Antimicrobial management of Tropheryma whipplei endocarditis: the Spanish Collaboration on Endocarditis (GAMES) experience.

OBJECTIVES: Tropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei. PATIENTS AND METHODS: Seventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options. RESULTS: Follow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months). CONCLUSIONS: All treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective.

Epidemiological and clinical characteristics of Streptococcus tigurinus endocarditis.

BACKGROUND: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. METHODS: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. RESULTS: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. CONCLUSIONS: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.

Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-ß-lactamase-producing Enterobacteriaceae.

Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.

Impact of the MIC of piperacillin/tazobactam on the outcome for patients with bacteraemia due to Enterobacteriaceae: the Bacteraemia-MIC project.

OBJECTIVE: Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial. PATIENTS AND METHODS: A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6). CONCLUSIONS: We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.

High-dose daptomycin plus fosfomycin is safe and effective in treating methicillin-susceptible and methicillin-resistant Staphylococcus aureus endocarditis.

We describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptible Staphylococcus aureus [MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistant S. aureus [MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was tested in vitro against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistant S. aureus isolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.

Community-onset bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: risk factors and prognosis.

BACKGROUND: There is little clinical information about community-onset bloodstream infections (COBSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC). We investigated the prevalence and risk factors for COBSI due to ESBLEC, and described their clinical features and the impact of COBSI caused by ESBLEC on 14-day mortality. METHODS: Risk factors were assessed using a multicenter case-control-control study. Influence of ESBL production on mortality was studied in all patients with COBSI due to E. coli. Isolates and ESBLs were microbiologically characterized. Statistical analysis was performed using multivariate logistic regression. Thirteen tertiary care Spanish hospitals participated in the study. RESULTS: We included 95 case patients with COBSI due to ESBLEC, which accounted for 7.3% of all COBSI due to E. coli. The ESBL in 83 of these (87%) belonged to the CTX-M family of ESBL, and most were clonally unrelated. Comparison with both control groups disclosed association with health care (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.8), urinary catheter use (OR, 3.1; 95% CI, 1.5-6.5), and previous antimicrobial use (OR, 2.7; 95% CI, 1.5-4.9) as independent risk factors for COBSI due to ESBLEC. Mortality among patients with COBSI due to ESBLEC was lower among patients who received empirical therapy with beta-lactam/beta-lactam inhibitor combinations or carbapenems (8%-12%) than among those receiving cephalosporins or fluoroquinolones (24% and 29%, respectively). Mortality among patients with COBSI due to E. coli was associated with inappropriate empirical therapy irrespective of ESBL production. CONCLUSIONS: ESBLEC is an important cause of COBSI due to E. coli. Clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

Risk factors and prognosis of nosocomial bloodstream infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli.

Extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs) caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR]=4.8; 95% confidence interval [CI]=1.4 to 15.7), the previous use of oxyimino-beta-lactams (OR=6.0; 95% CI=3.0 to 11.8), and unknown BSI source (protective; OR=0.4; 95% CI=0.2 to 0.9), and duration of hospital stay (OR=1.02; 95% CI=1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR=3.9; 95% CI=1.2 to 12.9), a high-risk source (OR=5.5; 95% CI=1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR=6.5; 95% CI=1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-beta-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.

Twenty-year experience with cryopreserved arterial allografts for vascular infections.

