Felipe Zurbano

GESITRA-SEIMC/REIPI recommendations for the management of cytomegalovirus infection in solid-organ transplant patients

Cytomegalovirus infection remains a major complication of solid organ transplantation. In 2005 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, numerous publications have clarified or questioned the aspects covered in the previous document. These aspects include the situations and populations who must receive prophylaxis and its duration, the selection of the best diagnosis and monitoring technique and the best therapeutic strategy. For these reasons, we have developed new consensus guidelines to include the latest recommendations on post-transplant CMV management based on new evidence available.

Scedosporium inflatum infection in immunocompromised haematological patients

We report four cases of Scedosporium inflatum (S. inflatum) infection in severely immunocompromised haematological patients. Six well‐documented cases of S. inflatum disseminated infection in haematological patients have been reported: four in Australia and two in Spain. Their clinical and pathological characteristics are heterogenous, particularly in the Australian cases. However, the clinical and pathological profile emerging from our and other Spanish cases is homogenous and very similar to the clinico‐pathological spectrum of other disseminated mycoses, including Aspergillus and S. apiospermum. The optimal treatment of S. inflatum infection is unknown and the outcome in haematological patients is very poor. Eight patients died despite systemic antifungal treatment.

Registro Español de Trasplante Pulmonar: primer informe de resultados (2006-2010)

The Spanish Lung Transplant Registry (SLTR) began its activities in 2006 with the participation of all the lung transplantation (LT) groups with active programs in Spain. This report presents for the first time an overall description and results of the patients who received lung transplants in Spain from 2006 to 2010. LT activity has grown progressively, and in this time period 951 adults and 31 children underwent lung transplantation. The mean age of the recipients was 48.2, while the mean age among the lung donors was 41.7. In adult LT, the most frequent cause for lung transplantation was emphysema/COPD, followed by idiopathic pulmonary fibrosis, both representing more than 60% the total number of indications. The probability for survival after adult LT to one and three years was 72% and 60%, respectively, although in patients who survived until the third month post-transplantation, these survival rates reached 89.7% and 75.2%. The factors that most clearly influenced patient survival were the age of the recipient and the diagnosis that indicated the transplantation. Among the pediatric transplantations, cystic fibrosis was the main cause for transplantation (68%), with a one-year survival of 80% and a three-year survival of 70%. In adult as well as pediatric transplantations, the most frequent cause of death was infection. These data confirm the consolidated situation of LT in Spain as a therapeutic option for advanced chronic respiratory disease, both in children as well as in adults.

A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients.

Seventy‐six cytomegalovirus (CMV)‐seropositive lung transplant recipients receiving valganciclovir (900 mg/day) for CMV prophylaxis were compared with a group of 87 patients receiving oral ganciclovir (3000 mg/day). Prophylaxis was administered to day 120 post‐transplantation and follow‐up was 1 year. In addition, a study was conducted on risk factors for CMV infection/disease. CMV disease incidence was 7.9% and 16.1% for valganciclovir and oral ganciclovir, respectively (p = 0.11). Patients receiving valganciclovir had fewer viral syndromes (2.6% vs. 11.5%, p < 0.05), a similar rate of tissue‐invasive disease (5.2% vs. 4.6%, p = ns), longer time‐to‐onset of CMV infection/disease (197.5 vs. 155.2 days, p < 0.05), and a lower probability of infection/disease while on prophylaxis (1.3% vs. 12.6%, p < 0.01). Nonetheless, leukopenia incidence was higher with valganciclovir (15.8% vs. 2.3%, p < 0.01), as was the need for treatment withdrawal due to adverse effects (11.8% vs. 1.1%, p < 0.01). CMV infection was similar in both groups (32.9% vs. 34.5%). Induction therapy with basiliximab and glucocorticosteroid treatment were independent risk factors for developing CMV infection/disease. In conclusion, valganciclovir prophylaxis results in a low incidence of CMV disease in lung transplant recipients and appears more effective than oral ganciclovir. Despite the comparatively higher incidence of adverse events with valganciclovir, the drug can be considered safe for prophylaxis.

Prophylaxis with nebulized liposomal amphotericin B for Aspergillus infection in lung transplant patients does not cause changes in the lipid content of pulmonary surfactant

BACKGROUND Prophylaxis with inhaled liposomal amphotericin B has proven to be safe and effective for preventing infection due to Aspergillus spp in lung transplant recipients. However, the liposome contains a large quantity of phospholipids, and inhalation of these substances could potentially change the composition of pulmonary surfactant. The aim of this study was to determine the lipid composition of pulmonary surfactant in patients receiving inhaled liposomal amphotericin B prophylaxis. METHODS A prospective, open, controlled multicenter study was conducted in 2 groups: 19 lung transplant recipients who received regular prophylaxis with inhaled amphotericin B (study group) and 19 recipients who did not receive inhaled prophylaxis (control group). From both groups, 15 ml of the third aliquot of bronchoalveolar lavage fluid was obtained and phospholipid content determined in the active fraction of surfactant (large aggregates) and in the inactive fraction (small aggregates). Large aggregate cholesterol content was also determined. RESULTS Patient demographic data and characteristics were similar in the 2 groups. No between-group differences in median phospholipid content were found for large aggregates (study group, 0.4 [range, 0.18-1.9] μmol vs controls, 0.36 [range 2.15-0.12] μmol; p = 0.69) or small aggregates (study group, 0.23 [range, 0.1-0.58] μmol vs controls, 0.29 [range, 0.18-0.65] μmol; p = 0.33). The small aggregate-to-large aggregate phospholipid ratio, commonly used as a marker of alveolar injury, showed no differences between the groups (study group, 0.56 vs controls, 0.69; p = 0.28). Nor were there differences in the cholesterol content of large aggregates (study group, 0.04 μmol [range 0.01-0.1] vs controls, 0.04 μmol [range 0.02-0.27); p = 0.13). CONCLUSIONS These results seem to indicate that prophylaxis with nebulized liposomal amphotericin B does not cause changes in the lipid content of pulmonary surfactant.

