infection (csCMVi) as well as other important outcomes such as CMV disease, resistant, and refractory CMV infections and nonrelapse mortality. However, prophylactic strategies are not without some limitations, namely delayed onset CMV infections, delayed CMV-specific T cell immune reconstitution, increased drug costs and limited data within pediatric populations. Thus, this review aims to provide an overview of prophylaxis and pre-emptive CMV preventative strategies, and how they are applicable in the current era of letermovir prophylaxis.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Citomegalovirus , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos
10.
Transpl Infect Dis ; 25 Suppl 1: e14197, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37988269

RESUMO

In recent years, advancements in the treatment landscape for hematological malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia, have significantly improved disease prognosis and overall survival. However, the treatment landscape is changing and the emergence of targeted oral therapies and immune-based treatments has brought forth new challenges in evaluating and preventing invasive fungal diseases (IFDs). IFD disproportionately affects immunocompromised hosts, particularly those undergoing therapy for acute leukemia and allogeneic hematopoietic stem cell transplant. This review aims to provide a comprehensive overview of the pretransplant workup, identification, and prevention of IFD in patients with hematological malignancy. The pretransplant period offers a critical window to assess each patient's risk factors and implement appropriate prophylactic measures. Risk assessment includes evaluation of disease, host, prior treatments, and environmental factors, allowing a dynamic evaluation that considers disease progression and treatment course. Diagnostic screening, involving various biomarkers and radiological modalities, plays a crucial role in early detection of IFD. Antifungal prophylaxis choice is based on available evidence as well as individual risk assessment, potential for drug-drug interactions, toxicity, and patient adherence. Therapeutic drug monitoring ensures effective antifungal stewardship and optimal treatment. Patient education and counselling are vital in minimizing environmental exposures to fungal pathogens and promoting medication adherence. A well-structured and individualized approach, encompassing risk assessment, prophylaxis, surveillance, and patient education, is essential for effectively preventing IFD in hematological malignancies, ultimately leading to improved patient outcomes and overall survival.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Micoses , Humanos , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hematológicas/complicações
11.
J Biomed Inform ; 139: 104293, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36682389

RESUMO

Invasive fungal infections (IFIs) are particularly dangerous to high-risk patients with haematological malignancies and are responsible for excessive mortality and delays in cancer therapy. Surveillance of IFI in clinical settings offers an opportunity to identify potential risk factors and evaluate new therapeutic strategies. However, manual surveillance is both time- and resource-intensive. As part of a broader project aimed to develop a system for automated IFI surveillance by leveraging electronic medical records, we present our approach to detecting evidence of IFI in the key diagnostic domain of histopathology. Using natural language processing (NLP), we analysed cytology and histopathology reports to identify IFI-positive reports. We compared a conventional bag-of-words classification model to a method that relies on concept-level annotations. Although the investment to prepare data supporting concept annotations is substantial, extracting targeted information specific to IFI as a pre-processing step increased the performance of the classifier from the PR AUC of 0.84 to 0.92 and enabled model interpretability. We have made publicly available the annotated dataset of 283 reports, the Cytology and Histopathology IFI Reports corpus (CHIFIR), to allow the clinical NLP research community to further build on our results.


Assuntos
Infecções Fúngicas Invasivas , Humanos , Infecções Fúngicas Invasivas/epidemiologia , Registros Eletrônicos de Saúde , Processamento de Linguagem Natural , Fatores de Risco
12.
Support Care Cancer ; 31(8): 479, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37477843

RESUMO

PURPOSE: To understand the drivers and barriers for COVID-19 vaccination in people with cancer in Australia. METHODS: A cross-sectional, online survey, distributed nationally following the establishment of community vaccination programs, wider availability of COVID-19 vaccines and emergence of new variants. Consisting of 21 questions, the survey was designed to determine the behavioural and social drivers of vaccination, participant demographics, underlying disease and treatment, and vaccination status. It was open from the 10th of August 2021 to the 7th of September 2021, recruiting people who had a previous history of cancer (diagnosed or treated in the past 5 years). RESULTS: A total of 1506 responses were included in the final analysis. Overall, 87.8% reported a positive attitude toward vaccination and 83.1% had received at least one dose of a COVID-19 vaccine. Perceived risk of COVID-19 infection (for self and others) and engagement with a trusted health professional were key drivers for vaccination, while concerns about vaccine development, safety and side effects were barriers. Concerns about vaccination mostly stemmed from a place of misinformation, rather than a broader disregard of vaccines. Just over a third (497, 34.3%) of the respondents were concerned that the vaccine would impact their cancer treatment. CONCLUSION: Overall, participants had positive attitudes toward COVID-19 vaccination and thought it was safe. Findings supported the role of health professionals and cancer organisations as trusted information providers and calls for more, credible information to help people with cancer make informed decisions about the COVID-19 vaccine.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Neoplasias , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Austrália , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos Transversais , Vacinação , Pesquisas sobre Atenção à Saúde , Educação em Saúde
13.
Intern Med J ; 53(4): 619-624, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36929677

