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1.
Clin Infect Dis ; 73(12): 2306-2313, 2021 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-33421068

RESUMEN

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.


Asunto(s)
Daptomicina , Infecciones por Bacterias Grampositivas , Trasplante de Células Madre Hematopoyéticas , Enterococos Resistentes a la Vancomicina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Daptomicina/farmacología , Daptomicina/uso terapéutico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , Filogenia , Enterococos Resistentes a la Vancomicina/genética
2.
J Med Virol ; 92(1): 86-95, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31448830

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , Quimioprevención/economía , Costo de Enfermedad , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Infecciones por Citomegalovirus/tratamiento farmacológico , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Adulto Joven
3.
J Infect Dis ; 219(6): 898-907, 2019 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-30295846

RESUMEN

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.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/fisiología , Ensayo de Immunospot Ligado a Enzimas , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Anciano , Antígenos Virales/inmunología , Antivirales/uso terapéutico , Biomarcadores/sangre , Estudios de Cohortes , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Femenino , Humanos , Inmunidad Celular , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptores de Trasplantes , Carga Viral , Activación Viral
4.
J Antimicrob Chemother ; 73(11): 3162-3169, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30113677

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , Neoplasias Hematológicas/complicaciones , Leucopenia/complicaciones , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Ribavirina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/virología , Humanos , Leucopenia/virología , Masculino , Persona de Mediana Edad , Infecciones por Virus Sincitial Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
5.
BMC Infect Dis ; 17(1): 672, 2017 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-29017457

RESUMEN

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.


Asunto(s)
Desinfección/métodos , Quirófanos , Carga Bacteriana/efectos de la radiación , Desinfección/instrumentación , Humanos , Quirófanos/métodos , Rayos Ultravioleta , Xenón
6.
Cancer ; 122(14): 2186-96, 2016 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-27142181

RESUMEN

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.


Asunto(s)
Microbioma Gastrointestinal , Quimioterapia de Inducción/efectos adversos , Infecciones/etiología , Leucemia Mieloide Aguda/complicaciones , Adulto , Anciano , Biodiversidad , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Infecciones/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Metagenoma , Metagenómica/métodos , Persona de Mediana Edad , Pronóstico , ARN Ribosómico 16S/genética , Adulto Joven
7.
J Antimicrob Chemother ; 71(3): 727-30, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26612873

RESUMEN

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.


Asunto(s)
Infecciones por Adenoviridae/tratamiento farmacológico , Antivirales/efectos adversos , Antivirales/farmacocinética , Cistitis/tratamiento farmacológico , Citosina/análogos & derivados , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Organofosfonatos/efectos adversos , Organofosfonatos/farmacocinética , Administración Intravesical , Adolescente , Anciano , Antivirales/administración & dosificación , Cidofovir , Citosina/administración & dosificación , Citosina/efectos adversos , Citosina/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Organofosfonatos/administración & dosificación , Plasma/química , Estudios Prospectivos , Trasplante Homólogo/efectos adversos , Adulto Joven
8.
PLoS One ; 10(11): e0139851, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26556047

RESUMEN

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.


Asunto(s)
Microbioma Gastrointestinal/genética , Genoma Fúngico , Leucemia Mieloide Aguda/complicaciones , Mucor/genética , Mucormicosis/microbiología , Infecciones Oportunistas/microbiología , Antifúngicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neutropenia Febril Inducida por Quimioterapia , Proteínas Fúngicas/genética , Fungemia/microbiología , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Mucor/aislamiento & purificación , Mucormicosis/tratamiento farmacológico , Proteínas de Neoplasias/genética , Onicomicosis/complicaciones , Infecciones Oportunistas/tratamiento farmacológico
11.
J Med Microbiol ; 64(Pt 2): 191-4, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25627208

RESUMEN

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.


Asunto(s)
Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/efectos de la radiación , Desinfección/métodos , Microbiología Ambiental , Hipoclorito de Sodio/farmacología , Rayos Ultravioleta , Infecciones por Clostridium/prevención & control , Recuento de Colonia Microbiana , Humanos , Viabilidad Microbiana/efectos de los fármacos , Viabilidad Microbiana/efectos de la radiación
12.
J Infect Dis ; 211(4): 582-9, 2015 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-25156562

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/genética , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Secuencia de Aminoácidos , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Femenino , Genotipo , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Alineación de Secuencia , Texas/epidemiología , Carga Viral , Adulto Joven
13.
Ther Adv Infect Dis ; 2(3-4): 79-90, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25469234

RESUMEN

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.

14.
Pharmacotherapy ; 34(11): 1220-5, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25164587

RESUMEN

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.


Asunto(s)
Aminoglicósidos/uso terapéutico , Antibacterianos/uso terapéutico , Clostridioides difficile/efectos de los fármacos , Enterocolitis Seudomembranosa/tratamiento farmacológico , Huésped Inmunocomprometido/efectos de los fármacos , Neoplasias/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Aminoglicósidos/efectos adversos , Antibacterianos/efectos adversos , Instituciones Oncológicas , Clostridioides difficile/inmunología , Clostridioides difficile/patogenicidad , Prescripciones de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Registros Electrónicos de Salud , Enterocolitis Seudomembranosa/complicaciones , Enterocolitis Seudomembranosa/inmunología , Enterocolitis Seudomembranosa/microbiología , Femenino , Fidaxomicina , Formularios de Hospitales como Asunto , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Recurrencia , Estudios Retrospectivos , Texas , Adulto Joven
15.
Blood ; 123(21): 3263-8, 2014 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-24700783

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Síndromes de Inmunodeficiencia/complicaciones , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/cirugía , Infecciones del Sistema Respiratorio/complicaciones , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/inmunología , Incidencia , Masculino , Persona de Mediana Edad , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/inmunología , Ribavirina/uso terapéutico , Resultado del Tratamiento , Adulto Joven
16.
J Pediatr Hematol Oncol ; 36(6): e376-81, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24327130

RESUMEN

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.


Asunto(s)
Neoplasias Hematológicas/mortalidad , Infecciones por Virus Sincitial Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/mortalidad , Administración por Inhalación , Adolescente , Corticoesteroides/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Lactante , Masculino , Palivizumab , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Estudios Retrospectivos , Ribavirina/uso terapéutico , Factores de Riesgo , Resultado del Tratamiento
17.
J Antimicrob Chemother ; 68(8): 1872-80, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23572228

RESUMEN

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.


Asunto(s)
Aerosoles/administración & dosificación , Antivirales/administración & dosificación , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/mortalidad , Ribavirina/administración & dosificación , Administración por Inhalación , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Células Madre/efectos adversos , Análisis de Supervivencia , Texas , Trasplante , Resultado del Tratamiento , Adulto Joven
18.
Am J Blood Res ; 2(4): 203-18, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23226621

RESUMEN

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.

19.
Blood ; 119(12): 2738-45; quiz 2969, 2012 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-22246027

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia/complicaciones , Leucemia/mortalidad , Infecciones por Paramyxoviridae/complicaciones , Infecciones por Paramyxoviridae/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infecciones por Paramyxoviridae/tratamiento farmacológico , Factores de Riesgo , Adulto Joven
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