Timing in antibiotic therapy: when and how to start, de-escalate and stop antibiotic therapy. Proposals from a stablished antimicrobial stewardship program.

The current morbimortality of serious infections is unacceptable and there is a need to promote the increase in the efficacy of empirical and targeted antibiotherapy. This could be achieved by initiatives coming from ASP teams aimed at promoting increased efficacy of antibiotic therapy .In the optimization of the antibiotic therapy there are several critical points in which an adequate timing could achieve benefits in the survival of patients with severe infections: prompt initiation of empirical treatment; de-escalation performance, appropriate targeted treatment; and finally, curtail antibiotic duration.

Linezolid for infective endocarditis: A structured approach based on a national database experience.

ABSTRACT: Current data on the frequency and efficacy of linezolid (LNZ) in infective endocarditis (IE) are based on small retrospective series. We used a national database to evaluate the effectiveness of LNZ in IE.This is a retrospective study of IE patients in the Spanish GAMES database who received LNZ. We defined 3 levels of therapeutic impact: LNZ < 7 days, LNZ high-impact (≥ 7 days, > 50% of the total treatment, and > 50% of the LNZ doses prescribed in the first weeks of treatment), and LNZ ≥ 7 days not fulfilling the high-impact criteria (LNZ-NHI). Effectiveness of LNZ was assessed using propensity score matching and multivariate analysis of high-impact cases in comparison to patients not treated with LNZ from the GAMES database matched for age-adjusted comorbidity Charlson index, heart failure, renal failure, prosthetic and intracardiac IE device, left-sided IE, and Staphylococcus aureus. Primary outcomes were in-hospital mortality and one-year mortality. Secondary outcomes included IE complications and relapses.From 3467 patients included in the GAMES database, 295 (8.5%) received LNZ. After excluding 3 patients, 292 were grouped as follows for the analyses: 99 (33.9%) patients in LNZ < 7 days, 11 (3.7%) in LNZ high-impact, and 178 (61%) in LNZ-NHI. In-hospital mortality was 51.5%, 54.4%, and 19.1% respectively. In the propensity analysis, LNZ high-impact group presented with respect to matched controls not treated with LNZ higher in-hospital mortality (54.5% vs 18.2%, P = .04). The multivariate analysis showed an independent relationship of LNZ use with in-hospital mortality (odds ratio 9.06, 95% confidence interval 1.15--71.08, P = .03).Treatment with LNZ is relatively frequent, but most cases do not fulfill our high-impact criteria. Our data suggest that the use of LNZ as definitive treatment in IE may be associated with higher in-hospital mortality.

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study.

OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events. CONCLUSIONS: Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.

A pragmatic approach for mortality prediction after surgery in infective endocarditis: optimizing and refining EuroSCORE.

OBJECTIVE: To simplify and optimize the ability of EuroSCORE I and II to predict early mortality after surgery for infective endocarditis (IE). METHODS: Multicentre retrospective study (n = 775). Simplified scores, eliminating irrelevant variables, and new specific scores, adding specific IE variables, were created. The performance of the original, recalibrated and specific EuroSCOREs was assessed by Brier score, C-statistic and calibration plot in bootstrap samples. The Net Reclassification Index was quantified. RESULTS: Recalibrated scores including age, previous cardiac surgery, critical preoperative state, New York Heart Association >I, and emergent surgery (EuroSCORE I and II); renal failure and pulmonary hypertension (EuroSCORE I); and urgent surgery (EuroSCORE II) performed better than the original EuroSCOREs (Brier original and recalibrated: EuroSCORE I: 0.1770 and 0.1667; EuroSCORE II: 0.2307 and 0.1680). Performance improved with the addition of fistula, staphylococci and mitral location (EuroSCORE I and II) (Brier specific: EuroSCORE I 0.1587, EuroSCORE II 0.1592). Discrimination improved in specific models (C-statistic original, recalibrated and specific: EuroSCORE I: 0.7340, 0.7471 and 0.7728; EuroSCORE II: 0.7442, 0.7423 and 0.7700). Calibration improved in both EuroSCORE I models (intercept 0.295, slope 0.829 (original); intercept -0.094, slope 0.888 (recalibrated); intercept -0.059, slope 0.925 (specific)) but only in specific EuroSCORE II model (intercept 2.554, slope 1.114 (original); intercept -0.260, slope 0.703 (recalibrated); intercept -0.053, slope 0.930 (specific)). Net Reclassification Index was 5.1% and 20.3% for the specific EuroSCORE I and II. CONCLUSIONS: The use of simplified EuroSCORE I and EuroSCORE II models in IE with the addition of specific variables may lead to simpler and more accurate models.

Endocarditis caused by anaerobic bacteria.

