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Background Universal antiviral prophylaxis is the preferred preventive strategy for lung transplant recipients (LTRs) at risk of CMV infection. We compared the risk of CMV infection between CMV D+/R + and D-/R + LTRs after 3 months of prophylaxis. Methods This was a retrospective review of CMV R + LTRs transplanted between 2005 and 2013. Patients dying before completing 3 months, or receiving >180 days of prophylaxis were excluded. The primary outcome was proportion of LTRs who developed CMV infection and clinically significant CMV infection defined as CMV infection leading to preemptive therapy or CMV disease. Results We analyzed 90 D+/R + and 72 D-/R + with a median follow up of 730 days. CMV infection and disease was more common in D+/R + compared to D-/R+ (CMV infection 66% vs 40%; P = 0.001; CMV disease 13% vs 4% P = 0.045). Fifty-nine patients developed at least one episode of clinically significant CMV infection (41/90 [46%] D+/R + and 18/72 [25%] D-/R + P=0.007) with recurrence occurring in 29 LTRs (49% of patients with previous CMV infection), of which 22 (76%) were CMV D+/R+. Thirty percent had side effects related to CMV therapy. Conclusion Three months prophylaxis in D+/R + LTRs was associated with high rates of clinically significant CMV infection and recurrences.

Background: Daptomycin is an optimal choice for outpatient parenteral antibiotic therapy (OPAT) because of its safety, once-daily administration and its activity against Gram-positive bacteria. Although daptomycin is increasingly being used in OPAT, limited information about its safety in this scenario is available. Methods: We performed a prospective multicentre pilot study to evaluate the safety of daptomycin in outpatients with proved or suspected Gram-positive infections (DAPTODOM). The primary objective was to evaluate the safety and the secondary objective to evaluate the efficacy in OPAT. We also looked at the development of daptomycin resistance in those cases with microbiological failure. Results: We included 54 patients from 12 Spanish hospitals, 67% male with a mean age of 67.1 years. Most patients (87%) had chronic underlying diseases. The main reason for inclusion was skin and soft-tissue infections in 52%, followed by bacteremia or endocarditis in 34%. Staphylococcus aureus accounted for 44% of the isolates (24% were methicillin-resistant), coagulase-negative staphylococci 15% and enterococci 7%. Two patients (4%) had to be readmitted because of complications; only one patient had an adverse effect related to daptomycin (increase in serum creatine kinase levels), which disappeared after discontinuation (2%). At the end of follow-up, 96% of patients had good outcome and only 4% of patients did not have a clinical or microbiological cure. The use of a 2-minute bolus in 18 cases was not associated with adverse effects. Conclusions: Daptomycin was safe and efficacious in outpatients with Gram-positive bacterial infections and can be administered in 2-minute bolus infusion.

The ecophysiological investigations about epiphytic plants have focused on the establishment of mechanistic explanations of how plants respond to changes in their environment. The main objective of this work was to assess the drought and extreme temperature tolerance of Tillandsia dasyliriifolia individuals growing in two coastal dune scrub sites with different precipitation patterns and microhabitat distribution. This study was focused on the effect of plant size on tolerance parameters. Drought and extreme temperature tolerance were evaluated in small (S1, 9 cm) and large individuals (S2, 35 cm). Tolerance between sites was not different but varied between size classes. Tillandsia dasyliriifolia shows moderate tolerance to drought in comparison to more succulent plants. The 50% of the leaves in small plants died after 40 days of drought and after 60 days for large plants. T. dasyliriifolia also exhibits moderate tolerance to extreme temperatures tolerance, small plants tolerate a temperature range from 11 ºC to 40 ºC and the range for large plants is a little broader (9 °C to 43 °C).

Urinary tract infections (UTI) are one of the most common infections in solid organ transplant (SOT) recipients. A systematic review was performed to assess the management of UTI in SOT recipients. Recommendations are provided on the management of asymptomatic bacteriuria, and prophylaxis and treatment of UTI in SOT recipients. The diagnostic-therapeutic management of recurrent UTI and the role of infection in kidney graft rejection or dysfunction are reviewed. Finally, recommendations on antimicrobials and immunosuppressant interactions are also included.

To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery.Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals.A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery.Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

A 67-year-old man with significant smoking history presented with fever, unintentional weight loss, night sweats, productive cough, and progressive dyspnea. Multiple respiratory specimens grew Mycobacterium branderi. Computed tomography scanning of the chest revealed a cavitary right upper lung lesion. Bronchoscopy and thoracoscopic biopsy were negative for malignancy but showed necrotizing granulomatous inflammation, which was culture negative. Due to clinical and radiologic progression despite therapy with clarithromycin, ethambutol and moxifloxacin, the lesion was surgically resected and the patient's symptoms resolved. Mycobacteria were seen in histopathology but did not grow from resected tissue. The patient received an additional 6 months of medical therapy and remains asymptomatic 1 month after completing antimicrobials. Cases of M. branderi causing human infection are very rarely reported. This is a novel case of multi-drug resistant M. branderi pulmonary infection in an apparently immunocompetent patient, progressive despite medical therapy and requiring surgical resection for definitive management.

