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1.
Clin Microbiol Rev ; 37(2): e0009923, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38546225

RESUMO

SUMMARYAs Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.


Assuntos
Doença de Chagas , Hospedeiro Imunocomprometido , Humanos , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Doença de Chagas/imunologia , Doença de Chagas/terapia , Trypanosoma cruzi/imunologia
2.
J Clin Microbiol ; 62(3): e0153723, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349145

RESUMO

Rhodococcus equi is an opportunistic pathogen known to cause pulmonary and extrapulmonary disease among immunocompromised patients. Treatment is frequently challenging due to intrinsic resistance to multiple antibiotic classes. While non-equi Rhodococcus spp. are prevalent, their clinical significance is poorly defined. There is also limited data on antibiotic susceptibility testing (AST) of Rhodococcus infection in humans. We conducted a single-center, retrospective cohort study evaluating clinical characteristics, microbiologic profile, and AST of Rhodococcus infections between June 2012 and 2022 at our tertiary academic medical center. Identification of Rhodococcus spp. was performed by Sanger 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry, and AST was performed by agar dilution. Three hundred twenty-two isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R. equi/hoagii, R. corynebacterioides, and R. erythropolis were the most frequently isolated species, with 19% of isolates identified only to genus level. One hundred ninety-nine isolates evaluated for AST demonstrated high-level resistance to amoxicillin/clavulanate, cephalosporins, and aminoglycosides. More than 95% susceptibility to imipenem, vancomycin, linezolid, rifampin, and clarithromycin was observed. Non-equi species showed a significantly more favorable AST profile relative to R. equi. Clinically significant Rhodococcus infection was rare with 10 cases diagnosed (majority due to R. equi) and managed. The majority of patients received 2- or 3-drug combination therapy for 2-6 months, with favorable clinical response. Significant differences in AST were observed between R. equi and non-equi species. Despite high antimicrobial resistance to several antibiotic classes, imipenem and vancomycin remain appropriate empiric treatment options for R. equi. Future research evaluating mechanisms underlying antimicrobial resistance is warranted.


Assuntos
Infecções por Actinomycetales , Rhodococcus equi , Rhodococcus , Humanos , Rhodococcus/genética , Vancomicina/uso terapêutico , Estudos Retrospectivos , RNA Ribossômico 16S , Infecções por Actinomycetales/tratamento farmacológico , Antibacterianos/uso terapêutico , Rhodococcus equi/genética , Imipenem/uso terapêutico
3.
Eur J Clin Microbiol Infect Dis ; 43(9): 1679-1688, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38922376

RESUMO

PURPOSE: To identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical ventilation due to pneumonia. METHODS: A retrospective single-center study was performed at the intensive care unit (ICU) of the Department of Internal Medicine at Heidelberg University Hospital (Germany) including 246 consecutive patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia from 08/2004 to 07/2016. Microbiological and radiological data were collected and statistically analyzed for risk factors for ICU and 1-year mortality. RESULTS: ICU and 1-year mortality were 63.0% (155/246) and 81.0% (196/242), respectively. Pneumonia causing pathogens were identified in 143 (58.1%) patients, multimicrobial infections were present in 51 (20.7%) patients. Fungal, bacterial and viral pathogens were detected in 89 (36.2%), 55 (22.4%) and 41 (16.7%) patients, respectively. Human herpesviruses were concomitantly reactivated in 85 (34.6%) patients. As significant microbiological risk factors for ICU mortality probable invasive Aspergillus disease with positive serum-Galactomannan (odds ratio 3.1 (1.2-8.0), p = 0.021,) and pulmonary Cytomegalovirus reactivation at intubation (odds ratio 5.3 (1.1-26.8), p = 0.043,) were identified. 1-year mortality was not significantly associated with type of infection. Of interest, 19 patients had infections with various respiratory viruses and Aspergillus spp. superinfections and experienced high ICU and 1-year mortality of 78.9% (15/19) and 89.5% (17/19), respectively. CONCLUSIONS: Patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia showed high ICU and 1-year mortality. Pulmonary Aspergillosis and pulmonary reactivation of Cytomegalovirus at intubation were significantly associated with negative outcome.


