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1.
Clin Infect Dis ; 78(3): 775-784, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-37815489

RESUMO

BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). CONCLUSIONS: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing. CLINICAL TRIALS REGISTRATION: NCT04047719.


Assuntos
Pneumonia , Adulto , Humanos , Estudos Prospectivos , Pneumonia/etiologia , Análise de Sequência de DNA , Hospedeiro Imunocomprometido
2.
J Infect Dis ; 228(11): 1549-1558, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37983000

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) on nasopharyngeal swab (NPS), remains the most reliable and practical test to diagnose coronavirus disease 2019 (COVID-19). Current literature is sparse regarding the rates of discordance between NPS and bronchoalveolar lavage (BAL) in patients with cancer. METHODS: We conducted a retrospective cohort study of adult patients with cancer who had BAL samples tested for SARS-CoV-2 at a comprehensive cancer center. Patients without NPS PCR for SARS-CoV-2 before BAL were excluded. RESULTS: In a cohort of 345 patients, 12% and 17% tested positive for SARS-CoV-2 on NPS and BAL, respectively. There was a 6.3% NPS-/BAL+ discordance rate and a 9.5% NPS+/BAL- discordance rate. Patients with lymphoma (adjusted odds ratio [aOR] = 4.06; P = .007) and Hispanic patients (aOR = 3.76; P = .009) were more likely to have NPS-/BAL+ discordance on multivariate analysis. Among patients with NPS- /BAL- for SARS-CoV-2, an alternate infectious (23%) and a noninfectious etiology (16%) were identified in BAL. CONCLUSIONS: Our discordance rates between NPS and BAL were sufficient to recommend BAL in certain patients with cancer with a high clinical suspicion of COVID-19. BAL has value in identifying alternative etiologies of illness in patients with suspected or confirmed COVID-19.


Assuntos
COVID-19 , Neoplasias , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudos Retrospectivos , Lavagem Broncoalveolar , Teste para COVID-19 , Nasofaringe , Neoplasias/complicações , Neoplasias/diagnóstico
3.
Oncologist ; 28(11): e1065-e1074, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37156009

RESUMO

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially. METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models. RESULTS: We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0). CONCLUSION: Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Pneumonia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Incidência , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/epidemiologia , Fatores de Risco , Doenças Pulmonares Intersticiais/complicações , Estudos Retrospectivos
4.
Oncology (Williston Park) ; 37(2): 69-77, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36862845

RESUMO

COVID-19 continues to disproportionately affect patients with cancer because of their underlying immunocompromised state. Strategies to mitigate the impact of COVID-19 on patients with cancer include vaccination, which has demonstrated some level of protection, at least against serious complications such as respiratory failure and death, with limited safety concerns. In this narrative review, we discuss the current COVID-19 vaccines that are available in the United States, the published data regarding vaccine efficacy and safety in patients with cancer, current vaccination guidelines, and future directions.


Assuntos
COVID-19 , Neoplasias , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Neoplasias/complicações , Neoplasias/terapia , Pacientes , Vacinação
5.
Cancer ; 128(14): 2736-2745, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35452134

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality. METHODS: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were modeled as a time-dependent variable and incorporated a standard risk set modifying variables into the models. RESULTS: Thirty patients developed pneumonitis (12%). Of these, 17 had partial or complete resolution, whereas 13 patients died from pneumonitis. Increasing age (hazard ratio [HR], 1.04 per year; 95% confidence interval [CI], 1.00-1.08), and baseline shortness of breath increased pneumonitis risk (HR, 2.51; 95% CI, 1.13-5.55). Female sex (HR, 0.33; 95% CI, 0.15-0.70) and increasing platelet count (HR, 0.52 per log-unit increase; 95% CI, 0.30-0.92) decreased pneumonitis risk. In adjusted models, ICI-related pneumonitis significantly increased mortality (HR, 2.84; 95% CI, 1.84-4.37). CONCLUSIONS: ICI-related pneumonitis occurs at a high rate in AML patients and increases mortality. LAY SUMMARY: Immune checkpoint inhibitors (ICIs) remove inhibitory signals that reduce T-cell function and allow T-cells to better attack cancer cells. In acute myeloid leukemia (AML), the effectiveness of ICIs is limited in part by inflammation of the lung, called pneumonitis. This study reviewed 258 patients with AML who received ICIs and identified 30 patients who developed pneumonitis, nearly half of whom died. Older age and baseline shortness of breath increased pneumonitis risk, whereas female sex and higher baseline platelet counts decreased pneumonitis risk. Pneumonitis increased mortality by nearly 3-fold. This work highlights the significant harm imposed by pneumonitis after ICI therapies.


