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Aim: Volatile organic compounds (VOCs) are being studied as potential biomarkers in many infections. Therefore, this study aimed to analyze the volatile profile of three Gram-positive bacteria of clinical relevance to identify potential volatile biomarkers that allow their differentiation. Methods and results: L. monocytogenes, S. aureus, and E. faecalis clinical isolates were inoculated in a thioglycollate medium until grown. Then, VOCs were extracted by solid-phase microextraction, and the data obtained were subjected to multivariate analysis. According to our results, there was a high production of aldehydes in E. faecalis. In the case of alcohols, they only increased in L. monocytogenes, while ketones were produced significantly in all three bacteria, mainly due to acetoin. Acids were produced significantly in E. faecalis and L. monocytogenes. Conclusions: Potential biomarkers of L. monocytogenes could be 1-butanol and 2-methylbutanoic acid. In the case of E. faecalis, the VOC most related to its presence was nonanal. Lastly, potential biomarkers of S. aureus could be isoamyl butanoate and methionol, although some pyrazines have also been associated with this bacterium. Significance and impact of the study: The identification of potential biomarkers of these clinically relevant bacteria could open the way for the diagnosis of these infections through the analysis of volatile compounds.

Background. Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied. Objectives. To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA. Methods. Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020. Results. Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49–3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1–7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045). Conclusions. MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes

Aim: Volatile organic compounds (VOCs) are being studied as potential biomarkers in many infections. Therefore, this study aimed to analyze the volatile profile of three Gram-positive bacteria of clinical relevance to identify potential volatile biomarkers that allow their differentiation. Methods and results: L. monocytogenes, S. aureus, and E. faecalis clinical isolates were inoculated in a thioglycollate medium until grown. Then, VOCs were extracted by solid-phase microextraction, and the data obtained were subjected to multivariate analysis. According to our results, there was a high production of aldehydes in E. faecalis. In the case of alcohols, they only increased in L. monocytogenes, while ketones were produced significantly in all three bacteria, mainly due to acetoin. Acids were produced significantly in E. faecalis and L. monocytogenes. Conclusions: Potential biomarkers of L. monocytogenes could be 1-butanol and 2-methylbutanoic acid. In the case of E. faecalis, the VOC most related to its presence was nonanal. Lastly, potential biomarkers of S. aureus could be isoamyl butanoate and methionol, although some pyrazines have also been associated with this bacterium. Significance and impact of the study: The identification of potential biomarkers of these clinically relevant bacteria could open the way for the diagnosis of these infections through the analysis of volatile compounds.

We aimed to define a novel indicator for monitoring antimicrobial use specifically in the Emergency Department Observation Unit (EDOU) and to assess the long-term impact of an institutional education-based antimicrobial stewardship program (ASP) on the antimicrobial prescribing pattern and clinical outcomes in this setting. A quasi-experimental interrupted time-series study was performed from 2011 to 2022. An educational ASP was implemented at the EDOU in 2015. To estimate changes in antimicrobial use, we designed an indicator adjusted for patients at risk of antimicrobial prescribing: defined daily doses (DDDs) per 100 patients transferred from the Emergency Department to the Observation Unit (TOs) per quarter. The number of bloodstream infections (BSIs) and the crude all-cause 14-day mortality were assessed as clinical outcomes. Antimicrobial use showed a sustained reduction with a trend change of −1.17 DDD per 100 TO and a relative effect of −45.6% (CI95% −64.5 to −26.7), particularly relevant for meropenem and piperacillin-tazobactam, with relative effects of −80.4% (−115.0 to −45.7) and −67.9% (−93.9 to −41.9), respectively. The incidence density of all BSIs increased significantly during the ASP period, with a relative effect of 123.2% (41.3 to 284.7). The mortality rate remained low and stable throughout the study period, with an absolute effect of −0.7% (−16.0 to 14.7). The regular monitoring of antimicrobial use in the EDOU by using this new quantitative indicator was useful to demonstrate that an institutional education-based ASP successfully achieved a long-term reduction in overall antimicrobial use, with a low and steady BSI mortality rate.

