Antonio Plata

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}

Ampicillin Plus Ceftriaxone Is as Effective as Ampicillin Plus Gentamicin for Treating Enterococcus faecalis Infective Endocarditis

BACKGROUND The aim of this study was to compare the effectiveness of the ampicillin plus ceftriaxone (AC) and ampicillin plus gentamicin (AG) combinations for treating Enterococcus faecalis infective endocarditis (EFIE). METHODS An observational, nonrandomized, comparative multicenter cohort study was conducted at 17 Spanish and 1 Italian hospitals. Consecutive adult patients diagnosed of EFIE were included. Outcome measurements were death during treatment and at 3 months of follow-up, adverse events requiring treatment withdrawal, treatment failure requiring a change of antimicrobials, and relapse. RESULTS A larger percentage of AC-treated patients (n = 159) had previous chronic renal failure than AG-treated patients (n = 87) (33% vs 16%, P = .004), and AC patients had a higher incidence of cancer (18% vs 7%, P = .015), transplantation (6% vs 0%, P = .040), and healthcare-acquired infection (59% vs 40%, P = .006). Between AC and AG-treated EFIE patients, there were no differences in mortality while on antimicrobial treatment (22% vs 21%, P = .81) or at 3-month follow-up (8% vs 7%, P = .72), in treatment failure requiring a change in antimicrobials (1% vs 2%, P = .54), or in relapses (3% vs 4%, P = .67). However, interruption of antibiotic treatment due to adverse events was much more frequent in AG-treated patients than in those receiving AC (25% vs 1%, P < .001), mainly due to new renal failure (≥25% increase in baseline creatinine concentration; 23% vs 0%, P < .001). CONCLUSIONS AC appears as effective as AG for treating EFIE patients and can be used with virtually no risk of renal failure and regardless of the high-level aminoglycoside resistance status of E. faecalis.

Clinical Findings, Therapeutic Approach, and Outcome of Brucellar Vertebral Osteomyelitis

BACKGROUND Osteoarticular complications are the most common focal complications of brucellosis. Although vertebral osteomyelitis is the most frequent location in adults >30 years of age, little information is available about this serious complication of brucellosis, and great confusion surrounds its prognosis and the most appropriate treatment. METHODS We undertook a descriptive, retrospective, observational study of 96 patients who received a diagnosis of brucella vertebral osteomyelitis from September 1982 through December 2005 at a tertiary care hospital. All of the patients were treated for 3 months, after which they were followed up monthly for the first 3 months and then at 2-month intervals for the subsequent 6 months. RESULTS The incidence of vertebral osteomyelitis was 10.4%. The mean diagnostic delay was 12.7 weeks. Inflammatory spinal pain (occurring in 94.8% of patients) and fever (91.7%) were the most relevant clinical characteristics. Eight patients (8.3%) had motor weakness or paralysis. Paravertebral masses, epidural masses, and psoas abscesses were detected in 45.8%, 27.1%, and 10.4% of patients, respectively. Sixty-three patients (65.6%) received medication only, and 33 (34.4%) required surgical therapy in addition to medication. Twenty percent of patients experienced therapeutic failure. Attributable mortality was 2.1%, and severe functional sequelae were apparent in 6.2% of the patients. No significant differences were seen between patients who were treated with doxycycline-streptomycin and those treated with doxycycline-rifampicin. CONCLUSIONS Vertebral osteomyelitis is a serious complication of brucellosis. It generates a high rate of therapeutic failure and functional sequelae. In the absence of more-powerful controlled studies, the duration of treatment of brucellar vertebral osteomyelitis should be 3 months.

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.

