Search

Objective : To describe the clinical characteristics and outcome of Abiotrophia and Granulicatella infective endocarditis and compare them with Viridans group streptococci infective endocarditis. Methods : All patients in the International Collaboration on Endocarditis (ICE) - prospective cohort study (PCS) and the ICE-PLUS cohort were included (n=8112). Data from patients with definitive or possible IE due to Abiotrophia species, Granulicatella species and Viridans group streptococci was analyzed. A propensity score (PS) analysis comparing the ABI/GRA-IE and VGS-IE groups according to a 1:2 ratio was performed. Results : Forty-eight (0.64%) cases of ABI/GRA-IE and 1,292 (17.2%) VGS-IE were included in the analysis. The median age of patients with ABI/GRA-IE was lower than VGS-IE (48.1 years vs. 57.9 years; p=0.001). Clinical features and the rate of in-hospital surgery was similar between ABI/GRA-IE and VGS-IE (52.1% vs. 45.4%; p=0.366). Unadjusted in-hospital death was lower in ABI/GRA-IE than VGS-IE (2.1% vs. 8.8%; p=0.003), and cumulative six-month mortality was lower in ABI/GRA-IE than VGS-IE (2.1% vs. 11.9%; p

Community-acquired pneumonia (CAP) is a common infection with a constantly evolving etiological spectrum. This changing etiology conditions the adequate selection of optimal therapeutic regimens, both in empirical and definitive treatments. In recent years, new antimicrobials have been approved by regulatory authorities for use in CAP, although it is necessary to continue incorporating new antimicrobial agents that improve the activity profile in relation to the appearance of bacterial resistance in certain pathogens, such as pneumococcus, Staphylococcus aureus or Pseudomonas aeruginosa. Delafloxacin, omadacycline and lefamulin are the most recently approved antibiotics for CAP. These three antibiotics have shown non-inferiority to their comparators for the treatment of CAP with an excellent safety profile. However, in the 2019 ATS/IDSA guidelines, it has been considered that more information is needed to incorporate these new drugs into community-based treatment. New antimicrobials, such as solithromycin and nemonoxacin, are currently being studied in Phase III clinical trials. Both drugs have shown non-inferiority against the comparators and an acceptable safety profile; however, they have not yet been approved by the regulatory authorities. Several drugs are being tested in Phase I and II clinical trials. These include zabofloxacin, aravofloxacin, nafithromycin, TP-271, gepotidacin, radezolid, delpazolid, and CAL02. The preliminary results of these clinical trials allow us to assure that most of these drugs may play a role in the future treatment of CAP.

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections.

Antibiotic-induced modulation of the intestinal microbiota can lead to Clostridioides difficile infection (CDI), which is associated with considerable morbidity, mortality, and healthcare-costs globally. Therefore, identification of markers predictive of CDI could substantially contribute to guiding therapy and decreasing the infection burden. Here, we analyze the intestinal microbiota of hospitalized patients at increased CDI risk in a prospective, 90-day cohort-study before and after antibiotic treatment and at diarrhea onset. We show that patients developing CDI already exhibit significantly lower diversity before antibiotic treatment and a distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients. We find that antibiotic treatment-induced dysbiosis is class-specific with beta-lactams further increasing enterococcal abundance. Our findings, validated in an independent prospective patient cohort developing CDI, can be exploited to enrich for high-risk patients in prospective clinical trials, and to develop predictive microbiota-based diagnostics for management of patients at risk for CDI., Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea (AAD); however, markers predictive of CDI or AAD development are as yet lacking. Here, to identify markers predictive of CDI, the authors profile the intestinal microbiota of 945 hospitalised patients from 34 hospitals in 6 different European countries and show distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients.

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk., Here, the authors report the incidence of Clostridioides difficile infection (CDI) and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients of 50 years and above receiving newly initiated antibiotic treatment.

