Optimización del diagnóstico de hepatitis por citomegalovirus en receptores de trasplante hepático: diez años de experiencia / Cytomegalovirus hepatitis diagnosis optimization in liver transplant recipients: 10 years of experience

Resumen Introducción: Para los pacientes receptores de trasplante hepático (TH) la hepatitis por citomegalovirus (CMV) constituye una entidad de difícil diagnóstico. Nuestro objetivo fue determinar la real incidencia de hepatitis por CMV aplicando técnicas diagnósticas más específicas. Material y Métodos: Estudio retrospectivo/ prospectivo, en un centro de trasplante hepático. Período de estudio: años 2009 al 2019. Se incluyeron los TH que presentaron elementos sugestivos y/o específicos de CMV en la histopatología de la punción biopsia hepática (PBH), a los que se les realizó inmunohistoquimica (IHQ) en la PBH. Población control n = 17. Resultados: 41 casos cumplieron los criterios de inclusión. La IHQ fue positiva en n = 6 (14,6%). En la población control, la IHQ fue negativa en el 100% de los casos. Esto traduce un valor predictor negativo de 100% para la histopatología en el diagnóstico de hepatitis por CMV, con un valor predictor positivo de 14,6%. En 85% de los pacientes con IHQ negativa, hubo diagnósticos alternativos. La terapia antiviral en la fase retrospectiva se indicó en 48% y en la prospectiva en 21%. Conclusiones: Combinar la histopatología con la IHQ optimiza el diagnóstico de hepatitis por CMV; lo que permite la racionalización del uso de antivirales de alto costo y la búsqueda de etiologías diferenciales.

Abstract Background: Cytomegalovirus (CMV) hepatitis constitutes a challenging diagnostic entity in liver transplant (LT) recipients. Aim: To determine the real incidence of CMV hepatitis using more specific diagnostic tools as those currently used before. Methods: Retrospective/prospective study conducted in a hepatic transplant unit from 2009 to 2019. LT recipients with CMV specific or suggestive elements in histopathology of hepatic biopsies were included. Immunohistochemistry (IHQ) was performed in tissue samples of the studied cohort as well as in a control one. Results: 41 patients met the inclusion criteria. IHQ was diagnostic in 6 (14.6%), and was negative in 100% of the control population. The negative predictive value of the histopathology for CMV hepatitis diagnosis was 100% and the positive predictive value was 14.6%. 85% of patients in whom the IHQ was negative had alternative diagnosis Antiviral therapy in the retrospective analysis was indicated in 48% of patients and in 21% of the prospectively analyzed cohort. Conclusions: Histopathology and IHQ combination improves the diagnostic accuracy of CMV hepatitis which translates into a rational us of expensive antiviral therapy and to search for differential diagnosis

Trastornos neurocognitivos en pacientes VIH positivos: datos preliminares de una cohorte prospectiva uruguaya / Neurocognitive disorders in positive HIV patients: preliminary data of a Uruguayan prospective cohort

Introducción: la incidencia de formas leves y moderadas de trastornos neurocognitivos (TNC) en pacientes con VIH (virus de inmunodeficiencia humana) permanece en ascenso a pesar del uso de terapia antirretroviral (TARV). En la región existen escasos trabajos que estudiaron los TNC en VIH. Objetivos: describir características de pacientes con TNC, identificar posibles etiologías y si se realiza su búsqueda. Material y método: estudio transversal de recolección prospectiva. Se reclutaron en forma consecutiva pacientes de 18 a 60 años VIH positivos sin patología estructural del sistema nervioso central. Se aplicaron exámenes de laboratorio, preguntas para tamizaje de TNC, escala instrumental de actividades de la vida diaria (EIAVD) e internacional de demencia por VIH (EIDV), Adenbrooke's Cognitive Examination Revisado (ACE-R). ACE-R fue elegida como prueba de referencia de desempeño neurocognitivo. Se utilizó inventario de Beck para pesquisa de trastorno depresivo. Análisis estadístico con sistema SPSS. Resultados y discusión: se reclutaron 20 pacientes, se diagnosticó TNC en 9/20 (45%). Los médicos tratantes plantearon TNC en 2/9 pacientes. El análisis multivariado encontró asociación entre desempleo (p=0,012) y menor escolarización (p=0,035) en pacientes con TNC. Etiología de TNC en 9/9 fue multifactorial. Refirieron TNC en el tamizaje 8/9 pacientes. EIDV fue adecuada para detección de TNC severo, pero no para leve. EIAVD tampoco logró detectar algunos casos de TNC. Conclusiones: casi la mitad de pacientes presentaron TNC de causa multifactorial con asociación a desempleo y menor escolarización. Los médicos tratantes no plantearon este diagnóstico, lo que marca la importancia de la evaluación neuropsicológica sistemática en pacientes VIH.

