RESUMEN
Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.
Asunto(s)
Microbioma Gastrointestinal/inmunología , Inmunoterapia , Melanoma/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias Cutáneas/terapia , Animales , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/genética , Humanos , Melanoma/inmunología , Metagenoma , Ratones , Neoplasias Cutáneas/inmunologíaRESUMEN
Dramatic, overnight cost increases of important orphan and generic medications have recently come under public and government scrutiny. We highlight the case of aerosolized ribavirin, an important antiviral agent in hematopoietic stem cell transplantation which, because of substantial price increases, may now cost more than the transplant procedure itself.
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Antivirales/economía , Antivirales/uso terapéutico , Costos de los Medicamentos , Medicamentos Genéricos/economía , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Producción de Medicamentos sin Interés Comercial/economía , Neumonía Viral/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Ribavirina/economía , Ribavirina/uso terapéutico , Administración por Inhalación , Adulto , Aerosoles , Antivirales/administración & dosificación , Niño , Industria Farmacéutica/ética , Medicamentos Genéricos/uso terapéutico , Economía Hospitalaria/ética , Política de Salud/economía , Trasplante de Células Madre Hematopoyéticas/economía , Humanos , Lactante , Ribavirina/administración & dosificación , Resultado del TratamientoRESUMEN
Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine-Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.
Asunto(s)
Virus BK/patogenicidad , Enfermedad Injerto contra Huésped/mortalidad , Enfermedades Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Renales/mortalidad , Infecciones por Polyomavirus/mortalidad , Infecciones Tumorales por Virus/mortalidad , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Enfermedad Injerto contra Huésped/etiología , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/terapia , Humanos , Lactante , Recién Nacido , Enfermedades Renales/virología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/virología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Trasplante Homólogo , Infecciones Tumorales por Virus/virología , Adulto JovenRESUMEN
PURPOSE: Ertapenem is being increasingly utilized in cancer patients, but published data regarding its usage are limited. Our objective was to describe the various indications for ertapenem therapy and its safety and efficacy in cancer patients. METHODS: We conducted a retrospective cohort study of cancer patients who received monotherapy with ertapenem for at least 72 h, between January 2007 and February 2013. RESULTS: Among 97 unique patients who received ertapenem monotherapy, the most common indications were: (1) To facilitate discharge from the hospital of stable patients still requiring antimicrobial therapy (46 %). (2) Primary therapy of various documented infections (bacteremia, pneumonia, urinary tract infection, skin and skin structure infection) with ertapenem (28 %). (3) De-escalation from a different broad-spectrum agent or regimen to ertapenem within the hospital setting in patients not ready for discharge (25 %). The median age of the 97 patients studied was 59 years (range 9-87 years) with 52 % being men. Most patients had underlying hematologic malignancies (54 %), and 7 % were recipients of hematopoietic stem cell transplantation. Twenty-nine patients (30 %) were neutropenic, 26 % were diabetic, and 6 % had chronic lung disease. Primary ertapenem monotherapy was successful in all patients, de-escalation in 95.8 % of patients, and the strategy of discharge on outpatient therapy with ertapenem in 95.6 % of patients. Patients failing de-escalation or early discharge responded to alternative regimens. We documented no significant ertapenem associated toxicity or adverse events. CONCLUSIONS: Ertapenem appears to be safe and effective for several indications in cancer patients.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Utilización de Medicamentos , Neoplasias/complicaciones , Neutropenia/etiología , beta-Lactamas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Niño , Ertapenem , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven , beta-Lactamas/efectos adversosRESUMEN