BACKGROUND: Infective endocarditis (IE) caused by anaerobic bacteria is a rare and poorly characterized disease. Most data reported in the literature are from case reports [1-3]. Therefore, we assessed the situation of anaerobic IE (AIE) in Spain using the database of the Spanish Collaboration on Endocarditis (GAMES). METHODS: We performed a prospective study from 2008 to 2016 in 26 Spanish centers. We included 2491 consecutive cases of definite IE (Duke criteria). RESULTS: Anaerobic bacteria caused 22 cases (0.9%) of definite IE. Median age was 66 years (IQR, 56-73), and 19 (86.4%) patients were men. Most patients (14 [63.6%]) had prosthetic valve IE and all episodes were left-sided: aortic valves, 12 (54.5%); and mitral valves, 8 (36.4%). The most common pathogens were Propionibacterium acnes (14 [63.6%]), Lactobacillus spp (3 [13.63%]), and Clostridium spp. (2 [9.0%]), and the infection was mainly odontogenic. Fifteen of the 22 patients (68.2%) underwent cardiac surgery. Mortality was 18.2% during admission and 5.5% after 1 year of follow-up. When patients with AIE were compared with the rest of the cohort, we found that although those with AIE had a similar age and Charlson comorbidity index, they were more likely to have community-acquired IE (86.4% vs. 60.9%, p = 0.01), have undergone cardiac surgery (68.2% vs 48.7% p = 0.06), and have had lower mortality rates during admission (18.2% vs. 27.3%). CONCLUSION: IE due to anaerobic bacteria is an uncommon disease that affects mainly prosthetic valves and frequently requires surgery. Otherwise, there are no major differences between AIE and IE caused by other microorganisms.

[The role of antimicrobial stewardship programs in the control of bacterial resistance]. / El papel de los programas de optimización de la antibioterapia (PROA) en el control de las resistencias bacterianas.

In order to improve infection prognosis and reduce the existing microbial resistance problem (a challenge similar to that of climate change), a higher implication of the Administration, an increased level of social awareness and the development of specific corporate networks, including the pharmaceutical industry, is needed. However, we must first consolidate Antimicrobial Stewardship Programmes with experts who seek to improve antibiotic therapy effectivity in severe infections and to reduce global antibiotic exposure.

Left-sided infective endocarditis in patients with liver cirrhosis.

OBJECTIVE: To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery. METHODS: Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals. RESULTS: A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p < 0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p < 0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery. CONCLUSIONS: Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

Surgical treatment for infective endocarditis in elderly patients.

OBJECTIVES: We evaluate the clinical, echographic and prognostic characteristics of infective endocarditis (IE) in a large population of elderly patients, and the results of surgical approach. METHODS: Multicentric, prospective, observational cohort study with 961 consecutive left-sided IE: 356 patients aged ≥65 years were compared with 605 younger. Indications for cardiac surgery, potential surgical risk, time and outcome, were compared. RESULTS: Hospital-acquired endocarditis, comorbidity, renal failure and septic shock were more frequent in elderly, but embolisms were less. Intracardiac destruction and ventricular failure were similar in both groups, but significantly fewer elderly patients underwent cardiac surgery (36% vs 51%; p < 0.01), and this group showed a worse outcome (43.2% of mortality vs 27% in younger; p < 0.01), resulting age as an independent predictor of mortality (OR: 1.02 CI95%: 1.01-1.03). Compared with medical treatment, surgery showed lower percentages of mortality compared with medical treatment (23.3% vs 31.3%; p = 0.03) in younger group, but a high mortality was observed with both procedures (47.6% vs 40.3%; p = 0.1) in the elderly. CONCLUSIONS: Although similar percentages of heart failure and intracardiac complications, increasing age is associated with higher mortality in IE. Lower rates of surgical treatment and a worse outcome after operation are common features in elderly patients.

Effects of low or medium-dose of prednisone on insulin resistance in patients with systemic lupus erythematosus.

