Etiología de la insuficiencia renal en pacientes con endocarditis infecciosa. Papel de los antibióticos / Aetiology of renal failure in patients with infective endocarditis. The role of antibiotics

Fundamento y objetivos: La toxicidad renal de ciertos antibióticos (AB) es conocida. El objetivo de nuestro trabajo es conocer el posible efecto de los tratamientos AB en el desarrollo de insuficiencia renal (IR) en pacientes con endocarditis infecciosa (EI). Material y método: Recogida en un registro nacional multicéntrico de los datos referentes a la función renal, tanto previa como su deterioro si existiese, durante el tratamiento de las EI y relacionarlo con los posibles factores causantes, entre ellos los AB. Resultados: Entre 2008 y 2012 se han analizado 1.853 episodios de EI remitidos desde 26 centros españoles. De ellos, un 21,6% presentaban una alteración previa de la función renal. Desarrollaron IR de novo o un empeoramiento de la función renal previa un 38,7% de los casos. En aquellos pacientes que presentaban IR previa, el deterioro fue más frecuente (64 frente a 31,7%; p<0,001). Globalmente los pacientes con IR tenían más edad (70,6 frente a 67 años; p<0,01) y comorbilidades (índice de Charlson 5 frente a 4; p<0,01), y la EI era por Staphylococcus aureus (32,1 frente a 16,5%; p<0,01). El uso de AB potencialmente nefrotóxicos solo se asoció a IR en el grupo de pacientes sin IR previa (aminoglucósidos: OR=1,47 [IC 95% 1,096-1,988], p=0,010; aminoglucósidos-vancomicina: OR=1,49 [IC 95% 1,069-2,09], p=0,019]). Conclusiones: En pacientes sin IR previa, los AB nefrotóxicos se asocian a un deterioro de la función renal. En pacientes con IR previa al episodio de EI, el deterioro de renal fue más frecuente, pero parece estar más relacionado con la gravedad de la infección (AU)

Background and objectives: The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). Material and method: Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. Results: Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001). Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988], P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019). Conclusions: In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection (AU)

Aetiology of renal failure in patients with infective endocarditis. The role of antibiotics. / Etiología de la insuficiencia renal en pacientes con endocarditis infecciosa. Papel de los antibióticos.

BACKGROUND AND OBJECTIVES: The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). MATERIAL AND METHOD: Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. RESULTS: Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001). Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988], P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019). CONCLUSIONS: In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection.

[Applicability of pharmacogenetic studies in daily clinical practice]. / Aplicabilidad de los estudios farmacogenéticos en la práctica clínica.

In the last few years, research in pharmacogenetics and pharmacogenomics has identified distinct variants or markers that can help to define the benefits and risk of patients requiring antiretroviral treatment. The beneficial effect of the deletion 32 allele of the CCR5 coreceptor on the natural history of HIV infection and, to a certain extent, on treatment response is well known. The bases of immune reconstitution after initiation of antiretroviral therapy, although the subject of intense study, are probably multifactorial and polygenetic and consequently conclusions with clear applicability to clinical practice are currently lacking. Among the risks, no significant progress has been made in lipodystrophy. The origin of dyslipidemia associated with antiretroviral treatment and the excess cardiovascular risk conferred by some antiretroviral drugs is probably polygenetic and, at present, poorly defined. The genetic bases of efavirenz-induced neurological toxicity and of hyperbilirubinemia secondary to atazanavir are fairly well known, although their application in daily clinical practice has not been adequately assessed. Some aspects that help to understand the molecular bases of hypersensitivity reaction to nevirapine and of nevirapine-induced hepatotoxicity have been described but are not applicable in most cases and consequently further studies are required. Some data correlate tenofovir-induced renal toxicity with genetic variations in some transport proteins. The most significant advance for clinical practice is the correlation between the presence of the HLA-B*5701 allele and hypersensitivity reaction to abacavir. In particular, one clinical trial with a large number of patients from distinct ethnic groups found that the probability of not developing hypersensitivity reaction (immunologically confirmed) was 100% if the patient was HLA-B*5701-negative. These data suggest the need to implement this test in daily clinical practice.