Mortality Analysis of Patients Undergoing Lung Transplantation for Emphysema

Abstract Background The outcomes of lung transplantation 11 years after starting the transplantation program in our hospital are presented. Risk factors associated with short-, medium-, and long-term mortality in transplant recipients were analyzed. Patients and Methods All patients diagnosed with emphysema who underwent lung transplantation between March 1997 and June 2008 were included. The association between different study variables and early death and death at 1 year and 5 years was studied. The Kaplan-Meier method was used to analyze survival. A logistic regression model was used to study the association between early death and variables with a trend towards significance (P Results A total of 92 patients were included. Survival was 89.3%, 70%, and 54% at 1 month, 1 year, and 5 years after transplantation, respectively. Dehiscence of the surgical suture (P Conclusions Complications were responsible for short-term mortality, while age of the recipient was the most important factor in determining long-term survival. Mortality was higher in single-lung transplant recipients compared to double-lung transplant recipients.

Trasplante de pulmón en casos de enfisema: análisis de la mortalidad

BACKGROUND The outcomes of lung transplantation 11 years after starting the transplantation program in our hospital are presented. Risk factors associated with short-, medium-, and long-term mortality in transplant recipients were analyzed. PATIENTS AND METHODS All patients diagnosed with emphysema who underwent lung transplantation between March 1997 and June 2008 were included. The association between different study variables and early death and death at 1 year and 5 years was studied. The Kaplan-Meier method was used to analyze survival. A logistic regression model was used to study the association between early death and variables with a trend towards significance (P<.2) in the univariate analysis. The risk factors for mortality at 1 year and 5 years were analyzed by a Cox regression model. RESULTS A total of 92 patients were included. Survival was 89.3%, 70%, and 54% at 1 month, 1 year, and 5 years after transplantation, respectively. Dehiscence of the surgical suture (P<.001), duration of mechanical ventilation in the intensive care unit (P=.04), duration of the surgical procedure (P<.001), and single-lung transplantation (P=.007) were the variables associated with mortality. Extracorporeal circulation and the need for hemodiafiltration in the intensive care unit increased the short-term risk of death (P<.05). The age of the recipient was the variable associated with long-term mortality (P=.02). The duration of the surgical intervention was associated with an increase in short-, medium-, and long-term mortality. CONCLUSIONS Complications were responsible for short-term mortality, while age of the recipient was the most important factor in determining long-term survival. Mortality was higher in single-lung transplant recipients compared to double-lung transplant recipients.

Recommendations on the use of everolimus in lung transplantation

The antiproliferative effect of everolimus provides a therapeutic option in the immunosuppression therapy of lung transplantation, by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection. However, few data on the use of everolimus in lung transplantation have been published to date, and the specific indications of the drug, along with the most adequate time for its introduction or dosing, have not been defined yet. The aim of this article is to propose recommendations for the use of everolimus in lung transplant recipients, including indications, dosing schedules and the use of concomitant immunosuppression. This consensus document has been developed by experts of all the Spanish lung transplant groups from the review of the existing literature and the clinical experience.

Normativa para la selección de pacientes candidatos a trasplante pulmonar

The present guidelines have been prepared with the consensus of at least one representative of each of the hospitals with lung transplantation programs in Spain. In addition, prior to their publication, these guidelines have been reviewed by a group of prominent reviewers who are recognized for their professional experience in the field of lung transplantation. Within the following pages, the reader will find the selection criteria for lung transplantation candidates, when and how to remit a patient to a transplantation center and, lastly, when to add the patient to the waiting list. A level of evidence has been identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider this treatment for their patients. Finally, these guidelines also propose an information form in order to compile in an organized manner the patient data of the potential candidate for lung transplantation, which are relevant in order to be able to make the best decisions possible.

Epidemiology and immediate indirect effects of respiratory viruses in lung transplant recipients: a 5 year prospective study.

The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs) and the relationship of RVs to lung function, acute rejection (AR) and opportunistic infections in these patients are not well known. We performed a prospective cohort study (2009–2014) by collecting nasopharyngeal swabs (NPSs) from asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory tract infectious disease (URTID), lower respiratory tract infectious disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean follow‐up of 3.4 years (interquartile range 2.5–4.0 years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case–control analysis, AR was associated with RVs (hazard ratio [HR] 6.54), Pseudomonas aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID (HR 2.53) in the previous 3 mo. There was no association between RVs and Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs. LRTID produced significant lung function abnormalities. Associations were observed between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and between CMV replication or disease and URTID.