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1.
Clin Infect Dis ; 73(12): 2306-2313, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33421068

RESUMO

BACKGROUND: Vancomycin-resistant enterococci (VRE) are a major cause of morbidity and mortality in immunocompromised patients. Tracking the dissemination of VRE strains is crucial to understand the dynamics of emergence and spread of VRE in the hospital setting. METHODS: Whole genome sequencing (WGS) and phylogenetic analyses were performed to identify dominant VRE strains and potential transmission networks between 35 patients with VRE-positive rectal swabs and their rooms (main rooms and bathrooms) on the leukemia (LKM) and the hematopoietic cell transplant (HCT) floors. Sequence types (STs), drug resistance genes, and patients' outcomes were also determined. RESULTS: A total of 89 VRE strains grouped into 10 different STs, of which newly described STs were isolated from both floors (ST736, ST494, ST772, and ST1516). We observed highly genetically related strains transmitted between rooms, floors, and time periods in an average period of 39 days (ranging from 3 to 90 days). Of 5 VRE bacteremia events, 3 strains were lacking the pili operon fms14-17-13 (ST203) and the remaining 2 were resistant to daptomycin (DAP; ST736, ST664). Of 10 patients harboring DAP-resistant strains, only 2 were exposed to DAP within 4 months before strain recovery. CONCLUSIONS: Our comparisons of VRE strains derived from the environment and immunocompromised patients confirmed horizontal transfer of highly related genetic lineages of multidrug-resistant (particularly to DAP) VRE strains between HCT and LKM patients and their room environment. Implementing WGS can be useful in distinguishing VRE reservoirs where interventions can be targeted to prevent and control the spread of highly resistant organisms.


Assuntos
Daptomicina , Infecções por Bactérias Gram-Positivas , Transplante de Células-Tronco Hematopoéticas , Enterococos Resistentes à Vancomicina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Hospitais , Humanos , Testes de Sensibilidade Microbiana , Filogenia , Enterococos Resistentes à Vancomicina/genética
2.
J Med Virol ; 92(1): 86-95, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31448830

RESUMO

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a retrospective study to determine the clinical and economic burden of pre-emptive therapy (PET) for CMV infection in 100 consecutive hospitalized adult CMV positive serostatus allo-HCT recipients and compared their hospitalization cost with allo-HCT recipients hospitalized with graft vs host disease without CMV infection (control group) and across 19 US cancer centers for hospitalized patients with CMV infection between 2012 and 2015 (Vizient database). A total of 192 CMV episodes of PET for CMV infection occurred within 1 year post-HCT. PET consisted of ganciclovir (41% of episodes), foscarnet (40%), and valganciclovir (38%) with the longest average length of stay in foscarnet-treated patients (41 days). The average direct cost per patient admitted for PET was $116 976 (range: $7866-$641 841) compared with $12 496 (range: $2004-$43 069) in the control group (P < .0001). The total direct cost per encounter was significantly higher in patients treated with foscarnet and had nephrotoxicity ($284 006) compared with those who did not ($112 195). The average cost amongst the 19 US cancer centers, including our institution, was $42 327 with major disparities in cost and clinical outcomes. PET for CMV infection is associated with high economic burden in allo-HCT recipients.


Assuntos
Antivirais/uso terapêutico , Quimioprevenção/economia , Efeitos Psicossociais da Doença , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplantados/estatística & dados numéricos , Adulto , Idoso , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Adulto Jovem
3.
J Infect Dis ; 219(6): 898-907, 2019 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-30295846