BACKGROUND: Pseudomonas aeruginosa, especially multidrug-resistant (MDR) isolates, is an important pathogen in allogeneic hematopoietic stem cell transplant (HCT) recipients. The ability to identify patients at risk for these infections and administer appropriate empiric therapy, particularly during episodes of neutropenia, may improve outcomes and also direct infection control and antimicrobial stewardship efforts. Many transplant centers obtain routine surveillance stool cultures (SSCs) from HCT recipients to test for colonization with vancomycin-resistant enterococci, and extended-spectrum beta lactamase-producing Enterobacteriaceae. Our center initiated the performance of SSCs for P. aeruginosa, because of a perceived increase in the frequency of infection with MDR strains. The aim of this study was to determine the utility of this practice. METHODS: We conducted a 2-year (2010-2011) retrospective review of the medical records of all patients who underwent allogeneic HCT at our cancer center to (a) determine the frequency of fecal colonization with P. aeruginosa, including MDR strains; (b) to determine the overall frequency of subsequent P. aeruginosa infection, as well as the frequency of infection with MDR strains; (c) to ascertain the proportion of subsequent infections likely arising from the intestinal tract; and (d) to determine risk factors for progression from colonization to infection. RESULTS: Of 794 study patients, 58 (7.3%) had at least 1 positive SSC for P. aeruginosa; 19/58 (32.8%) developed a subsequent pseudomonal infection (11 with matching antimicrobial resistance patterns). On the other hand, 37/736 (5%) of the patients who were not colonized, developed a pseudomonal infection. The type of infection observed was pneumonia in 26 (46%) patients, bloodstream infection in 20 (36%), urinary tract infection in 8 (14%), and infections at other sites in 2 (4%). The incidence of MDR P. aeruginosa in the entire cohort was 2.2% (18 of 794): 12 had positive SSCs and 7 of these patients later developed MDR P. aeruginosa infections. Patients with acute myelogenous leukemia were more likely to be colonized and to develop subsequent infection. No infection-related deaths were observed during the first 30 days after infection. CONCLUSIONS: The incidence of P. aeruginosa colonization and subsequent infection was low. Patients who were not colonized had a low chance of developing P. aeruginosa infection. Most patients who developed infection did not have fecal colonization, suggesting a different source of infection. SSCs for P. aeruginosa provide incomplete information regarding the source of infection.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/aislamiento & purificación , Adolescente , Adulto , Anciano , Niño , Preescolar , Farmacorresistencia Bacteriana Múltiple , Heces/microbiología , Femenino , Humanos , Control de Infecciones , Masculino , Persona de Mediana Edad , Infecciones por Pseudomonas/microbiología , Estudios Retrospectivos , Vigilancia de Guardia , Texas/epidemiología , Trasplante Homólogo , Adulto JovenRESUMEN
BACKGROUND: Hematopoietic stem cell transplant (HCT) recipients are more susceptible to infections from vaccine-preventable diseases than the general population. Despite the development of international consensus guidelines addressing immunization after HCT, studies have shown that deviations from recommended immunization practices commonly occur. METHODS: An anonymous survey aimed at determining awareness of the guidelines and attitudes toward vaccination was distributed to our HCT clinicians. In parallel, we retrospectively evaluated patients' characteristics and post-HCT vaccine administration practices from 2010 to 2013. RESULTS: The majority of survey respondents (96%) were familiar with post-HCT vaccination protocols. Seventy-four percent of respondents reported that influenza vaccines were given to >70% of their patients, and 41% stated that they prescribed live vaccines to eligible patients. However, our pharmacy database review revealed that 38% of patients received the first series of vaccinations by the recommended 6 months post HCT, and 60% received them by 1 year after HCT. Most patients who had their vaccines withheld had relapsed disease or were undergoing treatment for graft-versus-host disease. Furthermore, we identified lower immunization rates in non-English speaking individuals, African-Americans, and Hispanic patients. CONCLUSIONS: Survey respondents reported being aware of current guidelines; however, adherence to the recommendations varied, likely connected to conflicting data on vaccine effectiveness and a lack of clear recommendations in complex clinical scenarios. Similar to the general population, patient barriers also could have contributed to lower vaccination rates in some cases. To decrease the large gap between the post-HCT vaccination guidelines and clinical practice, further studies on vaccine effectiveness and specific populations are warranted.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Trasplante de Células Madre Hematopoyéticas , Guías de Práctica Clínica como Asunto , Vacunación , Vacunas/administración & dosificación , Vacunas/inmunología , Recolección de Datos , Humanos , Pautas de la Práctica en Medicina , Estudios RetrospectivosRESUMEN
