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The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci . A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34-3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18-1.81), biliary (OR 1.84, CI 1.34-2.52) or urinary source (OR 1.86, CI 1.43-2.43), admission period (OR) 1.28, CI 1.18-1.38, and community-acquired infection (OR 0.57, CI 0.39-0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes., Importance: Multidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts., Competing Interests: C.G.-V. has received honoraria for talks on behalf of Gilead Sciences, MSD, Novartis, Pfizer, Janssen, and Lilly, as well as a grant from Gilead Sciences, Pfizer, and MSD. P.P.-A. has received honoraria for talks on behalf of Merck Sharp & Dohme, Gilead, Lilly, ViiV Healthcare, and Gilead Sciences. A.S. has received honoraria for talks on behalf of Merck Sharp & Dohme, Pfizer, Novartis, Angelini, Menarini, and Gilead Sciences, as well as grant support from Pfizer and Gilead Sciences. O.P. has received honoraria for talks on behalf of MSD, Qiagen, and expertise for Sanofi.

Early detection of disseminating vancomycin-resistant Enterococcus faecium (VREfm) in ICU wards is crucial for outbreak identification and the implementation of prompt infection control measures. Genotypic methods like pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) are costly and time-consuming, hindering rapid response due to batch dependency. Fourier-transform infrared spectroscopy (FT-IR) offers the potential for real-time outbreak detection and reliable strain typing. We utilized FT-IR to identify clonal VREfm dissemination and compared its performance to PFGE and WGS. Between February through October 2023, an unusually high number of VREfm were recovered at a tertiary hospital in Barcelona. Isolates were examined for antimicrobial susceptibility, carriage of vanA/vanB genes and clonality was also studied using FT-IR, PFGE, and WGS. Routine FT-IR inspections revealed recurring VREfm clustering during the outbreak's initial weeks. In total, 104 isolates were recovered from 75 patients and from multiple wards. However, only one isolate was recovered from an environmental sample, suggesting the absence of environmental reservoirs. An ST80 vancomycin-resistant ( vanA ) E. faecium strain was the main strain responsible for the outbreak, although a few additional VREfm strains were also identified, all belonging to CC17. PFGE and cgMLST (WGS) yielded identical clustering results to FT-IR, and WGS confirmed vanA/vanB gene carriage in all VREfm isolates. Infection control measures led to a rapid decline in VREfm isolates, with no isolates detected in November. FT-IR spectroscopy offers rapid turnaround times, sensitivity, and reproducibility, comparable to standard typing methods. It proved as an effective tool for monitoring VREfm dissemination and early outbreak detection.

Factor-inhibiting HIF (FIH) is an asparagine hydroxylase that acts on hypoxia-inducible factors (HIFs) to control cellular adaptation to hypoxia. FIH is expressed in several tumor types, but its impact in tumor progression remains largely unexplored. We observed that FIH was expressed on human lung cancer tissue. Deletion of FIH in mouse and human lung cancer cells resulted in an increased glycolytic metabolism, consistent with increased HIF activity. FIH-deficient lung cancer cells exhibited decreased proliferation. Analysis of RNA-Seq data confirmed changes in the cell cycle and survival and revealed molecular pathways that were dysregulated in the absence of FIH, including the upregulation of angiomotin (Amot), a key component of the Hippo tumor suppressor pathway. We show that FIH-deficient tumors were characterized by higher immune infiltration of NK and T cells compared with FIH competent tumor cells. In vivo studies demonstrate that FIH deletion resulted in reduced tumor growth and metastatic capacity. Moreover, high FIH expression correlated with poor overall survival in non-small cell lung cancer (NSCLC). Our data unravel FIH as a therapeutic target for the treatment of lung cancer.