Background Antimicrobial stewardship programs (ASPs) improve Staphylococcus aureus bacteremia (SAB) management. The objective of the current study was to evaluate the effect of unsolicited prospective audit and feedback (PAF) using a standardized SAB bundle form on the management of SAB. Methods Multicenter, pre-post quasi-experimental study of inpatients with SAB. The ASP developed an evidence-based SAB management bundle that included recommendations for infectious diseases consultation, blood culture clearance, appropriate empiric and definitive therapy, echocardiography, adequate treatment duration, and source control where applicable. ASP pharmacists performed PAF using a standardized form outlining bundle components. The primary outcome was bundle component adherence. Secondary outcomes were length of stay, 30-day readmission rate, and in-hospital and 30-day mortality rates. Results A total of 199 patients were included (preintervention group, 62; intervention group, 137). Bundle implementation with PAF resulted in significant improvements in infectious diseases consultation (56.5% in preintervention vs 93.4% in intervention group), appropriate definitive antibiotic therapy (83.9% vs 99.3%), ordering echocardiography (72.6% vs 95.6%), and adequate treatment duration (87.0% vs 100%) (all P < .001). Overall bundle adherence increased by 43.8% (P < .001). Readmission and 30-day mortality rates decreased, but this difference did not reach statistical significance. Conclusions Unsolicited PAF using a standardized SAB management bundle significantly improved adherence to evidence-based recommendations. This simple yet effective ASP-driven intervention can ensure consistent management of a highly morbid infection., The impact of unsolicited antimicrobial stewardship initiated prospective audit and feedback using a standardized Staphylococcus aureus bacteremia management bundle was evaluated. Adherence to evidence-based recommendations was significantly improved with this simple yet effective intervention.

INTRODUCTION Recurrent urinary tract infections (UTI) are a common clinical problem in kidney transplant recipients. Due to the complex urological anatomy derived from the implantation of the kidney graft, the spectrum of the disease and the broad underlying pathophysiological mechanisms. Recurrent UTI worsen the quality of life, decrease the graft survival and increase the costs of kidney transplantation. Areas covered: In this review, we describe the definitions, clinical characteristics, pathophysiological mechanisms and microbiology of recurrent urinary tract infections in kidney transplantations. The actual published literature on the management of recurrent urinary tract infections is based on case series, observational cohorts and very few clinical trials. In this review, the available evidence is compiled to propose evidence-based strategies to manage these complex cases. Expert commentary: The management of recurrent urinary tract infections in kidney transplant patients requires a proper diagnosis of the underlying mechanism. Early identification of structural or functional urological abnormalities, potentially amenable for surgical correction, is crucial for a successful management. The use of antibiotics to prevent recurrent infections should be carefully evaluated to avoid side effects and emergence of antibiotic-resistant microorganisms.

Some studies have shown that pre-transplant cytomegalovirus (CMV) serostatus is associated with heart transplant patient survival while others have not. We analyzed the relationship between pre-transplant donor/recipient CMV serostatus and long-term mortality in a retrospective cohort of heart transplant recipients at our center.Adult (Age17 years) heart recipients transplanted between July 1985-December 2015 were analyzed. Variables included age, sex, pre-transplant donor (D)/recipient (R) serostatus [D-/R-, D-/R+, D+/R+, D+/R-], CMV infection within 2 years of transplant and transplant eras divided by changes in CMV prevention strategies: Era 1 (Pre-ganciclovir, July 1985-April 1998), Era 2 (Oral ganciclovir, May 1998-December 2004), Era 3 (Valganciclovir, January 2005-December 2015). Survival analysis and Cox regression were performed at 10 years.A total of 620 heart transplants were included in our analysis; 20% were CMV mismatched pre-transplant. Thirty-eight percent of patients were infected with CMV within the first two post-transplant years. Survival analysis showed D/R CMV serostatus did not significantly impact survival of heart recipients at 10 years (P = 0.11). Survival was significantly different across eras for D-/R+, D+/R+, and D+/R+ (P = 0.043) but not D-/R- patients (P = 0.8). Cox regression revealed that patients transplanted in the valganciclovir era have an estimated 29% reduced risk of death (P = 0.047) compared to patients transplanted in the pre-ganciclovir era after controlling for age at transplantation, D/R CMV serostatus and CMV infection.Our review of the impact of CMV managed differently across eras suggests in heart transplantation there is no influence of D/R CMV serostatus on 10 year survival.

Posttransplant lymphoproliferative disorders (PTLD) are a complication of solid organ transplantation (SOT) associated with Epstein-Barr virus (EBV).We analyzed the incidence of and risk factors for PTLD among adult SOT recipients at our center over 30 years (1984-2013). We also compared PTLD incidence before and after a prevention strategy of EBV viral load monitoring in EBV serology mismatched patients was adapted in 2001 (ie, transplant era 1 [1983-2001] vs era 2 [2002-2013]).Among 4171 SOT patients, 109 developed PTLD. Cumulative incidence at 1, 10, and 20 years posttransplant was 0.95, 2.3, and 3.5 per 100 person-years, respectively. Beyond the first year peak of almost exclusively EBV-positive PTLD, a lower incidence of PTLD, predominantly EBV negative, persisted for 20 years. Thoracic transplant (hazard ratio [HR], 2.1; P = 0.007) and negative EBV serology (HR, 7.7; P0.001) were independent risk factors for PTLD on multivariate Cox regression analysis. EBV seronegativity significantly increased risk of early (HR, 18.5) and EBV-positive PTLD (HR, 14.2), as well as late (HR, 4.9) and EBV-negative PTLD (HR, 3.6) on univariate analyses. Risk of early PTLD was significantly reduced in the recent transplant era (0.8% era 2 vs 1.9% era 1 at 5 years, P = 0.002); this reduction was seen in recent era EBV seropositive (P = 0.035 at 5 years) but not seronegative recipients (P = 0.90 year 5), suggesting lack of impact of viral load monitoring.Adult SOT recipients face a prolonged risk of late PTLD, whereas risk of early PTLD may have declined in recent years.