RESUMO

BACKGROUND: Cytomegalovirus (CMV) infections in hematopoietic cell transplant (HCT) recipients cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI) can be determined by levels of interferon gamma (IFN-γ) production using an enzyme-linked immunospot (ELISPOT) CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of this assay to predict the outcome of low-level CMV reactivation in HCT recipients. METHODS: We followed 55 HCT recipients with low-level CMV reactivation up to 8 weeks from enrollment. Progression to clinically significant CMV infection (CS-CMVi) was defined as a CMV load >1000 IU/mL or > 500 IU/mL in patients receiving matched related/autologous or matched unrelated transplants, respectively, and initiation of antiviral treatment. RESULTS: Progression to CS-CMVi occurred in 31 (56%) of the HCT recipients. Spot counts of CMV-specific pp65 and IE1 antigens were significantly lower in patients who had CS-CMVi than in patients who did not. On multivariate analysis, the ELISPOT CMV responses and steroids use were the only predictors of progression to CS-CMVi. CONCLUSIONS: A strong association between low CMV-CMI and progression to CS-CMVi was observed in HCT recipients. The implementation of serial monitoring of CMV-CMI may identify patients at risk of progression to CS-CMVi that require antiviral therapy.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/fisiologia , ELISPOT , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Antígenos Virais/imunologia , Antivirais/uso terapêutico , Biomarcadores/sangue , Estudos de Coortes , Citomegalovirus/imunologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Imunidade Celular , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplantados , Carga Viral , Ativação Viral
4.
J Antimicrob Chemother ; 73(11): 3162-3169, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113677

RESUMO

Objectives: Respiratory syncytial virus (RSV) infection causes morbidity and mortality in cancer patients. However, studies describing this infection in patients with haematological malignancies are scarce. We sought to evaluate the clinical impact of RSV infection on this patient population. Methods: We reviewed the records of patients with haematological malignancies and RSV infections cared for at our institution between January 2000 and March 2013. Results: Of the 181 patients, 71 (39%) had AML, ALL or myelodysplastic syndrome, 12 (7%) had CML or CLL, 4 (2%) had Hodgkin lymphoma, 35 (19%) had non-Hodgkin lymphoma and 59 (33%) had multiple myeloma. Most patients [117 (65%)] presented with an upper respiratory tract infection (URTI) and 15 (13%) had a subsequent lower respiratory tract infection (LRTI). The overall LRTI rate was 44% and the 90 day mortality rate was 15%. Multivariable regression analysis showed that having both neutropenia and lymphocytopenia (adjusted OR = 7.17, 95% CI = 1.94-26.53, P < 0.01) and not receiving ribavirin-based therapy during RSV URTI (adjusted OR = 0.03; 95% CI = 0.01-0.11, P < 0.001) were independent risk factors for LRTI. Having both neutropenia and lymphocytopenia at RSV diagnosis was also a risk factor for death at 90 days after RSV diagnosis (adjusted OR = 4.32, 95% CI = 1.24-15.0, P = 0.021). Conclusions: Patients with haematological malignancies and RSV infections, especially those with immunodeficiency, may be at risk of LRTI and death; treatment with ribavirin during RSV URTI may prevent these outcomes.


Assuntos
Antivirais/uso terapêutico , Neoplasias Hematológicas/complicações , Leucopenia/complicações , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/virologia , Humanos , Leucopenia/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/mortalidade , Infecções Respiratórias/virologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
5.
BMC Infect Dis ; 17(1): 672, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-29017457

RESUMO

BACKGROUND: Environmental cleanliness is one of the contributing factors for surgical site infections in the operating rooms (ORs). To decrease environmental contamination, pulsed xenon ultraviolet (PX-UV), an easy and safe no-touch disinfection system, is employed in several hospital environments. The positive effect of this technology on environmental decontamination has been observed in patient rooms and ORs during the end-of-day cleaning but so far, no study explored its feasibility between surgical cases in the OR. METHODS: In this study, 5 high-touch surfaces in 30 ORs were sampled after manual cleaning and after PX-UV intervention mimicking between-case cleaning to avoid the disruption of the ORs' normal flow. The efficacy of a 1-min, 2-min, and 8-min cycle were tested by measuring the surfaces' contaminants by quantitative cultures using Tryptic Soy Agar contact plates. RESULTS: We showed that combining standard between-case manual cleaning of surfaces with a 2-min cycle of disinfection using a portable xenon pulsed ultraviolet light germicidal device eliminated at least 70% more bacterial load after manual cleaning. CONCLUSIONS: This study showed the proof of efficacy of a 2-min cycle of PX-UV in ORs in eliminating bacterial contaminants. This method will allow a short time for room turnover and a potential reduction of pathogen transmission to patients and possibly surgical site infections.


