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This article aims to review the main information taken into account for the update of the GESIDA PLWH quality indicators. Finally 54 indicators covering a major part of the clinical activity in PLWH were defined. They evaluate the detection and diagnosis of PLWH, their follow-up and prevention, initiation and adaptation of ART, women's specific aspects, comorbidities, hospitalization, and AIDS-related mortality.

Background Information on the characteristics of patients with nosocomial influenza and associated complications is scarce. This study compared epidemiological and clinical characteristics of patients admitted with hospital‐acquired influenza (HAI) to those with community‐acquired influenza (CAI) and analyzed risk factors associated with complications. Methods This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during the influenza season in Spain (October to May) from 2012‐2013 to 2015‐2016. Symptom onset before admission was included as CAI, and 2 days after admission or within 48 hours after previous discharge were considered as HAI. Results Overall, 666 patients with laboratory‐confirmed influenza were included; 590 (88.6%) and 76 (11.4%) had CAI and HAI, respectively. Baseline characteristics and vaccination rates were similar in both groups. Patients with HAI had significantly fewer symptoms, less radiological alterations, and earlier microbiological diagnosis than those with CAI. Eighty‐five (14.4%) and 20 (27.6%) CAI and HAI patients, respectively, experienced at least one complication, including septic shock, admission to the intensive care unit, mechanical ventilation or evolution to death (any one, P = .003). Univariate and multivariate binary logistic regression was performed to assess independent risk factors associated with the occurrence of complications: nosocomial infection, diabetes, oseltamivir treatment, having received no vaccination, microbiological delay, dyspnea, and the state of confusion were the most important significant factors. Conclusions Our study shows the need to implement microbiological diagnostic measures in the first 48 hours to reduce HAI frequency and associated complications.

Summary Background Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. Methods We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. Findings We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0–52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31–1·83), men who have sex with men (1·42, 1·09–1·86), and those with four or more chronic comorbidities (1·46, 1·09–1·97). Age at least 75 years (5·2, 1·8–15·3), non-Spanish origin (2·1, 1·3–3·4), and neuropsychiatric (1·69, 1·07–2·69), autoimmune disease (1·92, 1·14–3·23), respiratory disease (1·84, 1·09–3·09), and metabolic disease (2·59, 1·59–4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). Interpretation People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. Funding Fundacio "la Caixa". Translations For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.

Background: There are few shared assistance programs with Primary Health Care (PHC) in PLWH. The aim was to develop a Pilot Program of shared HIV care in PLWH ensuring proper HIV control. Methods: Design: Prospective pilot project of a shared care intervention.Setting: HIV specialized outpatient consultations for HIV infection at Son Espases University Hospital which serves 2000 patients. Subjects: Patients who attended HIV specialized consultation between January 1st and June 30th, 2017. Intervention: Basal questionnaire on health services used by patients. HIV Training Program on HIV in Primary Health Care (PHC). Pilot Program of shared assistance (PPAC) with PHC. Main Outcomes: Maintenance of undetectable HIV viral load, antiretroviral therapy (ART) adherence, AIDS and non-AIDS events, loss of follow up, and satisfaction questionnaire. Results: The basal questionnaire was filled out by 918 patients, with 108 (11.7%) patients reporting neither knowing nor having been visited by their GP. A total of 93 patients were included in the PPAC, with a mean age of 49.9 years (SD 11.7), and an average of 14.6 years since the HIV diagnosis. Eleven patients were followed up for less than six months and were excluded from the analysis. Median follow-up during the PPAC of the remaining 82 patients was 728 days (IQR 370-1070). Sixteen patients dropped out of the PPAC (19.5%), three died, three were lost to follow up, one was withdrawn due to medical criteria, and nine withdrew voluntarily.No patient presented any AIDS defining events, although eight patients presented non-AIDS events. All the patients had undetectable viral load (VL) and average ART adherence was 99.4% (SD1.4). The patient’s satisfaction score with PPAC was 8.64 (SD2.5).Conclusion: It is possible to establish shared care programs with PHC in selected patients with HIV infection, thereby reducing hospital visits while maintaining good adherence and virological control and achieving high patient satisfaction.

Introduction: Since 2015, integrase strand transfer inhibitors (INSTI)-based regimens have been considered as the preferred option for antiretroviral therapy (ART)-naive patients. The main objective of this study was to identify the ART-regimens selected for treatment-naive patients during 2015 in two tertiary hospitals, determine the rate of virological failure at 24 and 48 weeks, and compare the results with those of previous years (2012-2014). Material and methods: Four-year retrospective study. Adult ART-naive patients who had started treatment between 2012 and 2015 were selected. Clinical data, laboratory tests performed, and ART selected were recorded. Results: A total of 536 patients were included, 137 from 2015 and 399 from 2012-2014. The most common ART regimens prescribed in 2015, compared to 2012-2014, were INSTI-based regimens (68.6% vs. 4.8%), followed by non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (20.4% vs. 52.8%) and PI-based regimens (10.9% vs. 42.5%). Most patients received a single-tablet regimen (78.8% vs. 51.9%). In 2015, 72.3% of patients had a viral load (VL) < 50 copies/ml at week 24 and 83.9% at week 48, compared to 55.1% and 74.7%, respectively, in 2012-2014. During the 48-week follow-up, the ART regimen was changed in 22.6% of patients in 2015 and 29.3% in 2012-2014. The main reason was simplification (45.2% vs. 22.2%) followed by side effects (25.8% vs. 38.5%). Conclusions: In 2015, INSTI-based regimens were prescribed in nearly 70% of ART-naive patients. This change in trend in the starting ART regimen results in a greater number of patients achieving a VL < 50 copies/ml at weeks 24 and 48 and in a reduction in ART changes due to adverse effects.

