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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 Neurosurg Spine ; 39(3): 419-426, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37243554

RESUMO

OBJECTIVE: Vertebral osteomyelitis is a rare complication of coccidioidomycosis infection. Surgical intervention is indicated when there is failure of medical management or presence of neurological deficit, epidural abscess, or spinal instability. The relationship between timing of surgical intervention and recovery of neurological function has not been previously described. The purpose of this study was to investigate if the duration of neurological deficits at presentation affects neurological recovery after surgical intervention. METHODS: This was a retrospective study of all patients diagnosed with coccidioidomycosis involving the spine at a single tertiary care center between 2012 and 2021. Data collected included patient demographics, clinical presentation, radiographic information, and surgical intervention. The primary outcome was change in neurological examination after surgical intervention, quantified according to the American Spinal Injury Association Impairment Scale. The secondary outcome was the complication rate. Logistic regression was used to test if the duration of neurological deficits was associated with improvement in the neurological examination after surgery. RESULTS: Twenty-seven patients presented with spinal coccidioidomycosis between 2012 and 2021; 20 of these patients had vertebral involvement on spinal imaging with a median follow-up of 8.7 months (IQR 1.7-71.2 months). Of the 20 patients with vertebral involvement, 12 (60.0%) presented with a neurological deficit with a median duration of 20 days (range 1-61 days). Most patients presenting with neurological deficit (11/12, 91.7%) underwent surgical intervention. Nine (81.2%) of these 11 patients had an improved neurological examination after surgery and the other 2 had stable deficits. Seven patients had improved recovery sufficient to improve by 1 grade according to the AIS. The duration of neurological deficits on presentation was not significantly associated with neurological improvement after surgery (p = 0.49, Fisher's exact test). CONCLUSIONS: The duration of neurological deficits on presentation should not deter surgeons from operative intervention in cases of spinal coccidioidomycosis.


Assuntos
Coccidioidomicose , Abscesso Epidural , Doenças da Coluna Vertebral , Humanos , Coccidioidomicose/diagnóstico por imagem , Coccidioidomicose/cirurgia , Estudos Retrospectivos , Coluna Vertebral/cirurgia , Abscesso Epidural/diagnóstico , Abscesso Epidural/cirurgia
3.
Int Forum Allergy Rhinol ; 13(9): 1615-1714, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36680469

RESUMO

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. RESULTS: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.


Assuntos
Infecções Fúngicas Invasivas , Sinusite , Humanos , Estudos Prospectivos , Infecções Fúngicas Invasivas/diagnóstico , Doença Aguda , Prognóstico , Sinusite/diagnóstico , Sinusite/terapia , Sinusite/microbiologia
4.
Transpl Infect Dis ; 24(6): e13835, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35426225

RESUMO

The effect of vaccination on severity of subsequent COVID-19 in patients with hematologic malignancies (HMs) is unknown. In this single-center retrospective cohort study, we found no difference in severity of COVID-19 disease in vaccinated (n = 16) versus unvaccinated (n = 54) HM patients using an adjusted multiple logistic regression model. Recent anti-B-cell therapy was associated with more severe illness.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , COVID-19/prevenção & controle , Estudos Retrospectivos , Neoplasias Hematológicas/complicações , Modelos Logísticos , Vacinação
5.
Clin Case Rep ; 9(6): e04172, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34194767

RESUMO

Local and systemic complications of Bacillus Calmette-Guérin therapy are important to recognize as they require prolonged antimicrobial therapy; molecular genomic testing may be key to diagnosis when culture data are inconclusive.

6.
Clin Infect Dis ; 72(2): 340-350, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33501974

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features and outcomes of COVID-19 among immunosuppressed patients, who are at presumed risk of more severe disease but who may also have decreased detrimental inflammatory responses, are not well characterized. We review the existing literature on COVID-19 among immunocompromised populations ranging from patients with cancer and solid-organ transplant recipients to patients with HIV and those receiving immunomodulatory therapy for autoimmune disease. Patients with malignancy and solid-organ transplant recipients may be at increased risk of severe COVID-19 disease and death, whereas for those with other types of immunocompromise, current evidence is less clear. Overall, further prospective controlled studies are needed to determine the attributable risk of immunocompromising conditions and therapies on COVID-19 disease prognosis.


