Search

© 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).

BACKGROUND Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT). METHODS We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 [336 isolates]; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 [716 isolates]). RESULTS Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non-susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P ≤ 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug-resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended-spectrum beta-lactamase (ESBL)-producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase-producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL-producing and carbapenemase-producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B. CONCLUSION The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs.

BACKGROUND The interaction between interferon-stimulated genes (ISGs) expression, IL28B genotypes and hepatitis C treatment outcomes has been mainly evaluated in the liver tissue from hepatitis C virus (HCV)-monoinfected patients but with controversial results. Herein, we examined whether more easily accessible peripheral blood mononuclear cells (PBMCs) could be used for this purpose in HIV-HCV coinfected patients, a population in whom HCV-induced liver disease progression occurs more rapidly and treatment response is lower. METHODS Gene expression profiles were examined using the human whole genome Agilent microarray platform in PBMCs collected from HIV/HCV-coinfected patients who had completed a course of peginterferon/ribavirin therapy with validated outcomes. Patients were split out according to the achievement of sustained virological response (SVR) and IL28B rs12979860 genotypes. The GeneSpringGX software was used to select genes differentially expressed in the different groups. RESULTS Nineteen HIV/HCV-coinfected individuals receiving antiretroviral therapy and having undetectable plasma HIV-RNA were examined. Global gene expression profiles showed 42 genes differentially expressed according to treatment outcome and 56 according to IL28B genotype. Common genes were not found and functions differed for genes belonging to either group. Whereas at least 26 out of 37 repressed genes (70.3%) in SVR patients were ISGs, none of the 56 differentially expressed genes in carriers of distinct IL28B variants were ISGs (P

The objective was to evaluate the implementation of a systematic Strongyloides stercoralis screening programme in HIV infected immigrants attending an HIV Unit in Spain. An enzyme-linked immunosorbent assay (ELISA) was performed to assess the presence of Strongyloides IgG. Patients with a positive serology were treated with ivermectin; serologic follow-up testing was performed. 237 patients were screened (65.4 % men). Origin: 64.1 % came from Latin America, 16.5 % from Sub-Saharan Africa, 9.7 % from the Caribbean, 9.7 % from other areas. Strongyloides stercolaris IgG was positive in 13 cases (5.5 %). In the multivariate analysis, factors associated with a positive Strongyloides serology were illiteracy (OR: 23.31; p = 0.009) and eosinophilia (OR: 15.44; p

Background Xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (MLV)-related virus are recently described human gammaretroviruses that have been associated with prostate cancer and chronic fatigue syndrome. These studies have been controversial because a number of laboratories have been unable to find evidence of XMRV in similar groups of patients or controls. Because the existence of XMRV raises many questions, we decided to study its presence in a group of patients infected with HIV-1 with a high proportion of intravenous drug use and coinfection by hepatitis C virus. Methods Forty HIV-1-infected patients under follow-up in our institution were screened for XMRV/MLV by nested polymerase chain reaction using primers targeting the gag and env region. Specific primers for mouse mitochondrial DNA were used to rule out contamination. Results No evidence of XMRV or polytropic MLV-related sequences was found in any sample from patients or controls. Four samples yielded polymerase chain reaction bands whose sequence corresponded to murine endogenous retroviral sequences, however, contamination with mouse cell DNA was subsequently confirmed. Conclusions XMRV/MLV viruses do not seem to be associated with HIV-1 infection or intravenous drug use. Contamination of samples or reagents by genomic murine DNA or XMRV vectors could account for the sporadic detection of positive samples for XMRV and related agents.