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Introduction International travelers have grown significantly over last years, as well as imported diseases from tropical areas. Information in pediatric population is scarce. We describe demographic and clinical characteristics of febrile children coming from the tropics. Methods Retrospective review of patients under 18 years old, presenting at a tertiary hospital and surrounding primary health care centers between July 2002 and July 2018 with a stay in a tropical region during the previous year. Patients were selected from microbiological charts of thick smears for malaria or dengue serologies. Results 188 patients were studied: 52.7% were born in Spain with a median age of 3.0 years old (IQR 1.5–8.0). Main regions of stay were Sub-Saharan Africa (54.8%) and Latin America (29.8%), mostly for visiting their friends and relatives (56.3%), followed by recent arrival migrants (32.4%). Only 34% of travelers attended pre-travel consultation. More than 80% of these febrile children attended directly the Emergency Room. The most frequent diagnoses were febrile syndrome without source (56.4%), respiratory condition (15.4%) and acute diarrhea (11.7%). Around a half (52.1%) were managed as outpatients, but 46.2% were hospitalized and 7.4% were admitted to Intensive Care Unit. No specific diagnosis was achieved in 24% of cases. However, 29.7% were diagnosed with malaria. Conclusion Children with fever coming from tropical areas were at risk of severe infectious diseases. Malaria was diagnosed in one out of four and 7% required admission in PICU. This information emphasizes the need of reinforcing training about tropical diseases among first line physicians.

Background.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success.Methods.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy.Results.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using β-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with β-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34).Conclusions.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of β-lactams are confirmed and maybe also a potential benefit from adding rifampin.

Introduction In 2010, the AIDS Study Group (Grupo de Estudio del SIDA [GESIDA]) developed 66 quality care indicators. The aim of this study is to determine which of these indicators are associated with mortality and hospital admission, and to perform a preliminary assessment of a prediction rule for mortality and hospital admission in patients on treatment and follow-up. Methods A retrospective cohort study was conducted in the Hospital Universitario Son Espases (Palma de Mallorca, Spain). Eligible participants were patients with human immunodeficiency syndrome ≥18 years old who began follow-up in the Infectious Disease Section between 1 January 2000 and 31 December 2012. A descriptive analysis was performed to evaluate anthropometric variables, and a logistic regression analysis to assess the association between GESIDA indicators and mortality/admission. The mortality probability model was built using logistic regression. Results A total of 1944 adults were eligible (median age: 37 years old, 78.8% male). In the multivariate analysis, the quality of care indicators associated with mortality in the follow-up patient group were the items 7, 16 and 20, and in the group of patients on treatment were 7, 16, 20, 35, and 38. The quality of care indicators associated with hospital admissions in the follow-up patients group was the same as those in the mortality analysis, plus number 31. In the treatment group the associated quality of care indicators were items 7, 16, 20, 35, 38, and 40. Conclusions Some GeSIDA quality of care indicators were associated with mortality and/or hospital admissions. These indicators are associated with delayed diagnosis, regular monitoring, prevention of infections, and control of comorbidities.

Introduction Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immuneviral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. Methods We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. Results We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. Discussion Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population., This work was financed through ABAMI (Balearic Association of Infectious Diseases).The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naive-HIV-infected patients. Methods We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience's MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value). Results All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028). Conclusions DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naive HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection., This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Accion Estrategica en Salud, Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (2013-2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdireccion General de Evaluacion) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigacion Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid B2017/BMD-3703. Programa de Investigacion de la Consejeria de Sanidad de la Comunidad de Madrid to JLJ. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by ISCIII with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 Cancer Nanomedicine from the Bench to the Bedside supported by COST (European Cooperation in Science and Technology). AFR and MAJS are supported by Instituto de Salud Carlos III [grant number CP14/0010 and CP17CIII/00007, respectivelly].

Background: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART. Objectives: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain. Methods: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used. Results: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/ lamivudine was 1.7%, 1.9% and 0.7%, respectively. Conclusions: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.

Background: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique that provides in vivo microscopic imaging of the distal lung. We hypothesized that the intra-alveolar exudates characterizing Pneumocystis jirovecii pneumonia (PJP) can be identified by pCLE in vivo and help in its diagnosis. Objectives: We aimed to assess the usefulness of pCLE for the in vivo diagnosis of PJP. Methods: Thirty-two human immunodeficiency virus (HIV)-positive patients with new pulmonary infiltrates and fever were studied using pCLE. Real-time alveolar images were recorded during the bronchoscopy for off-line analysis by two independent observers. Bronchoalveolar lavage samples were also obtained and processed for microbiology and cytological evaluation, including Grocott stain for P. jirovecii. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of pCLE for the diagnosis of PJP in these patients were calculated. Results: Fourteen patients (44%) were confirmed to have PJP by cultures/staining. pCLE was well tolerated in all patients. It identified intra-alveolar exudates in 13 of them (41%), where 11 of them (85%) had positive Grocott stain for P. jirovecci, with 93% concordance between observers. Sensitivity, specificity, PPV and NPV of pCLE for the diagnosis of PJP were 79, 89, 85 and 84%, respectively. In smokers, these figures improved to be 92, 88, 85 and 94%. Conclusions: pCLE is a quick and safe procedure for on-site diagnosis of PJP in HIV+ patients with excellent specificity and sensitivity mainly in smokers.

[Background] HIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART., [Methods] We analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (n = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an in vitro system for the study of human HP processes., [Results] Immunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated in vitro during the human HP, especially during the fast HP., [Conclusion] Our results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset., This work was supported by grants from the Fondo de Investigación Sanitaria [FIS; PI14/01693, PI13/0796, PI16/0503], co-funded by Fondos Europeos para el Desarrollo Regional (FEDER), the Junta de Andalucía, Consejería de Economía, Innovación, Ciencia y Empleo [Proyecto de Investigación de Excelencia; CTS2593], AGAUR (2017SGR948) and GILEAD (GLD14/293). The Spanish AIDS Research Network of Excellence also supported this study (RD12/0017/0029 for I. Rosado, RD16/0025/0019 and RD16/0025/0006). YP was supported by the Consejería de Salud y Bienestar Social of Junta de Andalucía through the “‘Nicolás Monardes’” program [C-0013-2017].