At 30 years into the HIV infection epidemic, the optimal antiretroviral (ARV) regimen for infected patients with cancer remains unknown. We therefore sought to retrospectively study different ARV regimens used in this population. Data from HIV-infected patients seen at The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, from 2001 to 2012 were reviewed. Patients received nucleoside reverse transcriptase inhibitors (NRTIs) plus protease inhibitors (PIs), non-NRTIs (NNRTIs), integrase strand-transfer inhibitors (INSTIs), or combinations of these. A total of 154 patients were studied. Most patients were male (80%), white (51%) and had haematological malignancies (HMs) (58%). NRTIs were combined with PIs (37%), NNRTIs (32%), INSTIs (19%) or combinations of these (11%). INSTIs were the most commonly used in patients with HM and in those receiving high-dose steroids or topoisomerase inhibitors (p <0.05). Side-effects occurred in 35%, 14%, 3% and 6% of patients receiving PIs, NNRTIs, INSTIs and combinations, respectively (p 0.001). Grade 3-4 adverse events were uncommon. Multivariate logistic regression analysis demonstrated that INSTIs and NNRTIs were nine times (95% confidence interval (CI), 1.4-50.8) and 11 times (95% CI, 1.9-64.7) more likely to be effective at 6 months, respectively, than PIs. This is the largest reported analysis studying different ARV regimens in HIV-infected cancer patients. Combinations that included PIs were the least favourable. NNRTIs and INSTIs had comparable efficacy, but INSTIs appeared to be the better tolerated ARVs in patients with HM or those receiving various chemotherapeutic agents.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Femenino , Infecciones por VIH/etnología , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de la Proteasa del VIH/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/etnología , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Texas , Población Blanca , Adulto JovenRESUMEN
Disseminated adenoviral infection (AI) is associated with profound immunosuppression and poor outcome after allogeneic hematopoietic SCT (allo-HSCT). A better understanding of AI in allo-HSCT recipients can serve as a basis to develop more effective management strategies. We evaluated all adult patients who received allo-HSCT at MD Anderson Cancer Center between 1999 and 2008. Among the 2879 allo-HSCT patients, 73 (2.5%) were diagnosed with AI. Enteritis (26%) and pneumonia (24%) were the most common clinical manifestations; pneumonia was the most common cause of adenovirus-associated death. A multivariable Bayesian logistic regression showed that when the joint effects of all covariates were accounted for, cord blood transplant, absolute lymphocyte count (ALC) ≤ 200/mm(3) and male gender were associated with a higher probability of disseminated AI. The OS was significantly worse for patients with AI that was disseminated rather than localized (median of 5 months vs median of 28 months, P<0.001) and for patients with ALC ≤ 200/mm(3) (P<0.001). Disseminated AI, in patients who received allo-HSCT, is a significant cause of morbidity and mortality. Strategies for early diagnosis and intervention are essential, especially for high-risk patients.
Asunto(s)
Infecciones por Adenoviridae/etiología , Adenoviridae/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Infecciones por Adenoviridae/inmunología , Infecciones por Adenoviridae/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Antígenos HLA/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/inmunología , Cuidados Críticos/métodos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/inmunología , Huésped Inmunocomprometido , Femenino , Humanos , MasculinoRESUMEN
High-dose interleukin-2 (HDIL-2) has proven to be an effective treatment for metastatic renal cell carcinoma and melanoma. Previous studies have shown an increase in catheter-related bacteremia (CRB) in patients on HDIL-2. The primary objective of this study was to evaluate the effectiveness of minocycline and rifampin-coated catheters (M/R-C) in reducing CRB in cancer patients on HDIL-2. This was a retrospective study where non-coated catheters (NC-C) and M/R-C were used for the administration of HDIL-2 before and after December 2004, respectively. Data collected included demographics, cancer type, catheter type, antibiotic prophylaxis, and infection rates. A total of 107 episodes of catheter use for HDIL-2 were evaluated in 78 patients (30 episodes in patients with M/R-C vs. 77 with NC-C). A total of nine episodes of CRB were identified, all in patients with NC-C (M/R-C 0% vs. NC-C 12%; p=0.06). The median time to bacteremia was 11 days (range 1-315 days). A log-rank test showed a trend that the M/R-C group had lower probability of getting CRB than the NC-C group (p=0.06). The use of M/R-C in patients on HDIL-2 therapy for advanced melanoma and renal cell carcinoma may have reduced the risk of CRB to nil. CRB still occurred despite antibiotic prophylaxis in patients with NC-C.
