Hepatic transplant during SARS-CoV-2 (COVID-19) pandemic. A literature review.

ANTECEDENTES: En diciembre de 2019 se identificó en la ciudad de Wuhan, China, un nuevo beta coronavirus, el SARS-CoV-2, como agente causal de neumonía grave, conocida como COVID-19, lo cual ha provocado medidas estrictas de aislamiento, cierre de programas de trasplante hepático y la necesidad de modificar los protocolos de tratamiento. OBJETIVO: Documentar la información publicada sobre el impacto de la COVID-19 en la población con antecedente de trasplante hepático y establecer un protocolo de tratamiento. MÉTODO: Se buscaron en PubMed los términos MeSH "SARS-CoV-2", "COVID-19", "trasplante hepático" y "tratamiento". RESULTADOS: Hasta el momento se ha demostrado en la población con trasplante hepático una mayor facilidad para adquirir el virus, sin una diferencia en la mortalidad al compararla con la población general. La inmunosupresión debe continuar, sin suspender los inhibidores de la calcineurina. Del tratamiento específico, los esteroides son los que han demostrado el mayor beneficio clínico y una disminución de la mortalidad. CONCLUSIÓN: El trasplante hepático no se asocia de manera independiente a una mayor mortalidad. Otros factores, además del trasplante, deben tomarse en cuenta al momento de establecer la gravedad. BACKGROUND: In December 2019, a new beta coronavirus, SARS-CoV-2, was identified in the city of Wuhan, China, as a causative agent of severe pneumonia, known as COVID-19, which has led to strict isolation measures, closure of liver transplantation programs and the need to modify treatment protocols. OBJECTIVE: Document the information published so far on the impact of COVID-19 in the population with a history of liver transplantation and establish a treatment protocol. METHOD: MeSH terms were searched for "SARS-CoV-2", "COVID-19", "liver transplantation" and "treatment". RESULTS: Up to now, a greater ease in acquiring the virus has been shown in the liver transplant population, without a difference in mortality when compared to the general population. Immunosuppression should continue at the minimum tolerated levels, without suspending calcineurin inhibitors. Of the specific treatment, steroids are those that have shown the greatest clinical benefit and decreased mortality. CONCLUSION: Liver transplantation is not independently associated with higher mortality. Factors other than transplantation must be taken into account when considering the risk of severity.

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.

De vuelta a la clínica. Métodos I. Diseños de investigación. Mayor calidad de información, mayor certeza a la respuesta.

Research designs refer to the way information is obtained and are limited by ethical, economic and temporal viability. Research designs are standardized strategies to reduce biases, which in the architectural model of research are identified in the baseline state, the maneuver and the outcome; hence, there are no specific designs for each question. The design with the lowest probability of bias is the clinical trial, followed by cohort and case-control studies and, finally, by cross-sectional surveys. Among the main characteristics that give merit to research designs are the following: population inquiry, which refers to the situation of the population in relation to the clinical course/natural history of the disease; the maneuver, or action that is expected to modify the baseline state, which can be observational or experimental; follow-up, or documented monitoring that is given to each subject, which can be longitudinal or cross-sectional; and directionality, which can prolective or retrolective and refers to the timing of data collection for research purposes. It will always be better having a valuable question, even when answered with a design with higher risk of bias, than a question that is irrelevant or has no applicability.

Los diseños de investigación se refieren a la forma como se obtiene la información y están limitados por viabilidad ética, económica y temporal. Son estrategias estandarizadas para disminuir los sesgos que en el modelo arquitectónico de la investigación se identifican en el estado basal, maniobra y desenlace; de ahí que no hay diseños específicos para cada pregunta. El diseño con menor probabilidad de sesgos es el ensayo clínico, seguido de la cohorte, el estudio de casos y controles y, finalmente, la encuesta transversal. Entre las principales características que dan mérito a los diseños están las siguientes: la pesquisa de la población, que se refiere a la ubicación de la población en relación con el curso clínico o historia natural de la enfermedad; la maniobra, o acción que se espera modifique la condición basal, que puede ser observacional o experimental; el seguimiento, o monitoreo documentado que se le da a cada sujeto, que puede ser longitudinal o transversal; y la direccionalidad, prolectiva o retrolectiva, que alude al tiempo de recopilación de la información con fines de investigación. Siempre será mejor tener una pregunta valiosa, incluso cuando se responda con un diseño con mayor riesgo de sesgos, que una pregunta irrelevante o sin aplicabilidad.