Assuntos
Antineoplásicos Imunológicos , Leucemia Mieloide Aguda , Neoplasias Pulmonares , Pneumonia , Antineoplásicos Imunológicos/uso terapêutico , Dispneia/induzido quimicamente , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Estudos Retrospectivos
6.
Clin Infect Dis ; 73(8): 1346-1354, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33830182

RESUMO

BACKGROUND: Cytomegalovirus (CMV) reactivation is one of the most common infectious complications after allogeneic hematopoietic cell transplant (HCT) and may result in significant morbidity and mortality. Primary prophylaxis with letermovir demonstrated a reduction in clinically significant CMV infections (CS-CMVi) in clinical trials of CMV-seropositive HCT recipients. This study aims at exploring the effect of primary letermovir prophylaxis in this population on the incidence and outcomes of refractory or resistant CMV infections. METHODS: This is a single-center, retrospective cohort study of 537 consecutive CMV-seropositive allogeneic HCT recipients cared for between March 2016 and October 2018. Baseline demographics, HCT characteristics, CMV infections, treatment, and mortality data were collected from the electronic medical record. CMV outcomes were defined according to the recently standardized definitions for clinical trials. Characteristics and outcomes were assessed according to receipt of primary letermovir prophylaxis. RESULTS: Of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days after HCT; 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with reductions in CS-CMVi (hazard ratio [HR] 0.26; 95% confidence interval [CI], 0.16-0.41), CMV end-organ disease (HR 0.23; 95% CI, 0.10-0.52), refractory or resistant CMV infection (HR 0.15; 95% CI, 0.04-0.52), and nonrelapse mortality at week 48 (HR 0.55; 95% CI, 0.32-0.93). There was neither resistant CMV nor CMV-related mortality in the primary letermovir prophylaxis group. CONCLUSIONS: Primary letermovir prophylaxis effectively prevents refractory or resistant CMV infections and decreases nonrelapse mortality at week 48, as well as CS-CMVi and CMV disease after allogeneic HCT.


Assuntos
Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Acetatos , Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Quinazolinas , Estudos Retrospectivos , Transplantados
7.
Transpl Infect Dis ; 23(4): e13606, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33755273

RESUMO

Severe acute respiratory syndrome coronavirus 2 can lead to life-threatening coronavirus disease 2019 (COVID-19) infections in patients with hematologic malignancies, particularly among hematopoietic cell transplant (HCT) recipients. We describe two patients with COVID-19 during the pre-engraftment period after HCT and review previous reports of COVID-19 in HCT recipients. Because of significant mortality from COVID-19, primarily after allogeneic HCT, early, preemptive, and optimal directed therapy may improve outcomes and reduce the mortality rate but still needs to be established in clinical trials.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , SARS-CoV-2 , Transplantados
8.
Dermatol Online J ; 27(6)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34387060

RESUMO

Nontuberculous mycobacteria are pathogens with diverse manifestations in immunocompromised hosts. The lesser-known Mycobacterium haemophilum usually causes cutaneous infection. Diagnosis is challenging but is aided by molecular testing and multidisciplinary communication. We present an immunocompromised patient with disseminated cutaneous mycobacterial infection with digital tenosynovitis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções por Mycobacterium não Tuberculosas/patologia , Complicações Pós-Operatórias/patologia , Feminino , Humanos , Pessoa de Meia-Idade
9.
Curr Opin Infect Dis ; 32(6): 565-574, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31567572