Juilia Sellarès-Nadal, Joaquin Burgos, Vicenç Falcó, Benito Almirante Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Autonomous University of Barcelona, Barcelona, SpainCorrespondence: Benito AlmiranteInfectious Diseases Department, Hospital Universitari Vall d’Hebron, Avda. Vall d’Hebron, 119-129, Barcelona 08035, SpainTel +34 274 60 90Email benitoalmirante@gmail.comAbstract: Community-acquired pneumonia (CAP) is a common infection with a constantly evolving etiological spectrum. This changing etiology conditions the adequate selection of optimal therapeutic regimens, both in empirical and definitive treatments. In recent years, new antimicrobials have been approved by regulatory authorities for use in CAP, although it is necessary to continue incorporating new antimicrobial agents that improve the activity profile in relation to the appearance of bacterial resistance in certain pathogens, such as pneumococcus, Staphylococcus aureus or Pseudomonas aeruginosa. Delafloxacin, omadacycline and lefamulin are the most recently approved antibiotics for CAP. These three antibiotics have shown non-inferiority to their comparators for the treatment of CAP with an excellent safety profile. However, in the 2019 ATS/IDSA guidelines, it has been considered that more information is needed to incorporate these new drugs into community-based treatment. New antimicrobials, such as solithromycin and nemonoxacin, are currently being studied in Phase III clinical trials. Both drugs have shown non-inferiority against the comparators and an acceptable safety profile; however, they have not yet been approved by the regulatory authorities. Several drugs are being tested in Phase I and II clinical trials. These include zabofloxacin, aravofloxacin, nafithromycin, TP-271, gepotidacin, radezolid, delpazolid, and CAL02. The preliminary results of these clinical trials allow us to assure that most of these drugs may play a role in the future treatment of CAP.Keywords: community-acquired pneumonia, new antimicrobial drugs, fluoroquinolones, macrolides, tetracyclines, oxazolidinones

Background: Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID19) despite the scarcity of evidence. Methods: We report preliminary results from the Vall dHebron prospective cohort study at Vall dHebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed infection with the severe acute respiratory syndrome coronavirus2 (SARSCoV2) and who were treated with tocilizumab until March 25th. The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others. Results: 82 patients with COVID19 received at least one dose of tocilizumab. The mean (SD) age was 59.1 (19.8) years, 63% were male, 22% were of non Spanish ancestry, and the median (IQR) ageadjusted Charlson index at baseline was 3 (1 to 4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5 to 11) days. The median time from symptom onset to the first dose of tocilizumab was 9 (7 to 11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3 to 8.5 (age adjusted hazard ratio for mortality 2.1; 95% CI, 0.8 to 5.8) if tocilizumab was administered after the onset of ARDS. Conclusion: Time from lung injury onset to tocilizumab administration may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data from clinical trials becomes available.

Additional file 1. Comparison between patients with and without intra-abdominal origin of candidemia.

Laura Escolà-Vergé1,2Carlos Pigrau1,2 Benito Almirante1,21Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain; 2Spanish Network for Research in Infectious Diseases (REIPI), Madrid, SpainAbstract: The current prevalence of infections caused by multidrug-resistant (MDR) organisms is a global threat, and thus, the development of new antimicrobial agents with activity against these pathogens is a healthcare priority. Ceftolozane–tazobactam (C/T) is a new combination of a cephalosporin with a β-lactamase inhibitor that shows excellent in vitro activity against a broad spectrum of Enterobacteriaceae and Pseudomonas aeruginosa, including extended spectrum β-lactamase-producing (ESBL) strains and MDR or extensively drug-resistant (XDR) P. aeruginosa. In phase III randomized clinical trials, C/T demonstrated similar efficacy to meropenem for the treatment of complicated intra-abdominal infections (cIAIs) and superior efficacy to levofloxacin for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. The drug is generally safe and well tolerated and its PK/PD profile is very favorable. Observational studies with C/T have revealed good efficacy for the treatment of different types of infection caused by MDR or XDR P. aeruginosa, including some that originated from the digestive or urinary tracts. The place of C/T in therapy is not well defined, but its use could be recommended in a carbapenem-sparing approach for the treatment of infections caused by ESBL-producing strains or for the treatment of infections caused by P. aeruginosa if there are no other more favorable therapeutic options. Further clinical experience is needed to position this new antimicrobial drug for the empirical treatment of cIAIs or cUTIs.Keywords: ceftolozane-tazobactam, complicated intra-abdominal infections, complicated urinary tract infections, multidrug-resistant Pseudomonas aeruginosa