Assuntos
Neoplasias Hematológicas , Unidades de Terapia Intensiva , Respiração Artificial , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Neoplasias Hematológicas/complicações , Adulto , Alemanha/epidemiologia , Hospedeiro Imunocomprometido , Pneumonia/mortalidade , Pneumonia/microbiologia , Idoso de 80 Anos ou mais
4.
BMC Infect Dis ; 24(1): 1032, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333914

RESUMO

BACKGROUND: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-ß-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. METHODS: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve. RESULTS: Participants had a median age of 60 years (interquartile range [IQR] 49-68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71-0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. CONCLUSION: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.


Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Feminino , Masculino , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Pneumocystis carinii/isolamento & purificação , Fatores de Risco , Canadá/epidemiologia , Broncoscopia , Medição de Risco , Hospitalização , Curva ROC , Modelos Logísticos
5.
J Infect Dis ; 228(5): 627-636, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37249910

RESUMO

BACKGROUND: Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT. METHODS: In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis. RESULTS: Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium, Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia, Veillonella) to intestinal anaerobes (eg, Anaerobutyricum, Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96). CONCLUSIONS: Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers.


Assuntos
Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Bactérias/genética , Fezes/microbiologia
6.
J Infect Dis ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38019656

RESUMO

Kidney transplant recipients (KTRs) develop decreased antibody titers to SARS-CoV-2 vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population.

7.
Clin Infect Dis ; 76(3): e495-e498, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35959783

RESUMO

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination are reduced in solid organ transplant recipients (SOTRs). We report that increased levels of preexisting antibodies to seasonal coronaviruses are associated with decreased antibody response to SARS-CoV-2 vaccination in SOTRs, supporting that antigenic imprinting modulates vaccine responses in SOTRs.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplante de Órgãos , Vacinas , Humanos , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Transplante de Órgãos/efeitos adversos , SARS-CoV-2 , Estações do Ano , Transplantados , Vacinação
8.
Clin Infect Dis ; 77(9): 1282-1290, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37450614

RESUMO

BACKGROUND: Invasive aspergillosis (IA) in immunocompromised hosts carries high morbidity and mortality. Diagnosis is often delayed because definitive diagnosis requires invasive specimen collection, while noninvasive testing with galactomannan is moderately accurate. Plasma cell-free DNA polymerase chain reaction (cfDNA PCR) represents a novel testing modality for the noninvasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR with serum galactomannan for the diagnosis of IA during routine clinical practice. METHODS: We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from 1 September 2020 to 30 October 2022. Patients were categorized into proven, probable, possible, and no IA based on the EORTC/MSG definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan. RESULTS: Overall, 238 unique patients with Aspergillus plasma cfDNA PCR test results, including 63 positives and 175 nonconsecutive negatives, were included in this study. The majority were immunosuppressed (89.9%) with 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR were 86.0% (37 of 43; 95% confidence interval [CI], 72.7-95.7) and 93.1% (121 of 130; 95% CI, 87.4-96.3), respectively. The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants were 67.9% (19 of 28; 95% CI, 49.3-82.1) and 89.8% (53 of 59; 95% CI, 79.5-95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40 of 43; 95% CI, 80.9-98.5) in patients with a new diagnosis of IA. CONCLUSIONS: Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for noninvasive diagnosis of IA.