Background People living with HIV have accounted for 38–50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3). Methods A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive. Findings We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30–43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117–291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100–200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesion

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity

In 2019, the biggest listeriosis outbreak by Listeria monocytogenes (Lm) in the South of Spain was reported, resulting in the death of three patients from 207 confirmed cases. One strain, belonging to clonal complex 388 (Lm CC388), has been isolated. We aimed to determine the Lm CC388 virulence in comparison with other highly virulent clones such as Lm CC1 and Lm CC4, in vitro and in vivo. Four L. monocytogenes strains (Lm CC388, Lm CC1, Lm CC4 and ATCC 19115) were used. Attachment to human lung epithelial cells (A549 cells) by these strains was characterized by adherence and invasion assays. Their cytotoxicities to A549 cells were evaluated by determining the cells viability. Their hemolysis activity was determined also. A murine intravenous infection model using these was performed to determine the concentration of bacteria in tissues and blood. Lm CC388 interaction with A549 cells is non-significantly higher than that of ATCC 19115 and Lm CC1, and lower than that of Lm CC4. Lm CC388 cytotoxicity is higher than that of ATCC 19115 and Lm CC1, and lower than that of Lm CC4. Moreover, Lm CC388 hemolysis activity is lower than that of the Lm CC4 strain, and higher than that of Lm CC1. Finally, in the murine intravenous infection model by Lm CC388, higher bacterial loads in tissues and at similar levels of Lm CC4 were observed. Although a lower rate of mortality of patients during the listeriosis outbreak in Spain in 2019 has been reported, the Lm CC388 strain has shown a greater or similar pathogenicity level in vitro and in an animal model, like Lm CC1 and Lm CC4.

Objectives: The BIChromET selective medium for detecting piperacillin-tazobactam (TZP) and cefepime (FEP) resistant Pseudomonas aeruginosa was developed. Methods: The performance of this medium was first evaluated using a collection of 100 P. aeruginosa clinical strains (70 TZP-susceptible, 30 TZP-resistant, 58 FEP-susceptible, and 42 FEP-resistant). Then, we performed clinical validation by testing 173 respiratory clinical samples. Results: The BIChromET medium showed excellent sensitivity (TZP (avg. 96.7%); FEP (avg. 92.7%)) and specificity (TZP (avg. 98.9%); FEP (avg. 98%)) in distinguishing the detection limit ranging from 104 to 108 CFU/mL. Then, testing the bronchoalveolar lavage (BAL) and tracheobronchial aspirate (TBA) clinical specimens (N = 173) revealed the excellent performance of the medium with P. aeruginosa, showing 100% and 92.6% of categorical agreements with the results obtained via the broth microdilution methods (BMD) for TZP and FEP, respectively. Conclusion: This medium allows for easy and accurate detection of TZP/FEP-resistant isolates regardless of their resistance mechanisms.

Rapid determination of susceptibility to piperacillin-tazobactam (TZP) is very important since the development of antibiotic resistance and inadequate treatment could increase the risk of clinical failure in infected patients, especially if such resistance is unknown to the clinician. Therefore, based on color change from orange to yellow of phenol red due to glucose metabolism (bacterial growth) in the presence of an adequate concentration of TZP (10 mg/L piperacillin and 5 mg/L tazobactam), the RapidTZP test has been developed to detect TZP resistance in Escherichia coli and Klebsiella pneumoniae isolates in a maximum of 3 h. A total of 140 isolates, 43 of E. coli and 97 of K. pneumoniae, were used to evaluate the performance of the test, 60 being resistant to TZP. The sensitivity and specificity of the test were 98.24% and 100%, respectively. Additionally, the RapidTZP test was validated by a pellet obtained directly from blood culture bottles. A total of 37 positive blood cultures for E. coli and 43 for K. pneumoniae were used for validation, 8 of them resistant to TZP. The sensitivity and specificity shown in the evaluation were 100% for both parameters. This new test is easy, fast, and accurate, providing results in 3 h.

