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BACKGROUND: Recurrent Clostridioides difficile infection, associated with dysbiosis of gut microbiota, has substantial disease burden in the USA. RBX2660 is a live biotherapeutic product consisting of a broad consortium of microbes prepared from human stool that is under investigation for the reduction of recurrent C. difficile infection. METHODS: A randomized, double-blind, placebo-controlled, phase III study, with a Bayesian primary analysis integrating data from a previous phase IIb study, was conducted. Adults who had one or more C. difficile infection recurrences with a positive stool assay for C. difficile and who were previously treated with standard-of-care antibiotics were randomly assigned 2:1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of C. difficile infection diarrhea within 8 weeks of study treatment. RESULTS: Of the 320 patients screened, 289 were randomly assigned and 267 received blinded treatment (n = 180, RBX2660; n = 87, placebo). Original model estimates of treatment success were 70.4% versus 58.1% with RBX2660 and placebo, respectively. However, after aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo, with an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. More than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups. Overall, RBX2660 was well tolerated, with manageable adverse events. The incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo and was mostly driven by a higher incidence of mild gastrointestinal events. CONCLUSIONS: RBX2660 is a safe and effective treatment to reduce recurrent C. difficile infection following standard-of-care antibiotics with a sustained response through 6 months. CLINICAL TRIAL REGISTRATION: NCT03244644; 9 August, 2017.
Clostridioides difficile is a diarrhea-causing bacterium that is associated with potentially serious and fatal consequences. Antibiotics used to treat or prevent infections have a side effect of damaging the healthy protective gut bacteria (microbiota). Damage to the gut microbiota can allow C. difficile to over-grow and produce toxins that injure the colon. Paradoxically, the standard of care treatment of C. difficile infection (CDI) is antibiotics. Although initially effective for the control of diarrhea, antibiotics can leave a patient at risk for CDI recurrence after antibiotic treatment is stopped. Live biotherapeutic products are microbiota-based treatments used to repair the gut microbiota. These products have been shown to reduce the recurrence of CDI. RBX2660 is an investigational microbiota-based live biotherapeutic. RBX2660 contains a diverse set of microorganisms. RBX2660 has been developed to reduce CDI recurrence in adults following antibiotic treatment for recurrent CDI. This study was conducted to demonstrate that RBX2660 is effective and safe in treating patients with recurrent CDI. Treatment was considered successful in participants who did not experience CDI recurrence within 8 weeks after administration. Overall, statistical modeling demonstrated that 70.6% of participants treated with RBX2660 and 57.5% of participants treated with placebo remained free of CDI recurrence through 8 weeks. A 13.1 percentage point increase in treatment success was observed with RBX2660 treatment compared with placebo. In participants who achieved treatment success at 8 weeks, more than 90% remained free of CDI recurrence through 6 months. The most common side effects with RBX2660 treatment were abdominal pain and diarrhea. No serious treatment-related side effects were reported. The current data from the comprehensive clinical development program support a positive benefit-risk profile for RBX2660 in the reduction of CDI recurrence in adults following antibiotic therapy for recurrent CDI.
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Clostridioides difficile , Infecciones por Clostridium , Adulto , Humanos , Teorema de Bayes , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/prevención & control , Antibacterianos/efectos adversos , Resultado del Tratamiento , Recurrencia , Trasplante de Microbiota Fecal/efectos adversosRESUMEN
Introduction: Metabolic-associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome (MS). MAFLD patients have a higher prevalence of COVID-19. MAFLD also is associated with worse clinical outcomes of COVID-19, such as disease severity, intensive care unit (ICU) admission rate, and higher mortality rates. However, this evidence has not been well characterized in the literature. This meta-analysis aimed to determine the clinical outcomes of COVID-19 among MAFLD patients compared to the non-MAFLD group. Methods: A comprehensive search was conducted in the Cumulative Index of Nursing and Allied Health (CINAHL), PubMed/Medline, and Embase for studies reporting MAFLD prevalence among COVID-19 patients and comparing clinical outcomes such as severity, ICU admission, and mortality among patients with and without MAFLD. The pooled prevalence of MAFLD among COVID-19 patients and the pooled odds ratios (OR) with 95% confidence intervals (CI) for clinical outcomes of COVID-19 were calculated. Results: Sixteen observational studies met inclusion criteria involving a total of 11,484 overall study participants, including 1,746 MAFLD patients. The prevalence of COVID-19 among MAFLD patients was 0.29 (95% CI: 0.19-0.40). MAFLD was associated with the COVID-19 disease severity OR 3.07 (95% CI: 2.30-4.09). Similarly, MAFLD was associated with an increased risk of ICU admission compared to the non-MAFLD group OR 1.46 (95% CI: 1.12-1.91). Lastly, the association between MAFLD and COVID-19 mortality was not statistically significant OR 1.45 (95% CI: 0.74-2.84). Conclusions: In this study, a high percentage of COVID-19 patients had MAFLD. Moreover, MAFLD patients had an increased risk of COVID-19 disease severity and ICU admission rate.