Background: Our aim in this study was to evaluate the clinical and prognostic impact of communicating microbiological information in real time for adult patients with bloodstream infections (BSIs)., Methods: We retrospectively reviewed 6225 clinical episodes of bacteremia in a teaching hospital from January 2013 to December 2019. Bacteremia-associated mortality was compared when blood culture results were relayed to the infectious diseases specialist (IDS) in real time and periods when results were relayed the following morning. The impact of information availability using mortality at 30 days was used as the main outcome of the study., Results: The initial analysis (all microorganisms included) did not show an association of mortality and information delay to the IDS (odds ratio [OR], 1.18; 95% confidence interval [CI], .99-1.42). However, information delay of BSIs caused by fast-growing microorganisms such as Enterobacterales was associated with a significant increase in the odds of death at 30 days both in the univariate (OR, 1.76; 95% CI, 1.30-2.38) and multivariate analysis (OR, 2.22; 95% CI, 1.50-3.30). Similar results were found with mortality at 14 days and 7 days in the univariate (OR, 1.54; 95% CI, 1.08-2.20 and OR, 1.56; 95% CI, 1.03-2.37, respectively) and the multivariate analysis (OR, 2.05; 95% CI, 1.27-3.32 and OR, 1.92; 95% CI, 1.09-3.40, respectively)., Conclusions: Information delivered in real time has prognostic relevance and is likely to improve survival of patients with documented BSIs. Future studies should address the prognostic impact of adequate resource allocation (microbiologist/IDS with 24/7 coverage) in BSIs., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Real-life data about cefiderocol use to treat extensively drug-resistant bacteria are scarce. We aim to report our early experience in patients with difficult-to-treat infections and limited therapeutic options., Methods: Patients treated with cefiderocol from March 2018 to April 2022 in a tertiary-care hospital in Spain were included. Demographic, clinical, and microbiological data were collected up to 90 days after the end of treatment or until death. Survival status was recorded at 30 and 90 days., Results: Ten patients were included, seven of them critically ill. Ventilator-associated pneumonia (40%) and bacteremia (40%) were the main infections. Multidrug-resistant or extensively drug-resistant P. aeruginosa was the most frequently isolated pathogen (70%, of which six patients were infected with bacteria with difficult-to-treat resistance), followed by A. baumannii, E. coli, and A. xylosoxidans (10% each). Seven patients received combination therapy. Clinical and microbiological cures were achieved in 90% and 80% of patients, respectively. Two previously susceptible strains (20%) developed resistance to cefiderocol. Overall, 30-day and 90-day mortality rates were 10% and 50%, respectively, although two out of five patients died due to the infection. No serious adverse events were reported, except for one patient who developed thrombocytopenia., Conclusion: Cefiderocol seems to be an effective and safe rescue therapy for patients infected with difficult-to-treat pathogens, although there is a definite risk of the emergence of resistance., (© 2023. The Author(s).)

Every day, 800 women and 6700 newborns die from complications related to pregnancy or childbirth. A well-trained midwife can prevent most of these maternal and newborn deaths. Data science models together with logs generated by users of online learning applications for midwives can help improve their learning competencies. In this work, we evaluate various forecasting methods to determine the future interest of users for the different types of content available in the Safe Delivery App, a digital training tool for skilled birth attendants, broken down by profession and region. This first attempt at health content demand forecasting for midwifery learning shows that DeepAR can accurately anticipate content demand in operational settings, and could therefore be used to offer users personalized content and to provide an adaptive learning journey., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Vaccines against SARS-CoV-2 have alleviated infection rates, hospitalization and deaths associated with COVID-19. In order to monitor humoral immunity, several serology tests have been developed, but the recent emergence of variants of concern has revealed the need for assays that predict the neutralizing capacity of antibodies in a fast and adaptable manner. Sensitive and fast neutralization assays would allow a timely evaluation of immunity against emerging variants and support drug and vaccine discovery efforts. Here we describe a simple, fast, and cell-free multiplexed flow cytometry assay to interrogate the ability of antibodies to prevent the interaction of Angiotensin-converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of the original Wuhan-1 SARS-CoV-2 strain and emerging variants simultaneously, as a surrogate neutralization assay. Using this method, we demonstrate that serum antibodies collected from representative individuals at different time-points during the pandemic present variable neutralizing activity against emerging variants, such as Omicron BA.1 and South African B.1.351. Importantly, antibodies present in samples collected during 2021, before the third dose of the vaccine was administered, do not confer complete neutralization against Omicron BA.1, as opposed to samples collected in 2022 which show significant neutralizing activity. The proposed approach has a comparable performance to other established surrogate methods such as cell-based assays using pseudotyped lentiviral particles expressing the spike of SARS-CoV-2, as demonstrated by the assessment of the blocking activity of therapeutic antibodies (i.e. Imdevimab) and serum samples. This method offers a scalable, cost effective and adaptable platform for the dynamic evaluation of antibody protection in affected populations against variants of SARS-CoV-2., Competing Interests: MM, EG and SB are employees of and hold stock in BD Biosciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Egia-Mendikute, Bosch, Prieto-Fernández, Vila-Vecilla, Zanetti, Lee, Jiménez-Lasheras, García del Río, Antoñana-Vildosola, de Blas, Velasco-Beltrán, Serrano-Maciá, Iruzubieta, Mehrpouyan, Goldberg, Bornheimer, Embade, Martínez-Chantar, López-Hoyos, Mato, Millet and Palazón.)

