Clinical and prognostic differences between methicillin-resistant and methicillin-susceptible Staphylococcus aureus infective endocarditis.

BACKGROUND: S. aureus (SA) infective endocarditis (IE) has a very high mortality, attributed to the age and comorbidities of patients, inadequate or delayed antibiotic treatment, and methicillin resistance, among other causes. The main study objective was to analyze epidemiological and clinical differences between IE by methicillin-resistant versus methicillin-susceptible SA (MRSA vs. MSSA) and to examine prognostic factors for SA endocarditis, including methicillin resistance and vancomycin minimum inhibitory concentration (MIC) values > 1 µg/mL to MRSA. METHODS: Patients with SA endocarditis were consecutively and prospectively recruited from the Andalusia endocarditis cohort between 1984 and January 2017. RESULTS: We studied 437 patients with SA endocarditis, which was MRSA in 13.5% of cases. A greater likelihood of history of COPD (OR 3.19; 95% CI 1.41-7.23), invasive procedures, or recognized infection focus in the 3 months before IE onset (OR 2.9; 95% CI 1.14-7.65) and of diagnostic delay (OR 3.94; 95% CI 1.64-9.5) was observed in patients with MRSA versus MSSA endocarditis. The one-year mortality rate due to SA endocarditis was 44.3% and associated with decade of endocarditis onset (1985-1999) (OR 8.391; 95% CI (2.82-24.9); 2000-2009 (OR 6.4; 95% CI 2.92-14.06); active neoplasm (OR 6.63; 95% CI 1.7-25.5) and sepsis (OR 2.28; 95% CI 1.053-4.9). Methicillin resistance was not associated with higher IE-related mortality (49.7 vs. 43.1%; p = 0.32). CONCLUSION: MRSA IE is associated with COPD, previous invasive procedure or recognized infection focus, and nosocomial or healthcare-related origin. Methicillin resistance does not appear to be a decisive prognostic factor for SA IE.

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.

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.

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

BACKGROUND: Despite 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. METHODS: An 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. RESULTS: The 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. CONCLUSIONS: Several 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.

[Left-sided native valve endocarditis by coagulase-negative staphylococci: an emerging disease]. / 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.

Endocarditis en válvulas nativas izquierdas por estafilococos coagulasa negativos: una entidad en alza / Left-sided native valve endocarditis by coagulase-negative staphylococci: an emerging disease

Describir las características epidemiológicas, clínicas y pronósticas de la endocarditis sobre válvula nativa izquierda (EVNI) por estafilococos coagulasa negativos (ECN).PACIENTES Y MÉTODO. Estudio prospectivo multicéntrico delas endocarditis recogidas en la Cohorte Andaluza para el Estudio de las Infecciones Cardiovasculares en los años1984-2005.RESULTADOS. De las 470 EVNI recogidas, 39 (8,3%) fueron causadas por ECN con un aumento del 30% de incidencia en la última década. La edad media fue 58,32 15 años,27 pacientes (69,2%) eran varones y 21 (53,8%) tenían valvulopatía previa. En la mitad de los casos el origen se consideró nosocomial (el 90% tras manipulaciones vasculares). La mediana del intervalo entre la aparición de síntomas y el diagnóstico fue de 14 días (rango: 1-120). Las complicaciones más frecuentes fueron: insuficiencia renal (53,8%), complicaciones cardíacas (28,2%), afectación del sistema nervioso central (25,6%) y shock séptico (7%). La cirugía fue necesaria en 18 pacientes (46,2%) y 9 (23,1%) fallecieron. Los factores que se asociaron con una mortalidad mayor fueron la insuficiencia renal aguda (p 0,023), el fallo ventricular izquierdo (p 0,047) y un tiempo de evolución previo al diagnóstico inferior a 21 días (p 0,018). La EVNI por ECN ocurre en pacientes más ancianos (p 0,018), es con mayor frecuencia de origen nosocomial (p < 0,001) y desarrolla más fracaso renal agudo (p 0,001). La mortalidad es menor que la EVNI producida por Staphylococcus aureus (47,7%), pero mayor que la EVNI por Streptococcus viridans (10,6%).CONCLUSIONES. La EVNI por ECN es una entidad cuya incidencia está aumentando a expensas de una población de edad avanzada, que requiere frecuentemente maniobras diagnósticas o terapéuticas cruentas como consecuencia de sus enfermedades con comitantes. A pesar de ello, la mortalidad no parece ser mayor que en las EVNI causadas por otros patógenos (AU)îes

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 dueto CoNS is now increasing because of the ageing of the population. This implies more frequent invasive procedures (mainly vascular) as a consequence ofthe concomitant disease. Nonetheless, the mortality associated with LNVE due to CoNS does not seem to be greater than infection caused by other pathogens (AU)

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.

Clinical findings, diagnostic approach, and outcome of Brucella melitensis epididymo-orchitis.

We have studied 912 patients with brucellosis. Of these, 631 (69.2%) were male and 48 had epididymo-orchitis, giving an incidence of epididymo-orchitis of 7.6%. The duration of symptoms before diagnosis was 52.5 +/- 70 days. All the patients had fever, swelling, and scrotal pain, but only 2 (4.2%) reported urinary symptoms. Seven patients (14.5%) had leukocyte figures above 11 x 10(9)/L, and urine analysis was normal in 69% of the patients. Blood cultures were positive in 65.8% of cases. A total of 33 patients (68.8%) received a combination of doxycycline plus streptomycin and 13 (27.1%) doxycycline plus rifampin. The overall percentage of failure or relapse was 8.8%: 7.1% in the doxycycline plus streptomycin group and 20% in the doxycycline plus rifampin group. None of the patients required surgery. Pending clinical trials to confirm the results, conservative management with a combination of doxycycline for 2 months and streptomycin for 14 to 21 days appears to be adequate and could avoid unnecessary orchiectomy.

Development and evaluation of a PCR-enzyme-linked immunosorbent assay for diagnosis of human brucellosis.

In order to overcome some of the limitations of conventional microbiological techniques in the diagnosis of human brucellosis, a simple PCR-enzyme-linked immunosorbent assay (PCR-ELISA) was developed. After amplification of a 223-bp sequence of a gene that codes for the synthesis of an immunogenetic membrane protein specific for the Brucella genus (BCSP31), the digoxigenin-labeled amplified product was hybridized with a biotinylated capture probe which was complementary to the inner part of the amplicon. The hybrid was captured on streptavidin-coated microtiter plates and detected by using an antidigoxigenin Fab-peroxidase conjugate. The detection limit of the PCR-ELISA in a background of 3.5 micro g of human genomic DNA was 10 fg (two bacterial cells). The PCR-ELISA showed an analytical sensitivity higher than that of ethidium bromide staining and equal to that obtained by conventional PCR followed by dot blot hybridization. In 59 peripheral blood samples from 57 consecutive patients with active brucellosis and 113 control samples, the PCR-ELISA was found to be 94.9% sensitive and 96.5% specific, whereas the sensitivity of the blood culture was only 70.1%. Since the assay can be performed in 1 day, is very reproducible, is easily standardized, and avoids the risk of infection in laboratory workers, this PCR-ELISA seems to be a practical and reliable tool for the diagnosis of human brucellosis.