Prevalence and Prognostic Impact of Stroke in a National Cohort of Infective Endocarditis.

BACKGROUND: Stroke is a common complication of infective endocarditis (IE). Our aim was to describe the prevalence and prognostic impact of stroke in a national prospective cohort of IE. METHODS: Consecutive inclusion at 46 Spanish hospitals between 2008 and 2021. RESULTS: Out of 5667 IE cases, 1125 had acute stroke (19.8%): 811 ischemic strokes (618 cardioembolic strokes, 193 cardioembolic strokes with hemorrhagic transformation, 4 transient ischemic attacks, 3 lacunar infarctions), 125 intracranial hemorrhages, and 29 other neurological complications (cerebral abscesses, encephalitis, meningitis, seizures). Compared to patients without stroke, those with stroke had a similar mean age (69 years) but were more frequently female (68.2% vs. 63.7%, p=0.04) and had a higher incidence of intracardiac complications (35% vs 30%, p=0.01), surgical indication (69.9% vs 65.9%, p=0.001), in-hospital mortality (40.9% vs. 22.0%, p<0.001), and one-year mortality (46.2% vs 27.9%, p<0.001). The following variables were independently associated with stroke: mitral location (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.34-1.8, p<0.001), vascular phenomenon (OR 2.9, 95% CI 2.4-3.6, p=0.0001), acute renal failure (OR 1.2, 95% CI 1.0-1.4, p=0.021), septic shock (OR 1.3, CI 1.1-1.6, p=0.007), sepsis (OR 1.3, CI 1.1-1.6, p=0.005), surgery indicated but not performed (OR 1.4, 95% CI 1.2-1.7, p<0.001), community-acquired IE (OR 1.2, 95% CI 1-1.4, p=0.017), and peripheral embolization (OR 1.6, CI 1.4-1.9, p <0.001). Stroke was an independent predictor of in-hospital (OR 2.1, 95% CI: 1.78-2.51, p<0.001) and one-year mortality (hazard ratio 1.9, 95% CI 1.6-2.5). CONCLUSIONS: One fifth of patients with IE have concomitant stroke. Stroke is associated with mortality.

The Clinical Challenge of Prosthetic Valve Endocarditis: JACC Focus Seminar 3/4.

During the past 6 decades, there have been numerous changes in prosthetic valve endocarditis (PVE), currently affecting an older population and increasing in incidence in patients with transcatheter-implanted valves. Significant microbiologic (molecular biology) and imaging diagnostic (fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography) advances have been incorporated into the 2023 Duke-International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria, thus increasing the diagnostic sensitivity for PVE without sacrificing specificity in validation studies. PVE is a life-threatening disease requiring management by multidisciplinary endocarditis teams in cardiac centers to improve outcomes. Novel surgical options are now available, and an increasing set of patients may avoid surgical intervention despite indication. Selected patients may complete parenteral or oral antimicrobial treatment at home. Finally, patients with prosthetic valves implanted surgically or by the transcatheter approach are candidates for antibiotic prophylaxis before invasive dental procedures.

Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Infective Endocarditis After Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. METHODS: Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. RESULTS: A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P < .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P < .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P < .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P < .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). CONCLUSIONS: Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Expert Opinion on Dose Regimen and Therapeutic Drug Monitoring for Long-Term Use of Dalbavancin: Expert Review Panel.

BACKGROUND: Dalbavancin is a lipoglycopeptide with a long elimination half-life and is currently licensed for the treatment of acute bacterial skin and skin structure infections in adults. Dalbavancin's potential in treating off-label complex Gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking. OBJECTIVES: This study aimed to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require > 2 weeks of treatment. METHODS: A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin, which highlighted the heterogeneity in the regimens that were used. RESULTS: After review of the survey data and recent literature, this study presents expert panel proposals that accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to or exceeding 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3000 mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring > 2 weeks of treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in cases of renal failure. Specific dosing recommendations for other special populations require further investigation. CONCLUSIONS: These proposals based on expert opinion have been defined to encourage best practice with dalbavancin, to optimise its administration beyond the current approved licenced dose across different healthcare settings.