Assuntos
COVID-19 , Humanos , Hospedeiro Imunocomprometido , Pandemias , SARS-CoV-2 , Transplantados
7.
Transpl Infect Dis ; 23(3): e13563, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33434394

RESUMO

We report a liver transplant patient with disseminated Legionella micdadei infection with pulmonary, laryngeal, and suspected muscle involvement. This organism, which stains weakly acid-fast, primarily affects immunocompromised patients. The diagnosis is difficult to make; in this case, the organism was identified via molecular diagnostics on laryngeal and pulmonary biopsy tissue.


Assuntos
Legionella , Legionelose , Transplante de Fígado , Humanos , Legionellaceae , Pulmão
8.
Am J Transplant ; 21(6): 2145-2160, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33078555

RESUMO

Chronic lung allograft dysfunction (CLAD) remains the major complication limiting long-term survival among lung transplant recipients (LTRs). Limited understanding of CLAD immunopathogenesis and a paucity of biomarkers remain substantial barriers for earlier detection and therapeutic interventions for CLAD. We hypothesized the airway transcriptome would reflect key immunologic changes in disease. We compared airway brush-derived transcriptomic signatures in CLAD (n = 24) versus non-CLAD (n = 21) LTRs. A targeted assessment of the proteome using concomitant bronchoalveolar lavage (BAL) fluid for 24 cytokines/chemokines and alloimmune T cell responses was performed to validate the airway transcriptome. We observed an airway transcriptomic signature of differential genes expressed (DGEs) in CLAD marked by Type-1 immunity and striking upregulation of two endogenous immune regulators: indoleamine 2, 3 dioxygenase 1 (IDO-1) and tumor necrosis factor receptor superfamily 6B (TNFRSF6B). Advanced CLAD staging was associated with a more intense airway transcriptome signature. In a validation cohort using the identified signature, we found an area under the curve (AUC) of 0.77 for CLAD LTRs. Targeted proteomic analyses revealed a predominant Type-1 profile with detection of IFN-γ, TNF-α, and IL-1ß as dominant CLAD cytokines, correlating with the airway transcriptome. The airway transcriptome provides novel insights into CLAD immunopathogenesis and biomarkers that may impact diagnosis of CLAD.


Assuntos
Bronquiolite Obliterante , Transplante de Pulmão , Aloenxertos , Rejeição de Enxerto/genética , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Proteômica , Transcriptoma/genética
9.
Transpl Infect Dis ; 23(2): e13477, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32989856

RESUMO

Immunosuppressed patients such as solid organ transplant and hematologic malignancy patients appear to be at increased risk for morbidity and mortality due to coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Convalescent plasma, a method of passive immunization that has been applied to prior viral pandemics, holds promise as a potential treatment for COVID-19. Immunocompromised patients may experience more benefit from convalescent plasma given underlying deficits in B and T cell immunity as well as contraindications to antiviral and immunomodulatory therapy. We describe our institutional experience with four immunosuppressed patients (two kidney transplant recipients, one lung transplant recipient, and one chronic myelogenous leukemia patient) treated with COVID-19 convalescent plasma through the Expanded Access Program (NCT04338360). All patients clinically improved after administration (two fully recovered and two discharged to skilled nursing facilities) and none experienced a transfusion reaction. We also report the characteristics of convalescent plasma product from a local blood center including positive SARS-CoV-2 IgG and negative SARS-CoV-2 PCR in all samples tested. This preliminary evidence suggest that convalescent plasma may be safe among immunosuppressed patients with COVID-19 and emphasizes the need for further data on the efficacy of convalescent plasma as either primary or adjunctive therapy for COVID-19.