Background Valganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence. Methods Retrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L. Results A total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001). Conclusion VGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis. Disclosures All authors: No reported disclosures.

The Enterococcus species is the third main cause of infective endocarditis (IE) worldwide, and it is gaining relevance, especially among healthcare-associated cases. Patients with enterococcal IE are older and have more comorbidities than other types of IE. Classical treatment options are limited due to the emergence of high-level aminoglycosides resistance (HLAR), vancomycin resistance and multidrug resistance in some cases. Besides, few new antimicrobial alternatives have shown real efficacy, despite some of them being recommended by major guidelines (including linezolid and daptomycin). Ampicillin plus ceftriaxone 2 g iv./12 h is a good option for Enterococcus faecalis IE caused by HLAR strains, but randomized clinical trials are essential to demonstrate its efficacy for non-HLAR EFIE and to compare it with ampicillin plus short-course gentamicin. The main mechanisms of resistance and treatment options are also reviewed for other enterococcal species.

Infective endocarditis (IE) is a rare disease that is difficult to diagnose, its treatment is complex and expensive, and mortality is high (around 20%). In the field of IE, the most recent changes are epidemiological and include an increased number of cases of IE in patients with prosthetic valves and intracardiac devices and in the population receiving health care, an increased number of cases of Staphylococcus aureus IE, and changes in antibiotic sensitivity patterns with a particular impact on vancomycin. Infective endocarditis requires prolonged hospitalization and resourceintensive treatment because antibiotic therapy, intensive care, and surgical treatment form part of the therapeutic approach. Between 40% and 50% of patients require surgical treatment in the acute phase. In the year when IE is diagnosed, mortality is 30% with or without intervention. Mortality is high among certain groups, such as patients with prosthetic valves and especially those with intracranial hemorrhage. Early diagnosis and treatment can improve outcomes. Low suspicion of IE can delay effective treatment and increase mortality. In our experience, an appropriate therapeutic approach has a mean delay of 27 days when the patient is referred from another institution. The treatment of IE is a paradigm of collaboration. Multidisciplinary teams (MDT) dedicated to IE have pioneered the organization of tertiary hospital care devoted to the disease. In the last decade, the International Collaboration in Endocarditis group has had a strong impact on understanding IE. The British Heart Valve Society has recommended the collaboration of specialists in valvular heart disease and IE and recent reports have supported this model.

β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients., We thank the ESGBIS and the ESGICH study groups for supporting the study. This study was supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III—cofinanced by European Development Regional Fund “A way to achieve Europe” EDRF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection. J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III.

Information on the environmental variables that may affect the incidence of invasive aspergillosis (IA) is scarce. We sought to determine the relationship between airborne spore counts, climatic conditions and IA. We also examined whether circulating respiratory viruses predispose patients to IA in a multicentre cohort study of hospitalized adults with IA. Data on environmental mould spores, climatic conditions and circulating respiratory viruses were obtained from the Environmental Department of the Autonomous University of Barcelona, the Meteorological Service of Catalonia and the Acute Respiratory Infection Surveillance Project in Catalonia, respectively. Between 2008 and 2011, 165 patients with IA were identified. Diagnosis was based on one or more of the following: culture (125 cases), galactomannan antigen (98) and histology (34). One hundred and twenty-seven cases (77%) had criteria for probable IA and the remainder for proven IA. Environmental mould spore counts from the period 28–42 days preceding infection presented significant associations with admissions due to IA. None of the climatic conditions were associated with an increased risk of IA, but the presence of circulating respiratory viruses was associated with a higher risk of infection: the most strongly associated viruses were respiratory syncytial virus, influenza A(H1N1)pdm09 and adenovirus. In conclusion, the presence of high numbers of spores in the air increases the risk of admission due to IA. Circulating respiratory viruses appear to be associated with a higher risk of developing IA. Physicians should be aware of this association in order to optimize prevention and diagnosis strategies for IA during viral epidemic periods.

[EN] We report on findings from a common garden experiment showing that the magnitude of change in the production of phenolic compounds in response to different amounts of light availability is tissue-specific in saplings of big-leaf mahogany (Swietenia macrophylla). Moreover, we show that trade-offs between growth and the production of chemical defenses emerge only under light-limited conditions. These findings emphasize the need for considering the specificity of plant defensive responses to resource availability, as well as the influence of the abiotic environment (via trade-offs) on plant defense allocation patterns. [ES] En este trabajo demostramos que los cambios en la inversión en defensas químicas de plántulas de caoba (Swietenia macrophylla) en respuesta a diferentes regímenes de disponibilidad de luz difiere entre tejidos. De igual forma, encontramos que la expresión de compromisos de asignación de recursos entre crecimiento y defensas solo se presenta bajo condiciones de baja disponibilidad de luz. Nuestros resultados subrayan la importancia de considerar la especificidad de las respuestas en plantas a cambios en la disponibilidad de recursos, así como la influencia del contexto abiótico (a través de compromisos) sobre los patrones de asignación de defensas contra herbívoros. This research was supported by a CONACyT grant awarded to VPT (128856). LAR was funded by a GAANN fellowship and a UCMEXUS-CONACyT scholarship. XM received financial support from Postdoctoral Fulbright/Spanish Ministry of Education Grant Program. CONACyT: Consejo Nacional de Ciencia y Tecnología (México) U.S. Department of Education UCMEXUS: University of California Institute for Mexico and the United States Postdoctoral Fulbright/Spanish Ministry of Education Grant Program