The three-noes right-sided infective endocarditis: An unrecognized type of right-sided endocarditis.

The "3 noes right-sided infective endocarditis" (3no-RSIE: no left-sided, no drug users, no cardiac devices) was first described more than a decade ago. We describe the largest series to date to characterize its clinical, microbiological, echocardiographic and prognostic profile. Eight tertiary centers with surgical facilities participated in the study. Patients with right-sided endocarditis without left sided involvement, absence of drug use history and no intracardiac electronic devices were retrospectively included in a multipurpose database. A total of 53 variables were analyzed in every patient. We performed a univariate analysis of in-hospital mortality to determine variables associated with worse prognosis. the study was comprised of 100 patients (mean age 54.1 ± 20 years, 65% male) with definite 3no-RSIE were included (selected from a total of 598 patients with RSIE of all the series, which entails a 16.7% of 3no-RSIE). Most of the episodes were community-acquired (72%), congenital cardiopathies were frequent (32% of the group of patients with previous known predisposing heart disease) and fever was the main manifestation at admission (85%). The microbiological profile was led by Staphylococci spp (52%). Vegetations were detected in 94% of the patients. Global in-hospital mortality was 19% (5.7% in patients operated and 26% in patients who received only medical treatment, P < .001). Non-community acquired infection, diabetes mellitus, right heart failure, septic shock and acute renal failure were more common in patients who died. the clinical profile of 3no-RSIE is closer to other types of RSIE than to LSIE, but mortality is higher than that reported on for other types of RSIE. Surgery may play an important role in improving outcome.

Impact of Intermediate Susceptibility to Penicillin on Antimicrobial Treatment and Outcomes of Endocarditis Caused by Viridans and Gallolyticus Group Streptococci.

BACKGROUND: Evidence supporting combination treatment with a beta-lactam plus an aminoglycoside (C-BA) for endocarditis caused by viridans and gallolyticus group streptococci (VGS-GGS) with intermediate susceptibility to penicillin (PENI-I) is lacking. We assessed the clinical characteristics and outcomes of PEN-I VGS-GGS endocarditis and compared the effectiveness and safety of C-BA with third-generation cephalosporin monotherapy. METHODS: Retrospective analysis of prospectively collected data of a cohort of definite endocarditis caused by penicillin-susceptible and PENI-I VGS-GGS (penicillin minimum inhibitory concentration ranging from 0.25 to 2 mg/L) between 2008 and 2018 in 40 Spanish hospitals. We compared cases treated with monotherapy or with C-BA and performed multivariable analyses of risk factors for in-hospital and 1-year mortality. RESULTS: A total of 914 consecutive cases of definite endocarditis caused by VGS-GGS with complete or intermediate susceptibility to penicillin were included. A total of 688 (75.3%) were susceptible to penicillin and 226 (24.7%) were PENI-I. Monotherapy was used in 415 (45.4%) cases (cephalosporin in 331 cases) and 499 (54.6%) cases received C-BA. In-hospital mortality was 11.9%, and 190 (20.9%) patients developed acute kidney injury. Heart failure (odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.37-26.87; P = .018), central nervous system emboli (OR: 9.83; 95% CI: 2.17-44.49; P = .003) and intracardiac abscess (OR: 13.47; 95% CI: 2.24-81.08; P = .004) were independently associated with in-hospital mortality among PEN-I VGS-GGS cases, while monotherapy was not (OR: 1.01; 95% CI: .26-3.96; P = .982). CONCLUSIONS: Our findings support the use of cephalosporin monotherapy in PEN-I VGS-GGS endocarditis in order to avoid nephrotoxicity without adversely affecting patient outcomes.