Assuntos
Desinfecção/métodos , Salas Cirúrgicas , Carga Bacteriana/efeitos da radiação , Desinfecção/instrumentação , Humanos , Salas Cirúrgicas/métodos , Raios Ultravioleta , Xenônio
6.
Cancer ; 122(14): 2186-96, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27142181

RESUMO

BACKGROUND: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC). METHODS: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes. RESULTS: Baseline stool α-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α-diversity were observed over the course of IC, with a linear correlation between α-diversity change at the 2 sites (P = .02). Loss of both oral and stool α-diversity was associated significantly with the receipt of a carbapenem P < 0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04). CONCLUSIONS: The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186-96. © 2016 American Cancer Society.


Assuntos
Microbioma Gastrointestinal , Quimioterapia de Indução/efeitos adversos , Infecções/etiologia , Leucemia Mieloide Aguda/complicações , Adulto , Idoso , Biodiversidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Infecções/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Metagenoma , Metagenômica/métodos , Pessoa de Meia-Idade , Prognóstico , RNA Ribossômico 16S/genética , Adulto Jovem
7.
J Antimicrob Chemother ; 71(3): 727-30, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26612873

RESUMO

OBJECTIVES: The objective of this study was to evaluate the pharmacokinetics and safety of cidofovir administered via the intravesicular route to patients with haemorrhagic cystitis following allogeneic HSCT (allo-HSCT). METHODS: Patients with gross haematuria and confirmed BK or adenovirus viruria following allo-HSCT were prospectively enrolled in an open-label pharmacokinetic study (ClinicalTrials.gov registration: NCT01816646). Three hours after an oral probenecid dose (2 g), cidofovir (2.5-5 mg/kg in 50-100 mL of normal saline) was given via a transurethral catheter for up to 2 h of dwell time. Serial plasma samples were obtained over 24 h and assayed for cidofovir concentrations using LC-MS/MS. A custom pharmacokinetic model with a time-limited absorption compartment was fitted to the concentration-time profile of each patient. Systemic drug exposure was expressed as AUC0-24, by integrating the best-fit profile with respect to time. RESULTS: Six subjects (mean ±â€ŠSD age = 38 ±â€Š21 years) with baseline serum creatinine <1.4 mg/dL were enrolled. Mean values for volume of distribution, clearance and elimination half-life were 19.5 L, 5.6 L/h and 2.8 h, respectively. Compared with the reported AUC0-24 for an equivalent intravenous dose, intravesicular instillation of cidofovir resulted in 1%-74% of the corresponding systemic exposure. Owing to primarily lower abdominal pain, only two patients were able to tolerate a 2 h dwell time. One patient developed a >50% increase in serum creatinine within 7 days of administration. CONCLUSIONS: Intravesicular administration of cidofovir resulted in highly variable systemic exposures. The safety and efficacy of intravesicular cidofovir should be further evaluated before routine use.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/farmacocinética , Cistite/tratamento farmacológico , Citosina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Organofosfonatos/efeitos adversos , Organofosfonatos/farmacocinética , Administração Intravesical , Adolescente , Idoso , Antivirais/administração & dosagem , Cidofovir , Citosina/administração & dosagem , Citosina/efeitos adversos , Citosina/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , Plasma/química , Estudos Prospectivos , Transplante Homólogo/efeitos adversos , Adulto Jovem
8.
Blood ; 123(21): 3263-8, 2014 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-24700783

RESUMO

We developed an immunodeficiency scoring index for respiratory syncytial virus (ISI-RSV) infection, based on a cohort of 237 allogeneic hematopoietic cell transplant (allo-HCT) recipients, that can predict the risk of progression to lower respiratory tract infection (LRTI) and RSV-associated mortality. A weighted index was calculated using adjusted hazard ratios for immunodeficiency markers. Based on the ISI-RSV (range, 0-12), patients were stratified into low (0-2), moderate (3-6), and high (7-12) risk groups. A significant trend of increasing incidence of LRTI and RSV-associated mortality was observed as the risk increased from low to moderate to high (P < .001). Patients in the high-risk group had the greatest benefit of ribavirin-based therapy at the upper respiratory tract infection stage and the highest risk for progression to LRTI and death when antiviral therapy was not given (6.5 [95% confidence interval (CI), 1.8-23.6] and 8.1 [95% CI, 1.1-57.6], respectively). The ISI-RSV is designed to stratify allo-HCT recipients with RSV infection into groups according to their risk for progression to LRTI and RSV-associated mortality. Identification of high-risk groups using this index would distinguish patients who would benefit the most from antiviral therapy, mainly with aerosolized ribavirin. The ISI-RSV should be validated in a multi-institutional study.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes de Imunodeficiência/complicações , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/cirurgia , Infecções Respiratórias/complicações , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/imunologia , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Ribavirina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
9.
J Infect Dis ; 211(4): 582-9, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25156562