OBJECTIVES: The aim of this study was to analyse outcomes over 2 decades using cryopreserved vascular allografts to treat vascular infection. METHODS: We conducted a retrospective study of patients identified from our institutional database who were treated for primary or secondary vascular infection using implanted allografts. RESULTS: Between October 1992 and May 2014, 54 patients underwent surgery for vascular infection out of 118 patients implanted with cryopreserved vascular allografts. The 52 patients for whom we had full information form the basis of the study with a 96% follow-up. The average age was 64 ± 11 years; 87% were men; 65% had previous vascular surgery; 19% had emergency operations. A total of 75% of the patients had aortoiliofemoral infections. Five patients underwent surgery with cardiopulmonary bypass. Fifty percent required more than 1 allograft and 15% had concomitant procedures. Seventy-three percent (38/52) of specimen cultures yielded positive results with polymicrobial flora in 29%. Surgical specimens most frequently grew coagulase-negative staphylococci. The early postoperative reoperation rate was 15% for allograft-related complications. There were 20 (38%) early deaths, including deaths of acute myocardial infarction, anastomosis rupture and persistent sepsis and shock. Uncontrolled infection leading to septic shock and multiple organ failure was the cause of death in 50% of the cases. The mean duration of freedom from allograft reintervention was 12.2 years. The mean duration of freedom from allograft occlusion or limb loss was 12.1 years [95% confidence interval (CI) 9.9-14.4]. Of the 32 surviving patients, we had patency information for 66% obtained by angiography or computed tomography. The mean survival for the cohort was 5.9 years (95% CI 3.9-7.8). Mean freedom from cardiovascular infection-related death was 9.3 years (95% CI 7.2-11.4). CONCLUSIONS: Allografts can be indicated for treatment of primary/secondary infection and have remarkable results in multimorbid patients. Patients with vascular infection have a high-risk profile, around 40% mortality during the first 6 months, with reduction in overall mortality thereafter. We believe that allografts may play a role in the surgical treatment of vascular infection.

Cytokine-release patterns in elderly patients with systemic inflammatory response syndrome.

BACKGROUND: Information is scarce about the inflammatory responses to infection in elderly patients. OBJECTIVE: To investigate the inflammatory pattern in elderly patients with systemic inflammatory response syndrome (SIRS). METHODS: We assessed the value of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta) and C-reactive protein (CRP) in elderly patients with SIRS at the time of consultation in the emergency room and on the fourth day of hospitalization. RESULTS: Of 100 patients with SIRS, 92 had a clinical suspicion of infection and 46 were microbiologically confirmed. Basal TNF-alpha and IL-6 levels were higher in patients with bacteremia (p < 0.001 and p = 0.017, respectively). Basal levels of TNF-alpha (p < 0.001) and fourth-day levels of CRP (p = 0.004), TNF-alpha (p < 0.001) and IL-6 (p = 0.002) had a positive correlation with the length of hospitalization. Higher IL-6 levels on the fourth day showed a correlation with mortality (p = 0.016), while the other cytokines and CRP did not show this association. CONCLUSION: Febrile elderly patients showed an inflammatory response pattern to infection equivalent to that reported in younger patients. Despite some limitations of our study, among febrile elderly patients, pro-inflammatory cytokine levels can be good markers for evaluating the prognosis of infections.

[Listeria monocytogenes bacteremia: analysis of 110 episodes]. / Bacteriemia por Listeria monocytogenes: análisis de 110 casos.

BACKGROUND AND OBJECTIVE: Over the last years, we registered an increase in the number of listeriosis cases. The aim of this study was to analyze the co-morbidity, clinical presentation and prognosis of Listeria monocytogenes bacteremia episodes diagnosed over 15 years. PATIENTS AND METHOD: From January 1991 to April 2005, we prospectively recorded the medical records of 110 patients in whom L. monocytogenes was isolated from one or more blood cultures. In all patients, demographic, clinical presentation, antimicrobial treatment and outcome data were recorded. RESULTS: Twenty cases (18.2%) were recorded from 1991 to 1995; 27 (24.6%) from 1996 to 2000 and 63 (57.3%) from 2001 to April 2005 (p < 0.05). One hundred patients (90.9%) had one or more underlying diseases or immunosuppressive conditions, and 54 (49.9%) were under steroid therapy. In 63 patients, primary bacteremia developed, in 35 there was a central nervous system infection and 6 patients developed a spontaneous peritonitis (all patients with liver cirrhosis). Thirteen patients (11.8%) developed septic shock, and 18 (16.3%) died. The mortality rate of patients with meningitis who were treated empirically with a third generation cephalosporin was 50% (5 out of 10) whereas the mortality rate of those patients who received initially an antimicrobial agent active against L. monocytogenes was 12% (3 out of 25) (p = 0.05). CONCLUSIONS: The rate of systemic infection due to L. monocytogenes increased over the last years. Immunosuppressed patients should have a better knowledge of the guidelines needed to avoid eating potentially contaminated food. When empiric treatment is to be selected in immunosuppressed patients with unexplained fever and/or meningitis, a lack of activity against L. monocytogenes by cephalosporins should be considered.