Resumen La infeccion de adquisicion nosocomial es una causa de morbimortalidad en los pacientes hospitalizados. El tratamiento antibiotico empirico inadecuado se asocia a una peor evolucion clinica. Ante la sospecha de una infeccion de adquisicion hospitalaria es necesario iniciar un tratamiento antibiotico empirico, teniendo en cuenta la epidemiologia local de cada centro, las caracteristicas basales del paciente, los factores de riesgo de presentacion de microorganismos multirresistentes y la gravedad de la infeccion.

The development of high-level daptomycin resistance (HLDR; MIC of ≥256 mg/liter) after exposure to daptomycin has recently been reported in viridans group streptococcus (VGS) isolates. Our study objectives were as follows: to know whether in vitro development of HLDR after exposure to daptomycin was common among clinical isolates of VGS and Streptococcus bovis ; to determine whether HLDR also developed during the administration of daptomycin to treat experimental endocarditis caused by the daptomycin-susceptible, penicillin-resistant Streptococcus mitis strain S. mitis 351; and to establish whether combination with gentamicin prevented the development of HLDR in vitro and in vivo. In vitro studies were performed with 114 VGS strains (mitis group, 92; anginosus group, 10; mutans group, 8; and salivarius group, 4) and 54 Streptococcus bovis strains isolated from 168 consecutive patients with infective endocarditis diagnosed between 1995 and 2010. HLDR was only observed after 24 h of exposure to daptomycin in 27% of the mitis group, including 27% of S. mitis isolates, 47% of S. oralis isolates, and 13% of S. sanguis isolates. In our experimental model, HLDR was detected in 7/11 (63%) and 8/12 (67%) isolates recovered from vegetations after 48 h of daptomycin administered at 6 mg/kg of body weight/24 h and 10 mg/kg/24 h, respectively. In vitro , time-kill experiments showed that daptomycin plus gentamicin was bactericidal against S. mitis 351 at tested concentrations of 0.5 and 1 times the MIC and prevented the development of HLDR. In vivo , the addition of gentamicin at 1 mg/kg/8 h to both daptomycin arms prevented HLDR in 21 out of 23 (91%) rabbits. Daptomycin plus gentamicin was at least as effective as vancomycin plus gentamicin. In conclusion, HLDR develops rapidly and frequently in vitro and in vivo among mitis group streptococci. Combining daptomycin with gentamicin enhanced its activity and prevented the development of HLDR in most cases.

Enterococci are the third most common etiologic agent of infective endocarditis worldwide after staphylococci and streptococci and cause 10% to 15% of cases.1 Enterococcal infections are increasingly relevant, especially among the elderly and patients with comorbid conditions in the healthcare setting.2,3 Approximately 90% of cases of enterococcal endocarditis are caused by Enterococcus faecalis , with 3-month history of symptoms before diagnosis.4 The gentamicin dose schedule (3 mg/kg per 24 hours IV …

Mammalian target of rapamycin inhibitors (mTORi) prevents cytomegalovirus (CMV) infection in kidney transplant (KT) patients. From May 2010 to December 2013, all KT recipients were retrospectively analysed. Maintenance immunosuppression regimen was divided into mTORi or calcineurin inhibitors (CNI)-based regimen. Since June 2011, CMV-seropositive recipients (R+) treated with high-intensity immunosuppression and mTORi did not receive anti-CMV prophylaxis. We analysed 350 consecutive patients, of which 95 (27%) received mTORi and 255 (73%) CNI-based immunosuppression. A Cox-regression multivariate analysis showed that the use of mTORi-based immunosuppression during all follow-up reduced the risk of CMV infection (HR 0.36, 95% CI 0.15-0.89, P = 0.028) and confirmed in a propensity score-matched cohort (HR 0.4, 95% CI 0.1-0.9, P = 0.047). Early discontinuation of mTORi increased the risk of CMV infection (HR 3.2; 95% CI 1.7-6.0) in univariate analysis. The incidence of CMV infection was not higher among CMV R+ patients on mTORi and requiring high-intensity immunosuppression when CMV prophylaxis was not given. The use of mTORi protected for CMV infection in KT patients, allowing to avoid antiviral prophylaxis for R+ patients receiving high-intensity immunosuppression. The increased risk of CMV infection after early discontinuation of mTORi warrants further research.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 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, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues. This document summarizes the recommendations.

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.

