Juan Gálvez-Acebal

Neurological Complications of Infective Endocarditis Risk Factors, Outcome, and Impact of Cardiac Surgery: A Multicenter Observational Study

Background— The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. Methods and Results— This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P<0.01), although only moderate to severe ischemic stroke (HR 1.63) and brain hemorrhage (HR 1.73) were significantly associated with a poorer prognosis. Antimicrobial treatment reduced (by 33% to 75%) the risk of neurological complications. In patients with hemorrhage, mortality was higher when surgery was performed within 4 weeks of the hemorrhagic event (75% versus 40% in later surgery). Conclusions— Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.Background— The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. Methods and Results— This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P <0.01), although only moderate to severe ischemic stroke (HR 1.63) and brain hemorrhage (HR 1.73) were significantly associated with a poorer prognosis. Antimicrobial treatment reduced (by 33% to 75%) the risk of neurological complications. In patients with hemorrhage, mortality was higher when surgery was performed within 4 weeks of the hemorrhagic event (75% versus 40% in later surgery). Conclusions— Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered. # Clinical Perspective {#article-title-46}

Impact of an Evidence-Based Bundle Intervention in the Quality-of-Care Management and Outcome of Staphylococcus aureus Bacteremia

BACKGROUND Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. Several aspects of clinical management have been shown to have significant impact on prognosis. The objective of the study was to identify evidence-based quality-of-care indicators (QCIs) for the management of SAB, and to evaluate the impact of a QCI-based bundle on the management and prognosis of SAB. METHODS A systematic review of the literature to identify QCIs in the management of SAB was performed. Then, the impact of a bundle including selected QCIs was evaluated in a quasi-experimental study in 12 tertiary Spanish hospitals. The main and secondary outcome variables were adherence to QCIs and mortality. Specific structured individualized written recommendations on 6 selected evidence-based QCIs for the management of SAB were provided. RESULTS A total of 287 and 221 patients were included in the preintervention and intervention periods, respectively. After controlling for potential confounders, the intervention was independently associated with improved adherence to follow-up blood cultures (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.78-4.49), early source control (OR, 4.56; 95% CI, 2.12-9.79), early intravenous cloxacillin for methicillin-susceptible isolates (OR, 1.79; 95% CI, 1.15-2.78), and appropriate duration of therapy (OR, 2.13; 95% CI, 1.24-3.64). The intervention was independently associated with a decrease in 14-day and 30-day mortality (OR, 0.47; 95% CI, .26-.85 and OR, 0.56; 95% CI, .34-.93, respectively). CONCLUSIONS A bundle orientated to improving adherence to evidence-based QCIs improved the management of patients with SAB and was associated with reduced mortality.

Prognostic factors in left-sided endocarditis: results from the andalusian multicenter cohort

BackgroundDespite medical advances, mortality in infective endocarditis (IE) is still very high. Previous studies on prognosis in IE have observed conflicting results. The aim of this study was to identify predictors of in-hospital mortality in a large multicenter cohort of left-sided IE.MethodsAn observational multicenter study was conducted from January 1984 to December 2006 in seven hospitals in Andalusia, Spain. Seven hundred and five left-side IE patients were included. The main outcome measure was in-hospital mortality. Several prognostic factors were analysed by univariate tests and then by multilogistic regression model.ResultsThe overall mortality was 29.5% (25.5% from 1984 to 1995 and 31.9% from 1996 to 2006; Odds Ratio 1.25; 95% Confidence Interval: 0.97-1.60; p = 0.07). In univariate analysis, age, comorbidity, especially chronic liver disease, prosthetic valve, virulent microorganism such as Staphylococcus aureus, Streptococcus agalactiae and fungi, and complications (septic shock, severe heart failure, renal insufficiency, neurologic manifestations and perivalvular extension) were related with higher mortality. Independent factors for mortality in multivariate analysis were: Charlson comorbidity score (OR: 1.2; 95% CI: 1.1-1.3), prosthetic endocarditis (OR: 1.9; CI: 1.2-3.1), Staphylococcus aureus aetiology (OR: 2.1; CI: 1.3-3.5), severe heart failure (OR: 5.4; CI: 3.3-8.8), neurologic manifestations (OR: 1.9; CI: 1.2-2.9), septic shock (OR: 4.2; CI: 2.3-7.7), perivalvular extension (OR: 2.4; CI: 1.3-4.5) and acute renal failure (OR: 1.69; CI: 1.0-2.6). Conversely, Streptococcus viridans group etiology (OR: 0.4; CI: 0.2-0.7) and surgical treatment (OR: 0.5; CI: 0.3-0.8) were protective factors.ConclusionsSeveral characteristics of left-sided endocarditis enable selection of a patient group at higher risk of mortality. This group may benefit from more specialised attention in referral centers and should help to identify those patients who might benefit from more aggressive diagnostic and/or therapeutic procedures.

