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Background Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. Methods We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5 ' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. Results HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. Conclusion Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.

REIPI/ESGICH/ESGBIS/INCREMENT-SOT Group., There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages., This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001, RD16/0016/0002, RD16/0016/0008; RD16/0016/00010) and was cofinanced by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014‐2020; ESCMID Study Group for Infections in Compromised Hosts (ESGICH grant to J.M.A.); Sociedad Andaluza de Trasplante de Órgano Sólido (SATOT grant to L.M.-M.); ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS); and ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS). B.G.-G. (PI 18/01849) and E.P.-N. (PI 16/01631) have received research funds from the Spanish Ministry of Science and Innovation, ISCIII; M.F.-R. holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science and Innovation, ISCIII.

Current guidelines recommend against systematic screening for or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of posttransplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR], 1.1 to 10.5). Most episodes (96.4% [132/137]) were caused by Gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum beta-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [CI], 31.9% to 48.9%) for the whole cohort and 42.3% (95% CI, 31.2% to 54.0%) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR], 2.42; 95% CI, 1.11 to 5.29; P value = 0.027) and use of fosfomycin as salvage therapy (OR, 8.31; 95% CI, 1.67 to 41.35; P value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse events were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.

Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-gamma FluoroSpot assay after a median of 103days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-gamma-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-gamma-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value=.024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3months from COVID-19, with no meaningful differences with immunocompetent patients.

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-gamma-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (=0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P=0.086) but not CD4+ subsets (P=0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P=0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P=0.087). CONCLUSIONS: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.

BACKGROUND: We aimed at constructing a composite score based on EBVd and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in SOT recipients.; METHODS: Kidney and liver transplant recipients between May 2014-August 2016 at four participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole-blood EBVd were determined at months 1, 3 and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI.; RESULTS: Overall, 309 SOT recipients were followed-up for a median of 1,000 days from transplant (IQR: 822-1124). LI occurred in 104 patients (33.6%). The CLIV score consisted of the following variables at month 6: high-level EBVd (>1,500 IU/ml) and recurrent infection during the previous months (6 points); recipient age =70 years and chronic graft dysfunction (5 points); CMV mismatch (4 points); and CD8+ T-cell count

Objectives We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy. Methods Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Results Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P = 0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution. Conclusions T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.

Background. Influenza vaccine effectiveness is not optimal in solid organ transplant recipients (SOTR). We hypothesized that a booster dose might increase it. Methods. TRANSGRIPE 1-2 is a phase 3, randomized, controlled, multicenter, open-label clinical trial. Patients were randomly assigned (1:1 stratified by study site, type of organ, and time since transplantation) to receive 1 dose (control group) or 2 doses (booster group) of the influenza vaccine 5 weeks apart. Results. A total of 499 SOTR were enrolled. Although seroconversion at 10 weeks did not meet significance in the modified intention-to-treat population, seroconversion rates were significantly higher in the booster arm for the per- protocol population (53.8% vs 37.6% for influenza A(H1N1)pdm; 48.1% vs 32.3% for influenza A(H3N2); and 90.7% vs 75% for influenza B; P < .05). Furthermore, seroprotection at 10 weeks was higher in the booster group: 54% vs 43.2% for A(H1N1)pdm; 56.9% vs 45.5% for A(H3N2); and 83.4% vs 71.8% for influenza B (P < .05). The number needed to treat to seroprotect 1 patient was < 10. The clinical efficacy (99.2% vs 98.8%) and serious adverse events (6.4% vs 7.5%) were similar for both groups. Conclusions. In SOTR, a booster strategy 5 weeks after standard influenza vaccination is safe and effective and induces an increased antibody response compared with standard influenza vaccination consisting of a single dose.