Clostridium difficile-associated disease (CDAD) is the most common cause of nosocomial diarrhea. Information about CDAD in solid organ transplant (SOT) recipients is scarce. To determine its epidemiology and risk factors, we conducted a cohort study in which 4472 SOT patients were prospectively included in the RESITRA/REIPI (Spanish Research Network for the Study of Infection in Transplantation) database between July 2003 and July 2006. Forty-two episodes of CDAD were diagnosed in 36 patients. The overall incidence was 0.94%. Median onset of infection was 31.5 days (range 6–741); in half the cases, onset occurred during the first month after transplantation. In 26% of cases, there was no previous antibiotic use. Independent risk factors for CDAD using Cox regression analysis were previous use of first- and second-generation cephalosporins (HR 3.68; 95%CI 1.8–7.52; P

La infeccion invasiva por Candida es una complicacion cada vez mas frecuente en el paciente adulto hospitalizado. La disponibilidad de nuevos antifungicos con menor toxicidad y gran eficacia ha anadido gran complejidad al tratamiento de la infeccion fungica. De forma paralela, los costes derivados de dicho tratamiento se han incrementado de forma considerable. Encontrar el equilibrio entre el mayor beneficio para el paciente con el menor coste es en la actualidad uno de los objetivos de las recomendaciones en el tratamiento de la candidiasis invasiva. En esta revision se analizan dichas recomendaciones para el tratamiento de la candidemia y otras como la esofagitis, peritonitis, candidiasis ocular, osteoarticular, cardiovascular, del sistema nervioso central, infeccion urinaria y candidiasis cronica diseminada

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Candida peritonitis is a potentially life-threatening infection after abdominal transplantation, although there is scant information regarding its incidence and outcome. We analysed the incidence rate and outcome of Candida peritonitis in 717 liver or pancreas transplant recipients. Five cases of Candida peritonitis were diagnosed, representing the second most frequent cause of invasive fungal infection in the cohort. The incidence rate of Candida peritonitis during the first 30 days after transplantation was 6.5 cases/10 000 transplant days in pancreas recipients and 1.2 cases/10 000 transplant days in liver recipients (P = 0.035). Four of the five patients received an echinocandin in combination with other antifungal. All patients were alive and with good graft function at 1-year follow-up. In our series, Candida peritonitis in liver and pancreas transplant recipients was not uncommon and had a good prognosis.

Antiretroviral therapy has been immensely successful in reducing the incidence of opportunistic infections and death after HIV infection. This has resulted in heightened interest in noninfectious comorbidities including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C and exposure to antiretrovirals and other medications. Therefore, the differential diagnosis is vast. Early identification (through efficient screening) and prompt treatment of kidney disease in HIV-infected individuals are critical to lead to better outcomes. This review focuses on clinical and epidemiological issues, treatment strategies (including dialysis and kidney transplantation), and recent advances among kidney disease in the HIV population.

Daptomycin is a cyclic lipopeptide with a rapid bactericidal effect against Gram-positive bacteria. The pharmacokinetic properties of this drug allow once-daily intravenous infusion as the best posology (including a 2-minute bolus). Because of its ease of administration and excellent safety profile, daptomycin is a first-line agent for use as outpatient antimicrobial parenteral therapy (OPAT). The best evidence supporting this indication exists for the treatment of complicated and uncomplicated skin and soft tissue infections, as well as osteoarticular infections caused by Gram-positive bacteria. For the remaining indications, the use of daptomycin as OPAT should be analyzed in each patient. Information from the EUCORE Registry in Spain indicates that daptomycin has high rates of treatment success in both hospitalized patient and in those included in OPAT programs.

Solid organ transplant recipients (SOTR) are at risk of serious influenza-related complications. The impact of respiratory co-infection in SOTR with 2009 pandemic influenza A(H1N1) is unknown. A multicentre prospective study of consecutive cases of pandemic influenza A(H1N1) in SOTR was carried out to assess the clinical characteristics and outcome and the risk factors for co-infection. Overall, 51 patients were included. Median time from transplant was 3.7years, 5.9% of the cases occurred perioperatively and 7.8% were hospital-acquired. Pneumonia was diagnosed in 15 (29.4%) patients. Ten cases were severe (19.6%): 13.7% were admitted to intensive care units, 5.9% suffered septic shock, 5.9% developed acute graft rejection and 7.8% died. Co-infection was detected in 15 patients (29.4%): eight viral, six bacterial and one fungal. Viral co-infection did not affect the outcome. Patients with non-viral co-infection had a worse outcome: longer hospital stay (26.2±20.7 vs. 5.5±10.2) and higher rate of severe diseases (85.7% vs. 2.3%) and mortality (42.8% vs. 2.3%). Independent risk factors for non-viral co-infection were: diabetes mellitus and septic shock. Other factors associated with severe influenza were: delayed antiviral therapy, diabetes mellitus, time since transplantation

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow-up was 2.6 years (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe infections included a pretransplant Model for End-Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV-coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non-tacrolimus-based immunosuppression.

Cytomegalovirus (CMV) is the most important opportunistic pathogen in patients undergoing solid organ transplantation and increases mortality due to both direct and indirect effects. The most important risk factor for the development of CMV disease is discordant donor-recipient CMV serology (positive donor and negative recipient), which confers more than 50% risk of developing CMV disease if no prophylaxis is given. The use of highly potent antiviral agents for CMV prophylaxis in high-risk patients has changed the characteristics of CMV disease in this population. Other classical risk factors for CMV disease include acute graft rejection, the type of organ transplanted, coinfection with other herpesviruses and the type of immunosuppressive agents employed. New risk factors for this complication have recently been described, including variations in the CMV genotype between donor and recipient and genetic alterations in the recipient's innate immunity. The present review discusses classical risk factors and the latest findings reported on the development of CMV in organ transplant recipients.

