Resumen ejecutivo de la Declaración de consenso del Grupo de Estudio de la Infección en el Trasplante (GESITRA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y la Organización Nacional de Trasplantes (ONT) sobre los criterios de selección de donantes de órganos sólidos en relación con las enfermedades infecciosas

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.This work was supported by GESITRA/SEIMC, ONT and‘Plan Nacional de I+D+I’ and Instituto de Salud Carlos III(Fondo de Investigaciones Sanitarias 12/02269 and ProyectoIntegrado de Excelencia 13/00045), Subdirección General de Redesy Centros de Investigacion Cooperativa, Spanish Ministry of Econ-omy and Competitiveness, Spanish Network for Research inInfectious Diseases (REIPI RD16/0016), co-financed by the Euro-pean Development Regional Fund A way to achieve Europe

Antibiotic treatment versus no treatment for asymptomatic bacteriuria in kidney transplant recipients: a multicenter randomized trial

Background: whether antibiotic treatment of asymptomatic bacteriuria (AB) can prevent acute graft pyelonephritis (AGP) in kidney transplant (KT) recipients has not been elucidated. Methods: in this multicenter, open-label, nonblinded, prospective, noninferiority, randomized controlled trial, we compared antibiotic treatment with no treatment for AB in KT recipients in the first year after transplantation when urinary catheters had been removed. The primary endpoint was the occurrence of AGP. Secondary endpoints included bacteremic AGP, cystitis, susceptibility of urine isolates, graft rejection, graft function, graft loss, opportunistic infections, need for hospitalization, and mortality. Results: we enrolled 205 KT recipients between 2013 and 2015. AB occurred in 41 (42.3%) and 46 (50.5%) patients in the treatment and no treatment groups, respectively. There were no differences in the primary endpoint in the intention-to-treat population (12.2% [5 of 41] in the treatment group vs 8.7% [4 of 46] in the no treatment group; risk ratio, 1.40; 95% confidence interval, 0.40-4.87) or the per-protocol population (13.8% [4 of 29] in the treatment group vs 6.7% [3 of 45] in the no treatment group; risk ratio, 2.07, 95% confidence interval, 0.50-8.58). No differences were found in secondary endpoints, except for antibiotic susceptibility. Fosfomycin (P = .030), amoxicillin-clavulanic (P < .001) resistance, and extended-spectrum β-lactamase production (P = .044) were more common in KT recipients receiving antibiotic treatment for AB. Conclusions: antibiotic treatment of AB was not useful to prevent AGP in KT recipients and may increase antibiotic resistance. However, our findings should be regarded with caution, due to the small sample size analyzed

Risk factors, clinical features, and outcomes of listeriosis in solid-organ transplant recipients: a matched case-control study

BACKGROUND: Solid-organ transplant (SOT) recipients are classically considered to be at increased risk for listeriosis. However, risk factors for this infection have not been assessed. METHODS: We carried out a multicenter, matched case-control study (1:2 ratio) from January 1995 through December 2007. Control subjects were matched for center, transplant type, and timing. Conditional logistic regression was performed to identify independent risk factors. Clinical features and outcomes for all case patients were reviewed. RESULTS: Thirty patients (0.12%) with cases of listeriosis were identified among 25,997 SOT recipients at 15 Spanish transplant centers. In a comparison of case patients with 60 matched control subjects, the following independent risk factors for listeriosis were identified: diabetes mellitus (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.6-19.6; ), P = .007 history of cytomegalovirus infection or disease within the preceding 6 months (OR, 35.9; 95% CI, 2.1-620; P = .014), receipt of high-dose prednisone within the preceding 6 months (OR, 6.2; 95% CI, 1.8-21.1; P = .003), and trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (OR, 0.07; 95% CI, 0.006-0.76; P = .029). Twenty-six patients (86.7%) had bacteremia, and 7 had shock at presentation. Other manifestations included meningoencephalitis (10 cases), spontaneous peritonitis (2), pleural empyema (1), brain abscesses (1), and liver abscesses (1). The 30-day mortality rate was 26.7% (8 of 30 patients died). CONCLUSIONS: Listeriosis in SOT recipients is uncommon but causes high mortality. Diabetes mellitus, cytomegalovirus infection or disease, and receipt of high-dose steroids are independent risk factors for this infection, whereas TMP-SMZ prophylaxis is a protective factor

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation

Background: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. Methods: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-? [IFN-?] ? 0.2 IU/mL) indicated a positive CMV-CMI. Results: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-? level (>12 IU/mL vs ?12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-? level ?12 IU/mL. Conclusions: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-? level, but not the ATG dose, shows a strong association with the kinetics of this recovery.This work was supported by the Fundación Progreso y Salud, Consejería de Salud y Familias, Junta de Andalucía (grant number PI-0294-2014); Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (grant number CP 18/00073 to M. F. R.); Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia e Innovación, Spanish Network for Research in Infectious Diseases (grant numbers REIPI RD16/0016/0002, RD16/0016/0003, RD16/0016/0007, RD16/0016/0008, RD16/0016/0009 and RD16/0016/0012); cofinanced by European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014- 2020; Spanish Network for Research in Renal Diseases (grant numbers RD16/0009/0006, RD16/0009/0008, RD16/0009/0013, RD16/0009/0014, RD16/0009/0019, RD16/0009/0034); Centro de Investigación Biomédica en Red Enfermedades Respiratorias (grant number CB06/06/0058); and Spanish Group for the Study of Infection in Transplantation and the Immunocompromised Host of the Spanish Society of Infectious Diseases and Clinical Microbiolog