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated. (C) 2015 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinics. All rights reserved.

Objectives: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naiive patients >50 years old who started combination antiretroviral therapy (cART). Design: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). Methods: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. Results: We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247 cells/mu l, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P= 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.

[EN] The incidence of prosthetic joint infection (PJI) is expected to increase in the coming years. PJI has serious consequences for patients, and high costs for the health system. The complexity of these infections makes it necessary to organize the vast quantity of information published in the last several years. The indications for the choice of a given surgical strategy and the corresponding antimicrobial therapy are specifically reviewed. The authors selected clinically relevant questions and then reviewed the available literature in order to give recommendations according to a pre-determined level of scientific evidence. The more controversial aspects were debated, and the final composition was agreed at an ad hoc meeting. Before its final publication, the manuscript was made available online in order that all SEIMC members were able to read it and make comments and suggestions., [ES] Se prevé un incremento de la incidencia de infección de las prótesis articulares (IPA) en los próximos años. Las IPA plantean graves consecuencias para los pacientes y un alto coste el sistema sanitario. La complejidad de estas infecciones hace que sea necesario organizar la inmensa cantidad de información publicada en los últimos años. En estas guías se revisan específicamente las indicaciones para la elección de una estrategia quirúrgica dada y el tratamiento antimicrobiano correspondiente. Los autores seleccionaron las preguntas clínicamente relevantes y revisaron la literatura disponible con el fin de proporcionar recomendaciones de acuerdo con un grado de evidencia científica predeterminada. Los aspectos más controvertidos fueron debatidos y la redacción final se acordó en una reunión ad hoc. Antes de su publicación, el manuscrito estuvo abierto a comentarios y sugerencias de los miembros de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18–5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23–5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09–0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

Resumen Objetivo Averiguar si existe asociacion entre la transfusion perioperatoria de 1-2 unidades de hematies y la morbilidad hospitalaria, la mortalidad a 30 dias y la supervivencia a largo plazo en los pacientes operados en cirugia cardiaca. Diseno Estudio de cohorte prospectivo. Ambito UCI de un hospital universitario. Pacientes Se valoro a todos los pacientes mayores de 17 anos operados de cirugia cardiaca e ingresados en la UCI desde noviembre del 2002 hasta diciembre del 2009. Se analizo a los pacientes que no recibieron transfusion de hematies (n = 703) y a los que recibieron transfusion perioperatoria de 1-2 unidades de hematies (n = 959). Variables de interes Se analizo el efecto de la transfusion sobre la morbilidad hospitalaria y la mortalidad a 30 dias. El seguimiento de los enfermos dados de alta vivos del hospital finalizo el 31 de diciembre del 2011. La asociacion de la transfusion con la supervivencia a largo plazo se evaluo con el metodo de Kaplan-Meier. La evaluacion de los posibles factores predictivos de mortalidad a largo plazo se realizo mediante la construccion de modelos de regresion de Cox. Resultados La frecuencia de complicaciones postoperatorias cardiacas y no cardiacas fue mayor en los pacientes que recibieron transfusion. La mortalidad a 30 dias de estos ultimos fue mayor que en los pacientes no transfundidos (1% vs. 0,1%, p = 0,02). La presencia de anemia preoperatoria se asocio a un mayor uso de transfusion. La transfusion de hematies no fue un factor de riesgo de mortalidad a largo plazo (Hazard ratio = 1,4; intervalo de confianza del 95%, 0,9-2,1). Conclusiones La transfusion perioperatoria de 1-2 unidades de hematies en los pacientes operados de cirugia cardiaca se asocia a un incremento de la morbilidad hospitalaria y la mortalidad a 30 dias, y no tiene efecto en la mortalidad a largo plazo.

Background: The role that intensive care unit (ICU)-acquired pneumonia plays in the long-term outcomes of cardiac surgery patients is not well known. This study examined the association of pneumonia with in-hospital mortality and long-term mortality after adult cardiac surgery. Methods: A total of 2750 patients admitted to our ICU after cardiac surgery from January 2003 to December 2009 are the basis for this observational study. Patients who developed ICU-acquired pneumonia were matched with patients without it in a 1:2 ratio. The matching criteria were age, urgent or scheduled surgery, surgical procedure, and the propensity score for pneumonia. Multiple regression analysis was used to find predictors of hospital mortality. The relationship between pneumonia and long-term survival was analyzed with Kaplan-Meier survival estimates and a risk-adjusted Cox proportional regression model for patients discharged alive from hospital. Results: Pneumonia was diagnosed in 32 (1.2%) patients and there were 19 cases per 1000 days of mechanical ventilation. Patients with pneumonia had a significantly higher hospital mortality rate (28% vs 6.2%, P = .003) and a higher mortality at the end of follow-up (53% vs 19%, P < .0001) than those without it. Regression analysis showed that pneumonia was a strong predictor of hospital mortality. Five-year survival was as follows: pneumonia, 62%; control, 81%; and cohort patients, 91%. The Cox model showed that, after adjusting for confounding factors, patients with pneumonia (hazard ratio = 3.96, 95% confidence interval [CI]: 1.41-11.14) had poorer long-term survival. Conclusion: Pneumonia remains a serious complication in patients operated for cardiac surgery and is associated with increased hospital mortality and reduced long-term survival.

Background Interatrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported. Methods We conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable. Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables. Results We obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar. Conclusions In a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count).

A 30-year-old man, without previous medical record, was admitted to our centre due to persistent hacking cough for the previous 2 months, accompanied by nocturnal sweating, unquantified weight loss and low-grade fever. The patient was finally diagnosed of pulmonary tuberculosis (TB). During admission, a right forehead swelling was detected, painful to palpation, fluctuating and not attached to the skin, without cutaneous alterations or neurological impairment. Surgical debridement was performed and intraoperative cultures were positive for mycobacteria TB. The patient completed 9 months of antituberculous therapy and fully recovered.