Assuntos
Aspergilose , Ácidos Nucleicos Livres , Infecções Fúngicas Invasivas , Humanos , Estudos Retrospectivos , Aspergilose/diagnóstico , Aspergillus/genética , Reação em Cadeia da Polimerase/métodos , Mananas , Infecções Fúngicas Invasivas/diagnóstico , Sensibilidade e Especificidade
9.
J Clin Microbiol ; 61(2): e0173322, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36715514

RESUMO

Leptotrichia species are anaerobic, Gram-negative bacilli increasingly recognized as pathogens capable of causing invasive infections such as bloodstream infection (BSI), particularly among immunocompromised patients. However, there is a paucity of data regarding epidemiology, antimicrobial susceptibility, optimal treatment, and clinical outcomes among patients with Leptotrichia bacteremia. Patient risk factors, treatment approaches, and outcomes of a retrospective cohort of adult patients with Leptotrichia BSI at a tertiary medical center (Mayo Clinic Rochester [MCR]) were evaluated. Concurrently, species, temporal trends, and antimicrobial susceptibility testing (AST) results of Leptotrichia isolates submitted to a reference laboratory (Mayo Clinic Laboratories) over the past 10 years were examined. We identified 224 blood culture isolates of Leptotrichia species, with 26 isolates from patients treated at MCR. The most frequent species included L. trevisanii (49%), L. buccalis (24%), and L. wadei (16%). Leptotrichia species demonstrated >90% susceptibility to penicillin, metronidazole, ertapenem, and piperacillin-tazobactam. However, 96% (74/77) of isolates were resistant to moxifloxacin. For patients treated at MCR, the mean patient age was 55 years (standard deviation [SD], 17), with 9 females (35%), and all were neutropenic at the time of BSI. The primary sources of infection were gastrointestinal (58%), intravascular catheter (35%), and odontogenic (15%). Patients were treated with metronidazole (42%), piperacillin-tazobactam (27%), or carbapenems (19%). The mean duration of treatment was 11 days (SD, 4.5), with a 60-day all-cause mortality of 19% and no microbiologic relapse. Leptotrichia species are rare but important causes of BSI in neutropenic patients. Due to evolving antimicrobial susceptibility profiles, a review of AST results is necessary when selecting optimal antimicrobial therapy.


Assuntos
Anti-Infecciosos , Bacteriemia , Sepse , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Metronidazol , Leptotrichia , Estudos Retrospectivos , Bacteriemia/microbiologia , Combinação Piperacilina e Tazobactam , Bactérias Gram-Negativas , Antibacterianos , Testes de Sensibilidade Microbiana
10.
Infect Immun ; 90(7): e0019822, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35861565

RESUMO

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are important causative agents for foodborne diseases worldwide. Besides antibiotic treatment, vaccination has been deemed as the most effective strategy for preventing EPEC- and EHEC-caused foodborne illnesses. Despite substantial progress made in identifying promising antigens and efficacious vaccines, no vaccines against EPEC or EHEC have yet been licensed. Mice are inherently resistant to EPEC and EHEC infections; infection with Citrobacter rodentium (CR), the murine equivalent of EPEC and EHEC, in mice has been widely used as a model to study bacterial pathogenesis and develop novel vaccine strategies. Mirroring the severe outcomes of EPEC and EHEC infections in immunocompromised populations, immunocompromised mouse strains such as interleukin-22 knockout (Il22-/-) are susceptible to CR infection with severe clinical symptoms and mortality. Live attenuated bacterial vaccine strategies have been scarcely investigated for EPEC and EHEC infections, in particular in immunocompromised populations associated with severe outcomes. Here we examined whether live attenuated CR strain with rational genetic manipulation generates protective immunity against lethal CR infection in the susceptible Il22-/- mice. Our results demonstrate that oral administration of live ΔespFΔushA strain promotes efficient systemic and humoral immunity against a wide range of CR virulence determinants, thus protecting otherwise lethal CR infection, even in immunocompromised Il22-/- mice. This provides a proof of concept of live attenuated vaccination strategy for preventing CR infection in immunocompromised hosts associated with more severe symptoms and lethality.