Streptococcus agalactiae left-sided infective endocarditis. Analysis of 27 cases from a multicentric cohort

SUMMARY OBJECTIVE To evaluate the current trends in the clinical characteristics and the prognosis of Streptococcus agalactiae infective endocarditis (IE), uncommon disease associated with high mortality. METHODS Descriptive analysis of 27 cases of a large cohort (961 episodes) of infective endocarditis collected in seven hospitals of Andalusia (Spain) between 1984 and 2008. RESULTS Native valves were affected in most cases (85. 2%), multiple valves were frequently involved (22.2%). The median age of the patients was 65 (51-76) years (59.3% men), with a comorbidity, according to the Charlson index, of 2.6+/-2.3. The most frequent underlying diseases were diabetes mellitus (25.9%), chronic obstructive pulmonary disease (14.8%), neoplasms (14.8%), urological disorders (11%) and chronic liver disease (11%). Clinical presentation was characterized by rapid worsening (median of 9 (5.7-15) days from onset of symptoms until diagnosis), a high rate of embolisms (37%) and cardiac complications (abscesses, fistulas or valve rupture) - 37% of cases. Surgery was performed in 12 patients (44.4%) and a high mortality (40.7%) was observed. CONCLUSION S. agalactiae IE is a serious disease with aggressive course and high mortality rate and affects patients with debilitating diseases. We must be alert of the development of complications and consider early valve surgery when it is necessary.

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.

Endocarditis en válvulas nativas izquierdas por estafilococos coagulasa negativos: una entidad en alza

OBJECTIVES: To describe the epidemiological, clinical, and prognostic characteristics of patients with left-sided native valve endocarditis (LNVE) caused by coagulase-negative staphylococci (CoNS). PATIENTS AND METHOD: Prospective multicenter study of endocarditis cases reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2005. RESULTS: Among 470 cases of LNVE, 39 (8.3%) were caused by CoNS, a number indicating a 30% increase in the incidence of this infection over the last decade. The mean age of affected patients was 58.32 +/- 15 years and 27 (69.2%) were men. Twenty-one patients (53.8%) had previous known valve disease and half the episodes were considered nosocomial (90% of them from vascular procedures). Median time interval from the onset of symptoms to diagnosis was 14 days (range: 1-120). Renal failure (21 cases, 53.8%), intracardiac damage (11 cases, 28.2%), and central nervous system involvement (10 cases, 25.6%) were the most frequent complications. There were only 3 cases (7.7%) of septic shock. Surgery was performed in 18 patients (46.2%). Nine patients (23.1%) died, overall. Factors associated with higher mortality in the univariate analysis were acute renal failure (P = 0.023), left-sided ventricular failure (P = 0.047), and time prior to diagnosis less than 21 days (P = 0.018). As compared to LNVE due to other microorganisms, the patients were older (P = 0.018), had experienced previous nosocomial manipulation as the source of bacteremia (P < 0.001), and developed acute renal failure more frequently (P = 0.001). Mortality of LNVE due to CoNS was lower than mortality in Staphylococcus aureus infection, but higher than in Streptococcus viridans infection. CONCLUSIONS: Left-sided native valve endocarditis due to CoNS is now increasing because of the ageing of the population. This implies more frequent invasive procedures (mainly vascular) as a consequence of the concomitant disease. Nonetheless, the mortality associated with LNVE due to CoNS does not seem to be greater than infection caused by other pathogens.OBJECTIVES To describe the epidemiological, clinical, and prognostic characteristics of patients with left-sided native valve endocarditis (LNVE) caused by coagulase-negative staphylococci (CoNS). PATIENTS AND METHOD Prospective multicenter study of endocarditis cases reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2005. RESULTS Among 470 cases of LNVE, 39 (8.3%) were caused by CoNS, a number indicating a 30% increase in the incidence of this infection over the last decade. The mean age of affected patients was 58.32 +/- 15 years and 27 (69.2%) were men. Twenty-one patients (53.8%) had previous known valve disease and half the episodes were considered nosocomial (90% of them from vascular procedures). Median time interval from the onset of symptoms to diagnosis was 14 days (range: 1-120). Renal failure (21 cases, 53.8%), intracardiac damage (11 cases, 28.2%), and central nervous system involvement (10 cases, 25.6%) were the most frequent complications. There were only 3 cases (7.7%) of septic shock. Surgery was performed in 18 patients (46.2%). Nine patients (23.1%) died, overall. Factors associated with higher mortality in the univariate analysis were acute renal failure (P = 0.023), left-sided ventricular failure (P = 0.047), and time prior to diagnosis less than 21 days (P = 0.018). As compared to LNVE due to other microorganisms, the patients were older (P = 0.018), had experienced previous nosocomial manipulation as the source of bacteremia (P < 0.001), and developed acute renal failure more frequently (P = 0.001). Mortality of LNVE due to CoNS was lower than mortality in Staphylococcus aureus infection, but higher than in Streptococcus viridans infection. CONCLUSIONS Left-sided native valve endocarditis due to CoNS is now increasing because of the ageing of the population. This implies more frequent invasive procedures (mainly vascular) as a consequence of the concomitant disease. Nonetheless, the mortality associated with LNVE due to CoNS does not seem to be greater than infection caused by other pathogens.