Linezolid may be an interesting alternative for prosthetic joint infection (PJI) due to its bioavailability and its antimicrobial spectrum. However, experience in this setting is scarce. The aim of the study was to assess linezolid's clinical and microbiological efficacy, and also its tolerance. This was a prospective, multicenter, open-label, non-comparative study of 25 patients with late-chronic PJI caused by Gram-positive bacteria managed with a two-step exchange procedure plus 6 weeks of linezolid. Twenty-two (88%) patients tolerated linezolid without major adverse effects, although a global decrease in the platelet count was observed. Three patients were withdrawn because of major toxicity, which reversed after linezolid stoppage. Among patients who completed treatment, 19 (86%) demonstrated clinical and microbiological cure. Two patients presented with clinical and microbiological failure, and one showed clinical cure and microbiological failure. In conclusion, linezolid showed good results in chronic PJI managed with a two-step exchange procedure. Tolerance seems acceptable, though close surveillance is required.

To study the characteristics and outcomes of pneumococcal infections in patients aged ≥65 years since the authorization of the 13-valent pneumococcal conjugate vaccine (PCV-13) in Spain.All pneumococcal pneumonias, empyemas or primary bacteraemias treated at two hospitals in Majorca from 2010 to 2015 were included. Clinical variables, serotypes, and antibiotic susceptibility were collected.Two hundred and forty-nine pneumonias, 11 primary bacteraemias, and 2 empyemas in 243 patients were studied; 181 (69.1%) men, median age 76 years (range: 66-99). Seven (2.6%) were pneumococcal-vaccinated. Bacteraemia was present in 127 (61.9%) cases and related to a higher severity, p= 0.02, and not having chronic lung disease, p = 0.002. Ninety-seven (37%) episodes involved complications and 30 (11.5%) patients died. Mortality was related with the presence of complications at admission, p 0.001. Only septic shock was more frequent in patients ≥65 years during the period 2010-2015 compared to the period 2006-2010: 38 of 262 (14.5%) vs. 17 of 212 (8%), p = 0.02. Most infections (57.6%) were due to PCV-13 serotypes but were not related to a worse prognosis. The proportion of PCV-13 serotypes tended to decrease from 61% (non-invasive) and 80% (invasive) in 2010-2011 to 33% and 47% in 2014-2015. The antibiotic susceptibility remained stable.Rates of pneumococcal vaccination in elderly patients with pneumococcal infections were very low. Except for septic shock, the main outcome variables (including mortality) were similar to the ones observed in the period preceding PCV-13 authorization. PCV-13 serotypes were responsible for most infections although they showed a decreasing trend.

Awareness of risk factors for death could help identify patients in need of more intensive medical support., The 2013–2016 outbreak of Ebola virus disease (EVD) in West Africa infected >28,000 people, including >11,000 who died, and disrupted social life in the region. We retrospectively studied clinical signs and symptoms and risk factors for fatal outcome among 31 Ebola virus–positive patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. We found a higher rate of bleeding manifestations than reported elsewhere during the outbreak. Significant predictors for death were shorter time from symptom onset to admission, male sex, high viral load on initial laboratory testing, severe pain, diarrhea, bloody feces, and development of other bleeding manifestations during hospitalization. These risk factors for death could be used to identify patients in need of more intensive medical support. The lack of fever in as many as one third of EVD cases may have implications for temperature-screening practices and case definitions.

Levofloxacin plus rifampicin (L+R) is the treatment of choice for acute staphylococcal prosthetic joint infection (PJI) managed with debridement and implant retention (DAIR). Long courses have been empirically recommended, but some studies have suggested that shorter treatments could be as effective. Our aim was to prove that a short treatment schedule was non-inferior to the standard long schedule. An open-label, multicentre, randomised clinical trial (RCT) was performed. Patients with an early post-surgical or haematogenous staphylococcal PJI, managed with DAIR and initiated on L+R were randomised to receive 8 weeks of treatment (short schedule) versus a long schedule (3 months or 6 months for hip or knee prostheses, respectively). The primary endpoint was cure rate. From 175 eligible patients, 63 were included (52% women; median age, 72 years): 33 patients (52%) received the long schedule and 30 (48%) received the short schedule. There were no differences between the two groups except for a higher rate of polymicrobial infection in the long-schedule group (27% vs. 7%; P = 0.031). Median follow-up was 540 days. In the intention-to-treat analysis, cure rates were 58% and 73% in patients receiving the long and short schedules, respectively (difference −15.7%, 95% CI −39.2% to 7.8%). Forty-four patients (70%) were evaluable per-protocol: cure rates were 95.0% and 91.7% for the long and short schedules, respectively (difference 3.3%, 95% CI −11.7% to 18.3%). This is the first RCT suggesting that 8 weeks of L+R could be non-inferior to longer standard treatments for acute staphylococcal PJI managed with DAIR.

Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection. (C) 2016 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

Background. Several series predicting the prognosis of staphylococcal prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR) have been published, but some of their conclusions are controversial. At present, little is known regarding the efficacy of the different antibiotics that are used or their ability to eliminate methicillin-resistant S. aureus (MRSA) infection. Methods. This was a retrospective, multicenter, observational study of cases of PJI by S. aureus that were managed with DAIR (2003–2010). Cases were classified as failures when infection persistence/relapse, death, need for salvage therapy, or prosthesis removal occurred. The parameters that predicted failure were analyzed with logistic and Cox regression. Results. Out of 345 episodes (41% men, 73 years), 81 episodes were caused by MRSA. Fifty-two were hematogenous, with poorer prognoses, and 88% were caused by methicillin-susceptible S. aureus (MSSA). Antibiotics were used for a median of 93 days, with similar use of rifampin-based combinations in MSSA- and MRSA-PJI. Failure occurred in 45% of episodes, often early after debridement. The median survival time was 1257 days. There were no overall prognostic differences between MSSA- and MRSA-PJI, but there was a higher incidence of MRSA-PJI treatment failure during the period of treatment (HR 2.34), while there was a higher incidence of MSSA-PJI treatment failure after therapy. Rifampin-based combinations exhibited an independent protective effect. Other independent predictors of outcome were polymicrobial, inflammatory, and bacteremic infections requiring more than 1 debridement, immunosuppressive therapy, and the exchange of removable components of the prosthesis. Conclusions. This is the largest series of PJI by S. aureus managed with DAIR reported to date. The success rate was 55%. The use of rifampin may have contributed to homogenizing MSSA and MRSA prognoses, although the specific rifampin combinations may have had different efficacies.

