Molecular (ticks) and serological (humans) study of Crimean-Congo hemorrhagic fever virus in the Iberian Peninsula, 2013-2015.

INTRODUCTION: Crimean-Congo hemorrhagic fever (CCHF) is a viral disease, mainly transmitted through tick bite, of great importance in Public Health. In Spain, Crimean-Congo hemorrhagic fever virus (CCHFV) was detected for the first time in 2010 in Hyalomma lusitanicum ticks collected from deer in Cáceres. The aim of this study was to investigate the presence of CCHFV in ticks from Cáceres, and from other Spanish areas, and to evaluate the presence of antibodies against the virus in individuals exposed to tick bites. METHODS: A total of 2053 ticks (1333 Hyalomma marginatum, 680 H. lusitanicum and 40 Rhipicephalus bursa) were analyzed using molecular biology techniques (PCR) for CCHFV detection. The determination of specific IgG antibodies against CCHFV in 228 serum samples from humans with regular contact with ticks (at risk of acquiring the infection) was performed by indirect immunofluorescence assay. RESULTS: The CCHFV was not amplified in ticks, nor were antibodies against the virus found in the serum samples analyzed. CONCLUSION: The absence of the CCHFV in the ticks studied and the lack of antibodies against the virus in individuals exposed to tick bites would seem to suggest a low risk of acquisition of human infection by CCHFV in Spain.

Tuberculosis prophylaxis with levofloxacin in liver transplant patients is associated with a high incidence of tenosynovitis: safety analysis of a multicenter randomized trial.

BACKGROUND: It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver transplant recipients. This study was designed to investigate the efficacy and safety of levofloxacin. METHODS: An open-label, prospective, multicenter, randomized study was conducted to compare the efficacy and safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and isoniazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was measured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication were recorded. RESULTS: CONSORT guidelines were followed in order to present the results. The safety committee suspended the study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levofloxacin arm). The reason for suspension was an unexpected incidence of severe tenosynovitis in the levofloxacin arm (18.2%). Although the clinical course was favorable in all cases, tenosynovitis persisted for 7 weeks in some patients. No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31) and 54.5% of patients randomized to levofloxacin (18/33, P = .094) completed prophylaxis. No patient developed tuberculosis during the study follow-up (median 270 days). CONCLUSIONS: Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.

[Marcus Aurelius Antonius (121-180AD), philosopher and Roman emperor, and Galen's plague]. / Marco Aurelio Antonino (121-180d. C.), filósofo y emperador de Roma, y la peste de Galeno.

The study of the aetiologies of diseases in Ancient Times is usually a speculative intellectual exercise. When some authors attribute a specific aetiology to an old disease, there is a great risk of committing a methodological error, known as presentism by the modern historiography. The authority of the investigator, more than the weight of the scientific truth, is usually the reason why the diagnosis has remained over the years. The great epidemic of the years 164-165AD and afterwards, could have been smallpox (haemorrhagic form). Claude Galen, the famous doctor, described the symptoms in several books of his great Opera Omnia. For this reason, it is currently known among the scholars as Galen's plague. The epidemic was described for the first time in Seleucia (Mesopotamia). Until now, the actual geographic origin is unknown. We propose here that the beginning might be the kingdom of the old Han dynasty (now the Chinese Popular Republic). The epidemic swept the Roman Empire, from the east to the west, and from the southern to the northern borders. An immediate consequence of the infection was a high morbidity and mortality. In this sense, Galen's epidemic was one of the many factors that caused the fall and destruction of the Roman Empire. On the other hand, there is a general agreement among historians, biographers and researchers that the philosopher emperor Marcus Aurelius Antoninus (121-180AD was affected by the infection in the epidemic wave of 164-165AD. The death of Marcus Aurelius occurred on March 17 in the year 180AD, in Vindobonne, or perhaps Sirminium (near to Vienna). Many authors propose that the cause of the emperor's death was the same epidemic. We consider that it is not possible to demonstrate any of those speculative diagnoses. Finally, the epidemic of 189-190AD, that we have named of Commodus, was probably a different disease to the Galen's plague. There were several kinds of animals affected (anthropozoonoses). In this sense, this infection resembles more the previous Athens plague (430BC) or the epidemic of Justinian (552AD) than that of Galen's.

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.

Suppuration as diagnostic criterium of peri-implantitis.