† Background and Aims Mixed reproductive strategies may have evolved as a response of plants to cope with environmental variation. One example of a mixed reproductive strategy is dimorphic cleistogamy, where a single plant produces closed, obligately self-pollinated (CL) flowers and open, potentially outcrossed (CH) flowers. Frequently, optimal environmental conditions favour production of more costly CH structures whilst economical and reliable CL structures are produced under less favourable conditions. In this study we explore (1) the effect of light and water on the reproductive phenology and (2) the effect of pollen supplementation on resource allocation to seeds in the cleistogamous weed Ruellia nudiflora. † Methods Split-plot field experiments were carried out to assess the effect of shade (two levels: ambient light vs. a reduction of 50 %) and watering (two levels: non-watered vs. watered) on the onset, end and duration of the production of three reproductive structures: CH flowers, CH fruit and CL fruit. We also looked at the effect of these environmental factors on biomass allocation to seeds (seed weight) from obligately self-pollinated flowers (CL), open-pollinated CH flowers and pollen-supplemented CH flowers. † Key Results CH structures were produced for a briefer period and ended earlier under shaded conditions. These conditions also resulted in an earlier production of CL fruit. Shaded conditions also produced greater biomass allocation to CH seeds receiving extra pollen. † Conclusions Sub-optimal (shaded) conditions resulted in a briefer production period of CH structures whilst these same conditions resulted in an earlier production of CL structures. However, under sub-optimal conditions, plants also allocated more resources to seeds sired from CH flowers receiving large pollen loads. Earlier production of reproductive structures and relatively larger seed might improve subsequent success of CL and pollen-supplemented CH seeds, respectively.

Antecedentes La duracion del tratamiento antibiotico endovenoso de la endocarditis infecciosa (EI) oscila entre 2 y 6 semanas. Aunque varios estudios indican que el tratamiento antibiotico a domicilio endovenoso (TADE) es seguro para el tratamiento domiciliario de la EI sobre valvula nativa no complicada por estreptococos del grupo viridans (EGV) la experiencia en Espana con TADE en la EI es limitada y los datos sobre otros tipos de endocarditis y TADE son escasos en todo el mundo. Metodos Estudio unicentrico, prospectivo, de una cohorte de todos los pacientes con EI admitidos en el programa TADE en el Hospital Clinico de Barcelona entre enero de 1997 y diciembre de 2006. Resultados Durante el periodo de estudio se diagnosticaron 392 episodios consecutivos de EI en pacientes no consumidores de drogas, de los cuales 73 episodios (19%) fueron admitidos en el programa de TADE: 42 EI sobre valvula nativa, 23 EI sobre valvula protesica y 8 EI sobre cable de marcapasos. El porcentaje de inclusion en la TADE fue mayor para la EI por EGV o Streptococcus bovis (S. bovis) (32%) que para el resto de etiologias (14%; p < 0,001). Doce pacientes (16%) fueron reingresados debido a las complicaciones de los cuales tres fallecieron (4%). El uso de glucopeptidos fue el unico factor predictor de reingreso hospitalario (OR [intervalo de confianza del 95%] 4,5 [1,2; 16,8] p = 0,026). No se observaron diferencias entre las EI por EGV y S. bovis y las EI estafilococicas (Staphylococcus aureus y estafilococos coagulasa-negativos) incluidas en el TADE. Los pacientes incluidos estuvieron una mediana de 17 dias en tratamiento domiciliario (rango intercuartilico de 11 a 26,5), lo que permitio un ahorro de 1.466 dias de estancia hospitalaria. Conclusiones Estos datos sugieren que la TADE en la EI es una estrategia terapeutica segura y eficaz en el tratamiento domiciliario de pacientes seleccionados con EI por EGV y otras etiologias, aunque los pacientes que reciben glucopeptidos precisan un mayor control clinico

A full understanding of the ecology and evolution of plant tolerance to damage requires the measurement of a diversity of traits (including multiple fitness-correlates) and underlying mechanisms. Here, we address the compensatory response to defoliation in the perennial herb Ruellia nudiflora, measure biomass allocation patterns and relate them to compensation, and address multiple mechanisms and traits that determine compensatory ability. We used maternal full-sib lines of R. nudiflora and conducted a defoliation experiment in which half the plants of each line were subjected to removal of 40% of leaf area (the other half remained undamaged). Fitness-correlated traits, physiological traits, and leaf longevity were measured during a 2-month period after defoliation. Using another set of plants, we conducted a second defoliation experiment and measured the concentration of non-structural carbohydrates to test for root-to-shoot carbon mobilization as a compensatory mechanism. R. nudiflora showed full compensation in terms of fruit output, and compensatory ability was positively correlated with investment in root biomass in the absence of damage. In addition, defoliated plants produced shorter-lived leaves and had a greater concentration of starch in roots, suggesting that reduced leaf longevity and accumulation of below-ground carbon reserves act as compensatory mechanisms. By measuring multiple fitness-correlates and induced traits, we provide a comprehensive evaluation of R. nudiflora compensatory responses to herbivory.