Q fever endocarditis in Spain. Clinical characteristics and outcome.

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

Current management of bloodstream infections.

Bloodstream infection (BSI) is a frequent complication of invasive infections. The presence of bacteremia has therapeutic and prognostic implications. Here we review recent changes in the epidemiology, diagnosis and treatment of BSI (excluding candidemia). The evidence of the impact of healthcare-association in many community-onset episodes and the increase in drug-resistant pathogens causing BSI in the community and hospitals is reviewed. The emergence of molecular methods as an alternative tool for the diagnosis of BSI and novel aspects of clinical management, particularly of some multidrug-resistant organisms. Several quality indicators related to the diagnosis and management of bacteremia in hospitals are proposed.

Effect of Statin Therapy in the Outcome of Bloodstream Infections Due to Staphylococcus aureus: A Prospective Cohort Study

Introduction Statins have pleiotropic effects that could influence the prevention and outcome of some infectious diseases. There is no information about their specific effect on Staphylococcus aureus bacteremia (SAB). Methods A prospective cohort study including all SAB diagnosed in patients aged ≥18 years admitted to a 950-bed tertiary hospital from March 2008 to January 2011 was performed. The main outcome variable was 14-day mortality, and the secondary outcome variables were 30-day mortality, persistent bacteremia (PB) and presence of severe sepsis or septic shock at diagnosis of SAB. The effect of statin therapy at the onset of SAB was studied by multivariate logistic regression and Cox regression analysis, including a propensity score for statin therapy. Results We included 160 episodes. Thirty-three patients (21.3%) were receiving statins at the onset of SAB. 14-day mortality was 21.3%. After adjustment for age, Charlson index, Pitt score, adequate management, and high risk source, statin therapy had a protective effect on 14-day mortality (adjusted OR = 0.08; 95% CI: 0.01–0.66; p = 0.02), and PB (OR = 0.89; 95% CI: 0.27–1.00; p = 0.05) although the effect was not significant on 30-day mortality (OR = 0.35; 95% CI: 0.10–1.23; p = 0.10) or presentation with severe sepsis or septic shock (adjusted OR = 0.89; CI 95%: 0.27–2.94; p = 0.8). An effect on 30-day mortality could neither be demonstrated on Cox analysis (adjusted HR = 0.5; 95% CI: 0.19–1.29; p = 0.15). Conclusions Statin treatment in patients with SAB was associated with lower early mortality and PB. Randomized studies are necessary to identify the role of statins in the treatment of patients with SAB.

Incidence and clinical impact of infective endocarditis after transcatheter aortic valve implantation

AIMS To describe the characteristics of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS This study was performed using the GAMES database, a national prospective registry of consecutive patients with IE in 26 Spanish hospitals. Of the 739 cases of IE diagnosed during the study, 1.3% were post-TAVI IE, and these 10 cases, contributed by five centres, represented 1.1% of the 952 TAVIs performed. Mean age was 80 years. All valves were implanted transfemorally. IE appeared a median of 139 days after implantation. The mean age-adjusted Charlson comorbidity index was 5.45. Chronic kidney disease was frequent (five patients), as were atrial fibrillation (five patients), chronic obstructive pulmonary disease (four patients), and ischaemic heart disease (four patients). Six patients presented aortic valve involvement, and four only mitral valve involvement; the latter group had a higher percentage of prosthetic mitral valves (0% vs. 50%). Vegetations were found in seven cases, and four presented embolism. One patient underwent surgery. Five patients died during follow-up: two of these patients died during the admission in which the valve was implanted. CONCLUSIONS IE is a rare but severe complication after TAVI which affects about 1% of patients and entails a relatively high mortality rate. IE occurred during the first year in nine of the 10 patients.

