Infectious Endocarditis Caused by Pseudomona aeruginosa on Bicuspid Aortic Valve.

We report the case of a 53-year-old man with psoriatic arthritis, suffering from a malignant and recidivant myoepithelioma in his right axilla and arm, and undergoing two surgeries, with the last one being performed a month prior to actual admission. After the last surgery, he was admitted to hospital with fever without a source. After physical examination, laboratory tests, blood cultures and transthoracic and transesophageal echocardiography, he was diagnosed with infectious endocarditis (IE) on a bicuspid aortic valve (BAV) caused by Pseudomona aeruginosa (PA). Antibiogram-guided antibiotic therapy with meropenem and tobramicin was initiated. However, in the presence of repetitive spleen infarctions and a large vegetation, 12 days after admission, a bioprosthesis aortic valve implantation was performed. The postsurgical evolution was favorable and prolonged antibiotic course with meropenem and tobramicin was completed. The pathological anatomy and the native valve cultured confirmed an IE caused by PA. Gram-negative non-HACEK IE cases are infrequent, accounting for 1.8% of the total IE cases. PA is the second most frequent bacillus in this group, causing endocarditis more prevalently when associated with healthcare procedures rather than injectable drug use. No prior case study has identified IE caused by PA related to a BAV in the last years.

Bartonella Endocarditis in Spain: Case Reports of 21 Cases.

Blood culture negative endocarditis (BCNE) is frequent in infective endocarditis (IE). One of the causes of BCNE is fastidious microorganisms, such as Bartonella spp. The aim of this study was to describe the epidemiologic, clinical characteristics, management and outcomes of patients with Bartonella IE from the "Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES)"cohort. Here we presented 21 cases of Bartonella IE. This represents 0.3% of a total of 5590 cases and 2% of the BCNE from the GAMES cohort. 62% were due to Bartonella henselae and 38% to Bartonella quintana. Cardiac failure was the main presenting form (61.5% in B. hensalae, 87.5% in B. quintana IE) and the aortic valve was affected in 85% of the cases (76% in B. henselae, 100% in B. quintana IE). Typical signs such as fever were recorded in less than 40% of patients. Echocardiography showed vegetations in 92% and 100% of the patients with B. henselae and B. quintana, respectively. Culture was positive only in one patient and the remaining were diagnosed by serology and PCR. PCR was the most useful tool allowing for diagnosis in 16 patients (100% of the studied valves). Serology, at titers recommended by guidelines, only coincided with PCR in 52.4%. Antimicrobial therapy, in different combinations, was used in all cases. Surgery was performed in 76% of the patients. No in-hospital mortality was observed. One-year mortality was 9.4%. This article remarks the importance for investigating the presence of Bartonella infection as causative agent in all BCNE since the diagnosis needs specific microbiological tools and patients could benefit of a specific treatment.

Brief Report: Patients' Experiences and Opinions After Desimplification of Their Single-Tablet Regimens for the Treatment of HIV Infection: A Survey in a Multicentre Cohort.

OBJECTIVES: The aims of this study were to describe patients' experiences after single-tablet regimen (STR) desimplification and its impact on self-reported treatment adherence and quality of life. METHODS: We performed a survey among all patients from the multicenter cohort of the Spanish HIV/AIDS Network who had desimplified the STRs dolutegravir/abacavir/lamivudine (DGT/ABC/3TC) or rilpivirine/tenofovir disoproxil fumarate/emtricitabine to their separate components (DTG + generic ABC/3TC or RPV + generic TDF/FTC) between December 2016 and November 2018. RESULTS: Among 216 patients who fulfilled inclusion criteria, 138 (63.9%) completed the questionnaire. Most of the patients (78.3%) knew what generic drugs are, only 8.7% believed that treatment with 2 pills is less effective than treatment with an STR, and 67.4% agreed that it is reasonable to take 2 pills instead of 1 for HIV treatment to decrease costs for the health care system. After desimplification, 13.0% of the patients stated they had more secondary effects, 8.0% had forgotten one or more doses more frequently than before, and 10.9% had sometimes forgotten to take 1 pill, but not the other. A proportion of 30.4% reported not being happy to take more pills a day, and 10.1% experienced a worse quality of life after the treatment desimplification. CONCLUSIONS: After STR desimplification, most of the patients had a fair knowledge about generic antiretrovirals, and they agreed to desimplify their STR to decrease costs. Although almost a third of the respondents were not happy to take 2 pills a day, only a minority reported worse adherence or quality of life.

Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors.

The elite controller (EC)-long term non-progressor (LTNP) phenotype represent a spontaneous and advantageous model of HIV-1 control in the absence of therapy. The transcriptome of peripheral blood mononuclear cells (PBMCs) collected from EC-LTNPs was sequenced by RNA-Seq and compared with the transcriptomes from other phenotypes of disease progression. The transcript abundance estimation combined with the use of supervised classification algorithms allowed the selection of 20 genes and pseudogenes, mainly involved in interferon-regulated antiviral mechanisms and cell machineries of transcription and translation, as the best predictive genes of disease progression. Differential expression analyses between phenotypes showed an altered calcium homeostasis in EC-LTNPs evidenced by the upregulation of several membrane receptors implicated in calcium-signaling cascades and intracellular calcium-mobilization and by the overrepresentation of NFAT1/Elk-1-binding sites in the promoters of the genes differentially expressed in these individuals. A coordinated upregulation of host genes associated with HIV-1 reverse transcription and viral transcription was also observed in EC-LTNPs -i.e. p21/CDKN1A, TNF, IER3 and GADD45B. We also found an upregulation of ANKRD54 in EC-LTNPs and viremic LTNPs in comparison with typical progressors and a clear alteration of type-I interferon signaling as a consequence of viremia in typical progressors before and after receiving antiretroviral therapy.