Despite recent advances in prevention and treatment, cytomegalovirus (CMV) is still a major complication in transplant patients. This study sought to analyze the incidence of CMV disease and its impact on patient and graft survival.Between June 2003 and December 2009, we included all kidney, liver, heart, and double transplant patients who underwent solid organ transplantation. They had 1-year posttransplant follow-up.Among the 1427 patients who received kidney (n = 661), liver (n = 494), heart (n = 89), or double (n = 183) transplants, 103 (7.2%) displayed CMV disease. The incidence by type of transplant was: heart (n = 17, 19%), liver (n = 35, 7%), kidney (n = 41, 6.2%), or double transplant (n = 10, 5.5%; P.001). In 59% of cases, the infection developed during the first 3 months after transplantation. CMV infections ranged from viral syndrome (n = 47, 45%) to tissue-invasive disease (n = 56, 55%), including 38% with gastrointestinal involvement. Relapsing episodes occurred in 12 patients (11%). Discordant donor/recipient CMV serology was present in 151 patients (donor positive/receptor negative), including 34 (22.5%) who developed primary CMV disease (P.001). Coinfections mostly bacterial, were diagnosed in 38% of patients. An acute rejection episode was present in 31% of patients with CMV disease compared to 20% without this complication (P = .017). Crude mortality was significantly higher among patients with CMV disease (n = 18 patients [18%] vs 92 patients [7%]; P.001).Our data confirmed that CMV disease was associated with worse transplant outcomes, with higher incidences of acute rejection episodes and mortality.

The guidelines on the treatment of invasive fungal disease by Aspergillus spp. and other fungi issued by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) are presented. These recommendations are focused on four clinical categories: oncology-haematology patients, solid organ transplant recipients, patients admitted to intensive care units, and children. An extensive review is made of therapeutical advances and scientific evidence in these settings. These guidelines have been prepared according the SEIMC consensus rules by a working group composed of specialists in infectious diseases, clinical microbiology, critical care medicine, paediatrics and oncology-haematology. Specific recommendations on the prevention of fungal infections in these patients are included.

A 40-year-old man with severe chronic idiopathic CD4+ lymphocytopenia complicated with opportunistic infections was successfully treated with non-myeloablative allogeneic hematopoietic stem cell transplantation. After conditioning with fludarabine plus low dose of total-body irradiation, CD34+ peripheral blood stem cells obtained by leukapheresis from his HLA-identical sister were infused. T cell and myeloid complete chimerism was achieved at day +28 and remained stable during the follow-up period. The patient did not develop infectious complications during the procedure. At 35 months of follow-up, his CD4+ T cell count was 1019 cells per microliter. Non-myeloablative allogeneic hematopoietic stem cell transplantation should be considered a treatment option for patients with severe forms of idiopathic CD4+ lymphocytopenia.

Background Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce. Methods We prospectively analyzed all patients undergoing SOT from July 2003 to March 2008, who survived the ¢rst 6 months after surgery and with a minimum 1-year follow-up. Risk factors associated with the development of bacterial and cytomegalovirus (CMV) LI and survival were identi¢ed. Results Overall, 942 SOT recipients (491 kidney, 280 liver, 65 heart, and 106 double transplants) were included. During the study period 147 patients (15.6%) developed 276 episodes of LI (incidence rate, 0.43 per 1000 transplantation-days). Bacteria were the most prevalent etiology (88.0%). Primary sources of infection included urinary tract (36.9%), intra-abdominal (16.7%), and sepsis without source (13.4%). Independent risk factors for late bacterial infection were: age (hazard ratio (HR) (per year) 1.0; 95% con¢dence interval (CI): 1.0^1,0), female gender (HR 1.7; 95%CI: 1.1^2.6), anti-hepatitis C virus (HCV) positive serostatus (HR 1.8; 95%CI: 1.1^3.0), chronic allograft dysfunction (HR 3.2; 95%CI: 1.7^6.1), early CMV disease (HR 2.2; 95%CI 1.2^4.1), and early bacterial infection (HR 2.5; 95%CI 1.6^3.8). The occurrence of chronic allograft dysfunction was an independent risk factor for late CMVd isease (HR 6.5; 95%CI: 1.7^24.6), whereas immunosuppression based on mammalian target of rapamycin inhibitors protected against the development of late CMV disease (HR 0.3; 95%CI: 0.1^1.0). Cox model selected anti-HCV positive serostatus (adjusted HR (aHR) 2.67; 95%CI: 1.27^5.59), age (aHR (per year) 1.06; 95%CI: 1.02^1.10), and the occurrence of LI (aHR 9.12; 95%CI: 3.90^21.33) as independent factors for mortality. Conclusions LI did not constitute an uncommon complication in our cohort, and patients at risk may bene¢t from close clinical monitoring.

The rate of compliance with antifungal drug use guidelines by transplant physicians is mostly unknown. We performed a nationwide electronic survey to assess antifungal use by different types of transplant physicians. Sixty-one percent (53/87) of the transplant programs responded (accounting for 85% of heart transplant procedures, 65% of kidney transplantations, and 71.5% of liver transplantations). Antifungal prophylaxis was used in 41.5% programs (liver 93.3%, heart 30.8%, and kidney 16%). Prophylaxis was universal in 32% of the programs and targeted only to selected patients in 68%, mainly indicated after re-transplantation (73.3%), re-intervention (66.7%) and hemodialysis (60%). Main drugs for universal prophylaxis were fluconazole and itraconazole (42.9% each), while fluconazole (60%), L-amphotericin B (AMB), and caspofungin (13.4% each) were preferred for targeted prophylaxis. Overall, 84.9% of the programs used galactomannan for the diagnosis of invasive aspergillosis (only 34% in BAL) and 66.6% used voriconazole as first-line monotherapy. Combination first-line therapy for invasive aspergillosis was used by 31.3%, mainly with voriconazole with caspofungin (40%) or anidulafungin (26.7%) or L-AMB-caspofungin (26.7%). Adherence of transplant physicians to current recommendations on antifungal treatment and prophylaxis is poor. An international consensus that responds to differences in patients and centers and emphasizes patient safety is clearly needed.