Reappraisal of [18F]FDG-PET/CT for diagnosis and management of cardiac implantable electronic device infections.

INTRODUCTION AND OBJECTIVES: The role of [18F]FDG-PET/CT in cardiac implantable electronic device (CIED) infections requires better evaluation, especially in the diagnosis of systemic infections. We aimed to determine the following: a) the diagnostic accuracy of [18F]FDG-PET/CT in each CIED topographical region, b) the added value of [18F]FDG-PET/CT over transesophageal echocardiography (TEE) in diagnosing systemic infections, c) spleen and bone marrow uptake in differentiating isolated local infections from systemic infections, and d) the potential application of [18F]FDG-PET/CT in follow-up. METHODS: Retrospective single-center study including 54 cases and 54 controls from 2014 to 2021. The Primary endpoint was the diagnostic yield of [18F]FDG-PET/CT in each topographical CIED region. Secondary analyses described the performance of [18F]FDG-PET/CT compared with that of TEE in systemic infections, bone marrow and spleen uptake in systemic and isolated local infections, and the potential application of [18F]FDG-PET/CT in guiding cessation of chronic antibiotic suppression when completed device removal is not performed. RESULTS: We analyzed 13 (24%) isolated local infections and 41 (76%) systemic infections. Overall, the specificity of [18F]FDG-PET/CT was 100% and sensitivity 85% (79% pocket, 57% subcutaneous lead, 22% endovascular lead, 10% intracardiac lead). When combined with TEE, [18F]FDG-PET/CT increased definite diagnosis o fsystemic infections from 34% to 56% (P=.04). Systemic infections with bacteremia showed higher spleen (P=.05) and bone marrow metabolism (P=.04) than local infections. Thirteen patients without complete device removal underwent a follow-up [18F]FDG-PET/CT, with no relapses after discontinuation of chronic antibiotic suppression in 6 cases with negative follow-up [18F]FDG-PET/CT. CONCLUSIONS: The sensitivity of [18F]FDG-PET/CT for evaluating CIED infections was high in local infections but much lower in systemic infections. However, accuracy increased when [18F]FDG-PET/CT was combined with TEE in endovascular lead bacteremic infection. Spleen and bone marrow hypermetabolism could differentiate bacteremic systemic infection from local infection. Although further prospective studies are needed, follow-up [18F]FDG-PET/CT could play a potential role in the management of chronic antibiotic suppression therapy when complete device removal is unachievable.

Species and biotypes of Streptococcus bovis causing infective endocarditis / Especies y biotipos de Streptococcus bovis causantes de endocarditis infecciosa

Introduction: Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticus susp. gallolyticus are well known; there are hardly any descriptions of IE caused by other species or biotypes. Methods: Retrospective cohort study, from 1990 to 2019, of all SBEC IE in adults in three Spanish hospitals, Lugo (LH), Barcelona (BH) and Ferrol (FH) where the population is mainly rural, urban and mixed, respectively. The incidence of IE was analyzed in 3 areas. Clinical characteristics of IE (277 cases, 258 biotyped) were compared according to SBEC species and biotypes. Results: There are significant differences between the incidence of SBEC IE in HL (27.9/106) vs. HF and HB (8.8 and 7,1, respectively, p<0.001). We found significant differences (SbI vs. SbII) in mean age (68.5 vs. 73 years; p<0.01), duration of symptoms before diagnosis (46.9±46.5 vs. 30.4±40.9 days; p<0.01), presence of comorbidities: 39.1% (78) vs. 54.2% (32; p<0.04), predisposing heart illness:62.3% (124) vs. 81.3% (48; p<0.006), particularly, prosthetic or intravascular devices IE: 24.6% (49) vs. 52.4% (31; p<0.001), bi-valve involvement:23.6% (47) vs. 11.8% (7; p<0.05) and heart failure: 24.6% (49) vs. 38.9% (23; p<0.03). There were no significant differences in embolic events, need for surgery or mortality. The association with CRC was high in both groups: 77.7% vs. 66.6%. Conclusions: IE due to SBEC has geographical variations in incidence and different clinical characteristics among biotypes. The association with CRC was high.(AU)