El estigma asociado a los trastornos mentales en el paciente geriátrico: una revisión integradora / Mental health-related stigma in the geriatric patient: an integrative review

Objetivos: Analizar el estigma asociado a la enfermedad mental. Metodología: Se realizó una revisión integradora de carácter descriptivo, realizando una búsqueda bibliográfica utilizando palabras clave relacionadas con el estigma social, el estigma personal y la enfermedad mental. Resultados: Tras la aplicación de los criterios de inclusión establecidos, se seleccionaron y estudiaron un total de 21 artículos. Conclusiones: La literatura consultada muestra que el estigma hacia los trastornos mentales sigue siendo un problema en la sociedad actual, y que acarrea graves consecuencias tanto para los pacientes como para sus familiares (AU)

Objectives: To analyze the stigma associated with mental illness. Methodology: An integrative descriptive review was carried out. The bibliographic search was accomplished using keywords related to social stigma, personal stigma and mental illness. Results: After applying the established inclusion criteria, a total of 21 articles were selected and studied. Conclusions: The spoted literature shows that stigma towards mental disorders continues to be a problem in today’s society, and that it has serious consequences for both patients and their families (AU)

Group A streptococcal infections in injection drug users in Barcelona, Spain: epidemiologic, clinical, and microbiologic analysis of 3 clusters of cases from 2000 to 2003.

An unexplained resurgence of Group A streptococci (GAS) infections has been observed since the mid-1980s in the United States and Europe, particularly among intravenous drug users (IDUs). Several risk factors have been identified. Mutations in the capsule synthesis regulator genes (csrRS) have been associated with an increase in virulence. From January 1998 to December 2003, we conducted a prospective and retrospective descriptive analysis of invasive GAS soft-tissue infections in IDUs in Barcelona, Spain. Clinical features were collected, and we conducted a surveillance study to identify risk factors associated with GAS soft-tissue infections. We analyzed chromosomal DNA by low cleavage restriction enzymes and used pulsed-field gel electrophoresis (PFGE) and variable gene sequence typing (VGST) of the emm gene to disclose the epidemiologic relationship between the strains. We analyzed the influence of clonality (M-type) and mutations in csrRS genes of these strains on clinical features. We identified 44 cases, all of which were grouped in 3 clusters: fall 2000, fall 2002, and fall 2003. Cellulitis with or without abscesses (75%) and fever (90.9%) were the most common clinical manifestations. Distant septic complications were infrequent (18.2%). Although all patients had severe infections (mainly bacteremic needle abscesses), their outcome with antibiotic therapy, usually beta-lactam, was successful in all cases. However, surgery was needed in 40.9% of patients. Through the surveillance study we found that infected patients had a higher number of drug injections per day (odds ratio [OR], 18.84; 95% confidence interval [CI], 4.83-79.4; p<0.00001), shared paraphernalia for drug use more frequently (OR, 11.11; 95% CI, 3.24-39.04; p<0.0001), were in a higher proportion both currently unemployed and homeless (OR, 4.22; 95% CI, 1.5-12.15; p<0.0001), were not in a methadone maintenance program (OR, 0.03; 95% CI, 0-0.19; p<0.00001), and more often bought drugs at a specific site (OR, 33.92; 95% CI, 7.44-174.93; p<0.00001) and from a specific dealer (OR, 72; 95% CI, 8-3090; p<0.00001), compared with patients not infected. The fall 2000 cluster was polyclonal, whereas the other 2 clusters were mainly due to the same strain of GAS (emm 25.2), and were defined as epidemic outbreaks. Clinically, the cases due to the clonal strain presented abscesses and needed surgery more frequently (p<0.001 and p=0.005, respectively). On the other hand, mutations in the csrRS genes were not associated with invasive GAS soft-tissue infection. There has been an increase in the number of cases of invasive GAS soft-tissue infections in IDUs in Barcelona, which seems to be related to drug users' habits and their socioeconomic status. Clonality (emm 25.2) but not mutations in the csrRS genes was associated with more severe GAS soft-tissue infections.