Prognostic factors of infective endocarditis in patients on hemodialysis: A case series from a National Multicenter Registry

BACKGROUND Infective endocarditis (IE) is a severe complication associated with high mortality. OBJECTIVES To examine the clinical characteristics of IE in hemodialysis (HD) patients and to determine prognostic factors related to HD. METHODS From January 2008 to April 2015, 2488 consecutive patients with definite IE were included. Clinical characteristics of IE patients on HD were compared with those of IE patients who were not on HD. RESULTS A total of 126 patients (63% male, median age: 66years; IQR: 54-74years) with IE (5.1%) were on HD. Fifty-two patients died during hospitalization (41%) and 17 additional patients (14%) died during the first year. The rate of patients who underwent surgery during hospitalization was lower in HD patients (38 patients, 30%) than in non-HD patients (1177 patients, 50%; p<0.001). Age >70years (OR: 4.1, 95% CI: 1.7-10), heart failure (OR: 3.3, 95% CI: 1.4-7-6), central nervous system (CNS) vascular events (OR: 6.7, 95% CI: 2.1-22) and septic shock (OR: 4.1, 95% CI: 1.4-12.1) were independently associated with fatal outcome in HD patients. Of the 38 patients who underwent surgery, 15 (39.5%) died during hospitalization. CONCLUSIONS HD patients with IE present a high mortality. Advanced age and complications, such as heart failure, CNS stroke or septic shock, are associated with mortality.

Dalbavancin in the treatment of different gram-positive infections: a real-life experience

Dalbavancin is a lipoglycopeptide with a very prolonged half-life enabling treatment with a single intravenous administration that has been approved to treat complicated skin and soft-tissue infections. Information on the efficacy and safety of dalbavancin in other situations is very scarce. This retrospective study included adult patients who received at least one dose of dalbavancin between 2016 and 2017 in 29 institutions in Spain. The primary objective was to report the use of dalbavancin in clinical practice, including its efficacy and tolerability. The potential impact of dalbavancin on reducing the length of hospital stay and hospital costs was also evaluated. A total of 69 patients received dalbavancin during the study period (58.0% male; median age 63.5 years). Dalbavancin was used to treat prosthetic joint infection (29.0%), acute bacterial skin and skin-structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly caused by Staphylococcus aureus (27 isolates), coagulase-negative staphylococci (24 isolates) and Enterococcus spp. (11 isolates). All but two patients received previous antibiotics for a median of 18 days. Dalbavancin was administered for a median of 21 days (range 7-168 days), and concomitant antimicrobial therapy was prescribed to 25 patients (36.2%). The overall clinical success rate of dalbavancin was 84.1%. Adverse events, mainly mild in intensity, were reported in nine patients. Overall, dalbavancin was estimated to reduce hospitalisation by 1160 days, with an estimated overall cost reduction of €211 481 (€3064 per patient). Dalbavancin appears to be an effective therapy for many serious Gram-positive infections.

Broadened Definition of Health Care–Associated Infective Endocarditis and Risk of Misclassification for Some Community-Acquired Episodes

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