Assuntos
COVID-19/terapia , Rejeição de Enxerto/prevenção & controle , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Adulto , Idoso , COVID-19/imunologia , Feminino , Humanos , Imunização Passiva/métodos , Transplante de Rim , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do Tratamento , Soroterapia para COVID-19
10.
Cell Rep Med ; 1(4)2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32754722

RESUMO

Lung transplantation can be lifesaving in end-stage cystic fibrosis (CF), but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Persistent upper airway Pseudomonas aeruginosa (PsA) colonization can seed the allograft. While de novo PsA infection is associated with CLAD in non-CF recipients, this association is less clear for CF recipients experiencing PsA recolonization. Here, we evaluate host and pathogen contributions to this phenomenon. In the context of PsA infection, brushings from the airways of CF recipients demonstrate type 1 interferon gene suppression. Airway epithelial cell (AEC) cultures demonstrate similar findings in the absence of pathogens or immune cells, contrasting with the pre-transplant CF AEC phenotype. Type 1 interferon promoters are relatively hypermethylated in CF AECs. CF subjects in this cohort have more mucoid PsA, while non-CF PsA subjects have decreased microbiome α diversity. Peri-transplant protocols may benefit from consideration of this host and microbiome equilibrium.


Assuntos
Fibrose Cística/imunologia , Interferons/genética , Infecções por Pseudomonas/imunologia , Adulto , Idoso , Estudos de Coortes , Fibrose Cística/complicações , Células Epiteliais , Feminino , Expressão Gênica/genética , Humanos , Interferons/metabolismo , Pulmão/citologia , Pulmão/microbiologia , Transplante de Pulmão , Masculino , Microbiota/genética , Pessoa de Meia-Idade , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/patogenicidade , Escarro/microbiologia , Transplantados
11.
Curr Infect Dis Rep ; 21(12): 53, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773398

RESUMO

PURPOSE OF REVIEW: Modern advances in oncologic and end-organ therapies have led to an increase in immunocompromised patients and a corresponding rise in acute invasive fungal sinusitis (AIFS). Here, we present a comprehensive medical and surgical approach to the diagnosis and management of immunocompromised cancer and transplant patients with AIFS. RECENT FINDINGS: Aspergillus and Mucorales are the most common fungi to cause AIFS, though atypical fungal pathogens have been implicated particularly among patients on azole prophylaxis. Symptoms present in the majority of AIFS cases include fever, nasal congestion, and facial swelling. Nasal endoscopy and radiology are adjuncts to clinical exam with the gold standard diagnostic test still being histopathology, though molecular testing such as panfungal PCR is playing a larger role. The treatment of AIFS requires surgery, antifungal therapy, and reversal of immunosuppression. We recommend initiation of liposomal amphotericin B as an empiric therapy for AIFS, transitioned to targeted therapy when/if a fungal pathogen is identified. Goals of surgery include diagnostic sampling and debridement of necrotic tissue. Equally, if not more important, is reversal of underlying immune suppression. Immune-stimulating therapies hold promise for reducing mortality, but require additional study. Despite improvements in medical and surgical management of AIFS, mortality continues to approach 50%. Early diagnosis of this disease entity followed by aggressive surgical and medical management are important, including reversal of the underlying immunosuppression.

12.
Clin Infect Dis ; 68(2): 247-255, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-29800121

RESUMO

Background: Bendamustine is a potent chemotherapy agent increasingly used to treat indolent non-Hodgkin lymphoma (iNHL). While effective, it causes significant T-cell lymphopenia, which may increase risk of infection. We examined infectious complications associated with bendamustine-containing regimens among older patients with iNHL. Methods: For this Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort study, we identified 9395 patients with iNHL (follicular, marginal zone, Waldenström macroglobulinemia) treated with chemotherapy from 2006 to 2013. Thirteen percent received bendamustine-containing regimens. We compared baseline characteristics and infection incidence rates between patients treated with and without bendamustine. We conducted multivariate Cox proportional hazards regression (adjusting for demographics, comorbidities, disease and treatment characteristics, risk factors for infection, and antimicrobial prophylaxis) to determine infectious risks associated with bendamustine. Results: Bendamustine was associated with an increased risk of both common infections such as bacterial pneumonia (hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.21-4.85]) and opportunistic infections such as cytomegalovirus (HR, 3.98 [95% CI, 1.40-11.26]), varicella zoster virus (HR, 1.49 [95% CI, 1.18-1.89]), histoplasmosis (HR, 3.55 [95% CI, 1.10-11.42]), and Pneumocystis jirovecii pneumonia (when administered as third-line therapy: HR, 3.32 [95% CI, 1.00-11.11]). Risk of infections was more prominent in patients receiving bendamustine as part of later (third-line and above) regimens, and independently associated with well-established factors such as neutropenia and corticosteroid exposure. Conclusions: Bendamustine is associated with an increased risk of common and opportunistic infections in patients with iNHL. Further prospective investigation into the potential role of antimicrobial prophylaxis is needed in these patients.