Resumen Objetivo El papel de la anemia preoperatoria como factor de riesgo en la cirugia coronaria no esta bien establecido. El objetivo de este estudio es analizar la asociacion de la anemia preoperatoria con las complicaciones postoperatorias y la mortalidad hospitalaria en los enfermos operados de cirugia coronaria aislada en el Hospital de Son Dureta. Material y metodos Se incluyeron en este estudio todos los pacientes operados de cirugia coronaria aislada con circulacion extracorporea desde noviembre de 2002 hasta junio de 2007. La anemia preoperatoria se definio segun los criterios de la OMS como una hemoglobina inferior a 13 g/dl en los hombres e inferior a 12 g/dl en las mujeres. Los efectos adversos postoperatorios cardiacos y no cardiacos se analizaron en funcion de la presencia o ausencia de la anemia preoperatoria y de la estratificacion del riesgo quirurgico, sobre la base del valor del EuroSCORE logistico. Resultados Se incluyeron 623 pacientes. La incidencia de anemia preoperatoria fue del 34,5%. Esta incidencia fue mayor en pacientes con EuroSCORE de 4 o mas que con EuroSCORE inferior a 4 (el 41 y el 27%; p=0,0001). No hubo diferencias significativas entre la incidencia de complicaciones postoperatorias de los pacientes con anemia y sin anemia. La estancia media en la UCI y hospitalaria fue mas larga en los pacientes con anemia preoperatoria que en los pacientes sin ella (UCI: 3,2±2,5 dias y 3,7±2,8; p=0,004; hospitalaria: 17,5±11,3 dias y 14,7±10,2; p=0,001). La mortalidad hospitalaria fue del 0,8% (intervalo de confianza del 95%: 0,3–1,9). No hubo diferencias en la mortalidad de los pacientes con anemia preoperatoria y sin anemia preoperatoria (el 0,9 y el 0,7%; p=0,8). Conclusiones En este estudio, la anemia preoperatoria en los pacientes operados de cirugia coronaria aislada no se asocio con una mayor morbimortalidad hospitalaria, aunque la estancia hospitalaria fue mas larga. La limitacion del tamano de la muestra impide confirmar que la anemia preoperatoria sea o no un factor de riesgo en la cirugia coronaria.

There is evidence that Bartonella is an etiologic factor in human endocarditis. The objective of this article was to describe cases of endocarditis due to Bartonella observed at a tertiary-care hospital during 1995-2006. Overall, 140 cases of infective endocarditis were seen, of which 10 were blood culture-negative endocarditis, with 5 being due to Bartonella. In 4 cases, there had been contact with cats. Only 2 patients had pre-existing cardiac valvular disease. Three had extracardiac disease manifestations. In 3 cases, polymerase chain reaction (PCR) tests on cardiac valvular tissue gave positive results. Two patients had positive serology test results for Chlamydophila and another two, positive results for Coxiella burnetii. All 5 patients needed surgery, and the outcome was favorable in all 5. The presence of Bartonella must be considered in patients with blood culture-negative endocarditis. Although serological testing is essential for the diagnosis, cross-reactions between Bartonella and C burnetii or Chlamydophila are frequent, and PCR tests on cardiac valvular tissue, therefore, play an important diagnostic role.

Bartonella esta implicada como agente etiologico de la endocarditis en humanos. El objetivo del articulo es describir los casos de endocarditis por Bartonella diagnosticados en un hospital de tercer nivel durante el periodo 1995-2006. Hubo 140 casos de endocarditis infecciosa, de los cuales 10 cursaron con hemocultivos negativos (5 por Bartonella). Se habia producido contacto con gatos en 4 casos; solo 2 pacientes presentaban valvulopatia previa; 3 tuvieron clinica extracardiaca; en 3 se realizo PCR de tejido valvular, con resultado positivo; 2 pacientes tenian ademas serologia positiva para Chlamydophila y otros dos, para Coxiella burnetii. Los 5 precisaron tratamiento quirurgico. La evolucion fue favorable en todos. Se debe sospechar infeccion por Bartonella ante un paciente con endocarditis y hemocultivos negativos. La serologia es fundamental para el diagnostico, pero es habitual encontrar reacciones cruzadas entre Bartonella y C. burnetti o Chlamydophila, por lo que la PCR del tejido es importante para el diagnostico.

Background: A hypersensitivity reaction (HSR) is associated with abacavir (ABC), a nucleoside reverse transcriptase inhibitor. Genetic association of ABC HSR with the presence of HLA-B*5701 has been demonstrated in PREDICT-1 study, showing a prevalence of 5.6% in HIV-infected population. However the prevalence of this allele in HIV-infected patients in Spain has not been established yet. Method: This is a cross-sectional epidemiological study that included 1,198 patients in 74 centers that serve the HIV-infected population of Spain. HLA-B*5701 was checked both in the hospital lab and one central lab, showing an overall prevalence of this allele of 6%. Results: HLA-B*5701 was most prevalent in Caucasian population (6.5%). Concordance between the local and central lab was very high for positive and negative results (95.7% and 99.3%, respectively). Conclusion: These aspects define this test as a useful tool for the management of HIV-infected patients.