Table S1. Expression levels changes in RNAIII and agrA locus under the exposure to oxacillin subMICs in the stationary growth phase. aOXA: Oxacillin. bPOS: fold change positive in the expression level under exposure to oxacillin subMIC. NEG: fold change negative in the expression level under exposure to oxacillin subMICs. cBold numbers indicate statistical significant results (P

Fungemia due to rare yeasts constitutes an emerging but poorly investigated condition. Data on risk factors, clinical features, therapy, and outcome of episodes of fungemia due to rare (non-Candida, non-Cryptococcus) yeasts were analyzed in a population-based surveillance program conducted in 29 Spanish hospitals between May 2010 and April 2011. Species identification (DNA sequencing) and antifungal susceptibility testing (EUCAST and CLSI methods) were centrally performed. Fourteen out of 767 episodes of fungemia (1.8%) were due to rare yeasts: Trichosporon asahii, Magnusiomyces capitatus (three cases each), Rhodotorula mucilaginosa, Wickerhamomyces anomalus (two cases each), and Pichia kudriavzevii, Cyberlindnera fabianii, Kodamaea ohmeri, and Lodderomyces elongisporus (one case each). Misidentification by local laboratories was observed in two isolates. Breakthrough fungemia occurred in two episodes due to M. capitatus MIC values for echinocandins were generally high (particularly for M. capitatus, T. asahii, and R. mucilaginosa isolates [≥2 mg/l]), whereas T. asahii isolates showed MICs ≥1 mg/l to amphotericin B. Patients with fungemia due to rare yeasts were more likely to have hematological malignancies (28.6% vs. 7.8%; P-value = .021), chronic lung disease (50.0% vs. 22.3%; P-value = .023), and prior immunosuppression (57.1% vs. 22.2%; P-value = .005) compared to those with candidemia. The rate of clinical failure (persistent fungemia and/or 30-day mortality) was 46.2% and did not significantly differ from that observed in episodes of candidemia. In conclusion, non-Candida, non-Cryptococcus yeasts are uncommon causes of fungemia, with immunosuppression and chronic lung disease as predisposing factors. Outcome does not appear to be worse than that of candidemia. This study was supported by non-restrictive research grants from Gilead, MSD, Astellas, and Pfizer. This study was cofounded by Fundación SEIMC-GESIDA, by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (co-financed by the European Development Regional Fund [ERDF] “A way to achieve Europe”), and by the Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III. J.G. holds a research contract “Miguel Servet” (CPII15/00006) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III. These institutions had no involvement in the preparation of the manuscript No

There is little information about the efficacy of active alternative drugs to carbapenems except β-lactam/β-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems.

[Objectives] To compare results of amoxicillin/clavulanate susceptibility testing using CLSI and EUCAST methodologies and to evaluate their impact on outcome in patients with bacteraemia caused by Enterobacteriaceae., [Patients and methods] A prospective observational cohort study was conducted in 13 Spanish hospitals. Patients with bacteraemia due to Enterobacteriaceae who received empirical intravenous amoxicillin/clavulanate treatment for at least 48 h were included. MICs were determined following CLSI and EUCAST recommendations. Outcome variables were: failure at the end of treatment with amoxicillin/clavulanate (FEAMC); failure at day 21; and 30 day mortality. Classification and regression tree (CART) analysis and logistic regression were performed., [Results] Overall, 264 episodes were included; the urinary tract was the most common source (64.7%) and Escherichia coli the most frequent pathogen (76.5%). Fifty-two isolates (19.7%) showed resistance according to CLSI and 141 (53.4%) according to EUCAST. The kappa index for the concordance between the results of both committees was only 0.24. EUCAST-derived, but not CLSI-derived, MICs were associated with failure when considered as continuous variables. CART analysis suggested a ‘resistance’ breakpoint of > 8/4 mg/L for CLSI-derived MICs; it predicted FEAMC in adjusted analysis (OR = 1.96; 95% CI: 0.98–3.90). Isolates with EUCAST-derived MICs >16/2 mg/L independently predicted FEAMC (OR = 2.10; 95% CI: 1.05–4.21) and failure at day 21 (OR= 3.01; 95% CI: 0.93–9.67). MICs >32/2 mg/L were only predictive of failure among patients with bacteraemia from urinary or biliary tract sources., [Conclusions] CLSI and EUCAST methodologies showed low agreement for determining the MIC of amoxicillin/clavulanate. EUCAST-derived MICs seemed more predictive of failure than CLSI-derived ones. EUCAST-derived MICs >16/2 mg/L were independently associated with therapeutic failure., The study was funded by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain (Fondo de investigación en salud; PI10/02021) co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015).