Assuntos
Cloridrato de Bendamustina/efeitos adversos , Cloridrato de Bendamustina/uso terapêutico , Infecções/induzido quimicamente , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Análise Multivariada , Fatores de Risco
13.
Open Forum Infect Dis ; 5(12): ofy301, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30581881

RESUMO

Allogeneic hematopoietic stem cell transplant patients are at risk for common and atypical infections. Superior diagnostics can decrease infection-related morbidity and mortality. A novel plasma cell-free DNA next-generation sequencing test detected an uncommon presentation of Chlamydia trachomatis and recurrent and metastatic complications of Staphylococcus aureus bacteremia before standard microbiology.

14.
JAMA Pediatr ; 170(6): 570-6, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27088649

RESUMO

IMPORTANCE: Appropriate use of surgical antibiotic prophylaxis (AP) reduces surgical site infection rates, but prior data suggest variability in use patterns. OBJECTIVE: To assess national variability and appropriateness of AP in pediatric surgical patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 31 freestanding children's hospitals in the United States using administrative data from 2010-2013. The study included 603 734 children younger than 18 years who underwent one of the 45 most commonly performed operations. EXPOSURES: Receipt of surgical AP. MAIN OUTCOMES AND MEASURES: Primary outcomes included procedure- and hospital-specific rates of AP use and appropriateness of use based on clinical guidelines and consensus statements. We also assessed rates of Clostridium difficile infection and potential allergic reactions (using epinephrine administration as a surrogate event) after AP receipt. RESULTS: Of the 603 734 eligible patients, the mean (SD) patient age was 4.8 (4.4) years and 384 571 (63.7%) were boys. For the 671 255 operations evaluated, AP was administered for 348 119 (52%) of procedures. Intrahospital variation in AP use by procedure ranged from 11.5% to 100% (median, 78.1%). Overall, AP use was considered appropriate for 64.6% of cases. Appropriate use of AP by hospital varied from 47.3% to 84.4% with large variability by procedure within each hospital. For procedures for which AP was indicated, the median rate of appropriate use by hospital was 93.8%; however, for procedures for which AP was not indicated, the median rate of appropriate use by hospital was 52.0%. The odds of C difficile infection and epinephrine administration were significantly higher among children who received AP (odds ratio, 3.34; 95% CI, 1.66-6.73 and odds ratio 1.97; 95% CI, 1.92-2.02; respectively). CONCLUSIONS AND RELEVANCE: There is substantial national variability in the overall and appropriate use of AP for the most commonly performed operations in children both at a procedure and hospital level. A high proportion of AP use is inappropriate, potentially exposing many children to avoidable adverse events. Urgent attention should be directed to efforts to standardize the use of surgical AP in pediatrics.


Assuntos
Antibioticoprofilaxia/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Pré-Escolar , Clostridioides difficile , Infecções por Clostridium/prevenção & controle , Toxidermias/epidemiologia , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia , Procedimentos Desnecessários/estatística & dados numéricos
15.
PLoS One ; 10(11): e0140930, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26554923

RESUMO

BACKGROUND: Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. METHODS: We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. RESULTS: Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. CONCLUSIONS: Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.