Chagas disease (CD) is an emergent disease in Europe that can behave as an opportunistic infection in HIV positive patients. The objective of this study was to evaluate the implementation of a CD screening programme in an HIV unit. An immunochromatography (ICT) of Trypanosoma cruzi was performed as a screening tool in HIV-positive patients born in CD endemic countries. ELISA and IFAT were used to confirm the diagnosis. A total of 155 patients, 116 males and 38 females, were included. Mean age was 36.9 years (± 8.4) and mean length of stay in Spain at the screening was 7.1 years (± 4.7). T. cruzi ICT was positive in four cases (2.6%), being confirmed (by ELISA and IFAT) in three of those (1.9%). Factors associated with confirmed positive T.cruzi serology were: Bolivia origin (p=0.016), Bolivia or Argentina origin (p=0.002), Southern Cone origin (p=0.015), rural origin (p=0.023), previously living in an adobe-made (p=0.001) or thatch-roofed house (p

We present an HIV-1-infected patient with a profile of transmitted drug resistance (RT M41L, E44D, V118I, L210W, T215D) sustained during more than 10 years in the absence of treatment. Clonal analysis of different plasma and cellular samples within this period did not reveal any reversion to the wild-type genotype.

Background The influence of acute graft pyelonephritis (AGPN) on graft outcome in renal transplant recipients still remains controversial. Methods We retrospectively analysed 189 patients (113 males; mean age: 49.7 ± 13.1 years) undergoing renal transplantation at the University Hospital 12 de Octubre (Madrid, Spain) from January 2002 to December 2004, with a minimum follow-up of 36 months. Factors associated with AGPN were assessed by logistic regression analysis. Long-term graft function was compared according to the occurrence of this complication during follow-up. 'Decline in renal graft function' was defined as the increase in serum creatinine (SC) levels > 0.33 mg/dL between Month 3 and Year 1 after transplantation. Results Nineteen patients (10.0%) were diagnosed with 25 episodes of AGPN (incidence rate: 4.4 episodes per 100 patient-years). The presence of glomerulonephritis as the underlying disease [odds ratio (OR) 4.2; 95% confidence interval (95%CI): 1.3-14.1] and the previous occurrence of two to five (OR 9.4; 95%CI: 1.5-56.8) or more than five episodes of asymptomatic bacteriuria after transplantation (OR 19.8; 95%CI: 2.4-160.2) emerged as independent predictors for AGPN. A near-significant association was found for cytomegalovirus infection (OR 4.2; 95%CI: 0.9-18.4), whereas receiving a single-kidney transplant (vs. double-kidney) showed a protective effect (OR 0.2; 95%CI: 0.0-0.8). During the 36-month follow-up, levels of SC, creatinine clearance and 24-h proteinuria did not differ significantly between patients with or without AGPN, and this complication did not exert any effect on the risk for decline in renal graft function. Conclusions AGPN does not impair long-term graft function in renal transplant recipients.

The risk of developing invasive pneumococcal disease in transplant patients is estimated at 28 to 36 per 1000 patients/year according to the type of organ transplanted. This rate is much higher than the estimated incidence in the general population. This study reviews the current experience regarding the different types of vaccinations against Streptococcus pneumoniae in transplant patients, the immunogenic response to pneumococcal vaccine in these patients, the clinical experience to date with the use of pneumococcal vaccines, and the utility of a sequential vaccination regime including the heptavalent vaccine and vaccine for the 23 serogroups. The immunogenicity produced by pneumococcal vaccines in transplant patients is lower and not as long-lasting as in immunocompetent individuals, and the revaccination regimen inducing the most favorable immunological response is unknown. Nonetheless, pneumococcal vaccination provides clear benefits to transplant recipients and should be given before transplantation whenever possible.

Tenofovir is one of the drugs of choice in first-line combinations of antiretroviral therapy. Most data on safety and efficacy in this scenario initially came from clinical trials in which tenofovir was combined with non-nucleoside reverse transcriptase inhibitors. Because of this, as well as the possible interaction of tenofovir with some protease inhibitors and the suspicion that this combination could increase the risk of nephrotoxicity, analysis of the clinical experience available on the combination of tenofovir (associated with emtricitabine or another nucleoside analogue) with a protease inhibitor is essential. The present review reports data on efficacy and safety, mainly from clinical trials. Taken together, these studies provide sufficient information to indicate that the combination of tenofovir and protease inhibitors is safe and effective, justifying its selection in first-line therapy or rescue therapy after virological failure.