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe respiratory disease in adult hematopoietic cell transplant (HCT) recipients. RSV subgroups A and B have evolved into multiple genotypes. We report on a recently described RSV genotype (ON1) in a cohort of adult HCT recipients in Texas. METHODS: Twenty adult HCT recipients were enrolled as a part of an efficacy trial of ribavirin therapy. RSV identification and genotyping was performed using molecular techniques. RSV-specific neutralizing antibody (NAb) responses were measured. RESULTS: ON1 genotype was detected in 3 of 6 patients in the 2011-2012 season and in 8 of 14 patients in 2012-2013 season. Other genotypes detected were NA1 and BA. NAb levels were low at enrollment. Eight of 9 patients who cleared the RSV infection within 2 weeks mounted a ≥4-fold NAb response, compared with 2 of 8 who shed the virus for >2 weeks. The clinical course of those infected with ON1 was comparable to the course for individuals infected with other genotypes. CONCLUSION: This is the first report of RSV ON1 genotype in the United States, and ON1 genotype was dominant genotype in adult HCT recipients. Interestingly, faster viral clearance was associated with a ≥4-fold NAb response, likely indicating a reconstituted immune system.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Transplantados/estatística & dados numéricos , Adulto , Idoso , Sequência de Aminoácidos , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Feminino , Genótipo , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Alinhamento de Sequência , Texas/epidemiologia , Carga Viral , Adulto Jovem
10.
Blood ; 119(12): 2738-45; quiz 2969, 2012 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-22246027

RESUMO

Community respiratory viruses are significant causes of morbidity and mortality in patients with leukemia and hematopoietic stem cell transplant (HSCT) recipients. Data on characteristics and outcomes of parainfluenza virus (PIV) infections in these patients are limited. We reviewed the records of patients with leukemia and HSCT recipients who developed PIV infections to determine the characteristics and outcomes of such infections. We identified 200 patients with PIV infections, including 80 (40%) patients with leukemia and 120 (60%) recipients of HSCT. At presentation, most patients (70%) had an upper respiratory tract infection and the remaining patients (30%) had pneumonia. Neutropenia, APACHE II score more than 15, and respiratory coinfections were independent predictors of progression to pneumonia on multivariate analysis. Overall mortality rate was 9% at 30 days after diagnosis and 17% among patients who had PIV pneumonia, with no significant difference between patients with leukemia and HSCT recipients (16% vs 17%). On multivariate analysis, independent predictors of death were relapsed or refractory underlying malignancy, APACHE II score more than 15, and high-dose steroid use. Patients with leukemia and HSCT are at risk for serious PIV infections, including PIV pneumonia, with a significant mortality rate. We identified multiple risk factors for progression to pneumonia and death.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia/complicações , Leucemia/mortalidade , Infecções por Paramyxoviridae/complicações , Infecções por Paramyxoviridae/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infecções por Paramyxoviridae/tratamento farmacológico , Fatores de Risco , Adulto Jovem
11.
J Pediatr Hematol Oncol ; 36(6): e376-81, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24327130