Assuntos
Antifúngicos/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/complicações , Neoplasias Hematológicas/complicações , Mananas/sangue , Micoses/prevenção & controle , Infecções Oportunistas/prevenção & controle , Antifúngicos/administração & dosagem , Antifúngicos/economia , Neutropenia Febril Induzida por Quimioterapia/imunologia , Análise Custo-Benefício , Custos e Análise de Custo , Árvores de Decisões , Testes Diagnósticos de Rotina/economia , Esquema de Medicação , Custos de Medicamentos , Diagnóstico Precoce , Estudos Epidemiológicos , Estudos de Viabilidade , Galactose/análogos & derivados , Custos de Cuidados de Saúde , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/imunologia , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/economia , Pneumopatias Fúngicas/etiologia , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/economia , Micoses/etiologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/economia , Infecções Oportunistas/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
J Pediatr Surg ; 46(2): 366-71, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21292089

RESUMO

AIMS: The use of surgical antibiotic prophylaxis (AP) in children is poorly characterized. The aims of this study were to examine (1) trends in the use of AP for commonly performed operations, (2) appropriateness in the context of available guidelines, and (3) adverse events potentially attributable to AP. METHODS: We conducted a 5-year retrospective analysis of 22 children's hospitals (January 2005-March 2009) for all patients younger than 18 years who underwent 1 of the 40 commonly performed general and urological procedures. Indications for AP were defined by published specialty-specific guidelines. Clostridium difficile infection and surrogate events for drug allergy (diphenhydramine and epinephrine administrations) were examined as potential antibiotic-associated adverse events. RESULTS: Procedures of 246,316 were identified, of which 25% met criteria for AP. Eighty-two percent of the children received antibiotics during procedures when AP was indicated (range, 60%-96% by hospital), and 40% of the patients received antibiotics when there was no indication (range, 10%-83%). The likelihood of receiving AP was significantly different between hospitals for all procedures examined (P < .0001 for each procedure). Adverse events were significantly more frequent in children receiving AP than in those who did not (odds ratio [95% confidence interval] C difficile: 18.8 [6.9-51.5], P < .0001; epinephrine: 1.8 [1.7-2.0], P < .0001; diphenhydramine: 6.0 [5.6-6.5], P < .0001). CONCLUSIONS: Significant variation exists in the use of AP in the pediatric surgical population. Many children do not receive AP when indicated, and an even greater proportion may receive antibiotics when there is no indication. These findings may have profound implications from a public health perspective when extrapolated to all children undergoing surgical procedures.


Assuntos
Antibioticoprofilaxia/tendências , Cirurgia Geral/métodos , Pediatria/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/normas , Criança , Pré-Escolar , Uso de Medicamentos/tendências , Feminino , Cirurgia Geral/normas , Fidelidade a Diretrizes , Humanos , Masculino , Pediatria/normas , Período Perioperatório/métodos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Procedimentos Cirúrgicos Urológicos/métodos , Procedimentos Cirúrgicos Urológicos/normas
17.
Pediatr Infect Dis J ; 30(7): 580-4, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21233782

RESUMO

BACKGROUND: Pediatric Clostridium difficile infection (CDI)-related hospitalizations are increasing. We sought to describe the epidemiology of pediatric CDI at a quaternary care hospital. METHODS: Nested case-control study within a cohort of children <18 years tested for C. difficile between January and August 2008. The study included patients who were ≥ 1 year with a positive test and diarrhea; those without diarrhea (ie, presumed colonization) were excluded. Two unmatched controls per case were randomly selected from patients ≥ 1 year with a negative test. Potential predictors of CDI included age, gender, comorbidities, prior hospitalization, receipt of C. difficile-active antibiotics in the prior 24 hours, and recent (≤ 4 weeks) exposure to antibiotics or acid-blocking medications. Multivariate logistic regression models were created to identify independent predictors of CDI. RESULTS: Of 1891 tests performed, 263 (14%) were positive in 181 children. Ninety-five patients ≥ 1 year with CDI were compared with 238 controls. In multivariate analyses, predictors of CDI included solid organ transplant (odds ratio [OR], 8.09; 95% confidence interval [CI], 2.10-31.12), lack of prior hospitalization (OR, 8.43; 95% CI, 4.39-16.20), presence of gastrostomy or jejunostomy (G or J) tube (OR, 3.32; 95% CI 1.71-6.42), and receipt of fluoroquinolones (OR, 17.04; 95% CI, 5.86-49.54) or nonquinolone antibiotics (OR, 2.23; 95% CI, 1.18-4.20) in the past 4 weeks. Receipt of C. difficile-active antibiotics within 24 hours before testing was associated with a lower odds of CDI (OR, 0.22; 95% CI, 0.09-0.58). CONCLUSIONS: Recent antibiotic exposure and certain comorbid conditions (solid organ transplant, presence of a gastrostomy or jejunostomy tube) were associated with CDI. Diagnostic testing has less utility in patients being treated with C. difficile-active antibiotics.


Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Adolescente , Antibacterianos/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Massachusetts/epidemiologia , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos
18.
Biotechnol Bioeng ; 98(1): 141-54, 2007 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-17657776

RESUMO

This case study focuses on the scale-up of a Sp2/0 mouse myeloma cell line based fed-batch bioreactor process, from the initial 3-L bench scale to the 2,500-L scale. A stepwise scale-up strategy that involved several intermediate steps in increasing the bioreactor volume was adopted to minimize the risks associated with scale-up processes. Careful selection of several available mixing models from literature, and appropriately applying the calculated results to our settings, resulted in successful scale-up of agitation speed for the large bioreactors. Consideration was also given to scale-up of the nutrient feeding, inoculation, and the set-points of operational parameters such as temperature, pH, dissolved oxygen, dissolved carbon dioxide, and aeration in an integrated manner. It has been demonstrated through the qualitative and the quantitative side-by-side comparison of bioreactor performance as well as through a panel of biochemical characterization tests that the comparability of the process and the product was well controlled and maintained during the process scale-up. The 2,500-L process is currently in use for the routine clinical production of Epratuzumab in support of two global Phase III clinical trials in patients with lupus. Today, the 2,500 L, fed-batch production process for Epratuzumab has met all scheduled batch releases, and the quality of the antibody is consistent and reproducible, meeting all specifications, thus confirming the robustness of the process.


Assuntos
Anticorpos Monoclonais/biossíntese , Reatores Biológicos/microbiologia , Técnicas de Cultura de Células/instrumentação , Modelos Biológicos , Mieloma Múltiplo/metabolismo , Engenharia de Proteínas/instrumentação , Animais , Anticorpos Monoclonais Humanizados , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Camundongos , Mieloma Múltiplo/genética , Projetos Piloto , Engenharia de Proteínas/métodos
19.
Sex Transm Infect ; 83(4): 304-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17166889

RESUMO

This study aimed to systematically review and describe the evidence on chlamydia and gonorrhoea reinfection among men, and to evaluate the need for retesting recommendations in men. PubMed and STI conference abstract books from January 1995 to October 2006 were searched to identify studies on chlamydia and gonorrhoea reinfection among men using chlamydia and gonorrhoea nucleic acid amplification tests or gonorrhoea culture. Studies were categorised as using either active or passive follow-up methods. The proportions of chlamydial and gonococcal reinfection among men were calculated for each study and summary medians were reported. Repeat chlamydia infection among men had a median reinfection probability of 11.3%. Repeat gonorrhoea infection among men had a median reinfection probability of 7.0%. Studies with active follow-up had moderate rates of chlamydia and gonorrhoea reinfection among men, with respective medians of 10.9% and 7.0%. Studies with passive follow-up had higher proportions of both chlamydia and gonorrhoea reinfections among men, with respective medians of 17.4% and 8.5%. Proportions of chlamydia and gonorrhoea reinfection among men were comparable with those among women. Reinfection among men was strongly associated with previous history of sexually transmitted diseases and younger age, and inconsistently associated with risky sexual behaviour. Substantial repeat chlamydia and gonorrhoea infection rates were found in men comparable with those in women. Retesting recommendations in men are appropriate, given the high rate of reinfection. To optimise retesting guidelines, further research to determine effective retesting methods and establish factors associated with reinfection among men is suggested.


Assuntos
Infecções por Chlamydia/epidemiologia , Gonorreia/epidemiologia , Infecções por Chlamydia/prevenção & controle , Gonorreia/prevenção & controle , Humanos , Incidência , Masculino , Programas de Rastreamento , Guias de Prática Clínica como Assunto , Prevalência , Recidiva , Retratamento , Sexo sem Proteção
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