RESUMO

PURPOSE OF REVIEW: Refractory or resistant cytomegalovirus (CMV) infections are challenging complications after hematopoietic cell transplantation (HCT). Most refractory or resistant CMV infections are associated with poor outcomes and increased mortality. Prompt recognition of resistant or refractory CMV infections, understanding the resistance pathways, and the treatment options in HCT recipients are imperative. RECENT FINDINGS: New definitions for refractory and resistant CMV infections in HCT recipients have been introduced for future clinical trials. Interestingly, refractory CMV infections are more commonly encountered in HCT recipients when compared with resistant CMV infections. CMV terminase complex mutations in UL56, UL89, and UL51 could be associated with letermovir resistance; specific mutations in UL56 are the most commonly encountered in clinical practice. Finally, brincidofovir, maribavir, letermovir, and CMV-specific cytotoxic T-cell therapy expanded our treatment options for refractory or resistant CMV infections. SUMMARY: Many advances have been made to optimize future clinical trials for management of refractory or resistant CMV infections, and to better understand new resistance mechanisms to novel drugs. New drugs or strategies with limited toxicities are needed to improve outcomes of difficult to treat CMV infections in HCT recipients.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Citomegalovirus/efeitos dos fármacos , Farmacorresistência Viral , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antivirais/farmacologia , Citomegalovirus/genética , Infecções por Citomegalovirus/epidemiologia , DNA Viral , Gerenciamento Clínico , Humanos , Incidência , Mutação , Transplantados
10.
Haematologica ; 104(7): 1322-1331, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31221784

RESUMO

In the USA and other western nations, respiratory syncytial virus is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematologic malignancy or who have undergone a stem cell transplant. Multiple studies have been performed to evaluate the complications associated with respiratory syncytial virus infections. Other studies have evaluated therapeutic agents and strategies in which these agents can be used. There have also been numerous reports of outbreaks in bone marrow transplant units and oncology wards, where infection control measures have been invaluable in controlling the spread of disease. However, despite these novel approaches, respiratory syncytial virus continues to be potentially fatal in immunocompromised populations. In this review, we discuss the incidence of respiratory syncytial viral infections, risk factors associated with progression from upper respiratory tract infection to lower respiratory tract infection, other complications and outcomes (including mortality), management strategies, and prevention strategies in patients with a hematologic malignancy and in hematopoietic cell transplant recipients.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/etiologia , Neoplasias Hematológicas/patologia , Humanos , Hospedeiro Imunocomprometido , Prevalência , Infecções por Vírus Respiratório Sincicial/virologia , Infecções Respiratórias/patologia
11.
Infect Dis Clin North Am ; 38(1): 213-228, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280765

RESUMO

Immunocompromised hosts, which encompass a diverse population of persons with malignancies, human immunodeficiency virus disease, solid organ, and hematologic transplants, autoimmune diseases, and primary immunodeficiencies, bear a significant burden of the morbidity and mortality due to coronavirus disease-2019 (COVID-19). Immunocompromised patients who develop COVID-19 have a more severe illness, higher hospitalization rates, and higher mortality rates than immunocompetent patients. There are no well-defined treatment strategies that are specific to immunocompromised patients and vaccines, monoclonal antibodies, and convalescent plasma are variably effective. This review focuses on the specific impact of COVID-19 in immunocompromised patients and the gaps in knowledge that require further study.