Introducción: El complejo Streptococcus bovis/equinus (SBEC) es una de las principales causas de endocarditis infecciosa (EI), aunque su incidencia es muy variable según la zona geográfica. Las características de EI causada por Streptococcus gallolyticus subsp. gallolyticus son bien conocidas; apenas hay descripciones de EI causada por otras especies o biotipos. Métodos: Estudio de cohorte retrospectivo, desde 1990 hasta 2019, de todas las EI por SBEC en adultos en 3 hospitales españoles, Lugo (LH), Barcelona (BH) y Ferrol (FH) donde la población es mayoritariamente rural, urbana y mixta, respectivamente. Se analizó la incidencia de EI en 3 áreas. Se compararon las características clínicas de EI (277 casos, 258 biotipados) según las especies y biotipos de SBEC. Resultados: Existen diferencias significativas entre la incidencia de EI por SBEC en HL (27,9/106) vs. HF y HB (8,8 y 7,1, respectivamente, p<0,001). Encontramos diferencias significativas (SbI vs. SbII) en edad media (68,5 vs. 73 años; p<0,01), duración de los síntomas antes del diagnóstico (46,9±46,5 vs. 30,4±40,9 días; p<0,01); comorbilidades: 39,1 (78) vs. 54,2% (32; p<0,04); enfermedad cardíaca predisponente: 62,3 (124) vs. 81,3% (48; p<0,006), en particular, EI protésica o sobre dispositivos intravasculares: 24,6 (49) vs. 52,4% (31; p<0,001); afectación bivalva: 23,6 (47) vs. 11,8% (7; p<0,05) e insuficiencia cardiaca: 24,6 (49) vs. 38,9% (23; p<0,03). No hubo diferencias significativas en cuanto a eventos embólicos, necesidad de cirugía o mortalidad. La asociación con el CCR fue alta en ambos grupos: 77,7 vs. 66,6%. Conclusiones: La EI por SBEC tiene variaciones geográficas en la incidencia y diferentes características clínicas entre los biotipos. La asociación con el CCR fue elevada.(AU)

Epidemiological Changes and Improvement in Outcomes of Infective Endocarditis in Europe in the Twenty-First Century: An International Collaboration on Endocarditis (ICE) Prospective Cohort Study (2000-2012).

INTRODUCTION: Infective endocarditis (IE) has undergone important changes in its epidemiology worldwide. METHODS: The study aimed to compare IE epidemiological features and outcomes according to predefined European regions and between two different time periods in the twenty-first century. RESULTS: IE cases from 13 European countries were included. Two periods were considered: 2000-2006 and 2008-2012. Two European regions were considered, according to the United Nations geoscheme for Europe: Southern (SE) and Northern-Central Europe (NCE). Comparisons were performed between regions and periods. A total of 4195 episodes of IE were included, 2113 from SE and 2082 from NCE; 2787 cases were included between 2000 and 2006 and 1408 between 2008 and 2012. Median (IQR) age was 63.7 (49-74) years and 69.4% were males. Native valve IE (NVE), prosthetic valve IE (PVE), and device-related IE were diagnosed in 68.3%, 23.9%, and 7.8% of cases, respectively; 52% underwent surgery and 19.3% died during hospitalization. NVE was more prevalent in NCE, whereas device-related IE was more frequent in SE. Higher age, acute presentation, hemodialysis, cancer, and diabetes mellitus all were more prevalent in the second period. NVE decreased and PVE and device-related IE both increased in the second period. Surgical treatment also increased from 48.7% to 58.4% (p < 0.01). In-hospital and 6-month mortality rates were comparable between regions and significantly decreased in the second period. CONCLUSIONS: Despite an increased complexity of IE cases, prognosis improved in recent years with a significant decrease in 6-month mortality. Outcome did not differ according to the European region (SE versus NCE).

