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Background Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. Methods We conducted a multicentre retrospective observational study of patients who received ≥48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. Results The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20–0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18–1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08–1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16–5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18–0.85; P = 0.02). Conclusions Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.

Background Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. Methods Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. Results Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40–62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3–55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01–1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41–6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7–16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07–56.14), were associated with NTM infection. Conclusions Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

[Background] Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy., [Methods] In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia)., [Results] A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome., [Conclusions] Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed., This work was supported by the 2013–2016 National R&D&I Plan and the Carlos III Health Institute (grantPI15/00402 to J.T.C.). It also had the support of The Spanish Society of Nephrology (grant S.E.N. to C.F.), as well as support from the National R&D&I Plan 2013–2016 and the Carlos III Health Institute, General Sub-Directorate of Networks and Cooperative Research Centres, Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/000, RD16/0016/0003, RD16/0016/0007, RD16/0016/0008, RD16/0016/0009 and RD16/0016/0012), co-financed by the European Regional Development Fund “A way to achieve Europe,” Operational Programme Intelligent Growth 2014–2020; Spanish Network for Renal Disease Research (RedInRen, RD16/0009/0006, RD16/0009/0008, RD16/0009/0013, RD16/0009/0014, RD16/0009/0019, RD16/0009/0027, RD16/0009/0034); CIBERES (CB06/06/0058); the Spanish Group for the Study of Infection in Transplantation and the Immunosuppressed Host of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and Spanish Clinical Research Network funded by the ISCIII-Subdirectorate General for the Evaluation and Promotion of Research through projects PT13/0002/0010-PT17/0017/0012 and PT13/0002/0014-PT17/0017/0032 integrated in the 2013–2016 National R&D&I Plan and by the National Plan for Scientific and Technical Research and Innovation (2017–2020) and co-financed by the European Regional Development Fund.

Objectives: (1) To describe the epidemiology of patient safety (PS) incidents registered in an electronic notification system in primary care (PC) health centres, (2) to define a risk map, and (3) to identify the critical areas where intervention is needed. Design: Descriptive analytical study of incidents reported from 1 January to 31 December 2018, on the TPSC Cloud™ platform (The Patient Safety Company) accessible from the corporate website (Intranet) of the regional public health service. Setting: 24 Catalan Institute of Health PC health centres of the Tarragona region (Spain). Participants: Professionals from the PC health centres and a Patient Safety Functional Unit. Measurements: Data obtained from records voluntarily submitted to an electronic, standardised and anonymised form. Data recorded: healthcare unit, notifier, type of incident, risk matrix, causal and contributing factors, preventability, level of resolution and improvement actions. Results: A total of 1544 reports were reviewed and 1129 PS incidents were analysed: 25.0% of incidents did not reach the patient, 66.5% reached the patient without causing harm, and 8.5% caused adverse events. Nurses provided half of the reports (48.5%), while doctors reported more adverse events (70.8%, p &lt, 0.01). Of the 96 adverse events, 46.9% only required observation, 34.4% caused temporary damage that required treatment, 13.5% required (or prolonged) hospitalization, and 5.2% caused severe permanent damage and/or a situation close to death. Notably, 99.2% were considered preventable. The main critical areas were: communication (27.8%), clinical-administrative management (25.1%), care delivery (23.5%) and medicines (18.4%), few incidents were related to diagnosis (3.6%). Conclusions: PS incident notification applications are adequate for reporting incidents and adverse events associated with healthcare. Approximately 75% and 10% of incidents reach the patient and cause some damage, respectively, and most cases are considered preventable. Adequate and strengthened risk management of critical areas is required to improve PS.

[Objective] To prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes., [Methods] A randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis., [Results] 248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7–7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (–0.2%, 95%CI –10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments., [Conclusions] 7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments., This work received technical support from the Spanish Network of Research in Infectious Diseases (REIPI) and the Spanish Clinical Research Network (SCReN) of the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spanish Government (PT13/0002/0010).

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 β‐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., This study 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, Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), and Spanish Network for Research in Renal Diseases (REDInREN RD16/0009) and cofinanced by the European Development Regional Fund entitled A way to achieve Europe. M.F.-R. holds a research contract (Miguel Servet, CP18/00073), from the Spanish Ministry of Science and Innovation, ISCIII.