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Antibacterianos/administración & dosificación , Bacteriemia/prevención & control , Catéteres de Permanencia/efectos adversos , Minociclina/administración & dosificación , Neoplasias/complicaciones , Rifampin/administración & dosificación , Adulto , Anciano , Antibacterianos/uso terapéutico , Antineoplásicos/administración & dosificación , Bacteriemia/etiología , Cateterismo Venoso Central/efectos adversos , Femenino , Humanos , Interleucina-2/administración & dosificación , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Resultado del TratamientoRESUMEN
The overall risk of infections is lower in patients undergoing non-myeloablative allogeneic stem cell transplantation (NST) than in conventional stem cell transplant recipients. We sought to evaluate conditions associated with increased risk of infections after NST. In 81 patients, 187 infection episodes were noted; chronic lymphocytic leukemia (138 episodes/100 person-years) and recipients of matched unrelated donor graft (128 episodes/100 person-years) had higher risk of infection. Only half of the cytomegalovirus (CMV) infections occurred 31-100 days after transplantation. Most patients with CMV infection were non-neutropenic (100%), had lymphoma (76%), were younger (<55 years; 72%) and had received matched related donor (MRD) graft (72%). However, graft-versus-host disease (GVHD) was present in only 15% of these patients. Seven (78%) of nine invasive fungal infections (IFI) were diagnosed >100 days after NST and were associated with high mortality (78%). Most patients with IFI were also not neutropenic (100%), had received MRD graft (100%), had lymphoma (78%) and were given systemic steroids (78%); unlike CMV infection, 67% of these patients also had GVHD. On the basis of our results, we propose that NST recipients with lymphoma treated with high-dose corticosteroids for GVHD be considered for antifungal prophylaxis or pre-emptive antifungal therapy.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Linfocítica Crónica de Células B/complicaciones , Linfoma no Hodgkin/complicaciones , Micosis/etiología , Infecciones Oportunistas/prevención & control , Adulto , Anciano , Infecciones Bacterianas/etiología , Infecciones por Citomegalovirus/prevención & control , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/mortalidad , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Micosis/prevención & control , Estudios Retrospectivos , Acondicionamiento PretrasplanteRESUMEN
Parainfluenza virus is a major cause of respiratory illness in humans, manifesting from mild upper respiratory tract infection to bronchiolitis and pneumonia, especially in children. We report - to our knowledge - the first case of a nonimmunocompromised adult patient with human parainfluenza type 2 supraglottitis immediately after returning from China.
Asunto(s)
Crup/virología , Epiglotitis/virología , Virus de la Parainfluenza 2 Humana/aislamiento & purificación , Infecciones del Sistema Respiratorio/virología , Enfermedad Crónica , Tos/etiología , Cuidados Críticos , Crup/complicaciones , Epiglotitis/terapia , Fatiga/etiología , Ronquera/etiología , Humanos , Inmunocompetencia , Masculino , Persona de Mediana Edad , Líquido del Lavado Nasal/virología , Infecciones del Sistema Respiratorio/terapia , Saliva/virología , Resultado del TratamientoRESUMEN
Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in hematologic malignancy patients.