Assuntos
COVID-19 , Neoplasias , Humanos , SARS-CoV-2 , Soroterapia para COVID-19 , Hospedeiro Imunocomprometido , Neoplasias/complicações
12.
Front Immunol ; 15: 1366271, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779675

RESUMO

A patient in his 40s with splenic angiosarcoma metastatic to the liver underwent splenectomy, chemotherapy, and partial hepatectomy before being treated on a clinical trial with CTLA4 and PD1 inhibitors. He had received pneumococcal and meningococcal vaccines post-splenectomy. On week 10, he developed grade 3 immune-related colitis, successfully treated with the anti-tumor necrosis factor-alpha inhibitor infliximab and steroids. After 4 cycles of treatment, scans showed partial response. He resumed anti-PD1 therapy, and 6 hours after the second dose of anti-PD1 he presented to the emergency room with hematemesis, hematochezia, hypotension, fever, and oxygen desaturation. Laboratory tests demonstrated acute renal failure and septicemia (Streptococcus pneumoniae). He died 12 hours after the anti-PD1 infusion from overwhelming post-splenectomy infection (OPSI). Autopsy demonstrated non-viable liver tumors among other findings. In conclusion, patients undergoing immunotherapy and with prior history of asplenia should be monitored closely for OPSI as they may be at increased risk.


Assuntos
Hemangiossarcoma , Neoplasias Hepáticas , Esplenectomia , Neoplasias Esplênicas , Humanos , Esplenectomia/efeitos adversos , Masculino , Hemangiossarcoma/terapia , Neoplasias Esplênicas/secundário , Neoplasias Esplênicas/terapia , Evolução Fatal , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Adulto , Infecções Pneumocócicas/etiologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores
13.
Clin Microbiol Infect ; 30(6): 803-809, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38460821

RESUMO

OBJECTIVES: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. METHODS: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D-/R-, R+/LTV-, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D-/R- group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. RESULTS: The analysis included 1071 consecutive allo-HCT recipients: 131 D-/R-, 557 R+/LTV-, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D-/R- group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV- and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV-, R+/LTV+, and D-/R- groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12-2.99, p 0.017) for R+/LTV- compared with D-/R- and 1.05 (95% CI 0.62-1.77, p 0.85) for R+/LTV + compared with D-/R-. DISCUSSION: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.


Assuntos
Antivirais , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Antivirais/uso terapêutico , Transplante Homólogo/efeitos adversos , Idoso , Adulto Jovem , Citomegalovirus , Adolescente , Doença Enxerto-Hospedeiro/prevenção & controle , Acetatos/uso terapêutico , Quinazolinas/uso terapêutico , Prevenção Primária/métodos
14.
Clin Chest Med ; 44(2): 395-406, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37085228

RESUMO

Immunocompromised hosts, which encompass a diverse population of persons with malignancies, human immunodeficiency virus disease, solid organ, and hematologic transplants, autoimmune diseases, and primary immunodeficiencies, bear a significant burden of the morbidity and mortality due to coronavirus disease-2019 (COVID-19). Immunocompromised patients who develop COVID-19 have a more severe illness, higher hospitalization rates, and higher mortality rates than immunocompetent patients. There are no well-defined treatment strategies that are specific to immunocompromised patients and vaccines, monoclonal antibodies, and convalescent plasma are variably effective. This review focuses on the specific impact of COVID-19 in immunocompromised patients and the gaps in knowledge that require further study.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Soroterapia para COVID-19 , Hospedeiro Imunocomprometido
15.
Clin Microbiol Infect ; 29(1): 44-50, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35843567