Relato histórico de la infectología española / History of Infectious Diseases in Spain

En el presente manuscrito se hace un breve resumen de lo que ha sido la historia de la infectología en España. Se consideran cuatro secciones referidas, en primer lugar, a los orígenes de una especialidad fruto de la necesidad de contar con expertos que dieran solución de una forma práctica y moderna a los diferentes problemas planteados por los pacientes con enfermedades infecciosas. En segundo lugar, la aparición del sida al comienzo de los años ochenta dio lugar a un enorme florecimiento en el campo de las enfermedades infecciosas, que trajo consigo la creación de unidades específicas dedicadas no sólo al control de los problemas asociados directamente con la infección por el virus de la inmunodeficiencia humana, sino al tratamiento de las infecciones oportunistas con comitantes. En tercer lugar, en estos últimos años ha despuntado de forma alarmante el problema de la infección nosocomial, problema de plena actualidad que obliga a la presencia de infectólogos expertos en este campo. Finalmente, la emigración y los viajes han requerido de los especialistas en enfermedades infecciosas una formación especial en salud internacional, lo que acrecienta la importancia de la disciplina de infectología (AU)

This paper includes a brief summary of the clinical historyof the diagnosis and treatment of infectious diseases in Spain. Firstly, the origins of a specialty arising from the need for specialists to attend to, in a practical and modern form, the different health problems of patients affected by infectious diseases, are described. Secondly, the appearance of AIDS, at the beginning of the 1980’s, prompted the creation of specific units dedicated to the care of problems associated with human immunodeficiency virus (HIV) infection and the concomitant opportunistic infections arising from the immunodeficiency arising from the HIV infection. Thirdly, in the last decades and even today, nosocomial infections have appeared as an alarming problem, needing the presence of specialist physicians in this field. Finally, emigration and international travel require specialists ininfectious diseases with specific expertise in international health, once more highlighting the importance of the specialty of Infectious Diseases (AU)

Relato histórico de la infectología española / History of Infectious Diseases in Spain

En el presente manuscrito se hace un breve resumen de loque ha sido la historia de la infectología en España. Seconsideran cuatro secciones referidas, en primer lugar, alos orígenes de una especialidad fruto de la necesidad decontar con expertos que dieran solución de una formapráctica y moderna a los diferentes problemas planteadospor los pacientes con enfermedades infecciosas. Ensegundo lugar, la aparición del sida al comienzo de losaños ochenta dio lugar a un enorme florecimiento en elcampo de las enfermedades infecciosas, que trajo consigola creación de unidades específicas dedicadas no sólo alcontrol de los problemas asociados directamente con lainfección por el virus de la inmunodeficiencia humana, sino al tratamiento de las infecciones oportunistasconcomitantes. En tercer lugar, en estos últimos años hadespuntado de forma alarmante el problema de lainfección nosocomial, problema de plena actualidad queobliga a la presencia de infectólogos expertos en estecampo. Finalmente, la emigración y los viajes hanrequerido de los especialistas en enfermedades infecciosas una formación especial en salud internacional, lo que acrecienta la importancia de la disciplina de infectología

This paper includes a brief summary of the clinical history of the diagnosis and treatment of infectious diseases in Spain. Firstly, the origins of a specialty arising from the need for specialists to attend to, in a practical and modern form, the different health problems of patients affected by infectious diseases, are described. Secondly, the appearance of AIDS, at the beginning of the 1980’s, prompted the creation of specific units dedicated to the care of problems associated with human immunodeficiency virus (HIV) infection and the concomitant opportunistic infections arising from the immunodeficiency arising from the HIV infection. Thirdly, in the last decades and even today, nosocomial infections have appeared as an alarming problem, needing the presence of specialist physicians in this field. Finally, emigration and international travel require specialists in infectious diseases with specific expertise in international health, once more highlighting the importance of the specialty of Infectious Diseases (AU)

Aplicabilidad de los estudios farmacogenéticos en la práctica clínica / Applicability of pharmacogenetic studies in daily clinical practice