Asunto(s)
Mananos/sangre , Micosis/diagnóstico , beta-Glucanos/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Galactosa/análogos & derivados , Neoplasias Hematológicas/complicaciones , Humanos , Técnicas para Inmunoenzimas/métodos , Masculino , Persona de Mediana Edad , Proteoglicanos , Sensibilidad y EspecificidadRESUMEN
Cytomegalovirus (CMV) pneumonia is a life-threatening infection in patients with haematological malignancies (HMs) or in haematopoietic stem cell transplant (HSCT) recipients. To assess the incidence and risk factors for developing fatal CMV pneumonia in these patients, a case-control study based on 999 autopsies was performed at The University of Texas M. D. Anderson Cancer Center, Houston, Texas (January 1990 to December 2004). Twenty-five cases (patients who died with CMV pneumonia) were matched with 34 controls (patients who died without CMV pneumonia) by type of HM or HSCT, year of autopsy, age and gender. The incidence of CMV pneumonia declined between January 1990 to June /1997 and July 1997 to December 2004 (CMV pneumonia rates were 22/620 and 3/379 autopsies, respectively; p 0.006). Logistic regression analysis identified complete remission and sustained lymphopenia as independent predictors of CMV pneumonia (all p <0.05). The incidence of fatal CMV pneumonia has decreased over the last 15 years, which might reflect earlier diagnosis or the use of pre-emptive therapy or more effective preventive strategies. Complete remission of an HM does not preclude the development of CMV pneumonia among patients with prolonged lymphopenia.
Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/mortalidad , Citomegalovirus/aislamiento & purificación , Neoplasias Hematológicas/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neumonía Viral/virología , Factores de Riesgo , TexasRESUMEN
OBJECTIVES: To investigate the anti-adherence and antimicrobial durability of anti-infective catheters against multidrug-resistant (MDR) Staphylococcus aureus (resistant to vancomycin, rifampicin and methicillin) and MDR Gram-negative bacteria (Stenotrophomonas maltophilia, Acinetobacter baumannii/calcoaceticus and Enterobacter agglomerans) that are often associated with catheter-related bloodstream infections (CRBSIs). METHODS: Catheters impregnated with minocycline and rifampicin (M/R) or with silver-platinum and carbon (SPC) or with chlorhexidine and silver sulfadiazine (CHX/SS) were compared with non-coated catheters. Adherence of organisms was tested by using an established biofilm colonization model. All isolates were rifampicin-resistant. Antimicrobial durability was tested by soaking 1 cm segments of the catheter in serum and determining zones of inhibition against the tested organisms at weekly intervals. RESULTS: The M/R catheters showed significantly superior anti-adherence activity and more prolonged antimicrobial durability when compared with CHX/SS-central venous catheter (CVC), SPC-CVC and uncoated control catheters against MDR and vancomycin-resistant S. aureus (MDR VRSA) (all P values < or = 0.02), MDR S. maltophilia (all P values < 0.005) and MDR A. baumannii/calcoaceticus (all P values < 0.002), respectively. M/R-CVC and CHX/SS-CVC had comparable anti-adherence and antimicrobial durability against MDR E. agglomerans, and these two were superior to SPC-CVC and the uncoated control catheters (all P values < 0.001). CONCLUSIONS: M/R-CVC demonstrated superior anti-adherence activity and more prolonged antimicrobial durability when compared with other approved anti-infective catheters against MDR VRSA and/or MDR Gram-negative bacteria that are often associated with CRBSIs. This finding could explain their efficacy and better performance in clinical studies.