Due to the high prevalence of patients attending with urinary tract infection (UTI) symptoms, the use of flow-cytometry as a rapid screening tool to avoid unnecessary cultures is becoming a widely used system in clinical practice. However, the recommended cut-points applied in flow-cytometry systems differ substantially among authors, making it difficult to obtain reliable conclusions. Here, we present FlowUTI, a shiny web-application created to establish optimal cut-off values in flow-cytometry for different UTI markers, such as bacterial or leukocyte counts, in urine from patients with UTI symptoms. This application provides a user-friendly graphical interface to perform robust statistical analysis without a specific training. Two datasets are analyzed in this manuscript: one composed of 204 urine samples from neonates and infants (≤3 months old) attended in the emergency department with suspected UTI; and the second dataset including 1174 urines samples from an elderly population attended at the primary care level. The source code is available on GitHub. The web application can be executed locally from the R console. Alternatively, it can be freely accessed at. FlowUTI provides an easy-to-use environment for evaluating the efficiency of the urinary screening process with flow-cytometry, reducing the computational burden associated with this kind of analysis.

Background Seven CTX-M-27-producing Shigella sonnei strains were isolated at the University Hospital Virgen del Rocío (Seville, Spain) microbiology service from October to November 2021. Objectives To offer extensive information on the microbiological and molecular epidemiology results of the seven S. sonnei isolates and compare them with other previously documented CTX-M-27-producing S. sonnei associated with MSM transmission. Methods S. sonnei isolated from stool samples of patients with acute diarrhoea were identified through biochemical and serological typing. Whole characterization of the seven isolates was performed by sequencing with MinION Mk1C followed by genomic and molecular analysis. Results All the isolates were resistant to penicillins, cephalosporins, fluoroquinolones, cotrimoxazole and azithromycin. Sequencing showed the presence of several resistance determinants, outstanding blaCTX-M-27, azithromycin resistance genes [ermB and mph(A)], qnrB19 and mutations in the QRDRs. All isolates belonged to the same hierarchical clustering of cgMLST (HierCC) with five allele distance (HC5) scheme v1 from EnteroBase. However, they presented differences in plasmid composition, with all seven isolates harbouring IncFII, IncB/O/K/Z and ColE1-like while SH2, SH6 and SH7 had IncFIB only. Our isolates were closely related to others from Spain (HC5; 98748), Australia (HC5; 98748) and the UK (HC5; 98748), which were also associated with MSM transmission. Nevertheless, the structure of the non-chromosomal genetic elements and the genetic context of blaCTX-M-27 presented a certain variability compared with isolates from other countries and among them. Conclusions This study confirms the emergence of CTX-M-27-producing S. sonnei (ST152) associated with MSM transmission in Spain, adding it to the Europe outbreak list and reinforcing the necessity of active surveillance and control of this high-risk clone.

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.

Background. Outpatient parenteral antibiotic treatment (OPAT) programs are increasingly used to manage infective endocarditis (IE), but current criteria for indicating OPAT are markedly conservative. We aimed to investigate whether more liberal criteria for indicating OPAT in IE can be safely used. Methods. This was a prospective multicenter nationwide cohort study (2008–2018). Rates of readmission, recurrences, and 1-year mortality were compared between hospital-based antibiotic treatment (HBAT) and OPAT. Risk factors for readmission and mortality in OPAT patients were investigated by logistic regression. Patients did not fulfill OPAT-GAMES (Grupos de Apoyo al Manejo de la Endocarditis en ESpaña) criteria if they had any of the following: cirrhosis, severe central nervous system emboli, undrained abscesses, severe conditions requiring cardiac surgery in nonoperable patients, severe postsurgical complications, highly difficult-to-treat microorganisms, or intravenous drug use. Results. A total of 2279 HBAT patients and 1268 OPAT patients were included. Among OPAT patients, 307 (24.2%) did not fulfill OPAT-GAMES criteria. Overall, OPAT patients presented higher rates of readmission than HBAT patients (18.2% vs 14.4%; P =.004), but no significant differences were found in the propensity analysis. Patients not fulfilling OPAT-GAMES criteria presented significantly higher rates of readmission than HBAT and OPAT-GAMES (23.8%, 14.4%, 16.4%; P<.001), whereas no significant differences were found in mortality (5.9%, 8%, 7.4%; P=.103) or recurrences (3.9%, 3.1%, 2.5%; P=.546). Not fulfilling OPAT-GAMES criteria was associated with higher risk of readmission (odds ratio [OR], 1.43; 95% CI, 1.03–1.97; P=.03), whereas cardiac surgery was associated with lower risk (OR, 0.72; 95% CI, 0.53–0.98; P=.03). Conclusions. OPAT-GAMES criteria allow identification of IE patients at higher risk of long-term complications to whom OPAT cannot be safely administered.