Toxoplasmosis in transplant recipients, Europe, 2010-2014

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study

Background. We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. Methods. From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. Results. The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered ?high risk? for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid?related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. Conclusions. The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid?related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients

Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance

BACKGROUND: Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed. OBJECTIVES: To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance. STUDY DESIGN: Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015. RESULTS: Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis >/=6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance. CONCLUSIONS: Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients

Respuesta serológica y seguimiento de los pacientes con infección por el virus de la inmunodeficiencia humana vacunados frente a streptococcus pneumoniae

Consultable des del TDXTítol obtingut de la portada digitalitzadaLos pacientes con infección por VIH presentan alteraciones en la respuesta de los linfocitos B lo que deriva en una mayor susceptibilidad a las infecciones neumocócicas. Así, la incidencia de neumonía neumocócica es 6 veces mayor a la población general y la incidencia de bacteriemia aumenta hasta 100 veces. Existe una mayor frecuencia de cepas con resistencia elevada a la penicilina que en la población general lo cual influye en un peor pronóstico. Más del 80% de los serotipos que causan enfermedad en esta población están contenidos en la vacuna 23-valente polisacárida. Dado que existen escasos estudios que evalúen la respuesta serológica en estos pacientes a largo plazo y que sigan la aparición de enfermedades neumocócicas se diseñó un estudio clínico y serológico prospectivo con los objetivos de comparar la respuesta inmunitaria de los pacientes con infección por VIH frente a la población sana, evaluar la persistencia de la misma a lo largo del tiempo, y valorar la aparición de infecciones neumocócicas en los pacientes vacunados. Para ello constituímos un grupo de estudio de 60 pacientes con infección por VIH con un recuento de linfocitos T CD4+ superior a 200 elementos/ml y un grupo control constituido por 39 individuos sanos que fueron vacunados con la vacuna 23-valente polisacárida. Se extrajeron muestras de sangre previo, al mes, seis, y treinta y seis meses de la vacunación para determinar la IgG total específica antineumocócica mediante una técnica de ELISA modificada estandarizada en nuestro centro. El seguimiento clínico se realizó a través de la historia clínica proveniente de la consulta ambulatoria. En resumen, y como conclusiones de nuestro estudio podemos decir: 1. Los pacientes con infección por VIH presentan globalmente una respuesta serológica de anticuerpos específicos IgG frente a la vacuna neumocócica inferior a la de los controles sanos. Sin embargo, un tercio de los pacientes con infección por VIH producen una respuesta adecuada totalmente superponible a la de los controles sanos independiente de la cifra de linfocitos T CD4+. 2. En nuestro seguimiento realizado durante 5 años no se ha constatado ningún episodio de infección neumocócica. Por lo tanto, creemos que, dada la elevada incidencia de la enfermedad y la inocuidad de la vacuna neumocócica, ésta se debe recomendar a los pacientes con infección por VIH. 3. También hemos observado que se produce un rápido descenso de los títulos de anticuerpos de modo que a los 3 años los títulos han retornado a los niveles basales. Por ello creemos recomendada la revacunación en un periodo no superior a los 3 años.Patients with Acquired Immunodeficiency Syndrome (AIDS) have a profound impairment of their immunologic mechanisms, specially cell-mediated immunity, but abnormalities in B cell function have also been described in these patients and increased rates of bacterial pneumonia, most caused by Streptococcus pneumoniae, have been reported. Streptococcus pneumoniae is the most common cause of community acquired pneumonia (an incidence 6 times greater than in general population) and its bacteriemia related mortality is high, even with appropriate therapy. The worlwide emergence of drug resistant pneumococcal strains difficults its treatment and worsens its prognosis. The polysaccharide 23-valent vaccine contains more than 80% of the serotypes causing illnes. Till now most studies describe the serological response against pneumococcal antigens weeks after vaccination but very little is known about the persistence of the immunogenicity of antipneumococcal vaccination and the incidence of pneumococcal disease in this vaccinated population. The aim of this study was to compare the serological response to pneumococcal vaccination between a group of asymptomatic HIV infected patients and a group of healthy people, to determine the persistence of antipneumococcal antibodies 3 years after vaccination and to valorate the rate of pneumococcal infection in this group. The study group consisted of 60 patients with HIV infection with a CD4 lymphocyte count > 0.2 x 109/L and the control group consisted of 39 healthy individuals, all of them vaccinated with the 23-valent polysaccharide pneumococcal vaccine. A serum specimen was collected from each patient and control before vaccination, 4 weeks, 6 months and 3 years after vaccination. The specific IgG antibody to Streptococcus pneumoniae was measured by an ELISA test standardized in our Biochemistry Laboratory. Clinical evaluation was made trough the attendance to the outpatient clinic. In summary, the conclusions are: 1. In general, the specific IgG response to pneumococcal vaccine is lower in patients with HIV infection than in healthy subjects. However, 33% patients are able to mount an adequate response comparable to that of healthy subjects with independence to the CD4 lymphocyte count. 2. In the 5 year follow-up there has been no episodes of pneumococcal disease. Because of the high incidence rate of pneumococcal disease and the lack of side effects derived from the vaccination, we recommend it to the HIV infected population. 3. Finally, we have demonstrated that the specific IgG antibody titre return to baseline levels before 3 years, even in patients with a normal response, suggesting that in case of revaccination, this would have to be planned during this period