Asunto(s)
Antiinfecciosos/farmacología , Adhesión Bacteriana/efectos de los fármacos , Cateterismo , Equipos y Suministros/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Control de Infecciones/métodos , Staphylococcus aureus/efectos de los fármacos , Farmacorresistencia Bacteriana MúltipleRESUMEN
Few data exist on the etiology, presentation, prognosis, and management of fungal endophthalmitis (FE) in cancer patients. FE cases were identified by reviewing the ophthalmology reports and microbiology cultures of patients at The University of Texas M. D. Anderson Cancer Center. We retrospectively reviewed the medical records and obtained information related to malignancy, fungal infection and its management, visual outcome, and mortality. We compared FE caused by Candida spp. (CE) to FE caused by molds (ME). Of the 102 cancer patients with a fungal infection for whom an ophthalmology consult was requested, 23 met the criteria for definite (N = 6) or probable (N = 17) FE (8 with CE, 15 with ME). All of the patients with ME had hematologic malignancies, whereas half of the patients with CE had solid tumor (P = .008). Only patients with CE had a history of surgery within 30 days of FE diagnosis (38%, P = .03). Fungal pneumonia [17 (74%)] and disseminated infection [14, (61%)] were common. The most common presenting symptoms were decreased vision [16 (70%)] and ocular pain [14 (61%)]. All treated patients received systemic antifungals (combination therapy in 72% of the cases). Seven patients (30%) underwent vitrectomy. Only one patient received intraocular injection of amphotericin B along with systemic antifungals. Four-week mortality was high [13 (57%)], especially in ME (73%, P = .04). Among the eight surviving patients where visual acuity could be assessed, visual outcome improved or remained stable in five (63%). FE in cancer patients occurs in the setting of severe, frequently disseminated opportunistic mycoses, is caused predominantly by hyalohyphomycetes, and is a marker for high 4-week mortality.
Asunto(s)
Endoftalmitis/microbiología , Micosis/diagnóstico , Neoplasias/complicaciones , Adulto , Anciano , Antifúngicos/uso terapéutico , Candida/aislamiento & purificación , Endoftalmitis/mortalidad , Endoftalmitis/fisiopatología , Endoftalmitis/terapia , Femenino , Hongos/aislamiento & purificación , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Micosis/mortalidad , Micosis/fisiopatología , Micosis/terapia , Neumonía/microbiología , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Texas , VitrectomíaRESUMEN
BACKGROUND: Linezolid is the first approved synthetic oxazolidinone with activity against multidrug-resistant gram-positive pathogens. However, haematological toxic effects of linezolid frequently limit its prolonged use, especially in patients with poor marrow reserves such as those with cancer receiving chemotherapy. Previous authors have reported that administration of vitamin B6 with linezolid reversed pancytopenia in two patients. METHODS: This is an open-label study of 31 patients with cancer who received linezolid at 600 mg twice daily and vitamin B6 at 50 mg/day for at least 2 weeks mean therapy duration and they were matched to 62 control patients who received linezolid without vitamin B6 to determine whether the concomitant use of vitamin B6 attenuates the haematological toxicity of linezolid in patients with cancer. RESULTS: Patients were matched according to age, underlying disease, duration of therapy, creatinine level and use of chemotherapy. We found no significant differences in the rate of haematological toxic effects between the two patient groups. The rate of thrombocytopenia was 13% in the vitamin B6 group and 15% in the control group (P = 0.82). Also, the rate of leucopenia was 7% versus 5%, respectively (P = 0.75). None of the patients in the vitamin B6 group had anaemia compared with 5% in the control group. CONCLUSIONS: Vitamin B6 given at 50 mg/day may have an impact on anaemia but did not prevent linezolid-induced thrombocytopenia or leucopenia in cancer patients.