Clinical features and outcomes of bacteraemia due to OXA-48-like carbapenemase-producing Klebsiella pneumoniae in a tertiary hospital. / Características y evolución clínica de las bacteriemias por Klebsiella pneumoniae productora de carbapenemasa tipo OXA-48 en un hospital de tercer nivel.

INTRODUCTION: Limited therapeutic options and high mortality make the management of OXA-48-like carbapenemase-producing Klebsiella pneumoniae (KPOXA-48) bacteraemia complicated. The aim of the study was to describe the clinical characteristics of KPOXA-48 bacteraemia between October 2013 and December 2016. MATERIAL AND METHODS: The variables to analyse were retrospectively collected from medical records. Carbapenemase production was confirmed by phenotypic and molecular methods. RESULTS: A total of 38 patients with bacteraemia were included, mainly classified as hospital-acquired (n=31). The majority of cases were secondary bacteraemia (n=26), most commonly arising from the urinary tract (n=11). All isolates presented a multidrug-resistant profile with the extended spectrum beta-lactamase CTX-M-15 and the carbapenemase OXA-48-like production. The crude mortality rate with adequate targeted antibiotic therapy was 0%, rising to 55% with inadequate treatment (p=0.0015). CONCLUSIONS: This study highlights the importance of identifying this resistance mechanism, the patient factors, type of bacteraemia and adequacy of antibiotic therapy in the outcome of bacteraemia.

Tropheryma whipplei endocarditis in Spain: Case reports of 17 prospective cases.

Tropheryma whipplei endocarditis is an uncommon condition with very few series and <90 cases reported in the literature. The aim of the study was to analyze the epidemiological, clinical, and outcome characteristics of 17 cases of T. whipplei endocarditis recruited in our country from a multicentric cohort from 25 Spanish hospitals from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España.From a total of 3165 cases included in the cohort, 14.2% were diagnosed of blood culture negative endocarditis (BCNE) and 3.5% of these had T. whipplei endocarditis. This condition was more frequent in men. The average age was 60.3 years. Previous cardiac condition was present in 35.3% of the cases. The main clinical manifestation was cardiac failure (76.5%) while fever was only present in the 35.3%. Ecocardiography showed vegetations in 64.7% of patients. Surgery was performed in all but 1 cases and it allowed the diagnosis when molecular assays were performed. A broad range rRNA 16S polymerase chain reaction was used for first instance in all laboratories and different specific targets for T. whipplei were employed for confirmation. A concomitant Whipple disease was diagnosed in 11.9% of patients. All patients received specific antimicrobial treatment for at least 1 year, with no relapse and complete recovery.T. whipplei endocarditis is an uncommon condition with an atypical presentation that must be considered in the diagnosis of BCNE. The prognosis is very good when an appropriate surgical management and antimicrobial-specific treatment is given.

Similar inflammatory response in alcoholic and non-alcoholic sepsis patients.

UNLABELLED: It is well known that alcoholics are prone to severe infections and that the immune system is impaired by chronic ethanol abuse. The aim of this study is to compare serum inflammatory mediators in response to sepsis in chronic alcoholic with sepsis, non-alcoholics with sepsis and non-infected alcoholics. METHOD: We included 25 alcoholics with sepsis, 34 non-alcoholics with sepsis, 34 non-infected alcoholics admitted for programmed withdrawal, and 27 healthy control subjects. After initial evaluation, blood samples were taken for determination of serum cytokine levels. RESULTS: We found similar responses for the inflammatory mediators analyzed among our sepsis patients, regardless of alcohol abuse. The only difference was that alcoholics with sepsis showed lower CRP and G-CSF than non-alcoholic sepsis patients. There were no differences regarding leukocyte count. Alcoholics admitted for programmed withdrawal showed higher IL-6, IFN-γ, IL-10, Il-4 and ICAM-1 serum levels than healthy controls. Serum IL-5 levels were decreased in both alcoholic groups. CONCLUSION: The inflammatory response of alcoholics with sepsis is similar to that of non-alcoholic sepsis patients. However, the low G-CSF levels in alcoholic sepsis patients might suggest a predisposition to infections in alcohol abusers.

Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments.

Human immunodeficiency virus type 1 (HIV-1) antiviral drug resistance is a major consequence of therapy failure and compromises future therapeutic options. Nelfinavir and lopinavir/ritonavir-based therapies have been widely used in the treatment of HIV-infected patients, in combination with reverse transcriptase inhibitors. The aim of this observational study was the identification and characterization of mutations or combinations of mutations associated with resistance to nelfinavir and lopinavir/ritonavir in treated patients. Nucleotide sequences of 1,515 subtype B HIV-1 isolates from 1,313 persons with different treatment histories (including naïve and treated patients) were collected in 31 Spanish hospitals over the years 2002-2005. Chi-square contingency tests were performed to detect mutations associated with failure to protease inhibitor-based therapies, and correlated mutations were identified using statistical methods. Virological failure to nelfinavir was associated with two different mutational pathways. D30N and N88D appeared mostly in patients without previous exposure to protease inhibitors, while K20T was identified as a secondary resistance mutation in those patients. On the other hand, L90M together with L10I, I54V, A71V, G73S, and V82A were selected in protease inhibitor-experienced patients. A series of correlated mutations including L10I, M46I, I54V, A71V, G73S, and L90M appeared as a common cluster of amino acid substitutions, associated with failure to lopinavir/ritonavir-based treatments. Despite the relatively high genetic barrier of some protease inhibitors, a relatively small cluster of mutations, previously selected under drug pressure, can seriously compromise the efficiency of nelfinavir- and lopinavir/ritonavir-based therapies.