Objetivo Describir la metodologia y los resultados basales de la cohorte de pacientes con infeccion por virus de la inmunodeficiencia humana (VIH) de la Red de Investigacion de Sida (CoRIS). Metodos Cohorte abierta, prospectiva, multicentrica, de pacientes mayores de 13 anos con diagnostico de VIH sin tratamiento antirretroviral previo. La seleccion se realizo entre enero de 2004 y octubre de 2005 en 17 hospitales de 8 comunidades autonomas. Se recogieron variables sociodemograficas, epidemiologicas, clinicas y analiticas, junto con muestras biologicas iniciales y de seguimiento. Resultados Se han incluido 1.591 pacientes, 24% mujeres, mediana de edad 36 anos, el 74% diagnosticados de VIH en 2004 o 2005. El 27% provenian de otros lugares de origen, destacando Latinoamerica (16%) y Africa subsahariana (5%). El 32% tenian estudios secundarios y el 16% universitarios. La categoria de transmision mas frecuente fue la de hombres homosexuales (37%), seguida por la heterosexual (36%); y solo el 21% tenian antecedente de consumo de drogas inyectadas. Al ingreso en la cohorte la mediana de CD4 era 317 celulas/μl, la de carga viral 52.300 copias/ml y el 18% tenian diagnostico de sida. Las enfermedades diagnosticas de sida mas frecuentes fueron: neumonia por Pneumocystis jiroveci (6,1%), candidiasis esofagica (3,3%) y tuberculosis extrapulmonar (3,0%) y pulmonar (2,7%). Se registraron 35 fallecimientos (2,2%). El 33% de los pacientes han aportado muestras basales al BioBanco. Conclusiones CoRIS proporciona informacion relevante del perfil epidemiologico reciente de la infeccion por el VIH en nuestro medio, en el que predomina la transmision sexual. Se demuestra la viabilidad de esta cohorte, recogiendo datos clinicos y epidemiologicos junto con muestras biologicas, lo que abre grandes posibilidades de investigacion.

The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic—1,303 μg/L versus 1,161 μg/L—but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure.

Fundamento y objetivo Los objetivos de este estudio fueron describir el proceso de implementacion de la cohorte PISCIS y las caracteristicas clinicoepidemiologicas y las tendencias en el tratamiento antirretroviral (TARV) de los pacientes con infeccion por el virus de la inmunodeficiencia humana (VIH) incluidos desde 1998 hasta 2003. Pacientes y metodo Estudio de cohorte prospectivo de pacientes con infeccion por el VIH de 16 anos de edad o mayores atendidos en primera visita en 10 hospitales de Cataluna y uno de las Baleares. El analisis estadistico de las tendencias se realizo mediante el test de la χ2 de Mantel. Resultados Se incluyo a un total de 5.968 pacientes (edad media: 39,5 anos; 75% varones) con un tiempo medio de seguimiento de 26,4 meses (13.130 personas-ano). Del total, 2.763 fueron nuevos diagnosticos, en los que la via de transmision mas frecuente fue la heterosexual (43%), seguida de la homosexual (31%). Se observo una tendencia significativamente creciente en la proporcion de sujetos de edad inferior a 35 anos e inmigrantes. Un 43% tenian una cifra de linfocitos CD4 inferior a 200 celulas/μl en la determinacion mas cercana al diagnostico de la infeccion por el VIH. Del total, un 87% estaban en TARV en el ano 2003. Entre los pacientes no tratados previamente que iniciaron pautas de TARV con 3 o mas farmacos, se observo una disminucion de las pautas que incluian inhibidores de la proteasa (del 85% en 1998 al 25% en 2003; p Conclusiones Las cohortes de pacientes con infeccion por el VIH son viables en nuestro medio y tienen gran utilidad clinica y en salud publica. La via de transmision mas frecuente entre los nuevos diagnosticos es la heterosexual, el retraso en el diagnostico es elevado y las pautas de TARV han ido cambiando para adaptarse a las recomendadas por las guias.

The combination of indinavir, a protease inhibitor, and reverse-transcriptase inhibitors is widely used in the treatment of HIV-1 infection. However, precipitation of indinavir crystals in the renal tubular lumen due to the drug's aqueous insolubility may result in characteristic symptoms of flank pain or classic renal colic. An in vitro study has shown that addition of escin to synthetic urine containing indinavir delayed the crystallization time of indinavir.This study examined the efficacy and tolerability of the addition of escin to highly active antiretroviral therapy containing indinavir to delay the crystallization time of indinavir in urine.This was a multicenter, randomized, open-label, controlled, 4-period crossover trial in which each period lasted 4 weeks. HIV-1-infected adults receiving treatment with indinavir plus 2 nucleoside analogue reverse-transcriptase inhibitors in whom plasma viral loads had been undetectable (HIV-1 RNA200 copies/mL) for at least 6 months were randomly assigned to 1 of 2 groups based on the timing of the initiation of escin. Group I received escin during the second and third treatment periods, and group II received escin during the first and fourth treatment periods. The primary end point was the in vitro crystallization time of indinavir in 24-hour urine specimens, determined at the end of each 4-week period. Tolerability was assessed based on the number of patients with a rebound in plasma viral load and on the numbers of clinically and biologically relevant adverse events (including those requiring discontinuation of treatment). Clinical and laboratory evaluations were performed throughout each 4-week period.Fifty HIV-1-infected patients were enrolled, 47 were randomized to treatment (40 [85.1%] men, 7 [14.9%] women; median [interquartile range] age, 36 [34-45] years), and 30 completed the study. Urine pH and plasma and urine indinavir concentrations were unaffected by the addition of escin to antiretroviral treatment. The mean time to the onset of crystallization was 14.7 minutes with escin (95% Cl, 11.8-17.5) and 9.9 minutes without it (95% Cl, 6.7-13.1). Therefore, the addition of escin increased the mean crystallization time by 5.5 minutes (95% Cl, 1.5-9.5; P = 0.008), representing the overall capacity of study treatment to inhibit indinavir crystallization in the urine. Three of 47 patients had mild gastrointestinal symptoms associated with escin treatment. No episodes of nephrolithiasis were recorded during the study or after the completion of study treatment.The results of this prospective clinical trial of the effect of escin on indinavir crystallization time support the possibility that indinavir-associated nephrolithiasis may be prevented by means other than overhydration. Further research is needed in greater numbers of patients over longer follow-up times.