Background: Knowledge of resistance patterns is essential to choose empirical treatment. We aimed to determine the risk factors for antibiotic-resistant microorganisms (ARM) in intraabdominal infections (IAI) and their impact on mortality., Methods: Retrospective cohort study of patients with bacteremia from IAI origin in a single hospital between January 2006 and July 2017., Results: A total of 1485 episodes were recorded, including 381 (25.6%) due to ARM. Independent predictors of ARM were cirrhosis (OR 2; [95% CI 1.15-3.48]), immunosuppression (OR 1.49; 1.12-1.97), prior ceftazidime exposure (OR 3.7; 1.14-11.9), number of prior antibiotics (OR 2.33; 1.61-3.35 for 1 antibiotic), biliary manipulation (OR 1.53; 1.02-2.96), hospital-acquisition (OR 2.77; 1.89-4) and shock (OR 1.48; 1.07-2). Mortality rate of the whole cohort was 11.1%. Age (OR 1.03; 1.01-1.04), cirrhosis (OR 2.32; 1.07-4.38), urinary catheter (OR 1.99; 1.17-3.38), ultimately (OR 2.28; 1.47-3.51) or rapidly (OR 13.3; 7.12-24.9) fatal underlying disease, nosocomial infection (OR 2.76; 1.6-4.75), peritonitis (OR 1.95, 1.1-3.45), absence of fever (OR 2.17; 1.25-3.77), shock (OR 5.96; 3.89-9.13), and an ARM in non-biliary infections (OR 2.14; 1.19-3.83) were independent predictors of 30-day mortality. Source control (OR 0.24; 0.13-0.44) and 2015-2017 period (OR 0.29; 0.14-0.6) were protective., Conclusion: Biliary manipulation and septic shock are predictors of ARM. The presence of an ARM from a non-biliary focus is a poor-prognosis indicator. Source control continues to be of paramount importance., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

There is an ongoing need of developing sensitive and specific methods for the determination of SARS-CoV-2 seroconversion. For this purpose, we have developed a multiplexed flow cytometric bead array (C19BA) that allows the identification of IgG and IgM antibodies against three immunogenic proteins simultaneously: the spike receptor-binding domain (RBD), the spike protein subunit 1 (S1) and the nucleoprotein (N). Using different cohorts of samples collected before and after the pandemic, we show that this assay is more sensitive than ELISAs performed in our laboratory. The combination of three viral antigens allows for the interrogation of full seroconversion. Importantly, we have detected N-reactive antibodies in COVID-19-negative individuals. Here we present an immunoassay that can be easily implemented and has superior potential to detect low antibody titers compared to current gold standard serology methods.