Introduction: the incidence of mild and moderate neurocognitive disorders (NCDs) in HIV patients continues to increase in spite of antiretroviral therapy (ART). Only a few studies in the region focused on HIV associated NCDs. Objective: to describe the characteristics of NCDs patients, identify posible etiologies and decide whether to start the search. Method: transversal study with a prospective collection of data. HIV positive patients between 18 and 60 years old with no structural defects of the central nervous system (CNS) were consecutively recruited. Laboratory tests were applied as well as screening for CNS, the Instrumental activities of daily living (IADLs) scale, the International HIV Dementia Scale (IHDS), and the Adenbrooke's Cognitive Examination revised exam (ACE-R). The latter was chosen as the reference test for neurocognitive performance. The Beck Depression inventory (BDI) was used to identify drepression. Statistical analysis was conducted with the SPSS system. Results and discussion: 20 patients were recruited, NCD was diagnosed in 9 out of 20 patients (45%). Treating physicians spoke about NCD in 2 of the 9 patients. Multivariate analysis revealed an association between unemployment (p=0.012) and a lower schooling rate (p=0.035) in patients with NCDs. Etiology of NCD was multifactorial in all 9 patients. 8 out of 9 patients were referred as NCDs in the screening. IHDS was appropriate to identify severe NCDs, although it failed in mild cases. Also, IADLs failed to identify a few cases of NCDs. Conclusions: almost half of the patients presented multifactorial NCDs, associated to unemployment and a lower rate of schooling. Treating physicians did not consider this diagnosis, what reflects the importance of a systematic neuropsychological assessment in HIV patients.

Introdução: a incidência de formas leves e moderadas de transtornos neurocognitivos (TNC) em pacientes com VIH (vírus de imunodeficiência humana) continua crescendo apesar do uso da terapia antirretroviral (TARV). Poucos trabalhos estudaram TNC em pacientes VIH positivos na regiao. Objetivos: descrever as características dos pacientes com TNC, identificar possíveis etiologias e se são pesquisados no paciente. Método: estudo transversal com coleta de dados prospectiva. Foram incluídos de forma consecutiva pacientes com idades entre 18 e 60 anos VIH positivos sem patologia estrutural do sistema nervoso central (SNC). Foram realizados exames de laboratório, um questionário para triagem dos TNC, e foram aplicadas as escalas Instrumental de Atividades da Vida Diária (EIAVD), Internacional de Demência por VIH (EIDV) e Adenbrooke's Cognitive Examination Revisado (ACE-R). Esta última foi escolhida como prova de referencia de desempenho neurocognitivo. O inventário de Beck foi utilizado para pesquisa de transtorno depressivo. A análise estatística foi realizada com o pacote SPSS. Resultados e discussão: foram incluídos 20 pacientes sendo que os TNC foram diagnosticados em 9/20 (45%). Os médicos que atenderam esses pacientes diagnosticaram TNC em 2/9 pacientes. A análise multivariada mostrou uma associação entre desemprego (p=0,012) e menor escolarização (p=0,035) em pacientes com TNC. A etiologia dos TNC em 9/9 foi multifatorial. A triagem mostrou TNC em 8/9 pacientes. O teste EIDV foi adequado para a detecção dos TNC severos porém não para leves, e também não pode detectar alguns casos de TNC. Conclusões: quase a metade dos pacientes apresentou TNC de causa multifatorial associados a desemprego e menor escolarização. Os médicos que atenderam os pacientes não diagnosticaram esses transtornos o que mostra a importância da avaliação neuropsicológica sistemática em pacientes VIH.

Sepsis caused by New Delhi metallo-ß-lactamase (blaNDM-1) and qnrD-producing Morganella morganii, treated successfully with fosfomycin and meropenem: case report and literature review.

OBJECTIVES: The objective of this study was to describe the microbiological characteristics of an extensively drug-resistant (XDR) isolate of Morganella morganii obtained from a patient with sepsis of urinary origin and to describe the patient's clinical characteristics. We further aimed to perform a literature review of the situation in Latin America regarding Gram-negative bacillus (GNB) carriers of New Delhi metallo-ß-lactamase (NDM-1) and qnr genes and current reports on the treatment of infections caused by XDR enterobacteria, with particular attention to colistin-resistant isolates. METHODS: The patient's clinical data were obtained from his medical history. Microbiological identification and susceptibility testing were done using the VITEK 2 Compact System. Resistance genes were detected by PCR and sequencing. RESULTS: Blood and urine cultures grew an M. morganii isolate (Mm4232) harboring NDM-1 and qnrD1. The patient was treated successfully with fosfomycin and double doses of meropenem. There are no previous reports of the use of fosfomycin and meropenem to treat infections by XDR enterobacteria harboring NDM-1 carbapenemase. CONCLUSIONS: This is the first report of qnrD1 in South America. We consider that this report could be helpful to physicians implementing treatments for infections caused by XDR GNB, including colistin-carbapenem-resistant GNB.