OBJECTIVES: To determine the effect of low (< or =7.5 mg/day; LD-PRD group) or medium (>7.5 mg/day; MD-PRD group) doses of prednisone over the past 4 months on insulin levels and insulin resistance (IR) in SLE patients. METHODS: SLE patients were categorised in prednisone non-users (No PRD) (n=41), LD-PRD (n=71) and MD-PRD (n=16) users. We compared insulin levels, presence of increased IR using homeostasis model assessment (HOMA index), metabolic syndrome (MetS), and other clinical, metabolic and inflammatory parameters in the 3 groups. A Spearman's rho test was used to identify independent associations between daily prednisone dose, HOMA index and insulin levels and other parameters, after adjusting for confounders. RESULTS: No differences in increased IR, HOMA index and insulin between No PRD and LD-PRD were found. In contrast, the MD-PRD group was younger (p=0.001) and had higher insulin (p=0.015), higher HOMA index (p=0.019) and increased IR (OR 5.8, 95% CI (1.7-20), p=0.007) in comparison with the LD-PRD group. The HOMA index strongly correlated with body mass index (BMI) (rs=0.460, p<0.001) but not with clinical activity or inflammatory state after adjusting for confounders. Prednisone dose correlated with the HOMA index and insulin but not with inflammatory parameters (erythrocyte sedimentation rate p=0.075) after adjusting for confounder. CONCLUSIONS: Daily medium-dose prednisone use (>7.5 mg/d) but not low-dose (< or =7.5 mg/d) use increased insulin levels and IR in SLE, which may contribute to increased CV risk experienced by these patients.

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.

Correlation of asymptomatic hyperuricaemia and serum uric acid levels with arterial stiffness in women with systemic lupus erythematosus without clinically evident atherosclerotic cardiovascular disease.

The objective of this article was to evaluate whether serum uric acid (SUA) correlates with arterial stiffness and inflammation markers in a cohort of women with systemic lupus erythematosus (SLE) without overt atherosclerotic cardiovascular diseases, who attended a community hospital. One hundred and two women with SLE were assessed as part of this cross-sectional study. Carotid-femoral pulse wave velocity (PWV) was measured using an automatic device (Complior). C-reactive protein (CRP), fibrinogen and homocysteine levels as well as other metabolic results were recorded. Duration and activity of SLE, damage accrual and treatments were recorded. SLE women were categorized as having or not having hyperuricaemia (HU) according to SUA levels (greater than or up to 6.2 mg/dl, respectively). A multiple linear regression analysis was used to determine the independent link between SUA levels and other variables. Women with SLE and HU (n = 15, 15%) had a worse cardiovascular risk profile that included ageing, hypertension, obesity, higher total cholesterol levels, renal failure and presence of metabolic syndrome. Also, the duration of SLE was increased and damage accrual was greater. In the unadjusted analysis, SUA levels correlated with PWV, CRP, fibrinogen and homocysteine. However, in a multivariate linear regression analysis, SUA levels independently correlated with the duration of SLE, creatinine, total cholesterol and homocysteine levels but did not correlate with PWV. In conclusion, SUA was associated with arterial stiffness, but not independently of age and homocysteine levels. Nevertheless, SUA might be an ancillary indicator of subclinical atherosclerosis in SLE women without clinically evident atherosclerotic cardiovascular disease.

Efficacy of cognitive behavioural therapy for the treatment of chronic stress in patients with lupus erythematosus: a randomized controlled trial.

BACKGROUND: Chronic stress worsens the quality of life (QOL) of lupus patients by affecting their physical and psychological status. The effectiveness of a cognitive-behavioural intervention in a group of patients with lupus and high levels of daily stress was investigated. METHODS: Forty-five patients with lupus and high levels of daily stress were randomly assigned to a control group (CG) or a therapy group (TG); they received cognitive behavioural therapy (CBT) which consisted of ten consecutive weekly sessions. The following variables were evaluated at baseline and at 3, 9 and 15 months: (1) stress, anxiety, depression, (2) Systemic Lupus Erythematosus Disease Activity Index, somatic symptoms, number of flares, (3) anti-nDNA antibodies, complement fractions C3 and C4 and (4) QOL. A multivariate analysis of repeated measures and various analyses of variance were carried out. RESULTS: We found a significant reduction in the level of depression, anxiety and daily stress in the TG compared to the CG and a significant improvement in QOL and somatic symptoms in the TG throughout the entire follow-up period. We did not find any significant changes in the immunological parameters. CONCLUSIONS: CBT is effective in dealing with patients suffering from lupus and high levels of daily stress as it significantly reduces the incidence of psychological disorders associated with lupus and improves and maintains patients' QOL, despite there being no significant reduction in the disease activity index.

Morbimortalidad de la endocarditis aguda por Streptococcus agalactiae / Morbimortality of acute endocarditis caused by Streptococcus agalactiae

Introducción. El Streptococcus agalactiae es un agente causal infrecuente de endocarditis aguda. Suele afectar a pacientes con patología de base y tiene un mal pronóstico. Material y métodos. Estudio retrospectivo que compara las características clínicas de5 casos de endocarditis aguda por Streptococcus agalactiae atendidos en nuestro Hospital, en los últimos doce años, con 43 endocarditis producidas por otros microorganismos. Analizamos como variables dependientes el tamaño de la vegetación, la necesidad de cirugía, el desarrollo de complicaciones, el tiempo de hospitalización y la mortalidad global. Resultados. Todos los casos de endocarditis por estreptococo del grupo B (SGB) tenían mayor tamaño de la vegetación, todos requirieron cirugía y tuvieron estancias hospitalarias prolongadas y mortalidad del 40%, todo ello superior a las endocarditis por otros microorganismos. Conclusión. La endocarditis aguda por Streptococcus agalactiae es un cuadro grave que requiere cirugía precoz en su tratamiento, presenta mortalidad elevada, tasa alta de complicaciones y estancias hospitalarias prolongadas (AU)