RESUMO

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in children, especially those with cancer. Data on RSV infections in this vulnerable population is limited. We conducted a retrospective study of all RSV infections in children with cancer from 1998 to 2009 to determine characteristics and outcomes of these infections, identify risk factors for LRTI and mortality, and the effect of antiviral therapy on these outcomes. We identified 59 patients with a median age of 5 years; 53% had hematologic malignancy, 32% were hematopoietic stem cell transplant recipients, 39% had received corticosteroids, and 76% cytotoxic chemotherapy within 1 month before RSV infection. LRTI developed in 22 (37%) patients with a trend of higher rate in males (odds ratio=2.57 [0.86-7.62], P=0.09) and children with lymphocytopenia (odds ratio=2.95 [0.86-10.12], P=0.085). No significant differences were observed in the rates of progression to LRTI (3/10 [30%] vs. 19/49 [39%], P=0.729) and RSV-associated mortality (0/10 [0%] vs. 3/49 [6%], P=0.422) for patients receiving antiviral therapy at upper respiratory tract infection stage compared with those who did not. However, patients with LRTI had significantly better outcomes when treated with aerosolized ribavirin plus immunomodulators (mainly palivizumab) when compared with aerosolized ribavirin alone (mortality rates: 0/6 [0%] vs. 3/4 [75%], P=0.03). Ribavirin did not show any benefit in reducing LRTI or mortality; however, addition of palivizumab to the treatment regimen may be potentially beneficial, especially for children with LRTI.


Assuntos
Neoplasias Hematológicas/mortalidade , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/mortalidade , Administração por Inalação , Adolescente , Corticosteroides/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Palivizumab , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Estudos Retrospectivos , Ribavirina/uso terapêutico , Fatores de Risco , Resultado do Tratamento
12.
J Antimicrob Chemother ; 68(8): 1872-80, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23572228

RESUMO

OBJECTIVES: Respiratory syncytial virus (RSV) infections are well recognized as a significant cause of morbidity and mortality in allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients. We evaluated the spectrum of clinical manifestations, management (including ribavirin-based antiviral therapy) and outcomes of RSV infections and determined the risk factors associated with RSV lower respiratory tract infection (LRTI) and all-cause mortality. METHODS: In this retrospective study, we analysed clinical data from all laboratory-confirmed RSV infections in allo-HSCT recipients (n = 280) who presented at our institution from January 1996 to May 2009. RESULTS: Of the 280 patients, 80 (29%) developed LRTI within 20 days (median 1 day, range 0-19 days) and 44 (16%) died within 90 days (median 26 days, range 1-82 days) from RSV diagnosis. Multivariable logistic regression analyses identified several significant risk factors associated with RSV LRTI and all-cause mortality, including age, male sex, neutropenia, lymphocytopenia and lack of ribavirin-based antiviral therapy at the upper respiratory tract infection (URTI) stage. Aerosolized ribavirin-based therapy at the URTI stage was the single most significant factor in reducing the risk of RSV LRTI (83%), all-cause mortality (57%) and RSV-associated mortality (87%) in these patients (P < 0.05), irrespective of the year of RSV diagnosis. CONCLUSIONS: Our results demonstrate that RSV infections are a significant cause of morbidity and mortality in high-risk allo-HSCT recipients and ribavirin-based antiviral therapy at the URTI stage had a positive impact on both outcomes in this vulnerable population with multiple risk factors.


Assuntos
Aerossóis/administração & dosagem , Antivirais/administração & dosagem , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/mortalidade , Ribavirina/administração & dosagem , Administração por Inalação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversos , Análise de Sobrevida , Texas , Transplante , Resultado do Tratamento , Adulto Jovem
13.
J Antimicrob Chemother ; 66(12): 2850-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21948965

RESUMO

BACKGROUND: Uncontrolled case series have demonstrated decreased Clostridium difficile infection (CDI) recurrence in patients given rifaximin after standard antibiotic therapy. However, clinical trials assessing whether rifaximin decreases recurrent diarrhoea in patients with CDI have not been performed. The purpose of this study was to assess rates of recurrent diarrhoea in patients with CDI given rifaximin versus placebo immediately after standard therapy. METHODS: This was a randomized, double-blind, placebo-controlled pilot study. Patients with CDI and a Horn's index ≥1 were randomized to receive rifaximin 400 mg three times daily or placebo for 20 days given immediately after finishing standard anti-CDI antibiotics. Patients were followed for 3 months and assessed for recurrent diarrhoea that included CDI recurrence (return of diarrhoea with a positive toxin test) and patient self-reported return of non-CDI diarrhoea after a period of wellness. RESULTS: Sixty-eight patients aged 61 ± 18 years (50% male) were given rifaximin (n = 33) or placebo (n = 35). Twenty-four of 68 (35%) patients had recurrent diarrhoea either due to recurrent CDI (23.5%) or self-reported diarrhoea (11.5%). Recurrent diarrhoea occurred in 17 of 35 (49%) patients given placebo and 7 of 33 (21%) given rifaximin (P = 0.018). CDI recurrence occurred in 11 of 35 (31%) patients given placebo and 5 of 33 (15%) patients given rifaximin (P = 0.11). Self-reported diarrhoea occurred in 6 of 35 (17%) of patients given placebo and 2 of 33 (6%) given rifaximin (P = 0.15). CONCLUSIONS: Patients with CDI given a rifaximin chaser regimen experienced a decreased incidence of recurrent diarrhoea compared with placebo.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/prevenção & controle , Rifamicinas/administração & dosagem , Diarreia/tratamento farmacológico , Diarreia/prevenção & controle , Método Duplo-Cego , Humanos , Incidência , Projetos Piloto , Placebos/administração & dosagem , Rifaximina , Prevenção Secundária , Resultado do Tratamento
14.
Infect Control Hosp Epidemiol ; 36(12): 1461-3, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26329908