Objectives: To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain., Methods: Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids., Results: Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid., Conclusions: We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) is a novel coronavirus not previously recognized in humans until late 2019. On 31 December 2019, a cluster of cases of pneumonia of unspecified etiology was reported to the World Health Organization in China. The availability of adequate SARS-CoV-2 drugs is also limited, and the efficacy and safety of these drugs for COVID-2019 pneumonia patients need to be assessed by further clinical trials. For these reasons, there is a need for other strategies against COVID-19 that are capable of prevention and treatment. Physical exercise has proven to be an effective therapy for most chronic diseases and microbial infections with preventive/therapeutic benefits, considering that exercise involves primary immunological mediators and/or anti-inflammatory properties. This review aimed to provide an insight into how the implementation of a physical exercise program against COVID-19 may be a useful complementary tool for prevention, which can also enhance recovery, improve quality of life, and provide immune protection against SARS-CoV-2 virus infection in the long term. In summary, physical exercise training exerts immunomodulatory effects, controls the viral gateway, modulates inflammation, stimulates nitric oxide synthesis pathways, and establishes control over oxidative stress.

The syndecan (Sdc) family is comprised of four members of cell surface molecules (Sdc-1 to 4) with different biological functions. Syndecan-3 (Sdc-3) is known to be mainly expressed in the brain and nervous tissue and plays a key role in development, cell adhesion, and migration. Recent studies point to important roles for Sdc-3 in inflammatory disease, but the patterns of expression and significance of Sdc-3 in cancer remains unexplored. Here we show that Sdc-3 expression is upregulated on several cancer types, especially in solid tumors that are known to be hypoxic. The Cancer Genome Atlas program (TCGA) data demonstrated that Sdc-3 expression in the tumor microenvironment positively correlates with a hypoxia gene signature. To confirm a potential cause-effect, we performed experiments with tumor cell lines showing increased expression upon in vitro exposure to 1% oxygen or dimethyloxalylglycine, an inhibitor of prolyl hydroxylases, indicating that Sdc-3 expression is promoted by hypoxia inducible factors (HIFs). HIF-1α was responsible for this upregulation as confirmed by CRISPR-engineered tumor cells. Using single-cell RNA sequencing data of melanoma patients, we show that Sdc-3 is expressed on tumor associated macrophages, cancer cells, and endothelial cells. Syndecan-3 expression positively correlated with a macrophage gene signature across several TCGA cancer types. In vitro experiments demonstrated that hypoxia (1% oxygen) or treatment with IFN-γ stimulate Sdc-3 expression on RAW-264.7 derived macrophages, linking Sdc-3 expression to a proinflammatory response. Syndecan-3 expression correlates with a better patient overall survival in hypoxic melanoma tumors., (Copyright © 2020 Prieto-Fernández, Egia-Mendikute, Bosch, García del Río, Jimenez-Lasheras, Antoñana-Vildosola, Lee and Palazon.)

Aims: Atrial high-rate episodes (AHREs) compatible with silent AF detected in pacemakers (PM) are related to an increased risk of stroke and silent ischaemic brain lesions (IBL) on CT scan. AHREs soon after PM implantation could be related with the procedure itself and the prognosis might be different., Methods and Results: We analysed the incidence of AHREs >5 min and the presence of silent IBL in 110 patients (56% men, aged 75 ± 9 year-old) with PM and no history of AF, in relation to time from implantation (≤3 months vs. >3 months) and the atrial lead fixation (LF) (active vs. passive). Mean CHADS2 and CHA2DS2VASc scores were 1.9 ± 1.2 and 3.5 ± 1.5, respectively. Time from implantation was ≤3 months in 88 patients (80%). Active LF was used in 55 patients (50%). After 24 ± 9 months, AHREs were present in 40 patients (36.4%). CT-scan showed silent IBL in 26 patients (23.6%). The presence of AHREs at 3 months was more frequent in the patients with recent PM implantation (17% vs. 4.5%, P = 0.09) and significantly related to active LF (OR 5.36, 1.43-20.07; P < 0.05). The presence of silent IBL was related to the detection of AHREs during follow up (OR 3.12, 1.29-7.97; P < 0.05) but not with AHREs at first 3 months (OR 1.58, 0.49-5.05; P = 0.44)., Conclusions: AHREs occur frequently during the first 3 months after PM implantation and could be related with procedure itself and the use of active LF. AHREs in this period might not be related to worse outcomes and should be interpreted cautiously.