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

BACKGROUND There is little evidence of the impact of antimicrobial stewardship programmes on antimicrobial resistance. OBJECTIVES To study the efficacy and safety of a package of educational and interventional measures to optimize linezolid use and its impact on bacterial resistance. METHODS A quasi-experimental study was designed and carried out before and after implementation of a stewardship programme in hospitalized patients with Gram-positive infections treated with linezolid. RESULTS The intervention reduced linezolid consumption by 76%. The risk of linezolid-resistant CoNS isolates (OR = 0.37; 95% CI = 0.27-0.49; P

Way of life changes such as high consumption of processed foods rich in fat and sugar and sedentary lifestyle are associated with the increasing prevalence of metabolic syndrome (MetS) that affects about 35% in the American population. MetS is the main risk factor for diabetes mellitus, which is associated with vascular changes in the retina. However, the early consequences of MetS in the retina are not well described. We therefore aimed at characterizing the early effects of a high fructose and high fat diet (HFHF) on the function and structure of the rat retina, and evaluate the associations with metabolic changes. Brown Norway rats of 6 weeks of age were fed for 8 days, 5 weeks or 13 weeks with HFHF diet, or a standard chow. After only 4 weeks of this diet, rats exhibited a reduction in cone photoreceptor sensitivity to light. Moreover, we observed that MetS significantly exacerbated laser-induced choroidal neovascularization by 72% and 67% 2 weeks and 3 weeks post laser treatment, respectively. These retinal abnormalities were associated with deregulation of glucose metabolism but not lipid metabolism. These data showed retinal modifications in HFHF-induced MetS in the rat, at very early stage of the disease.

Cytomegalovirus; Immuno-guided prophylaxis; Lung transplantation Citomegalovirus; Profilaxis inmunoguiada; Trasplante de pulmón Citomegalovirus; Profilaxi immuno-guiada; Trasplantament de pulmó INTRODUCTION: Prolonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. The aim of the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis. METHODS AND ANALYSIS: Phase III randomised, open, multicentre, parallel, non-inferiority clinical trial to study the efficacy and safety of the combination of a prophylaxis strategy up to month +3 post-transplant followed by immuno-guided prophylaxis using the QuantiFERON-CMV technique up to month +12 post-transplant to prevent CMV disease in CMV-seropositive lung transplant recipients. This strategy will be compared with a combination of a usual prophylaxis strategy up to month +6 post-transplant followed by pre-emptive therapy up to month +12. To study the incidence of CMV disease, patients will be followed up to 18 months post-transplantation. A total of 150 patients are expected to be recruited for the study. ETHICS AND PUBLIC DISSEMINATION: The clinical trial has been approved by the Research Ethics Committees and authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS).If the hypothesis of this clinical trial is verified, the dissemination of the results could change clinical practice by increasing knowledge about the safety and efficacy of discontinuing valganciclovir prophylaxis in lung transplant recipients. We would like to acknowledge the support of the Spanish Network for Research in Infectious Disease (REIPI, RD16/0016), the Group for the Study of Infections in Transplant Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and SCReN (Spanish Clinical Research Network) funded by the ISCIII-Sub-Directorate General for Research Assessment and Promotion through project PT13/0002/0010-PT17/0017/0012 and PT17/0017/0032.

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions.SIGNIFICANCE STATEMENTIn the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning.

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.

The control of Plum pox virus (PPV), the most important viral disease that affects stone fruit trees, requires the use of reliable detection methods. The effectiveness of spot real-time reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of PPV in samples collected from nursery blocks was compared with a validated PPV detection technique, the double antibody sandwich indirect enzyme-linked immunosorbent assay (DASI-ELISA) using the PPV-specific monoclonal antibody 5B-IVIA/AMR. In total, 5047 nursery plants were analysed by both techniques. The agreement between the techniques was almost perfect (Cohen’s kappa index of 0·88 ± 0·01). The diagnostic parameters (sensitivity, specificity and likelihood ratios) of both techniques were simultaneously evaluated in 2473 nursery plants by latent class models using maximum likelihood functions and a Bayesian approach. The sensitivity and specificity of both techniques did not vary according to the latent model applied. Spot real-time RT-PCR was more sensitive while DASI-ELISA was more specific for PPV detection. In addition, the findings demonstrate that latent class models are a flexible and potent statistical method to estimate the accuracy of diagnostic tests for plant pathology.

Objective Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. Methods We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptides (mean of six measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T cells were calculated at baseline and day 15. Results Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count Conclusions Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.