De vuelta a la clínica. Métodos I. Diseños de investigación. Mayor calidad de información, mayor certeza a la respuesta / Back to the clinic. Methods I. Research designs. Higher quality of information, greater certainty to the answer

Resumen Los diseños de investigación se refieren a la forma como se obtiene la información y están limitados por viabilidad ética, económica y temporal. Son estrategias estandarizadas para disminuir los sesgos que en el modelo arquitectónico de la investigación se identifican en el estado basal, maniobra y desenlace; de ahí que no hay diseños específicos para cada pregunta. El diseño con menor probabilidad de sesgos es el ensayo clínico, seguido de la cohorte, el estudio de casos y controles y, finalmente, la encuesta transversal. Entre las principales características que dan mérito a los diseños están las siguientes: la pesquisa de la población, que se refiere a la ubicación de la población en relación con el curso clínico o historia natural de la enfermedad; la maniobra, o acción que se espera modifique la condición basal, que puede ser observacional o experimental; el seguimiento, o monitoreo documentado que se le da a cada sujeto, que puede ser longitudinal o transversal; y la direccionalidad, prolectiva o retrolectiva, que alude al tiempo de recopilación de la información con fines de investigación. Siempre será mejor tener una pregunta valiosa, incluso cuando se responda con un diseño con mayor riesgo de sesgos, que una pregunta irrelevante o sin aplicabilidad.

Abstract Research designs refer to the way information is obtained and are limited by ethical, economic and temporal viability. Research designs are standardized strategies to reduce biases, which in the architectural model of research are identified in the baseline state, the maneuver and the outcome; hence, there are no specific designs for each question. The design with the lowest probability of bias is the clinical trial, followed by cohort and case-control studies and, finally, by cross-sectional surveys. Among the main characteristics that give merit to research designs are the following: population inquiry, which refers to the situation of the population in relation to the clinical course/natural history of the disease; the maneuver, or action that is expected to modify the baseline state, which can be observational or experimental; follow-up, or documented monitoring that is given to each subject, which can be longitudinal or cross-sectional; and directionality, which can prolective or retrolective and refers to the timing of data collection for research purposes. It will always be better having a valuable question, even when answered with a design with higher risk of bias, than a question that is irrelevant or has no applicability.

Candida norvegensis fungemia in a liver transplant recipient / Fungemia por Candida norvegensis en un receptor de trasplante hepático

Background: The incidence of candidemia due to non-Candida albicans Candida species has been progressively increasing in recent years. The use of fluconazole as antifungal prophylaxis has been described as a risk factor for the development of infections by fluconazole resistant Candida strains. We report a case of Candida norvegensis bloodstream infection in a liver transplant recipient. Case report: A 61-year-old man, who received a third liver allograft and became worse with the onset of ischemic cholangiopathy and recurrent episodes of cholangitis, was admitted to our hospital due to the development of intra-abdominal abscesses. He received multiple antibiotic schemes, and after 3 months he was discharged, maintaining parenteral antibiotic at home. While he was on fluconazole prophylaxis, a breakthrough candidemia due to C. norvegensis occurred. In vitro susceptibilities of the isolate to several antifungal agents were as follows: amphotericin B MIC 0.5 mg/l, flucytosine 64 mg/l, fluconazole 64 mg/l, itraconazole 4 mg/l, voriconazole 0.75 mg/l, and caspofungin 0.047 mg/l. He was treated with anidulafungin with resolution of candidemia. Conclusions: The use of fluconazole for antifungal prophylaxis may lead to the emergence of fluconazoleresistant Candida infections, with C. norvegensis being a possible emerging pathogen in organ transplant recipients (AU)

Antecedentes: En los últimos años ha aumentado la incidencia de candidemia causada por especies del género Candida distintas de Candida albicans. Se ha descrito el uso de profilaxis antifúngica con fluconazol como factor de riesgo para el desarrollo de infecciones por cepas de Candida resistentes a este antifúngico. Se describe un caso de fungemia por Candida norvegensis en un receptor de un trasplante hepático. Caso clínico: Un varón de 61 años, receptor de un tercer trasplante hepático que se complica con una colangiopatía isquémica y episodios de colangitis de repetición, ingresó en nuestro hospital por presentar abscesos intraabdominales. Recibió múltiples esquemas antibióticos y, tras 3 meses de ingreso, se dio de alta manteniendo un tratamiento antibiótico parenteral en domicilio. Mientras recibía pro- filaxis con fluconazol, desarrolló una candidemia de brecha por C. norvegensis. Los valores de CMI in vitro del aislamiento para algunos antifúngicos fueron los siguientes: anfotericina B 0,5 mg/l, flucitosina 64 mg/l, fluconazol 64 mg/l, itraconazol 4 mg/l, voriconazol 0,75 mg/l y caspofungina 0,047 mg/l. El paciente recibió tratamiento con anidulafungina, con resolución de la candidemia. Conclusiones: El uso de fluconazol como profilaxis antifúngica puede conllevar la aparición de infecciones por especies de Candida resistentes a este antifúngico, siendo C. norvegensis un posible patógeno emergente en pacientes receptores de un órgano sólido (AU)

Candida norvegensis fungemia in a liver transplant recipient.