RESUMO

BACKGROUND: The burden that cytomegalovirus (CMV) portends for haematopoietic and solid-organ transplant recipients cannot be understated. Valganciclovir and ganciclovir have successfully been used for prevention and treatment of CMV infections, although with serious side effects such as leucopenia and some development of resistance. Until recently, available therapies for ganciclovir-resistant CMV have significant toxicities. Although advances have been made in the field, the unmet medical needs for effective and well-tolerated therapies are significant. OBJECTIVES: This review aims to summarise the current and emerging CMV antiviral drugs and discusses future perspectives in the field. SOURCES: We searched for relevant articles with pertinent keywords: "Cytomegalovirus OR CMV", "Transplant" and "Antiviral". Articles published after 2019 were given preference. Articles were reviewed by the authors for relevance and impact to the subject of interest. CONTENT: We outline in this review current advances in prophylaxis of CMV infection with letermovir, breakthrough CMV infections while on or after prophylaxis, the development of resistant and refractory CMV infections, and the newly approved anti-CMV agent, maribavir, in haematopoietic and solid-organ transplant recipients. IMPLICATIONS: Prevention of CMV infections after transplant has improved greatly over the past few years. Despite major advancements, breakthrough CMV infections and development of refractory and resistant CMV infections remain major complications post transplantation. We highlight emerging therapeutics that tolerably and effectively prevent and treat CMV infections, especially refractory and resistant cases.


Assuntos
Infecções por Citomegalovirus , Transplantados , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Antivirais/farmacologia , Ganciclovir/farmacologia , Ganciclovir/uso terapêutico , Citomegalovirus
16.
Am J Infect Control ; 51(12): 1302-1308, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37804272

RESUMO

BACKGROUND: Robust infection prevention and control (IPC) measures were deployed across health care institutions at the start of the COVID-19 pandemic, resulting in increased use of personal protective equipment, enhanced contact precautions, and an emphasis on hand hygiene. Here, we evaluate the effect of enhanced IPC practices on the occurrence of various hospital-associated infections (HAIs) in a comprehensive cancer center. METHODS: From September 2016 through March 2022, we calculated the incidence rates (IRs) of HAIs for C. difficile infection, multidrug-resistant organisms, respiratory viral infections (RVIs), and device-related infections. We analyzed the incidence rate ratios for all HAIs during the periods before the pandemic, during the pandemic, at the time of the surges, and in COVID-19-designated wards. RESULTS: When comparing the prepandemic to the pandemic period, the IR across all MRDOs was similar. We observed a decrease in the IR of central line-associated bloodstream infections and a stable IR of catheter-associated urinary tract infections. A significant decrease was observed in the IR of C. difficile infection. The total IR of nosocomial RVIs decreased, as did for each respiratory virus. A similar IR of nosocomial RVIs between COVID-19 community surge versus nonsurge periods was observed except for SARS-CoV-2, RSV, and influenza. multidrug resistant organisms were 5 times more likely to occur on the COVID-19 wards compared with the non-COVID-19 wards. CONCLUSIONS: Implementing strict IPC measures during the COVID-19 pandemic in a cancer hospital led to a significant decrease in many HAIs and a reduction in nosocomial RVIs.


Assuntos
COVID-19 , Clostridioides difficile , Infecção Hospitalar , Neoplasias , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2 , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Hospitais , Neoplasias/complicações , Neoplasias/epidemiologia
17.
Cancer Med ; 12(24): 22006-22022, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38063366

RESUMO

BACKGROUND: With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID-19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID-19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll-out and to identify risk factors associated with hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. METHODS: We performed a retrospective cohort study of cancer patients with COVID-19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models. RESULTS: Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID-19, severe COVID-19, and 30-day COVID-19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID-19 but with no impact on hospitalization or mortality due to COVID-19. CONCLUSION: Our study highlights a significant benefit of COVID-19 vaccination for cancer patients-specifically its protection against severe COVID-19.


Assuntos
COVID-19 , Neoplasias , Humanos , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos Retrospectivos , Neoplasias/epidemiologia , Neoplasias/terapia , Vacinação
18.
Clin Lymphoma Myeloma Leuk ; 23(8): 610-615, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37150651