Introducción: El número de pacientes inmigrantes infectados por el VIH ha aumentado en España en los últimos años y actualmente representan una parte importante de la epidemia. El objetivo de nuestro estudio es conocer las características clínico-epidemiológicas de los inmigrantes con infección VIH atendidos en una unidad monográfica en Madrid. Material y métodos: Estudio retrospectivo en el que se incluyen todos los pacientes nacidos en un país distinto de España atendidos en una unidad monográfica de VIH en Madrid entre 1992 y 2009. Resultados: Un total de 371 pacientes incluidos (53,1% latinoamericanos, 24,5% africanos subsaharianos, 22,4% otros), de los que el 60% eran varones. Incremento desde el 0,3% de los nuevos pacientes en 1992 al 49,2% en 2009. El principal motivo para realizarse la prueba del VIH fue el embarazo/parto en las mujeres (32,7%) y presentar una enfermedad de categoríaB en los hombres (17,4%). En el 92% el mecanismo de transmisión era sexual. La enfermedad asociada a sida más frecuente fue la tuberculosis. El porcentaje de pacientes con IgG positiva para VHA, VHC, Toxoplasma, Treponema, CMV y VVZ fue, respectivamente, del 90, del 7,7, del 60, del 26,7, del 96 y del 95%. El 5,4% tenían un Ags-VHB positivo y el 17%, un PPD positivo. En el colectivo de hombres que mantienen sexo con hombres el 62% tuvieron al menos un episodio de lúes. La prevalencia de HLA-B5701 fue del 6, del 0,9 y del 3,8% en la raza caucásica, amerindia y negra, respectivamente. Conclusiones: Los pacientes inmigrantes con infección por el VIH suponen un porcentaje importante de los nuevos pacientes. Se trata de un grupo heterogéneo en cuanto a sus características clínicas y epidemiológicas. 1.478 JCR (2012) Q4, 89/116 Microbiology, 57/69 Infectious diseases

The number of HIV-positive immigrants have increased in Spain in the last few years, and now represent a significant proportion of the epidemic. Our objective is to describe the clinico-epidemiological characteristics of HIV-positive immigrants seen in a specialist unit in Madrid.Retrospective study. Every patient born in a country other than Spain and attended an HIV Unit in Madrid between 1992 and 2009 was included.Of the 371 patients included, 53.1% were Latin Americans, 24.5% Sub-Saharan Africans, and 22.4% others), and 60% were males. Immigrants represented 0.3% of new patients in 1992 and rose to 49.2% in 2009. The principal reason for HIV testing had been pregnancy/delivery among women (32.7%) and having a category-B disease among men (17.4%). Sexual transmission accounted for 92% of patients. Tuberculosis was the principal AIDS-diagnosing illness. Respectively 90%, 7.7%, 60%, 26.7%, 96% and 95% of patients had an IgG for HAV, HCV, Toxoplasma, Treponema, CMV and VZV. VHB-Ags+: 5.4%; PPD+: 17%. At least one syphilis episode was recorded in 62% of the men who have sex with men (MSM). Prevalence of HLA-B5701 was 6%, 0.9% and 3.8% in Caucasians, Amerindians and Afro-Americans, respectively.Immigrants represent a significant proportion of new HIV-positive patients. It is a very heterogeneous group according to their clinical and epidemiological characteristics.

Boosted protease inhibitor monotherapy has emerged as an antiretroviral alternative option to avoid the use of nucleosides. After more than seven years of research with hundreds of patients exposed to this kind of therapy, controversy about its use remains. While European and Spanish guidelines for the use of antiretroviral therapy in adults include monotherapy as an alternative for simplification, experts in the USA express the view that this strategy cannot be currently recommended. Our conclusion, after more than seven years of research, is that simplification of a suppressive triple antiretroviral therapy to boosted protease inhibitor monotherapy has demonstrated safety and efficacy in a high proportion of patients. Although this is not a strategy to implement indiscriminately in all patients, it could be a good option for those patients with toxicity related to nucleoside reverse transcriptase inhibitors, or for trying to avoid such toxicities in virologically controlled patients without previous failure to protease inhibitors, restarting nucleosides if the viral load does not remain undetectable. If simplification to monotherapy is selected to treat some patients, twice-daily lopinavir/ritonavir, or preferably once-daily darunavir/ritonavir, should be chosen as data with other boosted protease inhibitors are inconclusive or even nonexistent. Nevertheless, more studies focusing on the control of HIV replication in viral reservoirs with monotherapy, as with triple therapy, are warranted.