Background Research priorities in Antimicrobial Stewardship (AMS) have rapidly evolved in the last decade. The need for a more efficient use of antimicrobials have fueled plenty of studies to define the optimal duration for antibiotic treatments, and yet, there still are large areas of uncertainty in common clinical scenarios. Pseudomonas aeruginosa has been pointed as a priority for clinical research, but it has been unattended by most randomized trials tackling the effectiveness of short treatments. The study protocol of the SHORTEN-2 trial is presented as a practical example of new ways to approach common obstacles for clinical research in AMS. Objective To determine whether a 7-day course of antibiotics is superior to 14-day schemes for treating bloodstream infections by P. aeruginosa (BSI-PA). Methods A superiority, open-label, randomized controlled trial will be performed across 30 Spanish hospitals. Adult patients with uncomplicated BSI-PA will be randomized to receive a 7 versus 14-day course of any active antibiotic. The primary endpoint will be the probability for the 7-day group of achieving better outcomes than the control group, assessing altogether clinical effectiveness, severe adverse events, and antibiotic exposure through a DOOR/ RADAR analysis. Main secondary endpoints include treatment failure, BSI-PA relapses, and mortality. A superiority design was set for the primary endpoint and non-inferiority for treatment failure, resulting in a sample size of 304 patients. Conclusions SHORTEN-2 trial aligns with some of the priorities for clinical research in AMS. The implementation of several methodological innovations allowed overcoming common obstacles, like feasible sample sizes or measuring the clinical impact and unintended effects.

Objectives The genus Enterobacter is a common cause of nosocomial infections. Historically, the most frequent Enterobacter species were those of Enterobacter cloacae complex and Enterobacter aerogenes. In 2019, E. aerogenes was re-classified as Klebsiella aerogenes owing to its higher genotypic similarity with the genus Klebsiella. Our objective was to characterise and compare the clinical profiles of bacteraemia caused by E. cloacae and K. aerogenes. Methods This 3-year multicentre, prospective cohort study enrolled consecutive patients with bacteraemia by E. cloacae or K. aerogenes. Baseline characteristics, bacteraemia features (source, severity, treatment), antibiotic susceptibility, resistance mechanisms and mortality were analysed. Results The study included 285 patients with bacteraemia [196 (68.8%) E. cloacae and 89 (31.2%) K. aerogenes]. The groups showed no differences in age, sex, previous use of invasive devices, place of acquisition, sources or severity at onset. The Charlson score was higher among patients with E. cloacae bacteraemia [2 (1–4) vs. 1 (0.5–3); P = 0.018], and previous antibiotic therapy was more common in patients with K. aerogenes bacteraemia (57.3% vs. 41.3%; P = 0.01). Mortality was 19.4% for E. cloacae and 20.2% for K. aerogenes (P = 0.869). Antibiotic susceptibility was similar for both species, and the incidence of multidrug resistance or ESBL production was low (6% and 5.3%, respectively), with no differences between species. Conclusion Bacteraemias caused by E. cloacae and K. aerogenes share similar patient profiles, presentation and prognosis. Patients with E. cloacae bacteraemia had more co-morbidities and those with K. aerogenes bacteraemia had received more antibiotics.