Objective To develop a score to predict mortality in patients with bloodstream infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE). Patients and Methods A multinational retrospective cohort study (INCREMENT project) was performed from January 1, 2004, through December 31, 2013. Patients with clinically relevant monomicrobial BSIs due to CPE were included and randomly assigned to either a derivation cohort (DC) or a validation cohort (VC). The variables were assessed on the day the susceptibility results were available, and the predictive score was developed using hierarchical logistic regression. The main outcome variable was 14-day all-cause mortality. The predictive ability of the model and scores were measured by calculating the area under the receiver operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score. Results The DC and VC included 314 and 154 patients, respectively. The final logistic regression model of the DC included the following variables: severe sepsis or shock at presentation (5 points); Pitt score of 6 or more (4 points); Charlson comorbidity index of 2 or more (3 points); source of BSI other than urinary or biliary tract (3 points); inappropriate empirical therapy and inappropriate early targeted therapy (2 points). The score exhibited an area under the receiver operating characteristic curve of 0.80 (95% CI, 0.74-0.85) in the DC and 0.80 (95% CI, 0.73-0.88) in the VC. The results for 30-day all-cause mortality were similar. Conclusion A validated score predictive of early mortality in patients with BSIs due to CPE was developed. Trial Registration clinicaltrials.gov Identifier: NCT01 764490.

REIPI/ESGBIS/INCREMENT Group: J. Gálvez, M. de Cueto, E. Salamanca, M. Falcone, A. Russo, G. Daikos, I. Karaiskos, E. M. Trecarichi, A. R. Losito, D. L. Paterson, A. Hernández, J. Gómez, E. Roilides, E. Iosifidis, Y. Doi, F. F. Tuon, F. Navarro, B. Mirelis, R. San Juan, M. Fernández-Ruiz, N. Larrosa, M. Puig, J. Molina, V. González, V. Rucci, E. Ruiz de Gopegui, C. I. Marinescu, M. C. Fariñas, M. E. Cano, M. Gozalo, J. R. Paño-Pardo, C. Navarro-San Francisco, S. Gómez-Zorrilla, F. Tubau, S. Pournaras, A. Tsakris, O. Zarkotou, Ö. K. Azap, M. Souli, A. Antoniadou, G. Poulakou, D. Virmani, I. Machuca, E. Pérez-Nadales, J. Torre-Cisneros, Ö. Helvaci, A. O. Sahin, R. Cantón, P. Ruiz, M. Bartoletti, M. Giannella, F. Riemenschneider, C. Badia, M. Xercavins, D. Fontanals, E. Jové., [Objectives] Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E., [Methods] A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality., [Results] The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24–20.08; P = 0.58) and 1.04 (0.44–2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43–3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43–2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46–2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems., [Conclusions] Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock., This study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015) and FIS (PI10/02021). The study was also supported in part by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program and the Geriatric Research Education and Clinical Center VISN 10 (VISN 10 GRECC) to R. A. B. The NIAID of the NIH under Award Numbers R01AI072219 and R01AI063517 also supported R. A. B.