A multicenter, comparative study was performed to determine the epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium tuberculosis and Mycobacterium kansasii in human immunodeficiency virus (HIV)-infected patients. From 1 January 1995 through 31 December 1999, 25 HIV-infected patients received diagnoses of M. kansasii infection, and another 75 were selected as control subjects from among patients who had M. tuberculosis infection. Variables associated with M. tuberculosis disease in the multivariate analysis were previous intravenous drug use (odds ratio [OR], 8; 95% confidence interval [CI], 1.5-41.4) and interstitial radiologic pattern (OR, 12.7; 95% CI, 1.7-94.3). Variables associated with M. kansasii were previous diagnosis of acquired immunodeficiency syndrome (OR, 15.8; 95% CI, 4.2-59.6) and concomitant opportunistic infections (OR, 14.2; 95% CI, 2-105.7). Clinical and radiologic features were similar for both groups, but epidemiological characteristics and prognosis were different. M. kansasii disease was associated more closely with level of immunosuppression and progression of HIV infection than was disease caused by M. tuberculosis.

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.

Background. It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver trans-plant recipients. This study was designed to investigate the efficacy and safety of levofloxacin.Methods. An open-label, prospective, multicenter, randomized study was conducted to compare the efficacyand safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and iso-niazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was mea-sured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication wererecorded.Results. CONSORT guidelines were followed in order to present the results. The safety committee suspendedthe study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levo-floxacinarm).Thereasonforsuspensionwasanunexpectedincidenceofseveretenosynovitisinthelevofloxacinarm(18.2%). Although the clinical coursewas favorable in all cases, tenosynovitis persisted for 7 weeks in some patients.No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31)and 54.5% of patients randomized to levofloxacin (18/33, P=.094) completed prophylaxis. No patient developedtuberculosis during the study follow-up (median 270 days).Conclusions. Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a highincidence of tenosynovitis that limits its potential utility.Keywords. tuberculosis; levofloxacin; tenosynovitis; investigator-driven clinical trial.Less than 30% of liver transplant recipients with a pos-itivetuberculinpurifiedproteinderivate(PPD)skintestcurrently receive prophylaxis with isoniazid because ofits potential hepatotoxicity [1–3],which can destabilizechronic liver diseasewhen used in the pretransplant pe-riod. For this reason some experts recommend that iso-niazid prophylaxis should not be initiated until aftertransplantation when liver function is stable [1–3].However, the prophylaxis with isoniazid is frequentlynever initiated or discontinued due to the elevation oftransaminase levels. In fact, some experts believe that,in this scenario, the risks of using isoniazid outweighits potential benefits [4]. Other alternatives [5, 6]arenot free of hepatotoxicity [2,7–11].

Background Vector-borne transmission of Trypanosoma cruzi is seen exclusively in the Americas where an estimated 8 million people are infected with the parasite. Significant research in southern Peru has been conducted to understand T. cruzi infection and vector control, however, much less is known about the burden of infection and epidemiology in northern Peru. Methodology A cross-sectional study was conducted to estimate the seroprevalence of T. cruzi infection in humans (n=611) and domestic animals [dogs (n=106) and guinea pigs (n=206)] in communities of Cutervo Province, Peru. Sampling and diagnostic strategies differed according to species. An entomological household study (n=208) was conducted to identify the triatomine burden and species composition, as well as the prevalence of T. cruzi in vectors. Electrocardiograms (EKG) were performed on a subset of participants (n=90 T. cruzi infected participants and 170 age and sex-matched controls). The seroprevalence of T. cruzi among humans, dogs, and guinea pigs was 14.9% (95% CI: 12.2 – 18.0%), 19.8% (95% CI: 12.7- 28.7%) and 3.3% (95% CI: 1.4 – 6.9%) respectively. In one community, the prevalence of T. cruzi infection was 17.2% (95% CI: 9.6 - 24.7%) among participants < 15 years, suggesting recent transmission. Increasing age, positive triatomines in a participant's house, and ownership of a T. cruzi positive guinea pig were independent correlates of T. cruzi infection. Only one species of triatomine was found, Panstrongylus lignarius, formerly P. herreri. Approximately forty percent (39.9%, 95% CI: 33.2 - 46.9%) of surveyed households were infested with this vector and 14.9% (95% CI: 10.4 - 20.5%) had at least one triatomine positive for T. cruzi. The cardiac abnormality of right bundle branch block was rare, but only identified in seropositive individuals. Conclusions Our research documents a substantial prevalence of T. cruzi infection in Cutervo and highlights a need for greater attention and vector control efforts in northern Peru., Author Summary Chagas disease causes significant morbidity and mortality throughout Central and South America. The epidemiology and control of this disease is subject to unique regional particularities, including the behavior and ecology of the local insect vector species. Significant resources have been allocated towards research and control efforts in southern Peru, yet very little is known about the prevalence and epidemiology of Trypanosoma cruzi in northern Peru. Our study highlights significant T. cruzi infection in northern Peru and is one of the first to document substantial transmission by the insect Panstrongylus lignarius. Our results illustrate major gaps in knowledge and the need for public health interventions targeted at Chagas disease in the region of Cutervo Province of northern Peru.