New commercial techniques for determination of the viral load (VL) in plasma are able to detect as few as 20 copies of HIV-1 RNA/ml. The relevance of this new technical threshold is uncertain. Upon multivariate analysis, factors associated with detection of VLs between 20 and 49 copies/ml by the Cobas TaqMan HIV-1 v2.0 assay in an HIV clinic were the basal VL and time on antiretroviral therapy.

Tenofovir is one of the drugs of choice in first-line combinations of antiretroviral therapy. Most data on safety and efficacy in this scenario initially came from clinical trials in which tenofovir was combined with non-nucleoside reverse transcriptase inhibitors. Because of this, as well as the possible interaction of tenofovir with some protease inhibitors and the suspicion that this combination could increase the risk of nephrotoxicity, analysis of the clinical experience available on the combination of tenofovir (associated with emtricitabine or another nucleoside analogue) with a protease inhibitor is essential. The present review reports data on efficacy and safety, mainly from clinical trials. Taken together, these studies provide sufficient information to indicate that the combination of tenofovir and protease inhibitors is safe and effective, justifying its selection in first-line therapy or rescue therapy after virological failure.

The risk of developing invasive pneumococcal disease in transplant patients is estimated at 28 to 36 per 1000 patients/year according to the type of organ transplanted. This rate is much higher than the estimated incidence in the general population. This study reviews the current experience regarding the different types of vaccinations against Streptococcus pneumoniae in transplant patients, the immunogenic response to pneumococcal vaccine in these patients, the clinical experience to date with the use of pneumococcal vaccines, and the utility of a sequential vaccination regime including the heptavalent vaccine and vaccine for the 23 serogroups. The immunogenicity produced by pneumococcal vaccines in transplant patients is lower and not as long-lasting as in immunocompetent individuals, and the revaccination regimen inducing the most favorable immunological response is unknown. Nonetheless, pneumococcal vaccination provides clear benefits to transplant recipients and should be given before transplantation whenever possible.

Presentamos el caso de una mujer de 53 anos que ingresa por neumonia del lobulo inferior derecho (LID). Unos dias antes de su ingreso habia sufrido una infeccion del pulgar derecho tras un traumatismo. En la exploracion fisica se objetivo una zona de aspecto necrotico con un halo inflamatorio en el pulgar derecho sin afectacion articular. En la analitica destacaban 34.460 leucocitos (92% blastos), anemia y trombopenia. En la radiografia de torax se apreciaba una condensacion en el LID y otra en el lobulo superior izquierdo (LSI) (fig. 1).

We sought to examine the impact of asymptomatic bacteriuria on renal transplant outcome by retrospectively analyzing 189 renal transplant recipients for whom systematic screening uncovered 298 episodes of asymptomatic bacteriuria in 96 recipients. These patients were treated and all were followed for 36 months. Significant risk factors included female gender, glomerulonephritis as the disease that led to transplantation, and double renal transplant. There were no differences in serum creatinine, creatinine clearance, or proteinuria between patients with and without bacteriuria. The incidence of pyelonephritis in these patients was 7.6 episodes per 100 patient-years compared with 1.07 in those without asymptomatic bacteriuria. Between two to five and more than five bacteriuria episodes were significant independent factors associated with pyelonephritis whereas more than five episodes was a significant independent factor associated with rejection. Thus, we found no differences in renal function prognosis between patients who do not develop asymptomatic bacteriuria and those uncovered by systematic screening and who received treatment following kidney transplantation. Despite this treatment, the incidence of pyelonephritis was much higher in the group of patients with detected asymptomatic bacteriuria.