Emerging issues on Staphylococcus aureus endocarditis and the role in therapy of daptomycin plus fosfomycin.

INTRODUCTION: Methicillin-resistant and -susceptible Staphylococcus aureus (MRSA/MSSA) infections are a major global health-care problem. Bacteremia with S. aureus exhibits high rates of morbidity and mortality and can cause complicated infections such as infective endocarditis (IE). The emerging resistance profile of S. aureus is worrisome, and several international agencies have appealed for new treatment approaches to be developed. AREAS COVERED: Daptomycin presents a rapid bactericidal effect against MRSA and has been considered at least as effective as vancomycin in treating MRSA bacteremia. However, therapy failure is often related to deep-seated infections, e.g. endocarditis, with high bacterial inocula and daptomycin regimens <10 mg/kg/day. Current antibiotic options for treating invasive S. aureus infections have limitations in monotherapy. Daptomycin in combination with other antibiotics, e.g. fosfomycin, may be effective in improving clinical outcomes in patients with MRSA IE. EXPERT OPINION: Exploring therapeutic combinations has shown fosfomycin to have a unique mechanism of action and to be the most effective option in preventing the onset of resistance to and optimizing the efficacy of daptomycin, suggesting the synergistic combination of fosfomycin with daptomycin is a useful alternative treatment option for MSSA or MRSA IE.

Pseudomonas aeruginosa Bloodstream Infection, Resistance, and Mortality: Do Solid Organ Transplant Recipients Do Better or Worse?

BACKGROUND: The prevalence of antimicrobial resistance of Pseudomonas aeruginosa (P. aeruginosa) in solid organ transplant (SOT) recipients is higher than that of the general population. However, the literature supporting this statement is scarce. Identifying patients at risk of carbapenem resistance (CR) is of great importance, as CR strains more often receive inappropriate empiric antibiotic therapy, which is independently associated with mortality in bloodstream infections (BSIs). METHODS: We prospectively recorded data from all consecutive BSIs from January 1991 to July 2019 using a routine purpose-designed surveillance database. The following variables were included: age, sex, type of transplant, use of vascular and urinary catheters, presence of neutropenia, period of diagnosis, treatment with steroids, origin of BSI, source of bacteremia, septic shock, ICU admission, mechanical ventilation, previous antibiotic treatment, treatment of bacteremia, and 30-day all-cause mortality. RESULTS: We identified 2057 episodes of P. aeruginosa BSI. Of these, 265 (13%) episodes corresponded to SOT recipients (130 kidney transplants, 105 liver, 9 hearts, and 21 kidney-pancreas). Hematologic malignancy [OR 2.71 (95% CI 1.33-5.51), p = 0.006] and prior carbapenem therapy [OR 2.37 (95% CI 1.46-3.86), p < 0.001] were associated with a higher risk of having a CR P. aeruginosa BSI. Age [OR 1.03 (95% CI 1.02-1.04) p < 0.001], urinary catheter [OR 2.05 (95% CI 0.37-3.06), p < 0.001], shock at onset [OR 6.57 (95% CI 4.54-9.51) p < 0.001], high-risk source [OR 4.96 (95% CI 3.32-7.43) p < 0.001], and bacteremia caused by CR strains [OR 1.53 (95% CI 1.01-2.29) p = 0.036] were associated with increased mortality. Correct empirical therapy was protective [OR 0.52 (95% CI 0.35-0.75) p = 0.001]. Mortality at 30 days was higher in non-SOT patients (21% vs. 13%, p = 0.002). SOT was not associated with a higher risk of having a CR P. aeruginosa BSI or higher mortality. CONCLUSIONS: In our cohort of 2057 patients with P. aeruginosa BSIs, hematologic malignancies and previous carbapenem therapy were independently associated with a risk of presenting CR P. aeruginosa BSI. Age, urinary catheter, high-risk source, bacteremia caused by carbapenem-resistant strains, and severity of the infection were independently associated with mortality, whereas correct empirical therapy was a protective factor. An increasing trend in the resistance of P. aeruginosa was found, with >30% of the isolates being resistant to carbapenems in the last period. SOT was not associated with a higher risk of carbapenem-resistant BSIs or higher mortality.