En estos últimos años, la investigación en el campo de la farmacogenética y la farmacogenómica está permitiendo identificar distintas variantes o marcadores que pueden ayudar a definir los beneficios y riesgos de los pacientes que precisan tratamiento antirretroviral. Es bien conocido el efecto beneficioso de la deleción 32 del correceptor CCR5 en la historia natural de la infección por el virus de la inmunodeficiencia humana (VIH) y, en cierta medida, en la respuesta al tratamiento. Las bases de la reconstitución inmunitaria tras el inicio del tratamiento antirretroviral, aunque se están estudiando intensamente, son probablemente multifactoriales y poligénicas, por lo que no hay, en la actualidad, conclusiones claras aplicables a la práctica clínica(AU)

Entre los riesgos, aún no se han producido avances significativos en el campo de la lipodistrofia. El origen de la dislipidemia asociada al tratamiento antirretroviral y el propio exceso de riesgo cardiovascular conferido por algunos fármacos antirretrovirales es, probablemente, de origen poligénico y aún no bien definido. Se conocen bastante bien las bases genéticas de la toxicidad neurológica por efavirenz y de la hiperbilirrubinemia secundaria a atazanavir, aunque su traslación a la clínica diaria aún no se ha valorado adecuadamente. Se han descrito algunos aspectos que ayudan a entender las bases moleculares de la reacción de hipersensibilidad (RHS) a la nevirapina y de toxicidad hepática por dicho fármaco, aunque no ®capturan» la mayoría de los casos, por lo que será necesario proseguir los estudios. Hay algunos datos que correlacionan la toxicidad renal por tenofovir con variaciones genéticas en algunas proteínas de transporte. El avance más significativo para la práctica clínica es la correlación de la presencia del alelo HLA-B*5701 con la RHS al abacavir (ABC); especialmente el hecho de que en un ensayo clínico con muchos pacientes y diferentes etnias el valor predictivo negativo de la prueba sea del 100%, es decir, la probabilidad de no desarrollar la RHS (comprobada inmunológicamente) es de 100% si el paciente es HLA-B*5701 negativo. Estos datos sugieren la necesidad de la implementación de esta prueba en la práctica clínica diaria(AU)

In the last few years, research in pharmacogenetics and pharmacogenomics has identified distinct variants or markers that can help to define the benefits and risk of patients requiring antiretroviral treatment. The beneficial effect of the deletion 32 allele of the CCR5 coreceptor on the natural history of HIV infection and, to a certain extent, on treatment response is well known. The bases of immune reconstitution after initiation of antiretroviral therapy, although the subject of intense study, are probably multifactorial and polygenetic and consequently conclusions with clear applicability to clinical practice are currently lacking. Among the risks, no significant progress has been made in lipodystrophy. The origin of dyslipidemia associated with antiretroviral treatment and the excess cardiovascular risk conferred by some antiretroviral drugs is probably polygenetic and, at present, poorly defined. The genetic bases of efavirenz-induced neurological toxicity and of hyperbilirubinemia secondary to atazanavir are fairly well known, although their application in daily clinical practice has not been adequately assessed. Some aspects that help to understand the molecular bases of hypersensitivity reaction to nevirapine and of nevirapineinduced hepatotoxicity have been described but are not applicable in most cases and consequently further studies are required. Some data correlate tenofovir-induced renal toxicity with genetic variations in some transport proteins. The most significant advance for clinical practice is the correlation between the presence of the HLA-B*5701 allele and hypersensitivity reaction to abacavir. In particular, one clinical trial with a large number of patients from distinct ethnic groups found that the probability of not developing hypersensitivity reaction (immunologically confirmed) was 100% if the patient was HLA-B*5701-negative. These data suggest the need to implement this test in daily clinical practice(AU)

[History of the infectious disease specialty in Spain]. / Relato histórico de la infectología española.

This paper includes a brief summary of the clinical history of the diagnosis and treatment of infectious diseases in Spain. Firstly, the origins of a specialty arising from the need for specialists to attend to, in a practical and modern form, the different health problems of patients affected by infectious diseases, are described. Secondly, the appearance of AIDS, at the beginning of the 1980's, prompted the creation of specific units dedicated to the care of problems associated with human immunodeficiency virus (HIV) infection and the concomitant opportunistic infections arising from the immunodeficiency arising from the HIV infection. Thirdly, in the last decades and even today, nosocomial infections have appeared as an alarming problem, needing the presence of specialist physicians in this field. Finally, emigration and international travel require specialists in infectious diseases with specific expertise in international health, once more highlighting the importance of the specialty of Infectious Diseases.