BACKGROUND: Suppuration (SUP) as a diagnostic parameter for monitoring dental implants is not yet well understood. The retrospective clinical and radiographic study was therefore performed to investigate the patient, implant, and site characteristics among individuals exhibiting SUP. METHODS: Demographic characteristics and clinical parameters were recorded. Radiographic features were analyzed using cone-beam computed tomography. Peri-implantitis was defined based on the consensus report of Workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions: probing depth (PD) ≥6 mm, presence of bleeding and/or SUP on gentle probing, and radiographic marginal bone loss (MBL) ≥3 mm. SUP was graded according to profuseness (dot versus line/drop) and time after probing (≥15 seconds versus <15 seconds after probing versus spontaneous). Simple binary logistic regression models were estimated using generalized estimation equations to explain the probability of SUP based on demographic, clinical, and radiographic variables. RESULTS: A total of 111 eligible patients (nimplants  = 501) were assessed. Of them, 57 (nimplants  = 334) were diagnosed with peri-implantitis according to the established case definition, and of these individuals, 31 (nimplants  = 96) presented SUP. Therefore, the prevalence of SUP was 27.92% in the total sample size and 54.38% in peri-implantitis patients. Overall, 28.74% implants displayed SUP within patients with peri-implantitis. SUP was more frequently found at buccal sites (51%) and proved less prevalent at mesio-lingual sites (16.7%). Defect morphology (OR = 6.59; P = 0.004), PD (OR = 1.63; P = 0.024), and MBL (OR = 1.35; P = 0.010) were significantly associated with the presence of SUP. Likewise, defect morphology (P = 0.02), PD (P = 0.003), and MBL (P = 0.01) were significantly correlated with the grade of SUP. CONCLUSION: The presence and grade of SUP are associated with peri-implant bone loss, probing depth, and defect morphology in patients with peri-implantitis.

Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir (1500/100 mg) together with 2 nucleos(t)ide reverse transcriptase inhibitors in real life: a multicentre prospective study.

BACKGROUND: Ritonavir-boosted saquinavir (SQVr) is nowadays regarded as an alternative antiretroviral drug probably due to several drawbacks, such as its high pill burden, twice daily dosing and the requirement of 200 mg ritonavir when given at the current standard 1000/100 mg bid dosing. Several once-daily SQVr dosing schemes have been studied with the 200 mg SQV old formulations, trying to overcome some of these disadvantages. SQV 500 mg strength tablets became available at the end of 2005, thus facilitating a once-daily regimen with fewer pills, although there is very limited experience with this formulation yet. METHODS: Prospective, multicentre study in which efficacy, safety and pharmacokinetics of a regimen of once-daily SQVr 1500/100 mg plus 2 NRTIs were evaluated under routine clinical care conditions in either antiretroviral-naïve patients or in those with no previous history of antiretroviral treatments and/or genotypic resistance tests suggesting SQV resistance. Plasma SQV trough levels were measured by HPLV-UV. RESULTS: Five hundred and fourteen caucasian patients were included (47.2% coinfected with hepatitis C and/or B virus; 7.8% with cirrhosis). Efficacy at 52 weeks (plasma RNA-HIV <50 copies/ml) was 67.7% (CI95: 63.6 - 71.7%) by intention-to-treat, and 92.2% (CI95: 89.8 - 94.6%) by on-treatment analysis. The reasons for failure were: dropout or loss to follow-up (18.4%), virological failure (7.8%), adverse events (3.1%), and other reasons (4.6%). The high rate of dropout may be explained by an enrollment and follow-up under routine clinical care condition, and a population with a significant number of drug users. The median SQV Cmin (n = 49) was 295 ng/ml (range, 53-2172). The only variable associated with virological failure in the multivariate analysis was adherence (OR: 3.36; CI95, 1.51-7.46, p = 0.003). CONCLUSIONS: Our results suggests that SQVr (1500/100 mg) once-daily plus 2 NRTIs is an effective regimen, without severe clinical adverse events or hepatotoxicity, scarce lipid changes, and no interactions with methadone. All these factors and its once-daily administration suggest this regimen as an appropriate option in patients with no SQV resistance-associated mutations.

Infective endocarditis after transcatheter aortic valve implantation: Contributions of a single-centre experience on incidence and associated factors. / Endocarditis infecciosa después de TAVI: aportaciones de la experiencia en un único centro sobre la incidencia y los factores asociados.