Objectives: To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients. Material and methods: Prospective study conducted at 21 Spanish hospitals including patients with MRSA bacteraemia diagnosed between June/2008 and December/2009. Episodes diagnosed in patients aged 75 or more years old (>= 75) were compared with the rest of them (= 75. Comorbidity was significantly higher in older patients (Charlson score >= 4: 52.8 vs. 44%; p = .037) as was the severity of the underlying disease (McCabe >= 1: 61.9 vs. 43.4%; p < .001). In this group the acquisition was more frequently health-care related (43.3 vs. 33.9%, p = .023), mostly from long-term care centers (12.1 vs. 3.7%, p < .001). An unknown focus was more frequent among >= 75 (19.9 vs. 13.8%; p = .050) while severity at presentation was similar between groups (Pitt score >= 3: 31.2 vs. 27.6%; p = .352). The prevalence of vancomycin resistant isolates was similar between groups, as was the appropriateness of empirical antibiotic therapy. Early (EM) and overall mortality (OM) were significantly more frequent in the >= 75 group (EM: 12.1 vs. 6%; p = .010 OM: 42.9 vs. 23%; p < .001). In multivariate analysis age >= 75 was an independent risk factor for overall mortality (aOR: 2.47, CI: 1.63-3.74; p < .001). Conclusion: MRSA bacteraemia was frequent in patients aged >= 75 of our cohort. This group had higher comorbidity rates and the source of infection was more likely to be unknown. Although no differences were seen in severity or adequacy of empiric therapy, elderly patients showed a higher overall mortality. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Preventing influenza infection early after transplantation is essential, given the disease's high mortality. A multicentre prospective cohort study in adult solid organ transplant recipients (SOTR) receiving the influenza vaccine during four consecutive influenza seasons (2009-2013) was performed to assess the immunogenicity and safety of influenza vaccination in SOTR before and 6 months after transplantation. A total of 798 SOTR, 130 of them vaccinated within 6 months of transplantation and 668 of them vaccinated more than 6 months since transplantation. Seroprotection was similar in both groups: 73.1% vs. 76.5% for A/(H1N1) pdm (p 0.49), 67.5% vs. 74.1% for A/H3N2 (p 0.17) and 84.2% vs. 85.2% for influenza B (p 0.80), respectively. Geometric mean titres after vaccination did not differ among groups: 117.32 (95% confidence interval (CI) 81.52, 168.83) vs. 87.43 (95% CI 72.87, 104.91) for A/(H1N1) pdm, 120.45 (95% CI 82.17, 176.57) vs. 97.86 (95% CI 81.34, 117.44) for A/H3N2 and 143.32 (95% CI 103.46, 198.53) vs. 145.54 (95% CI 122.35, 174.24) for influenza B, respectively. After adjusting for confounding factors, time since transplantation was not associated with response to vaccination. No cases of rejection or severe adverse events were detected in patients vaccinated within the first 6 months after transplantation. In conclusion, influenza vaccination within the first 6 months after transplantation is as safe and immunogenic as vaccination thereafter. Thus, administration of the influenza vaccine can be recommended as soon as 1 month after transplantation. Clinical Microbiology and Infection (C) 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Background Pneumonia frequently affects solid organ transplant (SOT) recipients, with high morbidity and mortality. However, the few studies on pneumonia in this population are mainly retrospective, single-center, and long-term studies, or include patients with only one type of SOT or a specific etiology. We performed a point prevalence study to investigate epidemiology, diagnosis, therapy, and outcome of pneumonia in an unselected SOT population. Methods Italian and Spanish transplant centers were invited to report on all SOT recipients with pneumonia treated during 2 separate weeks (1 each in February and June 2012). Results In total, 35 centers (18 in Italy, 17 in Spain) agreed to participate and collected 54 cases. The incidence of pneumonia was 10.1 episodes/1000 recipients/year. Pneumonia was classified as late (>6 months) in 70.4% of cases. Pneumonia was also classified as community-acquired (CAP), healthcare-associated (HCAP), and hospital-acquired (HAP) pneumonia in 40.7%, 38.9%, and 20.4% of cases, respectively. An attempt to microbiological diagnosis (≥1 sample) was made in 94.4% of patients, with a diagnostic yield of 60.7%. Causative agents included bacteria (87.1%), virus (29%), and fungi (6.4%). A multidrug-resistant bacterium was isolated in 18.2%, 40%, and 100% of patients with CAP, HCAP, and HAP (P = 0.007), respectively. Overall, 11.1% of patients were admitted to the intensive care unit, 3.7% developed graft rejection, and graft function deteriorated in 18.5%. In-hospital mortality was 1.9%. Conclusion Pneumonia remains a frequent problem in SOT recipients, although it occurs later in patients who are in better physical health. Therefore, harmful pathogens and worse outcome are less common than previously thought.