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Introduction: Modern laboratory techniques cannot differentiate between Clostridium difficile colonization and infection; therefore, testing must be indicated clinically. To reduce hospital-onset of C. difficile infections (HO-CDI), Ascension Via Christi Hospitals (AVCH) in Wichita intervened in three stages by introducing: 1) a C. diflcile testing algorithm; 2) an electronic medical record (EMR)-based decision support system to enforce said algorithm; and 3) phone calls from the infection prevention department to providers to discontinue tests not collected within 24 hours of the order. The goal of this study was to determine if these interventions improved the HO-CDI rate. Methods: At AVCH, the three study periods were compared: baseline with algorithm training only, the EMR intervention, and the EMR intervention with additional phone calls (EMR with phone calls). Data were abstracted from the hospital EMR. Results: A total of 311 charts were reviewed. Adherence to the algorithm increased from 34% at baseline to 52% after the EMR intervention (p = 0.010). During the EMR with phone calls period, more tests were discontinued (87%; n = 39) compared to baseline (54%; n = 15) and EMR (54%; n = 15; p = 0.003). The HO-CDI rate ranged from 8.5 cases per 10,000 patient-days at baseline, to 7.9 during EMR, to 4.0 during EMR with phone calls (p = 0.007). Conclusions: The EMR and EMR with phone call interventions were associated with a significant decrease in the HO-CDI rate and an increase in provider adherence to the algorithm.
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Introduction: The COVID-19 pandemic forced most Kansas schools to adopt remote or hybrid learning in 2020-2021. Wichita Collegiate School proceeded with an in-person teaching model. The purpose of this study was to determine if in-person learning can be done safely during the COVID-19 pandemic prior to vaccine use. Methods: Wichita Collegiate is a private school located in Sedgwick County, Kansas. The study population included 671 students (grades 1 - 12) and 130 staff. The procedures implemented during the school year (August 19, 2020 - May 21, 2021) included: mandatory face coverings, six feet physical distancing, and daily temperature checks. A registered nurse performed contact tracing and executed quarantine requirements per the U.S. Centers for Disease Control and Prevention guidelines. Results: Over the study period, 487 students and staff were tested for COVID-19 and 18.5% (n = 90) were positive. Overall, students and staff rate of COVID-19 infection was lower than the expected rate when compared to the surrounding community of Sedgwick County. Thorough contract tracing of positive cases revealed that 2.2% (n = 2) individuals were likely exposed to COVID-19 at school. Conclusions: This study suggested that transmission of COVID-19 was infrequent in a school setting with in-person attendance, even before widespread vaccine availability. By following public health guidelines and utilizing contact tracing, it was possible to limit the spread of COVID-19 during in-person learning. This has immediate implications for how schools safely returned to in-person learning in the post-vaccine era.