Species and biotypes of Streptococcus bovis causing infective endocarditis.

INTRODUCTION: Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticus susp. gallolyticus are well known; there are hardly any descriptions of IE caused by other species or biotypes. METHODS: Retrospective cohort study, from 1990 to 2019, of all SBEC IE in adults in three Spanish hospitals, Lugo (LH), Barcelona (BH) and Ferrol (FH) where the population is mainly rural, urban and mixed, respectively. The incidence of IE was analyzed in 3 areas. Clinical characteristics of IE (277 cases, 258 biotyped) were compared according to SBEC species and biotypes. RESULTS: There are significant differences between the incidence of SBEC IE in HL (27.9/106) vs. HF and HB (8.8 and 7,1, respectively, p<0.001). We found significant differences (SbI vs. SbII) in mean age (68.5 vs. 73 years; p<0.01), duration of symptoms before diagnosis (46.9±46.5 vs. 30.4±40.9 days; p<0.01), presence of comorbidities: 39.1% (78) vs. 54.2% (32; p<0.04), predisposing heart illness:62.3% (124) vs. 81.3% (48; p<0.006), particularly, prosthetic or intravascular devices IE: 24.6% (49) vs. 52.4% (31; p<0.001), bi-valve involvement:23.6% (47) vs. 11.8% (7; p<0.05) and heart failure: 24.6% (49) vs. 38.9% (23; p<0.03). There were no significant differences in embolic events, need for surgery or mortality. The association with CRC was high in both groups: 77.7% vs. 66.6%. CONCLUSIONS: IE due to SBEC has geographical variations in incidence and different clinical characteristics among biotypes. The association with CRC was high.

Molecular Epidemiology, Antimicrobial Susceptibility, and Clinical Features of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections over 30 Years in Barcelona, Spain (1990-2019).

Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSI) are a significant cause of mortality. We analysed the evolution of the molecular and clinical epidemiology of MRSA-BSI (n = 784) in adult patients (Barcelona, 1990−2019). Isolates were tested for antimicrobial susceptibility and genotyped (PFGE), and a selection was sequenced (WGS) to characterise the pangenome and mechanisms underlying antimicrobial resistance. Increases in patient age (60 to 71 years), comorbidities (Charlson's index > 2, 10% to 94%), community-onset healthcare-associated acquisition (9% to 60%), and 30-day mortality (28% to 36%) were observed during the 1990−1995 and 2014−2019 periods. The proportion of catheter-related BSIs fell from 57% to 20%. Current MRSA-BSIs are caused by CC5-IV and an upward trend of CC8-IV and CC22-IV clones. CC5 and CC8 had the lowest core genome proportions. Antimicrobial resistance rates fell, and only ciprofloxacin, tobramycin, and erythromycin remained high (>50%) due to GyrA/GrlA changes, the presence of aminoglycoside-modifying enzymes (AAC(6')-Ie-APH(2″)-Ia and ANT(4')-Ia), and mph(C)/msr(A) or erm (C) genes. Two CC22-IV strains showed daptomycin resistance (MprF substitutions). MRSA-BSI has become healthcare-associated, affecting elderly patients with comorbidities and causing high mortality rates. Clonal replacement with CC5-IV and CC8-IV clones resulted in lower antimicrobial resistance rates. The increased frequency of the successful CC22-IV, associated with daptomycin resistance, should be monitored.