Enteric fever in Barcelona: Changing patterns of importation and antibiotic resistance.

BACKGROUND: Enteric fever's incidence is decreasing among residents of high-income countries, although it's rising in travelers coming from low-resource endemic settings. The study's aim is to describe epidemiological, clinical and laboratory features of patients with enteric fever. METHODS: Retrospective descriptive study of enteric fever cases diagnosed at a Tropical Medicine Unit in Barcelona, 1993-2012. RESULTS: Out of 40 patients, 31(77,5%) were returning travelers, and 70% of them had been in Southern Asia. In the rest of patients without an antecedent of a recent travel, the infection occurred mainly before year 2000. The more frequently reported symptoms were fever and diarrhea, lacking significant differences between S. typhi and S. paratyphi infections. Quinolones were used as empiric treatment in 47.2% of patients, 36.1% received 3rd generation cephalosporins, 2.78% azithromycin and 13.89% other combinations. Resistance to quinolones in the S. paratyphi group (66.7%) was significantly higher compared with the S. typhi group (20%) (p:0.02). 22.5% of patients had treatment failure and 23.6% patients presented complications, none of them had been previously vaccinated. CONCLUSIONS: The diagnosis of enteric fever was more frequent among travelers coming from Southern-East Asia. Quinolone resistance is widely spread, particularly in S. paratyphi serotypes and should not be considered as first choice treatment anymore.

Utilidad de la ecografía torácica en infección neonatal por SARS-CoV-2 / Usefulness of chest ultrasound in a neonatal infection due to SARS-CoV-2

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Tumor de células de la granulosa juvenil neonatal, una entidad infrecuente / Neonatal juvenile granulosa cell tumor, a rare entity

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Tropheryma whipplei endocarditis in Spain: Case reports of 17 prospective cases.

Tropheryma whipplei endocarditis is an uncommon condition with very few series and <90 cases reported in the literature. The aim of the study was to analyze the epidemiological, clinical, and outcome characteristics of 17 cases of T. whipplei endocarditis recruited in our country from a multicentric cohort from 25 Spanish hospitals from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España.From a total of 3165 cases included in the cohort, 14.2% were diagnosed of blood culture negative endocarditis (BCNE) and 3.5% of these had T. whipplei endocarditis. This condition was more frequent in men. The average age was 60.3 years. Previous cardiac condition was present in 35.3% of the cases. The main clinical manifestation was cardiac failure (76.5%) while fever was only present in the 35.3%. Ecocardiography showed vegetations in 64.7% of patients. Surgery was performed in all but 1 cases and it allowed the diagnosis when molecular assays were performed. A broad range rRNA 16S polymerase chain reaction was used for first instance in all laboratories and different specific targets for T. whipplei were employed for confirmation. A concomitant Whipple disease was diagnosed in 11.9% of patients. All patients received specific antimicrobial treatment for at least 1 year, with no relapse and complete recovery.T. whipplei endocarditis is an uncommon condition with an atypical presentation that must be considered in the diagnosis of BCNE. The prognosis is very good when an appropriate surgical management and antimicrobial-specific treatment is given.