Carbapenem-resistant Acinetobacter baumannii (CRAb) is a major source of nosocomial infections in Spain associated with the production of OXA-58-like or OXA-24/40-like β-lactamase enzymes. We analysed the plasmids carrying the bla(OXA-24/40)-like gene in CRAb isolates obtained a decade apart.The presence of β-lactamases was screened for by PCR (metallo-β-lactamases, carbapenem-hydrolysing class D β-lactamases, GES and KPC) in 101 CRAb isolates obtained in two multicentre studies (GEIH/REIPI-Ab-2000 and GEIH/REIPI-Ab-2010; n = 493 Acinetobacter spp). We analysed the distribution and characterization of the plasmids carrying the bla(OXA-24/40)-like gene and sequenced two plasmids, AbATCC223p (2000) and AbATCC329p (2010) from A. baumannii ATCC 17978 transformants.Acquisition of the bla(OXA-24/40)-like gene was the main mechanism underlying resistance to carbapenems (48.7% in 2000 compared with 51.6% in 2010). This gene was mainly isolated in ST2 A. baumannii strains in both studies, although some novel STs (ST79 and ST80) appeared in 2010. The gene was located in plasmids (8-12 kbp) associated with the repAci2 or repAci2/repGR12 types. The sequences of AbATCC223p (8840 bp) and AbATCC329p (8842 bp) plasmids were similar, particularly regarding the presence of the genes encoding the AbkA/AbkB proteins associated with the toxin/antitoxin system. Moreover, the abkA/abkB gene sequences (96% identity) were also located in plasmids harbouring the bla(OXA-58)-like gene.The action of OXA-24/40 and OXA-58 β-lactamase-like enzymes represents the main mechanism underlying resistance to carbapenems in Spain in the last decade. AbkA/AbkB proteins in the toxin/antitoxin system may be involved in the successful dissemination of plasmids carrying the bla(OXA-24/40)-like gene, and probably also the bla(OXA-58)-like gene, thus contributing to the plasmid stability.

Visceral leishmaniasis (VL) is a rare disease in solid-organ transplant (SOT) recipients. Therefore, little is known about the risk factors and disease behavior in the transplant setting. This multicenter, matched case–control study (1:2 ratio) was designed to determine the risk factors, clinical features and outcomes of VL among this population. Control and case subjects were matched by center, transplant type and timing. Thirty-six VL cases were identified among 25 139 SOT recipients (0.1%). VL occurred 5.7-fold more frequently in Brazil than in Spain, presenting a median time of 11 months after transplantation. High-dose prednisone in the preceding 6 months was associated with VL. Patients were diagnosed over 1 month after symptom onset in 25% of cases. Thirty-one patients (86%) were febrile upon diagnosis, 81% exhibited visceromegaly and 47% showed pancytopenia. Concomitant infection was common. Parasites were identified in 89% of patients; the remaining patients were diagnosed by serology. The majority of the patients received amphotericin B. Relapses occurred in 25.7% of cases, and the crude mortality rate was 2.8%. VL after SOT is related to the VL prevalence in the general population. Delayed diagnosis frequently occurs. Liposomal amphotericin is the most commonly used therapy; mortality is low, although relapses are common.