RESUMO

Coronavirus disease 2019 (COVID-19) in immunocompromised patients can lead to severe and prolonged illness. Data are limited with regard to management of COVID-19 in this setting, particularly in persistent or recrudescent infection. The authors conducted an online survey among infectious diseases doctors to determine current approaches to treatment across Australasia. There was marked variability in responses relating to the diagnostic modalities and use of antiviral agents in patients with immunocompromise, highlighting the need for high-quality studies to guide treatment decisions in this group.


Assuntos
COVID-19 , Humanos , Antivirais/uso terapêutico , Hospedeiro Imunocomprometido , Inquéritos e Questionários , Australásia/epidemiologia
14.
Intern Med J ; 53(8): 1469-1477, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37093163

RESUMO

Infection remains a significant contributor to morbidity and mortality in patients with myeloma. This guideline was developed by a multidisciplinary group of clinicians who specialise in the management of patients with myeloma and infection from the medical and scientific advisory group from Myeloma Australia and the National Centre for Infections in Cancer. In addition to summarising the current epidemiology and risk factors for infection in patients with myeloma, this guideline provides recommendations that address three key areas in the prevention of infection: screening for latent infection, use of antimicrobial prophylaxis and immunoglobulin replacement and vaccination against leading respiratory infections (severe acute respiratory syndrome coronavirus 2, influenza and Streptococcus pneumoniae) and other preventable infections. This guideline provides a practical approach to the prevention of infection in patients with myeloma and harmonises the clinical approach to screening for infection, use of prophylaxis and vaccination to prevent infectious complications.


Assuntos
Anti-Infecciosos , COVID-19 , Mieloma Múltiplo , Humanos , Consenso , COVID-19/complicações , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Vacinação
15.
J Oncol Pharm Pract ; : 10781552231180875, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37322897

RESUMO

BACKGROUND: Investigation of infection risk with subcutaneous versus intravenous trastuzumab and rituximab administration in an individual patient data (IPD) and published data meta-analysis of randomised controlled trials (RCTs). METHODS: Databases were searched to September 2021. Primary outcomes were serious and high-grade infection. Relative-risk (RR) and 95% confidence intervals (95%CI) were calculated using random-effects models. RESULTS: IPD meta-analysis (6 RCTs, 2971 participants, 2320 infections) demonstrated higher infection incidence with subcutaneous versus intravenous administration, without reaching statistical significance (serious: 12.2% versus 9.3%, RR 1.28, 95%CI 0.93to1.77, P = 0.13; high-grade: 12.2% versus 9.9%, RR 1.32, 95%CI 0.98to1.77, P = 0.07). With exclusion of an outlying study in post-hoc analysis, increased risks were statistically significant (serious: 13.1% versus 8.4%, RR 1.53, 95%CI 1.14to2.06, P = 0.01; high-grade: 13.2% versus 9.3%, RR 1.56, 95%CI 1.16to2.11, P < 0.01). Published data meta-analysis (8 RCTs, 3745 participants, 648 infections) demonstrated higher incidence of serious (HR 1.31, 95%CI 1.02to1.68, P = 0.04) and high-grade (HR 1.52, 95%CI 1.17to1.98, P < 0.01) infection with subcutaneous versus intravenous administration. CONCLUSIONS: Results suggest increased infection risk with subcutaneous versus intravenous administration, although IPD findings are sensitive to exclusion of one trial with inconsistent results and identified risk-of-bias. Ongoing trials may confirm findings. Clinical surveillance should be considered when switching to subcutaneous administration. PROSPERO registration CRD42020221866/CRD42020125376.

16.
Mycopathologia ; 188(5): 731-743, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37040020

RESUMO

Invasive pulmonary aspergillosis remains a major cause of morbidity and mortality for immunocompromised children, particularly for patients with acute leukaemia and those undergoing haematopoietic stem cell transplantation. Timely diagnosis, using a combination of computed tomography (CT) imaging and microbiological testing, is key to improve prognosis, yet there are inherent challenges in this process. For CT imaging, changes in children are generally less specific than those reported in adults and recent data are limited. Respiratory sampling by either bronchoalveolar lavage or lung biopsy is recommended but is not always feasible in children, and serum biomarkers, including galactomannan, have important limitations. In this review we summarise the current paediatric data on available diagnostic tests for IPA and highlight key emerging diagnostic modalities with potential for future use.