Assuntos
Infecções por Enterobacteriaceae , Escherichia coli Êntero-Hemorrágica , Escherichia coli Enteropatogênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Administração Oral , Animais , Citrobacter rodentium , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli Enteropatogênica/genética , Hospedeiro Imunocomprometido , Camundongos
11.
J Clin Microbiol ; 60(12): e0103222, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36326257

RESUMO

There is an increasing body of literature on the utility of MALDI-TOF MS in the identification of filamentous fungi. However, the process still lacks standardization. In this study, we attempted to establish a practical workflow for the identification of three clinically important molds: Aspergillus, Fusarium, and Mucorales using MALDI-TOF MS. We evaluated the performance of Bruker Filamentous Fungi database v3.0 for the identification of these fungi, highlighting when there would be a benefit of using an additional database, the MSI-2 for further identification. We also examined two other variables, namely, medium effect and incubation time on the accuracy of fungal identification. The Bruker database achieved correct species level identification in 85.7% of Aspergillus and 90% of Mucorales, and correct species-complex level in 94.4% of Fusarium. Analysis of spectra using the MSI-2 database would also offer additional value for species identification of Aspergillus species, especially when suspecting species with known identification limits within the Bruker database. This issue would only be of importance in selected cases where species-level identification would impact therapeutic options. Id-Fungi plates (IDFP) had almost equivalent performance to Sabouraud dextrose agar (SDA) for species-level identification of isolates and enabled an easier harvest of the isolates with occasional faster identification. Our study showed accurate identification at 24 h for Fusarium and Mucorales species, but not for Aspergillus species, which generally required 48 h.


Assuntos
Fusarium , Mucorales , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fluxo de Trabalho , Aspergillus , Fungos
12.
Pediatr Blood Cancer ; 69(5): e29647, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35253346

RESUMO

Because they can experience neutropenia due to bone marrow failure, patients with Shwachman-Diamond syndrome (SDS) carry increased risk for serious infections compared with the general population; however, there has been a paucity of data on the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with SDS. We compiled results from a survey distributed to participants in the SDS Registry in May-June 2021. In this report, we describe the characteristics and outcomes of patients with SDS who had COVID-19. Patients reported a short clinical course without significant complications or cytopenias. Additionally, COVID-19 vaccines were well tolerated with minor side effects.


Assuntos
Doenças da Medula Óssea , COVID-19 , Insuficiência Pancreática Exócrina , Neutropenia , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Humanos , Síndrome de Shwachman-Diamond , Vacinação
13.
Transpl Infect Dis ; 24(5): e13928, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35980210

RESUMO

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk of severe outcomes associated with antimicrobial resistance (AMR). Antimicrobial stewardship programs (ASPs) play a vital role in mitigating the negative impacts of AMR. Pediatric evidence regarding ASP for SOT recipients is scarce, although many pediatric SOT centers have implemented different forms of ASP. METHODS: This article summarized the available evidence relating to AMR among pediatric SOT recipients and discussed key strategies for the successful implementation of ASP among this population. The focus is primarily on antibacterial and secondarily on antifungal management. RESULTS: The development of multidisciplinary antimicrobial stewardship teams for pediatric SOT recipients is essential for successful stewardship implementation. Key stakeholders may include but are not limited to SOT recipients and their caregivers, primary SOT teams (transplant physicians, transplant pharmacists, transplant unit nurses, and transplant outpatient care team), transplant surgery teams, transplant infectious diseases teams, hospital AST, microbiology teams, infection prevention teams, quality improvement teams, and information technology teams. CONCLUSION: As the evidence for optimal ASP in pediatric SOT is still evolving, it is important to measure the impact of implemented interventions.


Assuntos
Gestão de Antimicrobianos , Transplante de Órgãos , Antibacterianos/uso terapêutico , Antifúngicos , Criança , Humanos , Transplante de Órgãos/efeitos adversos , Transplantados
14.
Transpl Infect Dis ; 24(5): e13955, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36254502

RESUMO

Antibiotic allergy labels (AALs) are commonly reported, with well-defined prevalence in the general population; several studies have now focused efforts on immunocompromised hosts. Understanding the prevalence of reported allergy labels and methods of antibiotic allergy evaluation and delabeling strategies has the potential to improve prescribing practices and clinical outcomes in this high-antibiotic use group. In this review, we will discuss the current literature on the prevalence, impact, and evaluations of AALs in immunocompromised hosts with a focus on beta-lactam (penicillin) allergy and sulfa-antibiotic (antimicrobial sulfurs) allergy labels.