Antimicrobial stewardship programs (ASPs) in hematological patients are especially relevant. However, information about ASPs in this population is scarce. For 11 years, we quarterly assessed antimicrobial consumption and incidence and death rates of multidrug-resistant (MDR) bloodstream infections (BSI) in the hematology Department. Healthcare activity indicators were also monitored yearly. We performed an interrupted time-series analysis. Antimicrobials showed a sustained reduction with a relative effect of −62.3% (95% CI −84.5 to −40.1) nine years after the inception of the ASP, being especially relevant for antifungals (relative effect −80.4%, −90.9 to −69.9), quinolones (relative effect −85.0%, −102.0 to −68.1), and carbapenems (relative effect −68.8%, −126.0 to −10.6). Incidence density of MDR BSI remained low and stable (mean 1.10 vs. 0.82 episodes per 1000 occupied bed days for the pre-intervention and the ASP period, respectively) with a quarterly percentage of change of −0.3% (95% CI −2.0 to 1.4). Early and late mortality of MDR BSI presented a steady trend (quarterly percentage of change −0.7%, 95% CI −1.7 to 0.3 and −0.6%, 95% CI −1.5 to 0.3, respectively). Volume and complexity of healthcare activity increased over the years. The ASP effectively achieved long-term reductions in antimicrobial consumption and improvements in the prescription profile, without increasing the mortality of MDR BSI

Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at frst patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confrmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n= 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the fnal multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age≥ 70 years, SpO2, neutrophils > 7.5 × ­103 /µL, lactate dehydrogenase≥ 300 U/L, and C-reactive protein≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.

Introduction Mural infective endocarditis (MIE) is a rare type of endovascular infection. We present a comprehensive series of patients with mural endocarditis. Method sPatients with infectious endocarditis (IE) from 35 Spanish hospitals were prospectively included in the GAMES registry between 2008 and 2017. MIEs were compared to non-MIEs. We also performed a literature search for cases of MIE published between 1979 and 2019 and compared them to the GAMEs series. Results Twenty-seven MIEs out of 3676 IEs were included. When compared to valvular IE (VIE) or device-associated IE (DIE), patients with MIE were younger (median age 59 years, p < 0.01). Transplantation (18.5% versus 1.6% VIE and 2% DIE, p < 0.01), hemodialysis (18.5% versus 4.3% VIE and 4.4% DIE, p = 0.006), catheter source (59.3% versus 9.7% VIE and 8.8% DIE, p < 0.01) and Candida etiology (22.2% versus 2% DIE and 1.2% VIE, p < 0.01) were more common in MIE, whereas the Charlson Index was lower (4 versus 5 in non-MIE, p = 0.006). Mortality was similar.MIE from the literature shared many characteristics with MIE from GAMES, although patients were younger (45 years vs. 56 years, p < 0.001), the Charlson Index was lower (1.3 vs. 4.3, p = 0.0001), catheter source was less common (13.9% vs. 59.3%) and there were more IVDUs (25% vs. 3.7%). S. aureus was the most frequent microorganism (50%, p = 0.035). Systemic complications were more common but mortality was similar. Conclusion MIE is a rare entity. It is often a complication of catheter use, particularly in immunocompromised and hemodialysis patients. Fungal etiology is common. Mortality is similar to other IEs.

Background Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results Of 5336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When comparing SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs 3.5%, P = .116); valve disorder, including perforation (22.2% vs 18.1%, P = .584), pseudoaneurysm (16.7% vs 8.3%, P = .108), or prosthesis dehiscence (1.4% vs 6.3%, P = .170); paravalvular complications, including abscess (25% vs 18.8%, P = .264) and intracardiac fistula (5.6% vs 3.5%, P = .485); heart failure (34.7% vs 38.9%, P = .655); or embolic events (41.7% vs 32.6%, P = .248). Indications for surgery (70.8% vs 70.8%; P = 1) and mortality (13.9% vs 16.7%; P = .741) were similar between groups. Conclusions SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG.

Background: Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB. Methods: We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends. Results: A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) -1.5%, P < 0.001] and a -8.170 (-16.064 to -0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC -3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC -0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae. Conclusions: In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.