Fundamento Evaluar el impacto de la terapia antirretroviral (TAR) en la prevencion de la transmisionmaternofetal, en una poblacion de gestantes infectadas por el virus de la inmunodeficienciahumana (VIH). Pacientes y metodo Se estudiaron prospectivamente todas las gestantes infectadas por el VIHatendidas en nuestro hospital desde enero de 1995 a diciembre de 2000. Se ofrecio tratamientocon zidovudina (ZDV) en monoterapia o en combinacion, segun requerimientos de la gestante. Resultados Se obtuvieron 98 pares madre-nino de los cuales pudieron estudiarse 93. La tasade transmision vertical fue de 1,4% cuando la TAR se inicio durante el embarazo. El riesgo detransmision del VIH fue mayor en madres sin TAR durante el embarazo (riesgo relativo [RR] =18, intervalo de confianza [IC] del 95%, 2,2-145,4), en madres que solo recibieron ZDV enparto y nino frente a las que tomaron TAR durante el embarazo (RR = 16,4; IC del 95%, 1,8-145,6) y en madres usuarias de drogas por via parenteral activas (RR = 9,3; IC del 95%, 2,2-38,5), con diferencias significativas entre parto vaginal y cesarea. Conclusiones Se evidencio un notable beneficio de la TAR, sobre todo en el grupo de gestantesinfectadas por el VIH que iniciaron el tratamiento durante el embarazo. Se constata la necesidadde medidas preventivas.

We performed a cross-sectional study in 469 HIV-infected patients, whose mitochondrial haplogroups were genotyped to study their association with the clinical pattern of AIDS progression. The chance of not having an AIDS progression was 1.45 [95% of confidence interval (CI) = 1.02 to 2.05, P = 0.035) times greater in patients with cluster HV and 1.51 (95% CI = 1.06 to 2.18, P = 0.021) times greater in patients with haplogroup H. However, we only found significant values for haplogroup H (odds ratio = 1.52, 95% CI = 1.01 to 2.32, P = 0.049) in an ordinal logistic regression adjusted by gender, age at HIV infection, intravenous drug users, and hepatitis C virus infection. These data suggest that mitochondrial haplogroups might play a significant role in AIDS progression.

Objectives: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naive patients who are >= 50 years. Design: National, retrospective cohort analysis of patients who were >= 50 years old when they began the first cART (January 1, 2006 to December 31, 2009). Methods: We compared safety, effectiveness, and persistence of treatment in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitor (PI) versus NNRTI users and lopinavir/r versus efavirenz users. Results: We included 161 patients: median age was 54.6 years, 83% were men, median CD4 count was 191 cells/mu L, median viral load was 4.7 log, and median follow-up was 19 months (maximum, 48 months). Of these participants, 112 started with FTC/TDF and 49 with other nucleotide reverse transcriptase inhibitors (NRTIs). During follow-up, 21.9% of subjects developed at least one laboratory event >= grade 3, 5.6% interrupted cART due to adverse events, 19.3% had virologic failure, and 49.1% modified cART. There were no statistically significant differences between FTC/TDF and non-FTC/TDF users for any output except for persistence: The proportion of subjects who changed cART was 71.4% for non-FTC/TDF users and 38.6% for FTC/TDF users (log rank 0.001; adjusted hazard ratio, 2.10; 95% Cl, 1.34-3.29). Conclusions: In a population of HIV-infected subjects who were years old, our study suggests that the use of FTC/TDF is generally safe and effective, with a longer persistence as compared to other regimens.

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.

Before the advent of the influenza A(H1N1)pdm virus in 2009, the information available about the clinical manifestations and prognosis of influenza in immunosuppressed patients was scarce. With the 2009 pandemic, knowledge of the behavior, severity and importance of antiviral therapy for influenza A infection in immunocompromised hosts has increased considerably. The aim of the present manuscript is to review the main challenges of influenza in the most representative immunosuppressed populations such as solid organ transplant recipients, hematopoietic stem cell transplant recipients, patients with solid and hematological cancer and human immunodeficiency virus infected patients.

The major antiretroviral guidelines recommend starting ART in patients >50 y of age, regardless of CD4 cell count. However, no references to the preferred cART for these patients have been described. The combination FTC/TDF is one of the cornerstones of combined antiretroviral therapy (cART) in naive patients. We studied the persistence of coformulated FTC/TDF in this scenario. National, retrospective cohort analysis of HIV-infected patients >50 y at the time they began the first cART regimen (January 1, 2006 - December 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF vs. other NRTI regimens (no-TDF). We compared the persistence of treatment in FTC/TDF users vs. no-TDF (main groups). Among TDF users, we compared the persistence in PI vs. NNRTI users and in lopinavir/r vs. efavirenz users. Persistence was defined as the duration of the initial treatment; we analyzed time to any change or discontinuation according to initial regimen. We included 161 patients: median age: 54.6 y, 83% males, median CD4 count 191 cells/μl, median viral load 4.7 log, follow up: median 19 months, max 48 months. Of them, 112 started with FTC/TDF (53 with PIs, 57 with NNRTIs); and 49 with other NRTIs (no-TDF) (22 with PI, 23 NNRTI). During the follow-up period 79 patients (49%) modified their treatment, with statistically significant differences among groups, as shown in Table 1. In our study (antiretroviral-naive patients > 50 y), the persistence of FTC/TDF regimens was significantly higher than other NRTI regimens. According to the third agent, there was a trend to a higher persistence with NNRTI vs. PI. This reaches statistical significance when we compare EFV vs. LPV/r. In the absence of randomized clinical trials, our data may contribute to a better understanding on how cART works in this ageing population, which is progressively increasing. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Pedrol E et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18292 http://www.jiasociety.org/index.php/jias/article/view/18292 | http://dx.doi.org/10.7448/IAS.15.6.18292