Community-acquired pneumonia during the first post-pandemic influenza season: A prospective, multicentre cohort study

Summary Objectives To determine the aetiology, clinical features and prognosis of CAP during the first post-pandemic influenza season. We also assessed the factors associated with severe disease and tested the ability of a scoring system for identifying influenza A (H1N1)pdm09-related pneumonia. Methods Prospective cohort study carried out at 10 tertiary hospitals of Spain. All adults hospitalised with CAP from December 01, 2010 to March 31, 2011 were analysed. Results A total of 747 adults with CAP required hospitalisation. The aetiology was determined in 315 (42.2%) patients, in whom 154 (21.9%) were due to bacteria, 125 (16.7%) were due to viruses and 36 (4.8%) were mixed (due to viruses and bacteria). The most frequently isolated bacteria were Streptococccus pneumoniae. Among patients with viral pneumonia, the most common organism identified were influenza A (H1N1)pdm09. Independent factors associated with severe disease were impaired consciousness, septic shock, tachypnea, hyponatremia, hypoxemia, influenza B, and influenza A (H1N1)pdm09. The scoring system evaluated did not differentiate reliably between patients with influenza A (H1N1)pdm09-related pneumonia and those with other aetiologies. Conclusions The frequency of bacterial and viral pneumonia during the first post-pandemic influenza season was similar. The main identified virus was influenza A (H1N1)pdm09, which was associated with severe disease. Although certain presenting clinical features may allow recognition of influenza A (H1N1)pdm09-related pneumonia, it is difficult to express them in a reliable scoring system.

Influence of early surgical treatment on the prognosis of left-sided infective endocarditis: a multicenter cohort study.

OBJECTIVE To analyze the influence of early valve operation on mortality in patients with left-sided infective endocarditis (IE). PATIENTS AND METHODS A multicenter cohort study was carried out between 1990 and 2010. Data from consecutive patients with definite IE and possible left-sided IE were collected. Propensity score matching and adjustment for survivor bias were used to control for confounders. The primary outcome was in-hospital mortality. RESULTS A total of 1019 patients with a mean age of 61 years (interquartile range, 47-71 years) were included. Early surgical treatment was performed in 417 episodes (40.9%). By propensity score, we matched 316 episodes: 158 who underwent early surgical treatment and 158 who did not (medical treatment group). In-hospital mortality and late mortality were lower in the surgically treated group (26.6% vs 41.8%; absolute risk reduction [ARR], -15.2%; P=.004 and 29.7% vs 46.2%; ARR, -16.5%; P=.002, respectively). Operation was independently associated with a lower risk of in-hospital mortality (odds ratio, 0.42; 95% CI, 0.22-0.79; P=.007). Operation was associated with reduced mortality in patients with paravalvular complications (ARR, -40.5%), severe heart failure (ARR, -32%), and native valve endocarditis (ARR, -17.8%). CONCLUSION This study supports the benefit of surgical treatment in patients with left-sided IE carried out during the initial phase of hospitalization, especially in patients with moderate or severe heart failure and paravalvular extension of infection.

Is reduced vancomycin susceptibility a factor associated with poor prognosis in MSSA bacteraemia

OBJECTIVES The known data about the influence of vancomycin MIC on Staphylococcus aureus bacteraemia are contradictory. Our objective was to study the possible impact of vancomycin MIC ≥1.5 mg/L on short- and medium-term mortality. METHODS A prospective cohort study was carried out from March 2008 to January 2011 on adult patients with MSSA bacteraemia admitted to a tertiary hospital located in Seville (Spain). We studied the relationship between vancomycin MIC, accessory gene regulator (agr) type and absence of δ-haemolysin and poor prognosis. All isolates were genotyped by PFGE. Multivariate analysis, including a propensity score for having a vancomycin MIC of ≥1.5 mg/L, was performed by Cox regression. RESULTS One hundred and thirty-five episodes of bacteraemia due to MSSA were included in the analysis. Twenty-nine (21.5%) isolates had a vancomycin MIC of ≥1.5 mg/L by Etest. There were no differences in agr distribution or absence of δ-haemolysin between isolates with reduced vancomycin susceptibility (RVS) and those without. RVS was not more frequent in specific clones; RVS was not associated with higher 14 or 30 day crude mortality (relative risk = 0.44, 95% CI = 0.14-1.35; and relative risk = 1.01, 95% CI = 0.52-1.96) rates, and it did not show higher rates of complicated bacteraemia (14.2% versus 13.8%, P = 0.61). Cox regression analysis did not significantly modify the results for 14 day mortality (HR = 0.39, 95% CI = 0.11-1.34) or 30 day mortality (HR = 0.89, 95% CI = 0.39-2.04). CONCLUSIONS Contrary to previously published data, we did not find a relationship between RVS and higher mortality in patients with MSSA bacteraemia and we did not find a link with higher complicated bacteraemia rates.