Assuntos
Hipersensibilidade a Drogas , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Penicilinas , beta-Lactamas/efeitos adversos
15.
Handb Exp Pharmacol ; 272: 287-314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34671868

RESUMO

Immunosuppressive therapies are currently indicated for a wide range of diseases. As new agents emerge and indications evolve the landscape grows increasingly complex. Therapies can target pathologic immune system over-activation in rheumatologic or autoimmune disease, or conditioning and graft versus host disease (GVHD) prophylactic regimens may eliminate or inhibit host immune function to improve graft survival and risk of complication in solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT). With immunosuppressive therapy, infections occur. Complex disease states, host factors, and concomitant therapies contribute to a "net state" of immunosuppression that must be considered and may confound perceived increased infection risks in patients receiving treatment.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Terapia de Imunossupressão/efeitos adversos
16.
Clin Microbiol Rev ; 34(1)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33115722

RESUMO

Hosts with compromised or naive immune systems, such as individuals living with HIV/AIDS, transplant recipients, and fetuses, are at the highest risk for complications from cytomegalovirus (CMV) infection. Despite substantial progress in prevention, diagnostics, and treatment, CMV continues to negatively impact both solid-organ transplant (SOT) and hematologic cell transplant (HCT) recipients. In this article, we summarize important developments in the field over the past 10 years and highlight new approaches and remaining challenges to the optimal control of CMV infection and disease in transplant settings.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/prevenção & controle , Transplante de Órgãos/efeitos adversos , Antivirais/farmacologia , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Citomegalovirus/tratamento farmacológico , Diagnóstico Precoce , Humanos , Hospedeiro Imunocomprometido
17.
J Clin Microbiol ; 59(9): e0065421, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34011524

RESUMO

Stenotrophomonas maltophilia causes high-mortality infections in immunocompromised hosts with limited therapeutic options. Many U.S. laboratories rely on commercial automated antimicrobial susceptibility tests (cASTs) and use CLSI breakpoints (BPs) for S. maltophilia. However, contemporary data on these systems are lacking. We assessed performance of Vitek 2, MicroScan WalkAway, and Phoenix relative to that of reference broth microdilution for trimethoprim-sulfamethoxazole (SXT), levofloxacin (LEV), minocycline (MIN), and ceftazidime (CAZ) with 109 S. maltophilia bloodstream isolates. Using CLSI breakpoints, categorical agreement (CA) was below 90% on all systems and drugs, with the exception of SXT by MicroScan (98.1%) and Phoenix (98.1%) and MIN by MicroScan (100%) and Phoenix (99.1%). For SXT, Vitek 2 yielded a 77.1% CA. LEV and CAZ CA ranged from 67% to 85%. Very major errors (VME) were >3% for SXT (MicroScan, Phoenix), LEV (MicroScan), and CAZ (all systems). Major errors (ME) were >3% for SXT (Vitek 2), LEV (Phoenix), and CAZ (MicroScan, Phoenix). Minor errors were >10% for CAZ and LEV on all systems. Data were analyzed with EUCAST pharmacokinetic/pharmacodynamic CAZ, LEV, ciprofloxacin (CIP), and tigecycline (TGC) breakpoints when possible. CA was <90% for all. VME were >3% for CAZ (all systems), LEV (MicroScan), and TGC (Vitek 2), and ME were >3% for LEV (MicroScan), CAZ (all systems), ciprofloxacin (Vitek 2 and MicroScan), and TGC (Vitek 2, Phoenix). Minor errors (MI) were >10% for all agents and systems, by EUCAST breakpoints with an intermediate category (LEV, CAZ, CIP). Laboratories should use caution with cASTs for S. maltophilia, as a high rate of errors may be observed.