Objectives: We aim to evaluate the long-term efficacy of two different paclitaxel-coated balloons (PCBs) for the treatment of coronary in-stent restenosis (ISR)., Methods: Between February 2011 and February 2012, all consecutive patients with ISR lesions treated with the SeQuent® Please (B. Braun, Melsungen, Germany) PCB or with the DIOR® (Eurocor GmbH, Bonn, Germany) PCB at our institution were prospectively included and followed up for 36months by clinical observation. The primary endpoint was the clinically driven target lesion revascularization (TLR) rate at 36months., Results: 65 patients with 74 ISR lesions were included. 43 ISR lesions were treated with the SeQuent® Please PCB and 31 with the DIOR® PCB. Baseline clinical, lesion characteristics and procedural data did not significantly differ between the groups. The TLR rate was significantly lower in patients treated with the SeQuent® Please PCB compared with the DIOR® PCB (4.7% vs. 22. 6%, p=0.03) at 36months., Conclusions: This registry suggests that there are differences in terms of TLR between two clinically available PCBs. The SeQuent® Please PCB demonstrated lower TLR rate compared to the DIOR® PCB at 36months follow up., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Paclitaxel-coated balloons (PCB) have been demonstrated to be successful for the treatment of in-stent restenosis. Although their role in the treatment of de novo lesions has not been fully clarified, they are often used for this indication. This prospective study evaluated the long-term efficacy and safety of the SeQuent® Please PCB (B. Braun, Melsungen, Germany) angioplasty for de novo coronary lesions in routine real-world practice., Methods: Between January 2010 and January 2012, all consecutive patients with de novo coronary lesions treated with the SeQuent® Please PCB at our institution were included. The primary endpoint was the clinically driven target lesion revascularization (TLR) rate at 36 months. The secondary endpoint was the rate of major adverse cardiac events (MACE: cardiac death, myocardial infarction [MI], and TLR)., Results: Fifty-three patients with 56 lesions were included. The mean reference vessel diameter was 2.4±0.4 mm and the mean target lesion length was 18.1±6.2 mm. Procedural success was 98.2%. Coronary dissection occurred in 7 patients (12.5%) and no vessel thrombosis was documented. Additional BMS was implanted in 14 target lesions (25%). Follow-up rate was 94.3%. The TLR rate at 36 months was 5.4%. The MACE rate was 8.9%, with 1.8 % cardiac death and 3.6% MI., Conclusions: Treatment of de novo coronary lesions with the SeQuent® Please PCB provides good clinical outcomes demonstrated by the low TLR rate and low MACE rates at long-term follow-up.

Supratentorial liponeurocytoma is a rare tumor, predominantly appearing in young males. It most commonly affects the lateral ventricles, with involvement of the third ventricle being exceptional. It is defined as a low-grade neuroglial tumor, with areas of associated lipomatosis. The most common clinical manifestation is that resulting from the presence of secondary intracranial hypertension and hydrocephalus. We present the first case reported in Spain of this tumor type and one of the few appearing in the literature so far. We report the case of a 33-year-old male patient, suffering from crural sensitive symptoms and recent onset headache. The radiographic study revealed the presence of a large supratentorial tumor; intraventricular, multicystic, heterogeneous and with areas of associated lipomatosis. The patient underwent surgery and complete tumor resection was achieved. The definitive diagnosis was of supratentorial liponeurocytoma. The presence of a supratentorial intraventricular tumor with areas of fatty degeneration should lead us to consider this type of tumor in the differential diagnosis. Complete tumor resection is considered to be the treatment of choice., (Copyright © 2011 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.)