BACKGROUND: The incidence of candidemia due to non-Candida albicans Candida species has been progressively increasing in recent years. The use of fluconazole as antifungal prophylaxis has been described as a risk factor for the development of infections by fluconazole resistant Candida strains. We report a case of Candida norvegensis bloodstream infection in a liver transplant recipient. CASE REPORT: A 61-year-old man, who received a third liver allograft and became worse with the onset of ischemic cholangiopathy and recurrent episodes of cholangitis, was admitted to our hospital due to the development of intra-abdominal abscesses. He received multiple antibiotic schemes, and after 3 months he was discharged, maintaining parenteral antibiotic at home. While he was on fluconazole prophylaxis, a breakthrough candidemia due to C. norvegensis occurred. In vitro susceptibilities of the isolate to several antifungal agents were as follows: amphotericin B MIC 0.5 mg/l, flucytosine 64 mg/l, fluconazole 64 mg/l, itraconazole 4 mg/l, voriconazole 0.75 mg/l, and caspofungin 0.047 mg/l. He was treated with anidulafungin with resolution of candidemia. CONCLUSIONS: The use of fluconazole for antifungal prophylaxis may lead to the emergence of fluconazole-resistant Candida infections, with C. norvegensis being a possible emerging pathogen in organ transplant recipients.

Incidence and outcome of early Candida peritonitis after liver and pancreas transplantation.

Candida peritonitis is a potentially life-threatening infection after abdominal transplantation, although there is scant information regarding its incidence and outcome. We analysed the incidence rate and outcome of Candida peritonitis in 717 liver or pancreas transplant recipients. Five cases of Candida peritonitis were diagnosed, representing the second most frequent cause of invasive fungal infection in the cohort. The incidence rate of Candida peritonitis during the first 30 days after transplantation was 6.5 cases/10 000 transplant days in pancreas recipients and 1.2 cases/10 000 transplant days in liver recipients (P = 0.035). Four of the five patients received an echinocandin in combination with other antifungal. All patients were alive and with good graft function at 1-year follow-up. In our series, Candida peritonitis in liver and pancreas transplant recipients was not uncommon and had a good prognosis.

Decreased serum linezolid concentrations in two patients receiving linezolid and rifampicin due to bone infections.

Methicillin-resistant Staphylococcus is a common cause of orthopaedic implant infections. In such cases, rifampicin is the antibiotic of choice, but it should not be administered alone to avoid the selection of resistant mutants. Linezolid has activity against resistant staphylococci and a high oral bioavailability; therefore, it could be a good option for combining with rifampicin. We describe 2 patients admitted to our hospital due to orthopaedic implant infections, who received combination therapy with linezolid and rifampicin. In both cases, the trough serum concentration of linezolid during rifampicin treatment was below the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC(90)) for staphylococci, but increased after rifampicin withdrawal. This finding suggests an interaction between rifampicin and linezolid, and a possible explanation is discussed.

Toxoplasma gondii primary infection in renal transplant recipients. Two case reports and literature review.

Toxoplasmosis after solid organ transplantation is a complication associated with high morbidity and mortality. Universal prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is effective to prevent post-transplant toxoplasmosis. We report two cases of renal transplant recipients with negative antibodies against Toxoplasma gondii pretransplant who developed toxoplasmosis after TMP-SMX discontinuation. We have also performed a review of published cases of primary toxoplasmosis after renal transplantation. Of 20 cases reviewed, 11 were male and the mean age was 37.8 years (SD = 13.8). Donor serology for T. gondii was determined in 15 donors, two of them (13%) with negative immunoglobulin (Ig)G and four (27%) with positive IgG and IgM antibodies. Fever was present in 85% of primary toxoplasmosis and hematologic abnormalities were observed in 69% of the cases. Ten patients died (50%). All patients with fatal outcomes had clinical evidence of toxoplasmosis during the early post-transplant period (first 90 days), while no patient with late toxoplasmosis died (P = 0.003). Primary toxoplasmosis is associated with high mortality rates and TMP-SMX prophylaxis can delay the onset of symptoms resulting in an improvement of prognosis.