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INTRODUCTION: Stool assays used to diagnose Clostridioides difficile infection (CDI) do not differentiate acute CDI from asymptomatic carriers, which contributes to a falsely elevated rate of healthcare-facility onset (HO) CDI when CD stool assays are inappropriately ordered. The aim of this study was to investigate the rate of HO-CDI before and after implementing a mandatory clinical pathway prior to ordering stool tests when suspecting CDI. METHODS: A single-center retrospective observational study was conducted that spanned 12 months. All patients who developed diarrhea 48 hours after being admitted and whose primary physician requested a CD stool assay were included in the study. The intervention consisted of a mandatory sequence of questions that allowed providers to order a CD stool assay only if clinically indicated. RESULTS: Differences in HO-CDI rates pre- and post-intervention were analyzed. The HO-CDI rate during the pre-intervention and post-intervention periods were 24.1 and 0.0, respectively (p = 0.023). CONCLUSION: A marked reduction of the rate of HO-CDI occurred after implementing a mandatory clinical pathway. Setting up a mandatory pre-testing questionnaire could decrease the misclassification of asymptomatic carriers as HO-CDI and the unnecessary prescription of antibiotics in situations where it is not indicated.
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BACKGROUND: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens. METHODS: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections. RESULTS: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%. CONCLUSIONS: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.
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These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of blastomycosis, histoplasmosis, and coccidioidomycosis in the pre- and post-transplant period. Though each of these endemic fungal infections has unique epidemiology and clinical manifestations, they all share a predilection for primary pulmonary infection and may cause disseminated infection, particularly in immunocompromised hosts. Culture remains the gold standard for definitive diagnosis, but more rapid diagnosis may be achieved with direct visualization of organisms from clinical specimens and antigen-based enzyme immunoassay assays. Serology is of limited utility in transplant recipients. The mainstay of treatment for severe infections remains liposomal amphotericin followed by a step-down azole therapy. Cases of mild to moderate severity with no CNS involvement may be treated with azole therapy alone. The newer generation azoles provide additional treatment options, but supported currently with limited clinical efficacy data. Azole therapy in transplant recipients presents a unique challenge owing to the drug-drug interactions with immunosuppressant agents. Therapeutic drug monitoring of azole levels is an essential component of effective and safe therapy. Infection prevention centers around minimizing epidemiological exposures, early clinical recognition, and azole prophylaxis in selected individuals.
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Antifúngicos/uso terapéutico , Enfermedades Endémicas/prevención & control , Hongos/aislamiento & purificación , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Trasplante de Órganos/efectos adversos , Guías de Práctica Clínica como Asunto/normas , Enfermedades Endémicas/estadística & datos numéricos , Humanos , Micosis/etiología , Sociedades Médicas , Receptores de TrasplantesRESUMEN
INTRODUCTION: Traditional evaluation of meningitis includes cerebrospinal fluid (CSF) culture and gram stain to pinpoint specific causal organisms. The BioFire® FilmArray® Meningitis/Encephalitis (ME) Panel has been implemented as a more timely evaluation method. This study sought to assess if the BioFire® ME Panel was associated with a decreased length of stay or decreased antimicrobial duration when used in the diagnosis of meningitis or encephalitis. METHODS: A case, historical-control, chart review was performed on patients admitted to a regional medical center with CSF pleocytosis during Cohort 1 (the year prior to BioFire® ME Panel implementation) and Cohort 2 (the year after BioFire® ME Panel implementation). Length of hospital stay, duration of antimicrobials, and BioFire® ME Panel result were gathered and analyzed. RESULTS: Average length of stay for both cohorts was about four hospital days. Approximately three-fourths of all patients received antibiotic/antiviral treatment with an average of three days duration. No significant differences were observed between groups. The mean (median) duration of antimicrobials in the year prior to and after the BioFire® ME Panel implementation was 3.6 (3) and 3.1 (2) days, respectively (p = 0.835). The mean (median) length of stay in the year prior to and after the BioFire® ME Panel implementation was 5.8 (4) and 5.4 (4) days, respectively (p = 0.941). Among the patients admitted after the implementation of the BioFire® ME Panel, 4.3 % (n = 2) had a positive bacterial result, 38.3% (n = 18) had a positive viral result, and 57.4% (n = 27) had a negative result. Of the 27 negative results, 77.8% (n = 21) were treated with antimicrobial medication. CONCLUSIONS: This study suggested there is no difference between length of stay or antimicrobial duration in presumed meningitis cases assessed with traditional methods as compared to the BioFire® ME Panel.