Gram-positive bacteria account for >80% of all cases of endocarditis. Currently, staphylococci are the leading cause of endocarditis worldwide. Daptomycin is the drug of choice for empirical antibiotic therapy of staphylococcal endocarditis due to its optimal activity both against meticillin-susceptible Staphylococcus aureus and meticillin-resistant S. aureus (MRSA) strains. Daptomycin has not been proven to be superior to vancomycin in the treatment of MRSA endocarditis. However, daptomycin should be considered the drug of choice for the treatment of MRSA endocarditis caused by strains with a vancomycin minimum inhibitory concentration (MIC) of 2μg/mL, for heterogeneous vancomycin-intermediate S. aureus (hVISA) phenotypes and for glycopeptide-intermediate S. aureus (GISA) strains. Daptomycin is the drug of choice for rescue therapy in cases of MRSA endocarditis in which vancomycin has failed. The appropriate dose of daptomycin has not yet been established; however, for treatment of left-sided endocarditis the dose of daptomycin should be higher than the recommended dose of 6mg/kg/day. Combination antibiotic therapy with daptomycin (e.g. combined with fosfomycin) is a promising treatment for MRSA endocarditis and warrants further investigation. In vivo studies show that daptomycin is superior to vancomycin in the treatment of meticillin-resistant coagulase-negative staphylococci experimental endocarditis, although clinical data are required. Daptomycin could represent an efficacious treatment for vancomycin-resistant Enterococcus faecium endocarditis. Finally, the pharmacokinetic profile of daptomycin makes it an excellent drug for outpatient parenteral antimicrobial therapy., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: The length of treatment of infective endocarditis (IE) with parenteral antibiotics varies from 2 to 6 weeks. Although several studies indicate that outpatient parenteral antibiotic treatment (OPAT) could be safe for uncomplicated viridans-group streptococci (VGS) IE, the experience in Spain is limited and data on other types of endocarditis and OPAT are scarce worldwide., Methods: Prospective single center study of a cohort including all patients with IE admitted to the Hospital Clinic of Barcelona OPAT program from January 1997 to December 2006., Results: During the study period, 392 consecutive episodes of IE in non-drug abusers were attended to. Of these, 73 episodes (42 native-valve, 23 prosthetic-valve, and 8 pacemaker-lead) were admitted to the OPAT program (19%). The percentage of inclusion was higher for viridans group streptococci (VGS) or Streptococcus bovis (S. bovis) IE (32% of all VGS or S. bovis IE episodes diagnosed vs. 14% of the remaining etiologies, P<.001). Twelve patients (16%) were readmitted due to complications, of which 3 died (4%). Glycopeptides use was the only predictor factor of hospital readmission (OR 4.5, 95% confidence interval 1.2; 16.8, P=.026). No differences in OPAT outcome were found between VGS plus S. bovis IE and Staphylococcus aureus (S. aureus) plus coagulase-negative staphylococci IE. Patients spent a median of 17 day on OPAT (interquartile range 11-26.5), which enabled 1,466 days of hospital stay to be saved., Conclusions: These data suggest that OPAT for IE may be a safe and effective therapeutic approach in the treatment of selected patients with types of endocarditis other than uncomplicated VGS or S. bovis endocarditis, although patients taking glycopeptides need close clinical OPAT monitoring., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Objectives: To describe the clinical presentation of a large number of Q fever endocarditis (QFE) and its management considering the role of serology., Patients and Methods: Eighty-three patients with definite QFE (56 native and 27 prosthetic valve) with a long-term follow-up after stopping treatment (median: 48 months) were included. Final outcome (cure or relapse) was compared according with the serological titre at the end of therapy: less than 1:400 of phase I Ig G antibodies by indirect immunofluorescence (group 1, N=23) or more than 1:400 (group 2, N=30)., Results: Eleven patients (13.2%) died from QFE and other 8 died for other reasons not related to endocarditis during follow-up. Surgery was performed in 61 (73.5%) patients and combined antimicrobial treatment was long (median: 23 months, IQR: 12 - 36). Seven relapses were observed, but five of them had received an initial incomplete antibiotic regimen. In patients who completed the programmed treatment (range: 12 - 89 months), serological titres at the end of therapy were not useful for predicting the final outcome: one relapse in each group., Conclusions: QFE requires a prolonged antimicrobial treatment, but serological titres are not useful for determining its duration., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

