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1.
Clin Infect Dis ; 55 Suppl 2: S132-42, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22752862

RESUMEN

The microflora-sparing properties of fidaxomicin were examined during the conduct of a randomized clinical trial comparing vancomycin 125 mg 4 times per day versus fidaxomicin 200 mg twice per day for 10 days as treatment of Clostridium difficile infection (CDI). Fecal samples were obtained from 89 patients (45 received fidaxomicin, and 44 received vancomycin) at study entry and on days 4, 10, 14, 21, 28, and 38 for quantitative cultures for C. difficile and cytotoxin B fecal filtrate concentrations. Additionally, samples from 10 patients, each receiving vancomycin or fidaxomicin, and 10 samples from healthy controls were analyzed by quantitative real-time polymerase chain reaction with multiple group-specific primers to evaluate the impact of antibiotic treatment on the microbiome. Compared with controls, patients with CDI at study entry had counts of major microbiome components that were 2-3-log(10) colony-forming units (CFU)/g lower. In patients with CDI, fidaxomicin allowed the major components to persist, whereas vancomycin was associated with a further 2-4-log(10) CFU reduction of Bacteroides/Prevotella group organisms, which persisted to day 28 of the study, and shorter term and temporary suppression of both Clostridium coccoides and Clostridium leptum group organisms. In the posttreatment period, C. difficile counts similarly persisted in both study populations, but reappearance of toxin in fecal filtrates was observed in 28% of vancomycin-treated patient samples (29 of 94), compared with 14% of fidaxomicin-treated patient samples (13 of 91; P = .03). Similarly, 23% of vancomycin-treated patients (10 of 44) and 11% of fidaxomicin-treated patients (5 of 44) had recurrence of CDI. Whereas vancomycin and fidaxomicin are equally effective in resolving CDI symptoms, preservation of the microflora by fidaxomicin is associated with a lower likelihood of CDI recurrence.


Asunto(s)
Aminoglicósidos/uso terapéutico , Toxinas Bacterianas/metabolismo , Infecciones por Clostridium/tratamiento farmacológico , Citotoxinas/metabolismo , Intestinos/microbiología , Metagenoma , Vancomicina/uso terapéutico , Aminoglicósidos/administración & dosificación , Antibacterianos/uso terapéutico , Carga Bacteriana , Toxinas Bacterianas/análisis , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/genética , Clostridioides difficile/patogenicidad , Infecciones por Clostridium/microbiología , Citotoxinas/análisis , ADN Bacteriano/análisis , ADN Bacteriano/genética , Método Doble Ciego , Heces/microbiología , Fidaxomicina , Regulación Bacteriana de la Expresión Génica , Humanos , Límite de Detección , ARN Ribosómico 16S/análisis , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Prevención Secundaria , Vancomicina/administración & dosificación
2.
Retrovirology ; 7: 74, 2010 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-20836880

RESUMEN

BACKGROUND: The gut-associated lymphoid tissue (GALT) is the largest lymphoid organ infected by human immunodeficiency virus type 1 (HIV-1). It serves as a viral reservoir and host-pathogen interface in infection. This study examined whether different parts of the gut and peripheral blood lymphocytes (PBL) contain different drug-resistant HIV-1 variants. METHODS: Gut biopsies (esophagus, stomach, duodenum and colon) and PBL were obtained from 8 HIV-1 infected preHAART (highly active antiretroviral therapy) patients at three visits over 18 months. Patients received AZT, ddI or combinations of AZT/ddI. HIV-1 Reverse transcriptase (RT)-coding sequences were amplified from viral DNA obtained from gut tissues and PBL, using nested PCR. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to phylogenetic analyses, and antiretroviral drug mutations were identified. RESULTS: Phylogenetic and drug mutation analyses revealed differential distribution of drug resistant mutations in the gut within patients. The level of drug-resistance conferred by the RT sequences was significantly different between different gut tissues and PBL, and varied with antiretroviral therapy. The sequences conferring the highest level of drug-resistance to AZT were found in the colon. CONCLUSION: This study confirms that different drug-resistant HIV-1 variants are present in different gut tissues, and it is the first report to document that particular gut tissues may select for drug resistant HIV-1 variants.


Asunto(s)
Fármacos Anti-VIH/farmacología , Sangre/virología , Colon/virología , Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Zidovudina/farmacología , ADN Viral/genética , ADN Viral/aislamiento & purificación , Duodeno/virología , Esófago/virología , Transcriptasa Inversa del VIH/genética , VIH-1/efectos de los fármacos , Humanos , Ganglios Linfáticos/virología , Masculino , Mutación Missense , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Estómago/virología , Carga Viral
3.
J Med Imaging Radiat Sci ; 43(1): 52-59, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31052021

RESUMEN

INTRODUCTION: Industrial radiographic film (exposed to light and then cut into a filmcard) is a tool used by radiation therapists (RTs) in the setup of patients before delivering external beam radiation therapy. At the Tom Baker Cancer Center (TBCC), filmcards are reused throughout the day on multiple patients and multiple body sites; thus the risk of cross-contamination exists. The primary objective of this study was to assess the risk of cross-contamination by determining the potential for bacteria to survive on filmcards, in an effort to reduce the risk of cross-infection. METHODS AND MATERIALS: This control study evaluated the potential of the following to survive on filmcards: coliforms, Pseudomonas, Staphylococcus spp. (specifically S. aureus and methicillin-resistant S. aureus [MRSA]), Enterococcus, and hemolytic streptococcus species. Thirty filmcards used by RTs throughout the day were collected and voluntarily placed in individual collection bags. Thirty control cards (unused filmcards) were also collected. Collection bags were stored at 4°C until cultured. A reference strain of MRSA (38591) was used in the MRSA survival assay, along with methicillin-sensitive S. aureus (MSSA) isolate (pure form). The MRSA survival experiment required eight larger, unused filmcards (four designated as negative controls and four positive control cards) to be cut into 28.5 × 6.5 cm. Microbiological plates were used to identify and select for bacteria. The various selective and differential plates contain growth factors, antimicrobials, and color indicators that can selectively allow some groups of bacteria to grow on the plate while inhibiting other types of bacteria. RESULTS: This study provides evidence to support that filmcards are a source of cross-contamination. 58% (17/29) of the used filmcards tested positive for pathogenic bacteria, compared to only 20% (6/30) of the control cards (P = 0.003). Staphylococcus aureus bacteria were present on 11/29 (38%) of the used filmcards, compared to 2/30 (6.7%) on the control filmcards (P = 0.005). Other colonies found on the used filmcards included strep bacteria (P = 0.24), entero bacteria (P = 0.24), and skin flora (P = 0.36); and although reported as statistically insignificant, these bacteria were viable and thus hold a level of clinical significance. In addition, this experiment provides evidence that certain bacteria (including MRSA found to survive on filmcards for at least 21 days) were viable on filmcards, but an incidental finding reports that fungi is also able to survive on filmcards. CONCLUSION: Filmcards used by RTs can harbor a number of pathogenic bacteria, including MRSA, and are therefore a source of cross-contamination. We recommend that the TBCC external beam radiation treatment program-and any other facilities providing external beam radiation therapy-adopt infection control policies that support discarding filmcards after each use (one-time per patient use) or adopt policies that endorse the elimination of filmcards entirely.

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