RESUMO

Isolates from patients who acquired vancomycin-resistant enterococci (VRE) were examined for the frequency of genetically indistinguishable strains on leukemia and stem cell transplant units at a major cancer center for 1 year. A total of 14 strains recurred, primarily on the same floor and in the same service unit an average of 49 days apart.


Assuntos
Infecção Hospitalar/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Enterococos Resistentes à Vancomicina/genética , Institutos de Câncer , Infecção Hospitalar/epidemiologia , Enterococcus/isolamento & purificação , Fezes/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/transmissão , Hospitais , Humanos , Leucemia , Reação em Cadeia da Polimerase , Transplante de Células-Tronco , Texas/epidemiologia
15.
J Med Microbiol ; 64(Pt 2): 191-4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25627208

RESUMO

The standard for Clostridium difficile surface decontamination is bleach solution at a concentration of 10 % of sodium hypochlorite. Pulsed xenon UV light (PX-UV) is a means of quickly producing germicidal UV that has been shown to be effective in reducing environmental contamination by C. difficile spores. The purpose of this study was to investigate whether PX-UV was equivalent to bleach for decontamination of surfaces in C. difficile infection isolation rooms. High-touch surfaces in rooms previously occupied by C. difficile infected patients were sampled after discharge but before and after cleaning using either bleach or non-bleach cleaning followed by 15 min of PX-UV treatment. A total of 298 samples were collected by using a moistened wipe specifically designed for the removal of spores. Prior to disinfection, the mean contamination level was 2.39 c.f.u. for bleach rooms and 22.97 for UV rooms. After disinfection, the mean level of contamination for bleach was 0.71 c.f.u. (P = 0.1380), and 1.19 c.f.u. (P = 0.0017) for PX-UV disinfected rooms. The difference in final contamination levels between the two cleaning protocols was not significantly different (P = 0.9838). PX-UV disinfection appears to be at least equivalent to bleach in the ability to decrease environmental contamination with C. difficile spores. Larger studies are needed to validate this conclusion.


Assuntos
Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/efeitos da radiação , Desinfecção/métodos , Microbiologia Ambiental , Hipoclorito de Sódio/farmacologia , Raios Ultravioleta , Infecções por Clostridium/prevenção & controle , Contagem de Colônia Microbiana , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação
17.
PLoS One ; 10(11): e0139851, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26556047

RESUMO

Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes.


Assuntos
Microbioma Gastrointestinal/genética , Genoma Fúngico , Leucemia Mieloide Aguda/complicações , Mucor/genética , Mucormicose/microbiologia , Infecções Oportunistas/microbiologia , Antifúngicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia , Proteínas Fúngicas/genética , Fungemia/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Mucor/isolamento & purificação , Mucormicose/tratamento farmacológico , Proteínas de Neoplasias/genética , Onicomicose/complicações , Infecções Oportunistas/tratamento farmacológico
18.
Pharmacotherapy ; 34(11): 1220-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25164587