INTRODUCTION: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is an emerging complication. There are incomplete and disparate data on its incidence. We present the experience of a single-centre of incidence, mortality and associated factors of IE after TAVI. METHODS: A retrospective observational study of IE cases in people who received a TAVI, between 06/01/2009 and 11/01/2017, in a university hospital, during a median follow-up period of 15.3months (interquartile range [IQR] 9.1-36.2). Incidence, clinical, microbiological and prognostic data, and factors associated with IE after TAVI were analysed. RESULTS: Eleven patients with IE of 200 TAVI were detected. Global incidence: 5.5% (2.77 cases per 100 patient-year). The median of days from TAVI to IE was 112 (IQR 36-578), the in-hospital mortality rate was 36.4%, and the one-year mortality rate was 54.5%. All the organisms identified were gram-positive (4 Enterococcus faecalis, 3 coagulase-negative Staphylococcus). The patients with IE after TAVI were significantly younger (median 78years, IQR 73-80, versus 82 years, IQR 79-84, P=.002), they had a higher EuroSCORE (5.1±2.4 versus 3.2±1.2, P<.001), and they more frequently had a history of neoplasia (18.2% versus 4.2%, P<.03) CONCLUSIONS: In our area, IE after TAVI has an incidence greater than that described in multicentre series, this is in line with the trend published in the literature. It leads to high mortality and is associated with a worse baseline clinical situation.

[Global HIV epidemiology and current migration]. / Epidemiologia del VIH/sida en el mundo y el fenómeno migratorio actual.

One of the current characteristics of migration is its tendency to concentrate in industrialized countries, as well as its feminization and diversity. From a healthcare point of view, the phenomenon of migration has aroused interest in the possible transfer of transmissible infectious diseases from some regions to others and the impact that this could have on public health. When discussing immigration and AIDS, there is a risk of stigmatizing vulnerable people, who are generally healthy. Some of the infectious diseases these people contract are partly due to the conditions experienced on the journey or once they are settled in the host country. The epidemiological pattern of HIV transmission in immigrants is the same as that in their countries of origin. Although the distribution of HIV subtypes is more or less localized, there is a tendency toward progressive dispersion of all subtypes in different geographical areas and toward new recombinant subtypes.

[Pathogenesis of lipodystrophy and metabolic syndromes associated with HIV infection]. / Patogenia de la lipodistrofia y de las alteraciones metabólicas asociadas a la infección por el VIH.

Lipodystrophy, and the metabolic alterations (dislipemia, insulin-resistance) associated with human immunodeficiency virus (HIV) infection, is a multifactorial syndrome due to the interaction of host related factors (cellular immune status, diet, gene mutations), viral factors (cytokine synthesis, polyunsaturated fatty acid or PUFA depletion), and pharmacological effects (mitochondrial DNA-polymerase inhibition, lipolysis inhibition, adiponectin synthesis reduction). HIV probably modifies the adipocyte differentiation and the lipid metabolism. This retroviral effect is mediated by proinflammatory cytokines (tumor necrosis factor) and the participation of other factors (drugs, diet), all in the context of a particular host genetic setting. The adipocyte (and several cellular receptors, fatty acids, membrane proteins, and cytokines) plays a central role in the pathogenesis of HIV-associated lipodystrophy.

Endocarditis infecciosa después de TAVI: aportaciones de la experiencia en un único centro sobre la incidencia y los factores asociados / Infective endocarditis after transcatheter aortic valve implantation: Contributions of a single-centre experience on incidence and associated factors

INTRODUCCIÓN: La endocarditis infecciosa (EI) sobre transcatheter aortic valve implantation (TAVI) es una complicación emergente. Existen datos incompletos y dispares sobre su incidencia. Se aporta la experiencia en nuestro centro sobre incidencia, mortalidad y factores asociados de la EI post-TAVI y se compara con datos de la literatura. MÉTODOS: Estudio retrospectivo observacional de los casos de EI diagnosticados en pacientes que habían recibido TAVI, entre el 1 de junio de 2009 y el 1 de noviembre de 2017, en un centro universitario tras una mediana de seguimiento de 15,3 meses (rango intercuartil [RIC] 9,1-36,2). Se analizaron la incidencia, los datos clínicos, microbiológicos y pronósticos, y los factores asociados a EI post-TAVI. RESULTADOS: Se detectaron 11 pacientes con EI de 200 TAVI. Incidencia global: 5,5% (2,77 casos por 100 años-paciente). La mediana de tiempo hasta la EI post-TAVI fue de 112 días (RIC 36-578), la tasa de mortalidad intrahospitalaria fue del 36,4% y la mortalidad al año, del 54,5%. Todos los microorganismos identificados fueron grampositivos (4 Enterococcus faecalis, 3 Staphylococcus coagulasa negativo). Los pacientes con EI post-TAVI eran significativamente más jóvenes (mediana 78, RIC 73-80, frente a 82, RIC 79-84, p = 0,002), tenían un EuroSCORE mayor (5,1 ± 2,4 frente a 3,2 ± 1,2, p < 0,001) y más frecuentemente antecedentes de neoplasia (18,2% frente al 4,2%, p < 0,03). CONCLUSIONES: En nuestro medio, la incidencia de EI post-TAVI es mayor que la descrita en series multicéntricas, lo que concuerda con la tendencia publicada en la literatura. Conlleva una elevada mortalidad y se asocia con una peor situación clínica basal