Infección de sitio quirúrgico en el Programa de Trasplante Hepático en Uruguay: alta incidencia de bacilos gramnegativos multirresistentes y extremadamente resistentes / Surgical site infection in the Liver Transplant Program in Uruguay: high incidence of multiresistant and extremely resistant gram-negative bacilli

Introducción: la infección de sitio quirúrgico (ISQ) en trasplante hepático (TH) significa para estos pacientes una importante causa de morbimortalidad. Objetivo: conocer la incidencia de ISQ, identificar microorganismos involucrados y factores favorecedores en vistas de optimizar nuestras estrategias de profilaxis. Material y método: estudio de cohorte en el cual los pacientes con trasplante hepático fueron incluidos prospectivamente en nuestra base de datos nacional, BaDaInTOS. Período de estudio: 14 de julio de 2009 a 31 de mayo 2013. Análisis estadístico: se utilizó chi cuadrado. Si el valor en tabla de contingencia fue menor o igual a 5 se usó el test exacto de Fisher. Se consideró significativo un valor de p < 0,05. Resultados: se trasplantaron 65 pacientes en este período. La frecuencia relativa acumulada de ISQ fue de 12 pacientes (18,46%); la distribución temporal muestra un aumento en su incidencia en los últimos 12 meses donde se presentaron siete episodios (58%) de todos los episodios de ISQ. La mediana de presentación fue de 17 días. Del total de pacientes con ISQ, 7 presentaron factores de riesgo para microorganismos multirresistentes en el pretrasplante. Se aislaron 16 microorganismos, 12 correspondieron a bacilos gramnegativos (BGN): (Klebsiella spp, n = 6), (Acinetobacter baumannii, n = 2), (Enterobacter cloacae, n = 1), (Aeromonas spp, n = 1), (Pseudomonas aeruginosa, n = 1), (E. coli, n = 1). En cuanto al perfil de resistencia: diez pacientes presentaron perfil de multirresistencia (MDR) y extremada resistencia (XDR). Conclusiones: uno de cada cinco pacientes presentó ISQ en nuestro centro, con una alta incidencia de BGN, MDR y XDR.

Polyclonal endemicity of Acinetobacter baumannii in ventilated patients in an intensive care unit in Uruguay.

OBJECTIVES: To identify the mechanisms responsible for respiratory infections by Acinetobacter baumannii in intubated patients and risk factors for digestive colonization and infection by A. baumannii. METHODS: We conducted a prospective study in an intensive care unit (ICU) between May 2005 and November 2006, including 175 consecutive patients at the beginning of invasive ventilation (day 1). We performed pharyngeal and rectal swabs on days 1, 4, 7, 10, 13, and 16. Respiratory samples were taken on days 1 and 7, or on suspicion of ventilator-associated pneumonia (VAP). RESULTS: We detected 62 patients with A. baumannii digestive colonization and 20 cases of A. baumannii lower respiratory infection (14 VAP and six purulent tracheobronchitis (PTB)). Digestive colonization by A. baumannii was an independent risk factor for lower respiratory tract infections with that microorganism (p<0.0001; relative risk 8.71, 95% confidence interval 2.73-27.77). Respiratory and rectal A. baumannii isolates from the same patients were compared by enterobacterial repetitive intergenic consensus (ERIC)-PCR; in 9/11 cases (eight VAP and one PTB) results suggested events of exogenous pneumonia with previous colonization, whereas the remaining two cases (two PTB) were suggestive of exogenous infection without previous colonization. CONCLUSIONS: In our unit the pathogenesis of VAP by A. baumannii is mixed, most cases corresponding to exogenous pneumonia with previous colonization.