As highly active antiretroviral treatment (HAART) is widely available, the incidence of Pneumocystis jirovecii pneumonia (PJP) has decreased significantly but still represents a significant cause of morbidity and mortality in developed countries. We analyzed all the cases with PJP in human immunodeficiency virus (HIV)-infected patients from 2000 to 2013 in a university hospital in Barcelona, Spain, and conducted a systematic literature review to evaluate data regarding incidence, mortality, and long-term survival after PJP in developed settings. One hundred thirty-six episodes of PJP were analyzed. During the study period, the incidence decreased significantly (from 13.4 cases/1000 patients-year to 3.3 cases/1000 patients-year, P 50 years (odds ratio 4.96, 95% confidence interval [CI] 1.45–15.14). Patients who survived were followed-up during a mean time of 44 months. Overall 5-year survival of patients after hospital discharge was 73%. Survival likelihood was 54% higher (88% [95% CI 81–96]) among HAART-adherent patients. Mean age and the proportion of patients with unknown HIV infection at the time of PJP diagnosis have increased in developed countries in the HAART era. Although the incidence has decreased, in-hospital mortality remains stable in this setting. Long-term survival is very high among HAART-adherent patients.

Although hematogenous pyogenic spinal infections have been related to hemodialysis (HD), catheter-related sepsis, and sporadically, to other nosocomial infections or procedures, in most recent studies and reviews the impact of nosocomial infection as a risk factor for vertebral osteomyelitis (VO) is not well established. The aim of our study was to describe the risk factors, infectious source, etiology, clinical features, therapy, and outcome of health care associated VO (HCAVO), and compare them with community-acquired VO (CAVO) cases. A retrospective cohort study of consecutive patients with hematogenous VO was conducted in our third-level hospital between 1987 and 2011. HCAVO was defined as onset of symptoms after 1 month of hospitalization or within 6 months after hospital discharge, or ambulatory manipulations in the 6 months before the diagnosis. Over the 25-year study period, among 163 hematogenous pyogenic VO, 41 (25%) were health care associated, a percentage that increased from 15% (9/61) in the 1987–1999 period to 31% (32/102) in the 2000–2011 period (P

Background: The aim of the study was to determine clinical and microbiological differences between patients with methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia (CRB) undergoing or not undergoing haemodialysis, and to compare outcomes. Methods: Prospective multicentre study conducted at 21 Spanish hospitals of patients with MRSA bacteraemia diagnosed between June 2008 and December 2009. Patients with MRSA-CRB were selected. Data of patients on haemodialysis (HD-CRB) and those not on haemodialysis (non-HD-CRB) were compared. Results: Among 579 episodes of MRSA bacteraemia, 218 (37.7 %) were CRB. Thirty-four (15.6 %) were HD-CRB and 184 (84.4 %) non-HD-CRB. All HD-CRB patients acquired the infection at dialysis centres, while in 85.3 % of the non-HD-CRB group the infection was nosocomial (p < .001). There were no differences in age, gender or severity of bacteraemia (Pitt score); comorbidities (Charlson score >= 4) were higher in the HD-CRB group than in the non-HD-CRB group (73.5 % vs. 46.2 %, p = .003). Although there were no differences in VAN-MIC >= 1.5 mg/L according to microdilution, using the E-test a higher rate of VAN-MIC >= 1.5 mg/L was observed in HD-CRB than in non-HD-CRB patients (63.3 % vs. 44.1 %, p = .051). Vancomycin was more frequently administered in the HD-CRB group than in the non-HD-CRB group (82.3 % vs. 42.4 %, p =, This study was supported by Ministerio de Ciencia e Innovacion, Instituto de Salud Carlos III (FIS 08/0335) and co-financed by the European Development Regional Fund 'A way to achieve Europe' ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD06/0008).; O. G. was recipient of a Rio Hortega Grant (CM08/228) from the Instituto de Salud Carlos III.