Assuntos
Stenotrophomonas maltophilia , Antibacterianos/farmacologia , Ceftazidima , Humanos , Testes de Sensibilidade Microbiana , Tigeciclina
18.
Pediatr Blood Cancer ; 68(12): e29253, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34310027

RESUMO

BACKGROUND: Fever in neutropenia (FN) remains a frequent complication in pediatric patients undergoing chemotherapy for cancer. Preventive strategies, like primary antibiotic prophylaxis, need to be evidence-based. PROCEDURE: Data on pediatric patients with any malignancy from the prospective multicenter SPOG 2015 FN Definition Study (NCT02324231) were analyzed. A score predicting the risk to develop FN with safety-relevant events (SRE; bacteremia, severe sepsis, intensive care unit admission, death) was developed using multivariate mixed Poisson regression. Its predictive performance was assessed by internal cross-validation and compared with the performance of published rules. RESULTS: In 238 patients, 318 FN episodes were recorded, including 53 (17%) with bacteremia and 68 (21%) with SRE. The risk-prediction score used three variables: chemotherapy intensity, defined according to the expected duration of severe neutropenia, time since diagnosis, and type of malignancy. Its cross-validated performance, assessed by the time needed to cover (TNC) one event, exceeded the performance of published rules. A clinically useful score threshold of ≥11 resulted in 2.3% time at risk and 4.1 months TNC. Using external information on efficacy and timing of intermittent antibiotic prophylaxis, 4.3 months of prophylaxis were needed to prevent one FN with bacteremia, and 5.2 months to prevent one FN with SRE, using a threshold of ≥11. CONCLUSIONS: This score, based on three routinely accessible characteristics, accurately identifies pediatric patients at risk to develop FN with SRE during chemotherapy. The score can help to design clinical decision rules on targeted primary antibiotic prophylaxis and corresponding efficacy studies.


Assuntos
Antineoplásicos , Bacteriemia , Neoplasias , Neutropenia , Antibacterianos/efeitos adversos , Antineoplásicos/efeitos adversos , Bacteriemia/diagnóstico , Criança , Febre/diagnóstico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/complicações , Neutropenia/prevenção & controle , Estudos Prospectivos
19.
Pediatr Dev Pathol ; 24(4): 366-370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33729851

RESUMO

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hepáticas/etiologia , Fígado/patologia , Células-Tronco Mesenquimais/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Proliferação de Células , Criança , Feminino , Doença Enxerto-Hospedeiro/complicações , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Transplante Homólogo
20.
Pediatr Blood Cancer ; 67(11): e28579, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32893954

RESUMO

New York City has emerged as one of the epicenters of the SARS-COV-2 pandemic, with the Bronx being disproportionately affected. This novel coronavirus has caused significant respiratory manifestations raising the concern for development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). We report a series of pediatric SCD SARS-COV-2-positive patients admitted with ACS. SARS-COV-2-positive SCD patients, who did not develop ACS, were the comparison group. Hydroxyurea use (P-value = .02) and lower absolute monocyte counts (P-value = .04) were noted in patients who did not develop ACS. These preliminary findings need to be further evaluated in larger cohorts.


Assuntos
Síndrome Torácica Aguda/complicações , Anemia Falciforme/complicações , COVID-19/complicações , Síndrome Torácica Aguda/diagnóstico , Síndrome Torácica Aguda/tratamento farmacológico , Adolescente , Anemia Falciforme/tratamento farmacológico , Antibacterianos/uso terapêutico , Antidrepanocíticos/uso terapêutico , COVID-19/diagnóstico , Teste para COVID-19 , Criança , Doxiciclina/uso terapêutico , Feminino , Hospitais Urbanos , Humanos , Hidroxiureia/uso terapêutico , Masculino , Cidade de Nova Iorque , Reação em Cadeia da Polimerase , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem , Tratamento Farmacológico da COVID-19
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