Summary Objectives The aim of this study was to determine the epidemiology and clinical impact of infections in patients awaiting heart transplantation. Methods We evaluated all patients considered for a heart transplant in our center over a period of 18 months over a period of 18 months from 2007 to 2009. The patients were followed up for 8 months or until death, transplant, or loss to follow-up. Results Ninety patients were included in the study. During follow-up, 25 infections were recorded in 22 heart transplant candidates (24.4%). Respiratory infections were the most frequent infection (12 bronchitis; 48.0%), followed by skin and soft tissue infections (four infections; 16.0%), intra-abdominal infections (four infectious diarrhea; 16.0%), bacteremia (three infections; 12.0%), and urinary tract infections (two infections; 2.0%). Age, comorbidity, sex, and diabetes were not found to be risk factors for infection. Twenty-four patients (26.7%) were transplanted during follow-up. Infection before transplantation was not associated with an increased risk of mortality or a higher rate of infection in the immediate post-transplant period. Conclusions Infections are common in heart transplant candidates, affecting almost 25% of them. Respiratory tract infections are the most frequent type of infection. However, they are not associated with increased mortality in the immediate post-transplant period.

Background Tobacco smoking is an important public health concern worldwide leading to both chronic disease and early death. In Latin America, smoking prevalence is estimated at approximately 30% and prior studies suggest that the prevalence in Peru is 22% to 38%. We sought to determine the prevalence of daily smoking in a poor peri-urban community in Lima, Peru. Methods We conducted a cross-sectional survey in a random sample of adults ≥40 years of age living in Pampas de San Juan de Miraflores, Lima, Peru. We asked participants to respond to a survey that included questions on sociodemographics, tobacco use and dependence. Results We enrolled 316 participants. Average monthly household income was ≤ 400 USD and nearly all homes had running water, sewage, and electricity. Most individuals had not completed high school. Smoking prevalence was 16% overall, yet daily smoking prevalence was 1.9%. Former daily smokers comprised 3.8% of current nonsmokers and 9.1% current occasional smokers. Average scores for the Fagerstrom Test for Nicotine Dependence for daily smokers and occasional smokers were 1.5 and 0, respectively. Conclusions Daily use of tobacco is uncommon among adults in peri-urban communities of Lima, Peru, unlike their counterparts in Lima and other Latin American capital cities. Tobacco dependence is also low. Hence, efforts aimed at primary prevention are of utmost importance in these communities. This study provides an accurate baseline using an internationally recognized assessment tool (Global Adult Tobacco Survey), allowing for accurate assessment of tobacco control interventions over time.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:44:08Z No. of bitstreams: 0 Made available in DSpace on 2013-08-22T18:44:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-01 Made available in DSpace on 2013-09-30T17:44:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:19:35Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T13:19:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-01 Visando estabelecer a contribuição dos parâmetros físicos na qualidade final da silagem de grãos úmidos de milho, foi conduzido experimento, no interior de câmara climatizada, simulando cinco condições de temperatura ambiente (5ºC 24h-1 por dia; 25ºC 24h-1 por dia; 40ºC 24h-1 por dia; 20ºC 16h-1 por dia + 5ºC 8h-1 por dia; 30ºC 16h-1 por dia + 20ºC 8h-1 por dia) e duas condições de pressão no interior dos tambores de armazenagem (com e sem pressão interna). Para se determinar os efeitos sobre o grau de disponibilidade do amido na silagem pronta, procedeu-se a análises para avaliar a qualidade final da silagem (teor de umidade, pH, ácidos orgânicos, amido total e granulometria). O delineamento estatístico utilizado foi o inteiramente ao acaso, num fatorial 5 x 2, com três repetições. Os resultados obtidos indicaram influência significativa tanto da temperatura quanto da pressão, sendo os efeitos mais benéficos verificados nos tratamentos '30ºC 16h-1 por dia + 20ºC 8h-1 por dia', '25ºC 24h-1 por dia' e 'ausência de pressão'. In order to establish the contribution of the physical parameters in the final quality of high-moisture corn silage, an experiment was conducted in the interior of a climate-controlled chamber, simulating five conditions of room temperature (5ºC 24 hours-1 per day; 25ºC 24 hours-1 per day; 40ºC 24 hours-1 per day; 20ºC 16 hours-1 per day + 5ºC 8 hours-1 per day; 30ºC 16 hours-1 per day + 20ºC 8 hours-1 per day) and two conditions of pressure in the interior of plastic storage recipient (with and without internal pressure). To determine the effect on the degree of availability of the starch in the ready silage, analyses were carried out to evaluate the final quality of the silage (moisture content, pH, organic acid, total starch and granulometry). The experimental design was completely randomized, with 5x2 factorial schemes, with three repetitions. The obtained results indicated a significant effect of both temperature and pressure parameters, with the better quality index observed in the treatments '30ºC 16 hours-1 per day + 20ºC 8 hours-1 per day', '25ºC 24 hours-1 per day' and 'absence of internal pressure'. Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências Agronômicas de Botucatu Departamento de Engenharia Rural Universidade Estadual Paulista Júlio deMesquita Filho Faculdade de Medicina Veterinária e Zootecnia de Botucatu Departamento deProdução e Exploração Animal Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências Agronômicas de Botucatu Departamento de Engenharia Rural Universidade Estadual Paulista Júlio deMesquita Filho Faculdade de Medicina Veterinária e Zootecnia de Botucatu Departamento deProdução e Exploração Animal