RESUMO

OBJECTIVES: To report our experience with the use of fidaxomicin (FDX), an oral macrocyclic antibiotic, in cancer patients with Clostridium difficile infection (CDI). METHODS: A single-center retrospective case series was conducted at The University of Texas MD Anderson Cancer Center. Patients with CDI treated with FDX from May 2011 to January 2013 were identified via the pharmacy database. Clinical response and recurrence after FDX initiation were evaluated. RESULTS: Twenty-two patients were included, most of whom were male (55%) with a mean age of 58 years (range: 20-83 yrs). The most common underlying malignancies were nine patients with lymphoma (41%), seven with leukemia (32%), and six with solid tumors (27%). Indications for FDX included recurrent CDI in 16 patients (72%) and failure of both metronidazole and oral vancomycin in 6 patients (28%). Nineteen patients (86%) were on concomitant antimicrobials during CDI treatment. Clinical response to FDX was 91%, and overall sustained clinical response was 82%. FDX was well tolerated with no major adverse events that were FDX related or discontinuations due to drug-related adverse events. CONCLUSION: In cancer patients, FDX is effective treatment for the first episode of CDI after failure of standard therapies and treatment of recurrent CDI. This was interesting given the large number of high-risk patients who continued to receive concomitant antimicrobial therapy, which is common in this immunocompromised patient population.


Assuntos
Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Enterocolite Pseudomembranosa/tratamento farmacológico , Hospedeiro Imunocomprometido/efeitos dos fármacos , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Institutos de Câncer , Clostridioides difficile/imunologia , Clostridioides difficile/patogenicidade , Prescrições de Medicamentos , Farmacorresistência Bacteriana Múltipla , Registros Eletrônicos de Saúde , Enterocolite Pseudomembranosa/complicações , Enterocolite Pseudomembranosa/imunologia , Enterocolite Pseudomembranosa/microbiologia , Feminino , Fidaxomicina , Formulários de Hospitais como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Recidiva , Estudos Retrospectivos , Texas , Adulto Jovem
19.
Ther Adv Infect Dis ; 2(3-4): 79-90, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25469234

RESUMO

The role of the environment in harboring and transmitting multidrug-resistant organisms has become clearer due to a series of publications linking environmental contamination with increased risk of hospital-associated infections. The incidence of antimicrobial resistance is also increasing, leading to higher morbidity and mortality associated with hospital-associated infections. The purpose of this review is to evaluate the evidence supporting the existing methods of environmental control of organisms: environmental disinfection, contact precautions, and hand hygiene. These methods have been routinely employed, but transmission of multidrug-resistant organisms continues to occur in healthcare facilities throughout the country and worldwide. Several new technologies have entered the healthcare market that have the potential to close this gap and enhance the containment of multidrug-resistant organisms: improved chemical disinfection, environmental monitoring, molecular epidemiology, self-cleaning surfaces, and automated disinfection systems. A review of the existing literature regarding these interventions is provided. Overall, the role of the environment is still underestimated and new techniques may be required to mitigate the role that environmental transmission plays in acquisition of multidrug-resistant organisms.

20.
Am J Blood Res ; 2(4): 203-18, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23226621

RESUMO

Advances in stem cell transplantation procedures and the overall improvement in the clinical management of hematopoietic cell transplant (HCT) recipients over the past 2 decades have led to an increase in survival duration, in part owing to better strategies for prevention and treatment of post-transplant complications, including opportunistic infections. However, post-HCT infections remain a concern for HCT recipients, particularly infections caused by community respiratory viruses (CRVs), which can lead to significant morbidity and mortality. These viruses can potentially cause lower respiratory tract illness, which is associated with a higher mortality rate among HCT recipients. Clinical management of CRV infections in HCT recipients includes supportive care and antiviral therapy, especially in high-risk individuals, when available. Directed antiviral therapy is only available for influenza infections, where successful use of neuraminidase inhibitors (oseltamivir or zanamivir) and/or M2 inhibitors (amantadine or rimantadine) has been reported. Data on the successful use of ribavirin, with or without immunomodulators, for respiratory syncytial virus infections in HCT recipients has emerged over the past 2 decades but is still controversial at best because of a lack of randomized controlled trials. Because of the lack of directed antiviral therapy for most of these viruses, prevention should be emphasized for healthcare workers, patients, family, and friends and should include the promotion of the licensed inactivated influenza vaccine for HCT recipients, when indicated. In this review, we discuss the clinical management of respiratory viruses in this special patient population, focusing on commercially available antivirals, adjuvant therapy, and novel drugs under investigation, as well as on available means for prevention.

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