Although hematogenous pyogenic spinal infections have been related to hemodialysis (HD), catheter-related sepsis, and sporadically, to other nosocomial infections or procedures, in most recent studies and reviews the impact of nosocomial infection as a risk factor for vertebral osteomyelitis (VO) is not well established. The aim of our study was to describe the risk factors, infectious source, etiology, clinical features, therapy, and outcome of health care associated VO (HCAVO), and compare them with community-acquired VO (CAVO) cases. A retrospective cohort study of consecutive patients with hematogenous VO was conducted in our third-level hospital between 1987 and 2011. HCAVO was defined as onset of symptoms after 1 month of hospitalization or within 6 months after hospital discharge, or ambulatory manipulations in the 6 months before the diagnosis. Over the 25-year study period, among 163 hematogenous pyogenic VO, 41 (25%) were health care associated, a percentage that increased from 15% (9/61) in the 1987-1999 period to 31% (32/102) in the 2000-2011 period (P < 0.01). The presumed source of infection was an intravenous catheter in 14 (34%), cutaneous foci in 8 (20%), urinary tract in 7 (17%), gastrointestinal in 3 (7%), other foci in 3 (7%), and unknown in 6 (15%). Staphylococcus aureus was the most frequently isolated microorganism (14 cases, 34%), followed by coagulase-negative Staphylococci (CoNS) in 6 (15%), and Enterobacteriaceae in 6 (15%) cases. Compared with CAVO cases, patients with HCAVO were older (mean 66.0 SD 13.0 years vs 60.5 SD 15.5 years), had more underlying conditions (73% vs 50%, P < 0.05), neoplasm/immunosuppression (39% vs 7%, P < 0.005), chronic renal failure (19% vs 4%, P < 0.001), a known source of infection (85% vs 54% P < 0.05), Candida spp (7% vs 0%, P < 0.01) or CoNS infections (15% vs 2%, P < 0.05), higher mortality (15% vs 6%, P = 0.069), and a higher relapse rate in survivors (9% vs 1%, P < 0.05). Presently, in our setting, one-third of hematogenous pyogenic VO infections are health care associated, and a third of these are potentially preventable catheter-related infections. Compared with CAVO, in health care associated hematogenous VO, mortality and relapse rates are higher; hence, further prevention measures should be assessed.

International audience; BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

International audience; The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p < 0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p < 0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p < 0.01) and younger age (OR 0.62; CI 0.49-0.90; p < 0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p < 0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.

Introduction. Invasive infections caused by Candida spp. in critically ill patients may significantly worsen their prognosis, so it is of great importance to establish an early detection and a suitable therapeutic strategy. The objective of this study was to define the differential role of echinocandins in treating certain critical patient profiles. Methodology. A scientific committee of 9 experts in infectious diseases, critical care, microbiology, and hospital pharmacy reviewed the existing evidence on the treatment of candidemia and invasive candidiasis in critically ill patients. After that, a questionnaire with 35 items was elaborated to be agreed by 26 specialists in the aforementioned disciplines using a modified Delphi method. Results. After two rounds of evaluation, a consensus was reached in terms of agreement in 66% of the items. Some of the consensuses achieved included: it is not necessary to adjust the dose of echinocandins during renal replacement therapy; the echinocandins are the empirical and/or directed treatment of choice for candidemia and invasive candidiasis associated with biofilms; these drugs may be used in the antifungal prophylaxis of high-risk liver transplantation. In the absence of additional clinical data, it should be noted that micafungin is the echinocandin with the most available scientific evidence. Conclusions. The experts consulted showed a high degree of agreement on some of the most controversial aspects regarding the management of candidemia and invasive candidiasis in critical patients, which could inform of practical recommendations for their treatment.

Introduction. Clostridium difficile infections have a high recurrence rate, which can complicate the prognosis of affected patients. It is therefore important to establish an early detection and an appropriate therapeutic strategy. The objective of this manuscript was to gather the opinion of an expert group about the predictive factors of poor progression, as well as when to use fidaxomicin in different groups of high-risk patients. Methods. A scientific committee of three experts in infectious diseases reviewed the most recent literature on the management of C. difficile infections, and the use of fidaxomicin. They developed a questionnaire of 23 items for consensus by 15 specialists in this type of infection using a modified Delphi method. Results. The consensus reached by the panelists was 91.3% in terms of agreement. The most important agreements were: recurrence is a risk criterion per se; fidaxomicin is effective and safe for the treatment of infections caused by C. difficile in critical patients, immunosuppressed patients, or patients with chronic renal failure; fidaxomicin is recommended from the first episode of infection to ensure maximum efficacy in patients with well-contrasted recurrence risk factors. Conclusions. The experts consulted showed a high degree of agreement on topics related to the selection of patients with poorer prognosis, as well as on the use of fidaxomicin in groups of high-risk patients, either in the first line or in situations of recurrence.