In order to establish the contribution of the physical parameters in the final quality of high-moisture corn silage, an experiment was conducted in the interior of a climate-controlled chamber, simulating five conditions of room temperature (5°C 24 hours-1 per day; 25°C 24 hours-1 per day; 40°C 24 hours-1 per day; 20°C 16 hours-1 per day + 5°C 8 hours-1 per day; 30°C 16 hours-1 per day + 20°C 8 hours-1 per day) and two conditions of pressure in the interior of plastic storage recipient (with and without internal pressure). To determine the effect on the degree of availability of the starch in the ready silage, analyses were carried out to evaluate the final quality of the silage (moisture content, pH, organic acid, total starch and granulometry). The experimental design was completely randomized, with 5x2 factorial schemes, with three repetitions. The obtained results indicated a significant effect of both temperature and pressure parameters, with the better quality index observed in the treatments ‘30°C 16 hours-1 per day + 20°C 8 hours-1 per day’, ‘25°C 24 hours-1 per day’ and ‘absence of internal pressure’. Visando estabelecer a contribuição dos parâmetros físicos na qualidade final da silagem de grãos úmidos de milho, foi conduzido experimento, no interior de câmara climatizada, simulando cinco condições de temperatura ambiente (5°C 24h-1 por dia; 25°C 24h-1 por dia; 40°C 24h-1 por dia; 20°C 16h-1 por dia + 5°C 8h-1 por dia; 30°C 16h-1 por dia + 20°C 8h-1 por dia) e duas condições de pressão no interior dos tambores de armazenagem (com e sem pressão interna). Para se determinar os efeitos sobre o grau de disponibilidade do amido na silagem pronta, procedeu-se a análises para avaliar a qualidade final da silagem (teor de umidade, pH, ácidos orgânicos, amido total e granulometria). O delineamento estatístico utilizado foi o inteiramente ao acaso, num fatorial 5 x 2, com três repetições. Os resultados obtidos indicaram influência significativa tanto da temperatura quanto da pressão, sendo os efeitos mais benéficos verificados nos tratamentos ‘30°C 16h-1 por dia + 20°C 8h-1 por dia’, ‘25°C 24h-1 por dia’ e ‘ausência de pressão’.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by the human polyomavirus JC (JCV). JCV has a hypervariable noncoding transcriptional control region (TCR) that spans the origin of replication of the JCV genome through to the first ATG start codon for late gene transcription. The archetype form of TCR is frequently found in the urine and kidneys of healthy and immunocompromised subjects. However the rearranged forms, whose prototype is Mad-1, possibly generated by deletion and duplication of segments of the archetype sequence, are found in the brain and cerebrospinal fluid (CSF) of PML patients. In this study the authors compared JCV TCR detected in paired CSF, plasma, and urine samples of 11 acquired immunodeficiency syndrome (AIDS) patients affected by PML to try to determine where the rearranged JCV TCRs are selected. In one patient, it was also possible to amplify and sequence the TCR in the brain and lymphocytes. Moreover, in 5/11 patients, the CSF, plasma, and urine samples corresponding to 2 months after PML development were available; and in another patient, it was possible to sequence the TCR in plasma and lymphocytes sampled 8 months before the onset of PML. The presence of the same TCR sequences in all the CSF and plasma samples taken from individual patients could strengthen the hypothesis that the blood is a compartment where JCV may replicate and undergo rearrangement of the TCR. This further supports the hypothesis that JCV reaches the brain by a hematogenous route and indicates that the JCV TCR sequences detected in plasma could be used as an early marker of JCV pathogenicity before the clinical appearance of PML in immunocompromised patients.