Introduction. Streptococcus agalactiae is an uncommon cause of acute endocarditis. It is more likely to occur in people with underlying diseases and usually evolves poorly. Materials and methods. We have conducted a retrospective study comparing the clinical features of Streptococcus agalactiae acute endocarditis attended in our Hospital during the last twelve years with the ones caused by other microorganisms; we have analized as dependent variables the vegetation size, surgery needing, complications, time of hospitalisation and global mortality. Results. All the cases by SGB had a great vegetation size, all needed surgery in its management with long hospitalisation periods, and the mortility was of 40%; everything was higher than other microorganism’s endocarditis. Conclusion. Streptococcus agalactiae acute endocarditis is a serious disease which requires early surgery in its management. Its mortality rate, complications and hospitalisation time are high (AU)

In-vitro radiosensitivity in patients with systemic lupus erythematosus.

To determine the "in-vitro" intrinsic cell radiosensitivity (RS) as a risk indicator of radiation-related side-effects in patients with systemic lupus erythematosus (SLE) compared with healthy subjects (control group). Moreover, we elucidated if clinical, therapeutic and biological parameters could affect the "in-vitro" intrinsic RS in patients with SLE. Intrinsic RS was determined by the quantification of the initial radiation-induced DNA double-strand breaks in peripheral lymphocytes, measured by pulsed-field gel electrophoresis from 52 patients with SLE and a control group consisting of 48 sex- and age-matched healthy subjects. No difference in intrinsic RS was found among both groups. However, SLE patients with anaemia, increased erythrocyte sedimentation rate and those with positive result for anti-La/SSB and anti-RNP antibodies showed significantly higher DNA double-strand breaks than those without them. In our study, patients with SLE did not have a higher intrinsic RS than healthy subjects. According to these results, and with the caution of being a limited laboratory study, the use of radiotherapy should not be avoided in patients with SLE when it is clinically needed.

Aplasia pura de serie roja como primera manifestación de síndrome de Sjögren primario / No disponible

No disponible

[Morbimortality of acute endocarditis caused by Streptococcus agalactiae]. / Morbimortalidad de la endocarditis aguda por Streptococcus agalactiae.

INTRODUCTION: Streptococcus agalactiae is an uncommon cause of acute endocarditis. It is more likely to occur in people with underlying diseases and usually evolves poorly. MATERIALS AND METHODS: We have conducted a retrospective study comparing the clinical features of Streptococcus agalactiae acute endocarditis attended in our Hospital during the last twelve years with the ones caused by other microorganisms; we have analized as dependent variables the vegetation size, surgery needing, complications, time of hospitalisation and global mortality. RESULTS: All the cases by SGB had a great vegetation size, all needed surgery in its management with long hospitalisation periods, and the mortility was of 40%; everything was higher than other microorganism's endocarditis. CONCLUSION. Streptococcus agalactiae acute endocarditis is a serious disease which requires early surgery in its management. Its mortality rate, complications and hospitalisation time are high.

Metabolic syndrome in patients with systemic lupus erythematosus from Southern Spain.

The aim of this cross-sectional study was to establish the frequency, phenotype and characteristics of metabolic syndrome (MS), as defined by the Adult Treatment Panel III, in a cohort of patients with systemic lupus erythematosus (SLE) and its possible association with cardiovascular diseases (CVD). A total of 160 patients with SLE and 245 age, sex, educational level and ethnically matched controls were included. Association with cardiovascular risk factors, SLE features, treatment of SLE and history of CVD were assessed in patients with SLE and controls with and without MS. MS was non-significantly increased in patients with SLE (20%) compared with controls (13%; P = 0.083). It was more commonly observed in patients with SLE < or =40 years old (15.8%) than in controls of the same age group (4.2%; P < 0.001). The mean number of MS criteria was significantly higher among patients with SLE than in controls. The frequency of CVD was also 28-fold higher among patients with SLE (11.3%) than in controls (0.4%). SLE with MS presented higher levels of inflammatory markers than SLE without MS. In a multivariate analysis, educational level, serum triglycerides, HDL-cholesterol and C3 serum levels and hydroxychloroquine use were independently associated with MS.