Las infecciones por bacterias multirresistentes son un serio problema a nivel mundial. La aparición constante de mecanismos de resistencia a los antibióticos junto con el limitado desarrollo de nuevos compuestos con actividad antibacteriana en los últimos años plantea la necesidad de abordar este problema de forma urgente. Esta Tesis Doctoral se ha centrado en el estudio de las infecciones por E. coli, en especial la bacteriemia y la infección intraabdominal, tanto desde el punto de vista del paciente como del microorganismo. Por un lado se analizaron las características clínicas y microbiológicas, así como factores de riesgo asociados con la mortalidad de los pacientes con bacteriemia por E. coli en comparación con pacientes con bacteriemia por K. pneumoniae. Este primer análisis mostró una serie de diferencias importantes entre uno y otro microorganismo. En la misma línea, se analizaron las características clínicas y microbiológicas de pacientes con infección intraabdominal por E. coli y su relación con la mortalidad, así como los factores de riesgo asociados al desarrollo de bacteriemia en este tipo de infección. Entre otros, la infección del tracto biliar parece jugar un papel importante, por lo que se decidió analizar la relación filogenética, el resistoma y el viruloma de un conjunto de aislados clínicos de E. coli causantes de infección biliar, con el objetivo de conocer si existen factores bacterianos que promuevan este tipo de infección. Aunque no existió relación filogenética entre los aislados, se encontraron numerosos factores de virulencia que podrían estar implicados en el desarrollo de infecciones del tracto biliar. Por otro lado, el siguiente objetivo fue estudiar la expresión de un factor de virulencia concreto como es la proteína de membrana externa A (OmpA) en E. coli, y su asociación con la mortalidad de los pacientes con bacteriemia por E. coli. Se analizó una amplia cohorte de aislados clínicos procedentes de pacientes con bacteriemia, en los q

During the COVID-19 pandemic, the implementation of antimicrobial stewardship strategies has been recommended. This study aimed to assess the impact of the COVID-19 pandemic in a tertiary care Spanish hospital with an active ongoing antimicrobial stewardship programme (ASP). For a 20-week period, we weekly assessed antimicrobial consumption, incidence density, and crude death rate per 1000 occupied bed days of candidemia and multidrug-resistant (MDR) bacterial bloodstream infections (BSI). We conducted a segmented regression analysis of time series. Antimicrobial consumption increased +3.5% per week (p = 0.016) for six weeks after the national lockdown, followed by a sustained weekly reduction of −6.4% (p = 0.001). The global trend for the whole period was stable. The frequency of empirical treatment of patients with COVID-19 was 33.7%. No change in the global trend of incidence of hospital-acquired candidemia and MDR bacterial BSI was observed (+0.5% weekly; p = 0.816), nor differences in 14 and 30-day crude death rates (p = 0.653 and p = 0.732, respectively). Our work provides quantitative data about the pandemic effect on antimicrobial consumption and clinical outcomes in a centre with an active ongoing institutional and education-based ASP. However, assessing the long-term impact of the COVID-19 pandemic on antimicrobial resistance is required.

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multina- tional, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. Theglobal cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operatng characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

Objective: To evaluate the ability of the BioFire FilmArray Blood Culture Identification (BCID) panel to rapidly detect pathogens producing late-onset ventilator-associated pneumonia (VAP), a severe infection often produced by Gram-negative bacteria. These microorganisms are frequently multidrug resistant and typically require broad-spectrum empiric treatment. Methods: In the context of an international multicentre clinical trial (MagicBullet), respiratory samples were collected at the time of suspicion of VAP from 165 patients in 32 participating hospitals in Spain, Greece and Italy. Microorganisms were identified using the BCID panel and compared with results ob- tained by conventional microbiologic techniques. Results: Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly identified species, representing 54.7% (70/128) of microorganisms. The BCID panel showed high global specificity (98.1%; 95% confidence interval, 96e100) and negative predictive values (96.6%) and a global sensitivity and positive predictive value of 78.6% (95% confidence interval, 70e88) and 87.3%, respectively, for these microorganisms. Importantly, the BCID panel provided results in only 1 hour directly from respiratory samples with minimal sample processing times. Conclusions: The BCID panel may have clinical utility in rapidly ruling out microorganisms causing VAP, specifically multidrug-resistant Gram-negative species. This could facilitate the optimization of empiric treatment.

Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature. We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n¼2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model. We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4–12.9; P<0.01). Valve surgery was protective (OR, 0.1; 95% CI, 0.04–0.4; P<0.01). Streptococcus pneumoniae IE is a community-acquired disease that mainly affects native aortic valves. Half