RESUMO

BACKGROUND: Bruton tyrosine kinase (BTK) inhibitors are used to treat B-cell hematologic malignancies. Ibrutinib has been associated with hepatitis B virus (HBV) reactivation. We sought to identify patients with hematologic malignancies who developed HBV reactivation after receiving first-generation (ibrutinib) or second-generation (acalabrutinib and zanubrutinib) BTK inhibitors. METHODS: We retrospectively studied all consecutive patients with hematologic malignancies with past HBV infection (HBV surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) or chronic HBV infection (HBsAg positive and anti-HBc positive) treated with BTK inhibitors at our institution from November 1, 2015, through November 1, 2022. RESULTS: Of 82 patients initially identified, 53 were excluded (11 because of false-positive anti-HBc results, and 42 because they were receiving anti-HBV prophylaxis owing to recent receipt of anti-CD20 monoclonal antibodies). The 29 remaining patients were further analyzed and 3 (10%; 2/28 with past and 1/1 with chronic HBV infection) were found to have HBV reactivation. One patient received ibrutinib, and 2 received acalabrutinib. All developed HBV-associated hepatitis requiring anti-HBV therapy and survived. One patient continued receiving acalarutinib. Among the patients with past HBV infection, 13 received ibrutinib and 1 (8%) had HBV reactivation; 14 received acalabrutinib and 1 (7%) had HBV reactivation (P = 1.0). CONCLUSIONS: HBV reactivation risk is intermediate in patients with past HBV infection who receive BTK inhibitors. For patients with past HBV infection who received BTK inhibitors, data are insufficient to recommend universal anti-HBV prophylaxis, but monitoring for HBV reactivation is warranted.


Assuntos
Neoplasias Hematológicas , Hepatite B , Humanos , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B/uso terapêutico , Estudos Retrospectivos , Hepatite B/etiologia , Hepatite B/tratamento farmacológico , Anticorpos Anti-Hepatite B/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Ativação Viral
19.
Transplant Cell Ther ; 29(1): 10-18, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36273782

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects immunocompromised and elderly patients. Not only are hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell recipients at greater risk for severe COVID-19 and COVID-19-related complications, but they also may experience suboptimal immune responses to currently available COVID-19 vaccines. Optimizing the use, timing, and number of doses of the COVID-19 vaccines in these patients may provide better protection against SARS-CoV-2 infection and better outcomes after infection. To this end, current guidelines for COVID-19 vaccination in HCT and CAR T-cell recipients from the American Society of Transplantation and Cellular Therapy Transplant Infectious Disease Special Interest Group and the American Society of Hematology are provided in a frequently asked questions format.


Assuntos
COVID-19 , Hematologia , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , Idoso , Humanos , Vacinas contra COVID-19 , Receptores de Antígenos Quiméricos/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2 , Linfócitos T , Vacinação
20.
Am J Infect Control ; 51(5): 506-513, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35901993

RESUMO

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) in health care settings endangers patients with cancer. As knowledge of the transmission of COVID-19 emerged, strategies for preventing nosocomial COVID-19 were updated. We describe our early experience with nosocomial respiratory viral infections (RVIs) at a cancer center in the first year of the pandemic (March 2020-March 2021). METHODS: Nosocomial RVIs were identified through our infection control prospective surveillance program, which conducted epidemiologic investigations of all microbiologically documented RVIs. Data was presented as frequencies and percentages or medians and ranges. RESULTS: A total of 35 of 3944 (0.9%) documented RVIs were determined to have been nosocomial acquired. Majority of RVIs were due to SARS CoV-2 (13/35; 37%) or by rhinovirus/enterovirus (12/35; 34%). A cluster investigation of the first 3 patients with nosocomial COVID-19 determined that transmission most likely occurred from employees to patients. Five patients (38%) required mechanical ventilation and 4 (31%) died during the same hospital encounter. CONCLUSIONS: Our investigation of the cluster led to enhancement of our infection control measures. The implications of COVID-19 vaccination on infection control policies is still unclear and further studies are needed to delineate its impact on the transmission of COVID-19 in a hospital setting.


Assuntos
COVID-19 , Infecção Hospitalar , Neoplasias , Humanos , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Vacinas contra COVID-19 , Estudos Prospectivos , Hospitais , Neoplasias/epidemiologia
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