The natural history of COVID-19 and predictors of mortality in older adults need to be investigated to inform clinical operations and healthcare policy planning. A retrospective study took place in 80 long-term nursing homes in Catalonia, Spain collecting data from March 1st to May 31st, 2020. Demographic and clinical data from 2,092 RT-PCR confirmed cases of SARS-CoV-2 infection were registered, including structural characteristics of the facilities. Descriptive statistics to describe the demographic, clinical, and molecular characteristics of our sample were prepared, both overall and by their symptomatology was performed and an analysis of statistically significant bivariate differences and constructions of a logistic regression model were carried out to assess the relationship between variables. The incidence of the infection was 28%. 71% of the residents showed symptoms. Five major symptoms included: fever, dyspnea, dry cough, asthenia and diarrhea. Fever and dyspnea were by far the most frequent (50% and 28%, respectively). The presentation was predominantly acute and symptomatology persisted from days to weeks (mean 9.1 days, SD = 10,9). 16% of residents had confirmed pneumonia and 22% required hospitalization. The accumulated mortality rate was 21.75% (86% concentrated during the first 28 days at onset). A multivariate logistic regression analysis showed a positive predictive value for mortality for some variables such as age, pneumonia, fever, dyspnea, stupor refusal to oral intake and dementia (p

Since the outbreak of COVID-19 pandemic, many national and international surgical societies have produced guidelines regarding the management of surgical patients. During the mitigation phase of the pandemic, most documents suggested to consider postponing elective procedures, unless this might have impacted the life expectancy of patients. As awareness and knowledge about COVID-19 are gradually increasing, and as we enter a phase when surgical services are resuming their activities, surgical strategies have to adapt to this rapidly evolving scenario. This is particularly relevant when considering screening policies and the associated findings. We herein describe a risk-based approach to the management of patients with surgical diseases, which might be useful in order to limit the risks for healthcare workers and patients, while allowing for resuming elective surgical practice safely.

Background Beta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE. Methods The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators. Results Among 1336 definite cases of streptococcal IE, 823 were caused by VGS and 147 by BHS. Patients with BHS IE had a lower prevalence of native valve (P < .005) and congenital heart disease predisposition (P = .002), but higher prevalence of implantable cardiac device predisposition (P < .005). Clinically, they were more likely to present acutely (P < .005) and with fever (P = .024). BHS IE was more likely to be complicated by stroke and other systemic emboli (P < .005). The overall in-hospital mortality of BHS IE was significantly higher than that of VGS IE (P = .001). In univariate analysis, variables associated with in-hospital mortality for BHS IE were age (odds ratio [OR], 1.044; P = .004), prosthetic valve IE (OR, 3.029; P = .022), congestive heart failure (OR, 2.513; P = .034), and stroke (OR, 3.198; P = .009). Conclusions BHS IE is characterized by an acute presentation and higher rate of stroke, systemic emboli, and in-hospital mortality than VGS IE. Implantable cardiac devices as a predisposing factor were more often found in BHS IE compared with VGS IE.

Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0–7 [low mortality score] vs 8–15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0–33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33–0·62]; p

[Background] Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality., [Methods] A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC., [Results] The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18–5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21–3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02–6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24–6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69–5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72–8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58–4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of, [Conclusions] We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality., This study was funded by: the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III co-financed by the European Development Regional Fund ‘A way to achieve Europe’ ERDF, the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), FIS grant PI10/02021 and FIS grant PI14/01832. B. G. G., J. R. B., A. P. and Y. C. also received funds from the COMBACTE-CARE project, Innovative Medicines Initiative (IMI), the European Union’s Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies. R. A. B. was also supported in part by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program and the Geriatric Research Education and Clinical Center VISN 10 (VISN 10 GRECC), and the NIAID of the NIH under award numbers R01AI072219 and R01AI063517.

We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts. PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies.

Purpose: Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce. Methods: We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011–2013) including patients from ICU, medical, and surgical wards. Results: A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) hadconcomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64 %) and C. glabrata (n = 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03–1.07, P\0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01–1.08, P = 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02–2.89, P = 0.019), septic shock (OR 3.29, 95 % CI 1.88–5.86, P\0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01–5.63, P\0.001) wereassociated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy. Conclusions: Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.