Assuntos
Aspergilose Pulmonar Invasiva , Adulto , Humanos , Criança , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/etiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Biomarcadores , Prognóstico , Tomografia Computadorizada por Raios X/efeitos adversos , Mananas , Sensibilidade e Especificidade
17.
Curr Opin Infect Dis ; 35(6): 536-544, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36255049

RESUMO

PURPOSE OF REVIEW: Reactivation of viral infections occurs frequently in immunosuppressed populations, particularly in solid organ (SOT) or allogeneic haematopoietic cell (HCT) transplant patients. Concurrent and sequential multivirus infections are common, yet risk factors and outcomes remain unclear. This review aims to identify the patients vulnerable to multivirus infections and characterize the impact of increased viral burden to formulate prevention and treatment strategies. RECENT FINDINGS: Incidences of up to 89% in SOT and 36% in HCT have been reported for two viruses, and 32% in SOT and 28% in HCT for at least three viruses. Risk factors appear related to an increased burden of immunosuppression, with most viral coinfections occurring within 12 months of transplantation. Direct viral complications such as cytomegalovirus disease are more frequent in coinfected patients, with documented prolonged duration of viraemia, higher viral load and increased end-organ disease. Graft dysfunction, acute rejection and graft-vs.-host disease (GVHD) have also been associated. Increased mortality is reported in the HCT population. SUMMARY: Multivirus infections occur in a significant proportion of transplant patients and is linked to immunosuppressive burden. There is increasing evidence that this leads to worse graft and patient outcomes. Further prospective studies are required to further comprehensively characterise viral epidemiology, mechanisms and treatment strategies to ameliorate this risk.


Assuntos
Infecções por Adenoviridae , Vírus BK , Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Citomegalovirus , Herpesvirus Humano 4 , Adenoviridae , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Adenoviridae/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores de Risco
18.
J Antimicrob Chemother ; 77(6): 1508-1524, 2022 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-35301533

RESUMO

Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.


Assuntos
Hematologia , Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Antifúngicos/uso terapêutico , Criança , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Micologia
19.
Pediatr Blood Cancer ; 69(7): e29469, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34854550

RESUMO

INTRODUCTION: Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. METHODS: A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). FINDINGS: The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. CONCLUSION: Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.


Assuntos
Neutropenia Febril , Neoplasias , Antibacterianos/uso terapêutico , Austrália , Criança , Análise Custo-Benefício , Neutropenia Febril/tratamento farmacológico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Qualidade de Vida
20.
Intern Med J ; 52(10): 1759-1767, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34448333

RESUMO

BACKGROUND: High-intensity chemotherapy and advances in novel immunotherapies have seen the emergence of cytomegalovirus (CMV) infections in cancer patients other than allogeneic haemopoietic cell transplantation (HCT). Aim To evaluate the epidemiology, clinical characteristics and outcomes of CMV infection in this population. METHODS: A retrospective review of cancer patients other than allogeneic HCT who had CMV DNAemia and/or disease from July 2013 till May 2020 at a quaternary cancer centre was performed. RESULTS: Of 11 485 cancer patients who underwent treatment during this period, 953 patients had CMV DNA testing performed and 238 of them had CMV DNAemia. After excluding patients with allogeneic HCT, 62 patients with CMV DNAemia were identified, of whom 10 had concurrent CMV disease. The most frequent underlying malignancies were B-cell lymphoproliferative disease (LPD) (31%; 19/62), T-cell LPD (21%; 13/62), chronic lymphocytic leukaemia (11%; 7/62) and multiple myeloma (10%; 6/62). Most patients had lymphopenia (77%; 48/62), multiple cancer therapies (63%; 39/62 received ≥2 previous therapies), co-infection (56%; 35/62 had ≥1 co-infection) and corticosteroid therapy (48%; 30/62) within 1 month before CMV diagnosis. CMV DNAemia and disease were observed in patients receiving novel immunotherapies, including bispecific antibody therapy, chimeric-antigen receptor T-cell therapy and immune checkpoint inhibitors. CONCLUSION: Patients with haematological malignancy, particularly B-cell LPD, T-cell LPD, chronic lymphocytic leukaemia and multiple myeloma, were frequently identified to have CMV DNAemia and disease. Lymphopenia, multiple cancer therapies, co-infection and recent receipt of systemic corticosteroids were also commonly observed. Future studies are necessary to determine optimal identification and management of CMV in these patients.


Assuntos
Coinfecção , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B , Linfopenia , Mieloma Múltiplo , Humanos , Citomegalovirus/genética , Inibidores de Checkpoint Imunológico , DNA Viral , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfopenia/etiologia , Receptores de Antígenos , Corticosteroides
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