RESUMEN
Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%-70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.
Asunto(s)
Encefalitis , Trasplante de Riñón , Meningitis , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Trasplante de Riñón/efectos adversos , Meningitis/complicaciones , Meningitis/diagnóstico , Encefalitis/diagnóstico , Encefalitis/epidemiología , Encefalitis/etiologíaRESUMEN
OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.
Asunto(s)
Aspergilosis Pulmonar Invasiva/etiología , Trasplante de Riñón/efectos adversos , Estudios de Casos y Controles , Femenino , Salud Global/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.
Asunto(s)
Rechazo de Injerto/mortalidad , Aspergilosis Pulmonar Invasiva/mortalidad , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias/mortalidad , Aspergillus , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Agencias Internacionales , Aspergilosis Pulmonar Invasiva/etiología , Aspergilosis Pulmonar Invasiva/patología , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de TrasplantesAsunto(s)
Candida parapsilosis/aislamiento & purificación , Candidemia/complicaciones , Endocarditis/complicaciones , Glomeruloesclerosis Focal y Segmentaria/etiología , Prótesis Valvulares Cardíacas/efectos adversos , Infecciones Relacionadas con Prótesis/complicaciones , Lesión Renal Aguda/etiología , Adulto , Anticuerpos Anticitoplasma de Neutrófilos , Antifúngicos/uso terapéutico , Candidemia/tratamiento farmacológico , Candidemia/inmunología , Susceptibilidad a Enfermedades , Quimioterapia Combinada , Endocarditis/tratamiento farmacológico , Endocarditis/inmunología , Endocarditis/microbiología , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/inmunología , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Glomérulos Renales/patología , Masculino , Prednisona/uso terapéutico , Infecciones Relacionadas con Prótesis/inmunología , Infecciones Relacionadas con Prótesis/microbiología , Cardiopatía Reumática/complicaciones , Cardiopatía Reumática/cirugía , Infarto del Bazo/etiologíaRESUMEN
Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.
Asunto(s)
Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Aspergilosis Pulmonar Invasiva/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Estudios de Casos y Controles , Funcionamiento Retardado del Injerto/patología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Aspergilosis Pulmonar Invasiva/patología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Receptores de TrasplantesAsunto(s)
Fármacos Anti-VIH/administración & dosificación , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Integrasa de VIH/genética , VIH/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Mutación Missense , VIH/genética , VIH/aislamiento & purificación , Infecciones por VIH/virología , Humanos , Masculino , Oxazinas , Piperazinas , PiridonasRESUMEN
In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Criptococosis/complicaciones , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Trasplante de Riñón , Índice de Severidad de la Enfermedad , Receptores de Trasplantes , Adalimumab , Adulto , Antiinflamatorios/uso terapéutico , Encéfalo/patología , Femenino , Humanos , Inmunosupresores , Imagen por Resonancia Magnética , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/etiología , Meningitis Criptocócica/patología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Anti-HLA donor-specific antibodies (DSAs) cause acute and chronic antibody-mediated rejection (AMR). However, the clinical relevance of anti-HLA-C antibodies remains unclear. We evaluated the clinical relevance of the presence of anti-HLA-C DSA at day 0 in renal transplant recipients. In this retrospective, case-controlled study, 608 patients who underwent kidney transplantation between August 2008 and March 2012 were screened for the presence of isolated anti-HLA-C DSA at day 0. A total of 22 renal transplant recipients were selected and followed for a period of 1 year. AMR was classified according to the Banff classification. The 22 patients were compared with 88 immunized patients. Acute AMR was diagnosed in six patients (27.3%). The median level of DSA at day 0 was 1179 (530-17,941). The mean fluorescence intensity in the anti-C group was 4966 (978-17,941) in the AMR group and 981 (530-8012) in the group of patients without AMR. Acute AMR was diagnosed less frequently in the 88 immunized individuals (9.1%) than in the DSA anti-C group (p = 0.033). The level of DSA at day 0 was predictive for AMR (p = 0.017). Patients with a high level of pretransplant anti-HLA-C DSAs are likely to develop acute AMR during the first year after transplantation.
Asunto(s)
Anticuerpos/inmunología , Rechazo de Injerto/inmunología , Antígenos HLA-C/inmunología , Trasplante de Riñón/efectos adversos , Donantes de Tejidos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Nocardiosis is a rare opportunistic infection caused by Nocardia spp., an aerobic actinomycete, that mainly affects patients with cell-mediated immunity defects, such as transplant recipients. Despite recent progress regarding Nocardia identification and changes in taxonomic assignment, many challenges remain for the diagnosis or management of nocardiosis. This opportunistic infection affects 0.04 to 3.5 % of patients with solid organ or hematopoietic stem cell transplantation, depending on the organ transplanted, cytomegalovirus (CMV) infection, corticosteroids dose and calcineurin inhibitors level. Nocardiosis diagnosis relies on appropriate clinical, radiological and microbiological workup that includes the sampling of an accessible involved site and molecular microbiology tools. In parallel, extensive clinical and radiological evaluations are mandatory, including brain imaging, even in the absence of neurological signs. In transplanted patients, differential diagnosis is challenging, with co-infections reported in 20 to 64 % of cases. As the antibiotic susceptibility pattern varies among species, the antimicrobial regimen before species identification should rely on the association of antibiotics active on all species of Nocardia. Bactericidal antibiotics are required in cases of severe or disseminated disease. Furthermore, in transplant recipients, combination therapy is difficult to manage because of cumulative toxicity and interactions with immunosuppressive agents. Because of a high recurrence rate, antibiotic therapy should be prescribed for 6 to 12 months.
Asunto(s)
Nocardiosis/epidemiología , Nocardia/aislamiento & purificación , Receptores de Trasplantes , Trasplante/efectos adversos , Antibacterianos/uso terapéutico , Humanos , Huésped Inmunocomprometido , Nocardiosis/diagnóstico , Nocardiosis/tratamiento farmacológicoRESUMEN
INTRODUCTION: Despite the dramatic decrease in opportunistic infections after the introduction of highly active antiretroviral therapy, Pneumocystis jirovecii pneumonia remains the major AIDS related infection in France. BACKGROUND: The clinical, radiological and microbiological diagnosis is usually easily made in HIV-infected patients. The preferred treatment is high dose trimethoprim-sulfamethoxazole, in association with steroids in cases of severe hypoxaemia. This has led to a dramatic reduction in mortality in these patients. Prophylactic treatment is mandatory in highly immunosuppressed patients (CD4 counts<200/µL) whose viraemia is not well controlled by antiretroviral therapy. VIEWPOINT: Whether PCR-based diagnosis would be useful for HIV-infected patients is a matter of debate, as is also the clinical significance of P. jirovecii colonization. The best alternative regimens for treating P. jirovecii pneumonia in cases of treatment failure or severe intolerance to trimethoprim-sulfamethoxazole are not clearly defined. CONCLUSION: In the context of universal HIV testing and recent guideline recommendations to start antiretroviral therapy early in the course of HIV infection, the frequency of P. jirovecii pneumonia should continue to decline in France.