Ceftriaxone and ciprofloxacin restriction in an intensive care unit: less incidence of Acinetobacter spp. and improved susceptibility of Pseudomonas aeruginosa / Restricción del uso de ceftriaxona y ciprofloxacino en una unidad de cuidados intensivos: menor incidencia de Acinetobacter spp. y mayor sensibilidad de Pseudomonas aeruginosa

Objective. To determine whether restricting the use of ceftriaxone and ciprofloxacin could significantly reduce colonization and infection with resistant Gram-negative bacilli (r-GNB). Methods. A two-phase prospective study (before/after design) was conducted in an intensive care unit in two time periods (2004–2006). During phase 1, there was no antibiotic restriction. During phase 2, use of ceftriaxone or ciprofloxacin was restricted. Results. A total of 200 patients were prospectively evaluated. In phase 2, the use of ceftriaxone was reduced by 93.6% (P = 0.0001) and that of ciprofloxacin by 65.1% (P = 0.041), accompanied by a 113.8% increase in use of ampicillin-sulbactam (P = 0.002). During phase 1, 48 GNB were isolated [37 r-GNB (77.1%) and 11 non-r-GNB (22.9%)], compared with a total of 64 during phase 2 [27 r-GNB (42.2%) and 37 non-r-GNB (57.8%)] (P = 0.0002). Acinetobacter spp. was isolated 13 times during phase 1 and 3 times in phase 2 (P = 0.0018). The susceptibility of Pseudomonas aeruginosa to ciprofloxacin increased from 40.0% in phase 1 to 100.0% in phase 2 (P = 0.0108). Conclusions. Restriction of ceftriaxone and ciprofloxacin reduced colonization byAcinetobacter spp. and improved the susceptibility profile of P. aeruginosa.

Objetivo. Determinar si la restricción del uso de ceftriaxona y ciprofloxacino reduce significativamente la colonización y la infección por bacilos gramnegativos resistentes. Métodos. Se efectuó un estudio prospectivo de dos fases (diseño antes/después de la intervención) en una unidad de cuidados intensivos en dos períodos sucesivos entre los años 2004 y 2006. Durante la fase 1, no hubo ninguna restricción de antibióticos. Durante la fase 2, se restringió el uso de ceftriaxona y ciprofloxacino. Resultados. Se evaluó prospectivamente a 200 pacientes en total. En la fase 2, el uso de ceftriaxona se redujo en 93,6% (P = 0,0001) y el de ciprofloxacino en 65,1% (P = 0,041), lo que se acompañó de un aumento de 113,8% en el uso de ampicilina/sulbactam (P = 0,002). Durante la fase 1, se aislaron 48 bacilos gramnegativos (37 resistentes [77,1%] y 11 no resistentes [22,9%]), en comparación con un total de 64 durante la fase 2 (27 resistentes [42,2%] y 37 no resistentes [57,8%]) (P = 0,0002). Se aisló Acinetobacter spp. 13 veces durante la fase 1 y 3 veces en la fase 2 (P = 0,0018). La sensibilidad de Pseudomonas aeruginosa al ciprofloxacino aumentó de 40,0% en la fase 1 a 100,0% en la fase 2 (P = 0,0108). Conclusiones. La restricción del uso de ceftriaxona y ciprofloxacino redujo la colonización por Acinetobacter spp. y mejoró el perfil de sensibilidad de P. aeruginosa.

Ceftriaxone and ciprofloxacin restriction in an intensive care unit: less incidence of Acinetobacter spp. and improved susceptibility of Pseudomonas aeruginosa.

OBJECTIVE: To determine whether restricting the use of ceftriaxone and ciprofloxacin could significantly reduce colonization and infection with resistant Gram-negative bacilli (r-GNB). METHODS: A two-phase prospective study (before/after design) was conducted in an intensive care unit in two time periods (2004-2006). During phase 1, there was no antibiotic restriction. During phase 2, use of ceftriaxone or ciprofloxacin was restricted. RESULTS: Atotal of 200 patients were prospectively evaluated. In phase 2, the use of ceftriaxone was reduced by 93.6% (P = 0.0001) and that of ciprofloxacin by 65.1% (P = 0.041), accompanied by a 113.8% increase in use of ampicillin-sulbactam (P = 0.002).During phase 1, 48 GNB were isolated [37 r-GNB (77.1%) and 11 non-r-GNB (22.9%)], compared with a total of 64 during phase 2 [27 r-GNB (42.2%) and 37 non-r-GNB (57.8%)](P = 0.0002). Acinetobacter spp. was isolated 13 times during phase 1 and 3 times in phase 2 (P = 0.0018). The susceptibility of Pseudomonas aeruginosa to ciprofloxacin increased from 40.0% in phase 1 to 100.0% in phase 2 (P = 0.0108). CONCLUSIONS: Restriction of ceftriaxone and ciprofloxacin reduced colonization by Acinetobacter spp. and improved the susceptibility profile of P. aeruginosa.