We performed an observational analysis of a prospective cohort of adults hospitalized for pandemic (H1N1) 2009 at 13 Spanish hospitals, from June to November 2009, to determine the risk factors, clinical features, and outcomes of pneumonia. Of 585 patients requiring hospitalization, chest radiography was obtained in 542. A total of 234 (43.1%) patients had pneumonia, of whom 210 underwent bacterial microbiologic studies. Of these patients, 174 (82.8%) had primary viral pneumonia and 36 (17.2%) had concomitant/secondary bacterial pneumonia. Bilateral pneumonia occurred in 48.3% of patients. Streptococcus pneumoniae was the most frequent pathogen among patients with bacterial pneumonia (26 of 36 patients). None of them had received pneumococcal vaccine. Compared with patients without pneumonia, those with pneumonia more frequently had shock during hospitalization (9.8% vs. 1%; p < 0.001), required intensive care unit admission (22.6% vs. 5.8%; p < 0.001), underwent mechanical ventilation (17.9% vs. 3.2%; p < 0.001), and had longer length of hospital stay (median, 7 d vs. 5 d; p < 0.001). In-hospital mortality was higher in patients with pneumonia than in the others (5.2% vs. 0%; p < 0.001). Absence of comorbid conditions (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.32-3.24) was found to be an independent risk factor for pneumonia, whereas early (≤ 48 h) oseltamivir therapy (OR, 0.29; 95% CI, 0.19-0.46) was a protective factor. In conclusion, pneumonia is a frequent complication among adults hospitalized for pandemic (H1N1) 2009 and causes significant morbidity. Mortality in pandemic (H1N1) 2009 is low, but occurs mainly in patients with pneumonia. Early oseltamivir therapy is a protective factor for this complication.

Background Data on the clinical effectiveness of oseltamivir in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) virus infection are scarce. We aimed to determine the effect of timing of oseltamivir administration on outcomes in hospitalized adults with A(H1N1). Methods Observational analysis of a prospective cohort of adults hospitalized with laboratory-confirmed A(H1N1) was performed at 13 Spanish hospitals. Time from onset of symptoms to oseltamivir administration was the independent variable. Outcomes were duration of fever, hospital length of stay (LOS), need for mechanical ventilation, and mortality during hospitalization. Multivariate logistic regression was used to describe the association between the independent variable and the outcomes. Results Five hundred thirty-eight hospitalized patients with A(H1N1) were studied. The median time from onset of symptoms to oseltamivir administration was 3 days (interquartile range [IQR], 2-5 days). With regard to outcomes, the median duration of fever was 2 days (IQR, 1-3 days), the median LOS was 5 days (IQR, 3-8 days), 49 patients (9.1%) underwent mechanical ventilation, and 11 patients (2%) died during hospitalization. In univariate analysis, prolonged duration of fever (above the median), prolonged LOS (above the median), need for mechanical ventilation, and mortality all increased with time to oseltamivir administration (χ 2 test for trend P = .001, P ≤ .001, P = .008, and P = .001, respectively). After adjustment for confounding factors, time from onset of symptoms to oseltamivir administration (+ 1-day increase) was associated with a prolonged duration of fever (OR, 1.10; 95% CI, 1.02-1.19), prolonged LOS (OR, 1.07; 95% CI, 1.00-1.15), and higher mortality (OR, 1.20; 95% CI, 1.06-1.35). Conclusions Timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults with A(H1N1), even in those who are admitted beyond 48 h after onset of symptoms.

Recent expert reviews recommend a conservative surgical strategy – debridement and irrigation, antibiotics and implant retention (DAIR) – for most early post-surgical prosthetic joint infections (PJI). However, differences exist in published series regarding success rates with DAIR, and the size of most series is small. In this prospective multicenter cohort study of early PJI managed by DAIR, factors associated with failure of the DAIR were analyzed. Out of 139 early PJI, 117 cases managed with DAIR were studied For 67 patients (57.3%), infection was cured and the implant was salvaged with definite antimicrobial therapy. In 35 (29.9%) DAIR failed and removal of the prosthesis was necessary during follow-up. Finally, 15 patients (12.8%) needed chronic suppressive antimicrobial therapy due to suspected or confirmed persistent infection. Infections due to methicillin-resistant S. aureus (72.7% failed; p 0.05) and those treated at one of the hospitals (80.0% failed; p

Objective: The aim of the study was to describe the clinical presentation and prognosis in HIV-1-infected patients with hospital admission and pandemic influenza A 2009 (H1 N1) confirmed, and compare this data with those of a general population. Design: This is a prospective study in nature. Methods: All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009(H1 N1) virus infection by real-time reverse transcriptase PCR assay or culture from June 12 to November 10, 2009 were recruited and followed up until 1 month after discharge. In the HIV group risk factors for HIV infection, AIDS criteria, last CD4 cell count and viral load, and antiretroviral therapy and pneumococcal vaccines were collected. Results: Five hundred and eighty-five patients were recruited, 26 with HIV-1 infection and 559 non-HIV. The HIV patients had a long-term well controlled infection with a median CD4 cell count 503 cells/μl and 84% with undetectable viral load, although more frequently they had chronic liver and chronic obstructive pulmonary disease. No significant differences were observed about reported symptoms and physical findings on hospital admission. About 50% of patients in both groups present radiological infiltrates and 30% present respiratory failures. Practically all the patients in both groups received influenza antiviral therapy and in each group 80% received antibacterial therapy. No differences were observed in clinical outcomes. Conclusion: In HIV patients, well controlled on HAART, the pandemic influenza virus AH1 N1 had a similar clinical outcome and prognosis to that of non-HIV patients.