The periannular extension of infection in prosthetic valve endocarditis (PVE) is a serious complication of infective endocarditis associated with high mortality. Periannular lesions in PVE occasionally rupture into adjacent cardiac chambers, leading to aortocavitary fistulae and intracardiac shunting. It is unknown whether the prognosis of patients with aortocavitary fistulae is worse than that of those with nonruptured abscesses. The aims of this study were to determine the distinctive clinical characteristics of patients with PVE and either aortocavitary fistulization or nonruptured abscesses. In a retrospective multicenter study of >872 PVE episodes, 150 patients (17%) with periannular complications in PVE in the aortic position were identified (29 with aortocavitary fistulization and 121 with nonruptured abscesses). Early-onset PVE was present in 73 patients (49%). Rates of heart failure (p = 0.09), ventricular septal defect (p <0.01), and third-degree atrioventricular block (p = 0.07) were higher in patients with fistulization. Surgical treatment was undertaken in 128 patients (83%). In-hospital mortality in the overall population was 39%. Multivariate analysis identified heart failure (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.6 to 6.8), renal failure (OR 2.5, 95% CI 1.2 to 5.2), and co-morbidity (OR 2.4, 95% CI 1.1 to 5.1) as independent risk factors for death. Fistulous tract formation was not associated with increased in-hospital mortality (OR 1.6, 95% CI 0.7 to 3.7). The actuarial 5-year survival rate in surgical survivors was 100% in patients with fistulae and 78% in patients with nonruptured abscesses (log-rank p = 0.14). In conclusion, aortocavitary fistulous tract formation in PVE complicated with periannular complications is associated with higher rates of heart failure, ventricular septal defect, and atrioventricular block than nonruptured abscesses. Despite the frequent complications, fistulous tract formation in the current era of infective endocarditis is not an independent risk factor for mortality.

Infective endocarditis is a rare disease associated with significant morbidity and mortality. In the past decades, there have been significant improvements in the management of infective endocarditis. Complications are frequent and include heart failure, embolic episodes, periannular complications, and central nervous system events. Surgical therapy has been fundamental in the reduction of mortality in complicated cases. This paper is an overview of the main complications of native and prosthetic infective endocarditis and its treatment.

Infective endocarditis (IE) is one of the most severe complications of parenteral drug abuse. The incidence of IE in intravenous drug abusers (IVDAs) is 2% to 5% per year, being responsible for 5% to 10% of the overall death rate. The prevalence of HIV infection among IVDAs with IE ranges between 30% and 70% in developed countries and HIV-infection by itself increases the risk of IE in IVDAs. The incidence of IE in IVDAs is currently decreasing in some areas, probably due to changes in drug administration habits by addicts to avoid HIV transmission. Overall, Staphylococcus aureus is the most common etiological agent, being usually sensitive to methicillin (MSSA). The tricuspid valve is the most frequently affected (60% to 70%), followed by the mitral and aortic valves (20% to 30%). HIV-positive IVDAs have a higher ratio of right-sided IE and S aureus IE than HIV-negative IVDAs. Response to antibiotic therapy is similar. Drug addicts with non-complicated MSSA right-sided IE can be treated with an i.v. short-course regimen of nafcillin or cloxacillin for 2 weeks, with or without addition of an aminoglycoside during the first 3 to 7 days. The prognosis of right-sided endocarditis is generally good; overall mortality is less than 5%, and with surgery is less than 2%. In contrast, the prognosis of left-sided IE is less favorable; mortality is 20% to 30%, and even with surgery is 15% to 25%. IE caused by GNB or fungi has the worst prognosis. Mortality between HIV-infected or non-HIV-infected IVDAs with IE is similar. However, among HIV-infected IVDAs, mortality is significantly higher in those who are most severely immunosuppressed, with CD4+ cell count < 200/microL or with AIDS criteria. Conversely, IE in HIV-infected patients who are not drug abusers is rare. The epidemiology of cardiac surgery in IVDAs and/or HIV-infected patients has changed in recent years. There is a decrease in IE and an increase of patients undergoing surgery (CABS) for coronary artery disease secondary to the hyperlipidemia and lipodystrophy induced by highly active antiretroviral therapy (HAART). Cardiac surgery in HIV-infected patients with or without IE does not worsen the prognosis because extracorporeal circulation did not affect the immune status after surgery. Morbidity and mortality seems to stay within the same range as the non-infected patients. In our experience, in the IE in HIV-infected IVDA group, the 1-year survival is 65% and the 5 and 10-year actuarial survival is 35%. For patients operated on for coronary artery disease, the 5-year survival is 100%.