Since the introduction of combined antiretroviral therapy (cART), solid organ transplantation (SOT) has become a therapeutic option for the HIV-positive population. In contrast with liver and kidney transplantation, only three simultaneous pancreas-kidney transplants (SPKT) have been reported among HIV-infected patients. Herein we have reported the first SPKT in an HIV-infected patient in Spain. The pancreas graft failed at 2 weeks and the patient died at 9 months because of a Pseudomonas aeruginosa infection. The three recipients reported in the literature lived, despite the failure of both the pancreas and kidney grafts in one subject. Despite the poor outcome of our case, HIV-1 infection was controlled after transplantation (stable CD4(+) cells and no AIDS-related events), and the kidney graft functioned with no episodes of rejection. The cART regimen used in the pretransplant period was switched at the time of transplantation to raltegravir and two nucleoside reverse transcriptase inhibitors (NRTI). Raltegravir has no interactions with immunosuppressive drugs. Target plasma levels of tacrolimus were achieved at a dose similar to that used in HIV-negative transplant recipients. The most adequate antiretroviral regimen for HIV-infected SOT recipients has not yet been established; however, one may consider switching protease inhibitors or non-NRTI-based regimens for a raltegravir-based regimen at the time of transplantation.

Toxoplasmosis after solid organ transplantation is a complication associated with high morbidity and mortality. Universal prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is effective to prevent post-transplant toxoplasmosis. We report two cases of renal transplant recipients with negative antibodies against Toxoplasma gondii pretransplant who developed toxoplasmosis after TMP-SMX discontinuation. We have also performed a review of published cases of primary toxoplasmosis after renal transplantation. Of 20 cases reviewed, 11 were male and the mean age was 37.8 years (SD = 13.8). Donor serology for T. gondii was determined in 15 donors, two of them (13%) with negative immunoglobulin (Ig)G and four (27%) with positive IgG and IgM antibodies. Fever was present in 85% of primary toxoplasmosis and hematologic abnormalities were observed in 69% of the cases. Ten patients died (50%). All patients with fatal outcomes had clinical evidence of toxoplasmosis during the early post-transplant period (first 90 days), while no patient with late toxoplasmosis died (P = 0.003). Primary toxoplasmosis is associated with high mortality rates and TMP-SMX prophylaxis can delay the onset of symptoms resulting in an improvement of prognosis.

We aimed to determine the epidemiology, risk factors, and impact of bacterial infection on pancreatic function after pancreas transplantation. Data for pancreas transplant recipients were retrospectively reviewed between 2000 and 2014 for at least 1 year. We collected and analyzed post-transplant data for bacterial infection, morbidity, and mortality. During the study period, 312 pancreas transplants were performed. In total, 509 episodes of bacterial infection were diagnosed in 191 patients (61%). Multidrug-resistant (MDR) organisms were present in 173 of the 513 isolated microorganisms (33%). Risk factors independently associated with bacterial infection were acute allograft rejection (OR 1.7, 95%CI 1.1-3), the need for post-transplant hemodialysis, (OR 5.3, 95%CI 1.8-15.7) and surgical re-intervention (OR 2.8, 95%CI 1.5-5.1), which was also considered a risk factor for infections caused by MDR bacteria. Graft survival was associated with the occurrence of one or more episodes of bacterial infection (log-rank test = 0.009). Surgical re-intervention was independently associated with graft loss (OR 2.5, 95%CI 1.3-4.7). To conclude, pancreas recipients frequently experienced bacterial infections associated with the need for hemodialysis or surgical re-intervention. Infection by MDR organisms is a growing concern in these patients and was related to graft survival. Graft loss was independently associated with surgical re-intervention.

BACKGROUND Pre-transplant cytomegalovirus (CMV) serostatus has been associated with lung transplant patient survival. We retrospectively analyzed the relationship between pre-transplant donor/recipient CMV serostatus and long-term mortality in a cohort of lung transplant recipients at our center. METHOD Adult (Age >17 years) lung recipients transplanted between July 1985-December 2015 were analyzed. Variables included age, sex, pre-transplant donor (D)/recipient (R) serostatus [D-/R-, D-/R+, D+/R+, D+/R-], CMV infection within 2 years of transplant and transplant eras divided by changes in CMV prevention strategies: Era 1 (pre-ganciclovir, July 1985-April 1998), Era 2 (oral ganciclovir, May 1998-December 2004), Era 3 (valganciclovir, January 2005-December 2015). Survival analysis and Cox regression were performed at 10 years. RESULTS A total of 652 lung recipients were analyzed. Twenty percent were CMV mismatched pre-transplant and 45% had CMV infection within 2 years post-transplant. Survival at 10 years appeared worse in D+ transplants (P = 0.027). D-/R- lungs did not have significantly different survival across eras (P = 0.76), but survival of D-/R+, D+/R+, D+/R- lungs improved (P