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Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.
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Anfotericina B/uso terapéutico , Infecciones Fúngicas del Sistema Nervioso Central/diagnóstico , Infecciones Fúngicas del Sistema Nervioso Central/tratamiento farmacológico , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Factores de Edad , Anticuerpos Antifúngicos/líquido cefalorraquídeo , Antígenos Fúngicos/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Infecciones Fúngicas del Sistema Nervioso Central/complicaciones , Infecciones Fúngicas del Sistema Nervioso Central/mortalidad , Femenino , Histoplasmosis/complicaciones , Histoplasmosis/mortalidad , Humanos , Huésped Inmunocomprometido , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Médula Espinal/efectos de los fármacosRESUMEN
Gastrointestinal histoplasmosis is common in patients with disseminated disease affecting both immunocompetent and immunocompromised patients. However, it is often unrecognized due to a lack of specific signs and symptoms. It has only rarely been reported to cause small bowel obstruction, during which surgical treatment was nearly always necessary. Little is known about the usefulness of endoscopic therapy in gastrointestinal histoplasmosis associated strictures. We report the case of a 32-year-old man with a history of hyperimmunoglobulin M syndrome who presented with small bowel obstruction secondary to disseminated gastrointestinal histoplasmosis. Treatment was successful with a through-the-scope balloon dilator in combination with medical therapy. This report adds to the limited data available on the benefit of endoscopic therapy in infectious strictures, particularly gastrointestinal histoplasmosis.
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Dilatación/métodos , Endoscopía Gastrointestinal/métodos , Gastroenteritis/complicaciones , Histoplasmosis/complicaciones , Hipergammaglobulinemia/complicaciones , Inmunoglobulina M , Obstrucción Intestinal/etiología , Obstrucción Intestinal/terapia , Adulto , Humanos , Obstrucción Intestinal/diagnóstico por imagen , MasculinoRESUMEN
We report a case of human herpesvirus-6 (HHV-6) encephalitis in a neutropenic patient who had undergone chemotherapy induction for acute myelogenous leukemia while on broad-spectrum antimicrobial therapy. The patient displayed symptoms of confusion, amnesia, and lethargy. Diagnosis was made via polymerase chain reaction analysis of cerebrospinal fluid. Electroencephalogram and magnetic resonance imaging of the brain were unremarkable. Following diagnosis, the patient was successfully treated with ganciclovir. HHV-6 encephalitis should be considered in immunocompromised patients who become encephalopathic.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Encefalitis Viral/diagnóstico , Quimioterapia de Inducción/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Infecciones por Roseolovirus/diagnóstico , Anciano , Antiinfecciosos/uso terapéutico , Biopsia , Médula Ósea/patología , Encéfalo/diagnóstico por imagen , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/microbiología , Neutropenia Febril Inducida por Quimioterapia/terapia , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/terapia , Electroencefalografía , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/virología , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Quimioterapia de Inducción/métodos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Imagen por Resonancia Magnética , Masculino , Pancitopenia/sangre , Pancitopenia/diagnóstico , Infecciones por Roseolovirus/líquido cefalorraquídeo , Infecciones por Roseolovirus/tratamiento farmacológico , Infecciones por Roseolovirus/virología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.