Asunto(s)
Acetamidas/efectos adversos , Enfermedades Hematológicas/prevención & control , Neoplasias/tratamiento farmacológico , Oxazolidinonas/efectos adversos , Vitamina B 6/uso terapéutico , Acetamidas/toxicidad , Adulto , Anciano , Femenino , Enfermedades Hematológicas/etiología , Humanos , Linezolid , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Oxazolidinonas/toxicidad , Vitamina B 6/fisiologíaRESUMEN
OBJECTIVE: Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infection. We sought to compare vancomycin-resistant (VR) Enterococcus faecalis bacteremia and VR Enterococcus faecium bacteremia in cancer patients with respect to risk factors, clinical presentation, microbiological characteristics, antimicrobial therapy, and outcomes. METHODS: We identified 210 cancer patients with VRE bacteremia who had been treated between January 1996 and December 2004; 16 of these 210 had VR E. faecalis bacteremia and were matched with 32 patients with VR E. faecium bacteremia and 32 control patients. A retrospective review of medical records was conducted. RESULTS: Logistic regression analysis showed that, compared with VR E. faecalis bacteremia, VR E. faecium bacteremia was associated with a worse clinical response to therapy (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.07-0.98]; P=.046) and a higher overall mortality rate (OR, 8.3 [95% CI, 1.9-35.3]; P=.004), but the VRE-related mortality rate did not show a statistically significant difference (OR, 6.8 [95% CI, 0.7-61.8]; P=.09). Compared with control patients, patients with VR E. faecalis bacteremia were more likely to have received an aminoglycoside in the 30 days before the onset of bacteremia (OR, 5.8 [95% CI, 1.2-27.6]; P=.03), whereas patients with VR E. faecium bacteremia were more likely to have received a carbapenem in the 30 days before the onset of bacteremia (OR, 11.7 [95% CI, 3.6-38.6]; P<.001). In a multivariate model that compared patients with VR E. faecium bacteremia and control patients, predictors of mortality included acute renal failure on presentation (OR, 15.1 [95% CI, 2.3-99.2]; P=.004) and VR E. faecium bacteremia (OR, 11 [95% CI, 2.7-45.1]; P<.001). No difference in outcomes was found between patients with VR E. faecalis bacteremia and control patients. CONCLUSIONS: VR E. faecium bacteremia in cancer patients was associated with a poorer outcome than was VR E. faecalis bacteremia. Recent receipt of carbapenem therapy was an independent risk factor for VR E. faecium bacteremia, and recent receipt of aminoglycoside therapy was independent risk factor for E. faecalis bacteremia.
Asunto(s)
Bacteriemia/mortalidad , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecium/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Resistencia a la Vancomicina , Adulto , Anciano , Aminoglicósidos/efectos adversos , Bacteriemia/complicaciones , Bacteriemia/epidemiología , Bacteriemia/microbiología , Carbapenémicos/efectos adversos , Estudios de Casos y Controles , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Texas/epidemiologíaRESUMEN
We present a case of serious treatment-refractory acyclovir- and foscarnet-resistant herpes simplex virus (HSV) type-1 orolingual infection that responded to oral cidofovir rinses after failure of acyclovir and foscarnet therapy. The use of 3% cidofovir in a saline rinse for refractory mucosal HSV infection appears promising but needs prospective evaluation.
Asunto(s)
Antivirales/administración & dosificación , Citosina/análogos & derivados , Herpesvirus Humano 1/aislamiento & purificación , Organofosfonatos/administración & dosificación , Estomatitis Herpética/tratamiento farmacológico , Estomatitis Herpética/inmunología , Administración Tópica , Antivirales/efectos adversos , Cidofovir , Citosina/administración & dosificación , Citosina/efectos adversos , Farmacorresistencia Viral Múltiple , Femenino , Humanos , Huésped Inmunocomprometido , Persona de Mediana Edad , Antisépticos Bucales , Organofosfonatos/efectos adversos , Trasplante de Células Madre , Estomatitis Herpética/virologíaRESUMEN
Simultaneously drawn quantitative blood cultures are used to diagnose catheter-related bloodstream infections. We conducted this study to determine the frequency with which central venous catheters were the source of bloodstream infections detected through paired positive blood cultures drawn from cancer patients and the potential for quantitative blood cultures to help predict outcome in neutropenic and non-neutropenic patients. From September 1999 to November 2000, we identified 169 patients with bloodstream infections. Of all bloodstream infections, 56% were catheter-related bloodstream infections. Gram-positive bacteremia was found to be catheter-related in 55% and 69% of patients with hematologic malignancy and solid tumors, respectively, whereas gram-negative bacteremia was catheter-related in only 19% of patients with underlying hematologic malignancy and in 60% of patients with solid tumor (P = 0.01). By multivariate analysis, poor response was associated with critical illness and persistent neutropenia (P < 0.01). In neutropenic patients with catheter-related bloodstream infections, peripheral quantitative blood cultures of >or=100 CFU/mL was also associated with poor response (P = 0.05). Central venous catheters were the major source of bloodstream infection, particularly in patients with solid tumors. In addition to critical illness and persistent neutropenia, quantitative blood cultures might be useful in predicting outcomes for neutropenic patients with catheter-related bloodstream infections.