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Antiinflamatorios/efectos adversos , Histoplasmosis/complicaciones , Infliximab/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/efectos adversos , Adalimumab/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , Antifúngicos/uso terapéutico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Niño , Etanercept/efectos adversos , Etanercept/uso terapéutico , Femenino , Histoplasmosis/tratamiento farmacológico , Humanos , Síndrome Inflamatorio de Reconstitución Inmune , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Infective endocarditis is an uncommon manifestation of infection with Histoplasma capsulatum. The diagnosis is frequently missed, and outcomes historically have been poor. We present 14 cases of Histoplasma endocarditis seen in the last decade at medical centers throughout the United States. All patients were men, and 10 of the 14 had an infected prosthetic aortic valve. One patient had an infected left atrial myxoma. Symptoms were present a median of 7 weeks before the diagnosis was established. Blood cultures yielded H. capsulatum in only 6 (43%) patients. Histoplasma antigen was present in urine and/or serum in all but 3 of the patients and provided the first clue to the diagnosis of histoplasmosis for several patients. Antibody testing was positive for H. capsulatum in 6 of 8 patients in whom the test was performed. Eleven patients underwent surgery for valve replacement or myxoma removal. Large, friable vegetations were noted at surgery in most patients, confirming the preoperative transesophageal echocardiography findings. Histopathologic examination of valve tissue and the myxoma revealed granulomatous inflammation and large numbers of organisms in most specimens. Four of the excised valves and the atrial myxoma showed a mixture of both yeast and hyphal forms on histopathology. A lipid formulation of amphotericin B, administered for a median of 29 days, was the initial therapy in 11 of the 14 patients. This was followed by oral itraconazole therapy, in all but 2 patients. The length of itraconazole suppressive therapy ranged from 11 months to lifelong administration. Three patients (21%) died within 3 months of the date of diagnosis. All 3 deaths were in patients who had received either no or minimal (1 day and 1 week) amphotericin B.
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Anfotericina B/administración & dosificación , Antígenos Fúngicos , Endocarditis , Histoplasma , Histoplasmosis , Itraconazol/administración & dosificación , Mixoma , Infecciones Relacionadas con Prótesis , Anciano , Anciano de 80 o más Años , Antifúngicos/administración & dosificación , Antígenos Fúngicos/sangre , Antígenos Fúngicos/orina , Válvula Aórtica/patología , Válvula Aórtica/cirugía , Ecocardiografía Transesofágica/métodos , Endocarditis/diagnóstico , Endocarditis/etiología , Endocarditis/inmunología , Endocarditis/terapia , Atrios Cardíacos/patología , Atrios Cardíacos/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Histoplasma/efectos de los fármacos , Histoplasma/inmunología , Histoplasmosis/complicaciones , Histoplasmosis/diagnóstico , Histoplasmosis/inmunología , Histoplasmosis/terapia , Humanos , Masculino , Registros Médicos Orientados a Problemas , Persona de Mediana Edad , Mixoma/complicaciones , Mixoma/patología , Mixoma/cirugía , Infecciones Relacionadas con Prótesis/complicaciones , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/terapia , Resultado del Tratamiento , Estados UnidosAsunto(s)
Fungemia/diagnóstico , Histoplasmosis/diagnóstico , Trasplante de Pulmón/efectos adversos , Sarcoidosis Pulmonar/cirugía , Progresión de la Enfermedad , Enfermedades Endémicas , Resultado Fatal , Fungemia/terapia , Histoplasmosis/terapia , Humanos , Italia , Trasplante de Pulmón/métodos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Sarcoidosis Pulmonar/patología , Factores de Tiempo , Receptores de TrasplantesRESUMEN
Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results.
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Antibacterianos/uso terapéutico , Aspergilosis/diagnóstico , Aspergillus/aislamiento & purificación , Pruebas Diagnósticas de Rutina/métodos , Reacciones Falso Positivas , Mananos/sangre , Suero/química , Anciano de 80 o más Años , Antibacterianos/química , Contaminación de Medicamentos , Femenino , Galactosa/análogos & derivados , Humanos , Técnicas para Inmunoenzimas/métodos , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/química , Ácido Penicilánico/uso terapéutico , Piperacilina/química , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Estados UnidosRESUMEN
BACKGROUND: To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. METHODS: All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. RESULTS: One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. CONCLUSIONS: Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.
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Histoplasmosis/epidemiología , Trasplante de Órganos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Niño , Preescolar , Femenino , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/inmunología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D(+)/R(-)) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. METHODS: We prospectively included D(+)/R(-) patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. RESULTS: Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P < .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI], .74-.98) and 0.27 (95% CI, .18-.37), respectively. CONCLUSIONS: This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis. CLINICAL TRIALS REGISTRATION: NCT00817908.