INTRODUCTION: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is an emerging complication. There are incomplete and disparate data on its incidence. We present the experience of a single-centre of incidence, mortality and associated factors of IE after TAVI. METHODS: A retrospective observational study of IE cases in people who received a TAVI, between 06/01/2009 and 11/01/2017, in a university hospital, during a median follow-up period of 15.3months (interquartile range [IQR] 9.1-36.2). Incidence, clinical, microbiological and prognostic data, and factors associated with IE after TAVI were analysed. RESULTS: Eleven patients with IE of 200 TAVI were detected. Global incidence: 5.5% (2.77 cases per 100 patient-year). The median of days from TAVI to IE was 112 (IQR 36-578), the in-hospital mortality rate was 36.4%, and the one-year mortality rate was 54.5%. All the organisms identified were gram-positive (4 Enterococcus faecalis, 3 coagulase-negative Staphylococcus). The patients with IE after TAVI were significantly younger (median 78 years, IQR 73-80, versus 82 years, IQR 79-84, P=.002), they had a higher EuroSCORE (5.1±2.4 versus 3.2 ± 1.2, P < .001), and they more frequently had a history of neoplasia (18.2% versus 4.2%, P < .03). CONCLUSIONS: In our area, IE after TAVI has an incidence greater than that described in multicentre series, this is in line with the trend published in the literature. It leads to high mortality and is associated with a worse baseline clinical situation

Oculopalpebral borreliosis as an unusual manifestation of Lyme disease.

PURPOSE: To report the case of acrodermatitis chronica atrophicans as an ocularpalpebral manifestation of Lyme borreliosis, with peripheral keratopathy and associated vasculitis. METHODS: Case report. RESULTS: A 16-year-old girl, with a 4-year history of recurrent left eye photophobia, intense redness, and superior eyelid edema, presented with lid erythema, ptosis, superficial venous tortuosity, conjunctival hyperemia, corneal thinning with precipitates, and vascularization. Borrelia burgdorferi was confirmed by immunoblotting. Treatments with doxycycline followed by ceftriaxone were only partially effective. Eyelid biopsy revealed spirochetes and vasculitis with deposition of immunoglobulin G. Oral cefuroxime for 28 days was ineffective. Due to the vasculitis, immunosuppression with azathioprine and topical cyclosporine were given for 4 months. Since then she has been free of flare-ups. CONCLUSIONS: Lyme borreliosis should be considered in patients with recurrent chronic lid edema and associated keratopathy.

Molecular (ticks) and serological (humans) study of Crimean-Congo hemorrhagic fever virus in the Iberian Peninsula, 2013-2015 / Estudio molecular (garrapatas) y serológico (humanos) del virus de la fiebre hemorrágica de Crimea-Congo en la Península Ibérica, 2013-2015

Introduction: Crimean-Congo hemorrhagic fever (CCHF) is a viral disease, mainly transmitted through tick bite, of great importance in Public Health. In Spain, Crimean-Congo hemorrhagic fever virus (CCHFV) was detected for the first time in 2010 in Hyalomma lusitanicum ticks collected from deer in Cáceres. The aim of this study was to investigate the presence of CCHFV in ticks from Cáceres, and from other Spanish areas, and to evaluate the presence of antibodies against the virus in individuals exposed to tick bites. Methods: A total of 2053 ticks (1333 Hyalomma marginatum, 680 H. lusitanicum and 40 Rhipicephalus bursa) were analyzed using molecular biology techniques (PCR) for CCHFV detection. The determination of specific IgG antibodies against CCHFV in 228 serum samples from humans with regular contact with ticks (at risk of acquiring the infection) was performed by indirect immunofluorescence assay. Results: The CCHFV was not amplified in ticks, nor were antibodies against the virus found in the serum samples analyzed. Conclusion: The absence of the CCHFV in the ticks studied and the lack of antibodies against the virus in individuals exposed to tick bites would seem to suggest a low risk of acquisition of human infection by CCHFV in Spain (AU)

Introducción: La fiebre hemorrágica de Crimea-Congo (FHCC) es una enfermedad vírica, transmitida fundamentalmente por garrapatas, con gran importancia en salud pública. La primera detección del virus de la fiebre hemorrágica de Crimea-Congo (vFHCC) en España se realizó en 2010 en garrapatas de la especie Hyalomma lusitanicum recogidas sobre ciervos en Cáceres. El objetivo de este estudio fue investigar la presencia del vFHCC en garrapatas de esta y otras zonas de España y evaluar la presencia de anticuerpos frente al virus en personas expuestas a picaduras de garrapatas. Métodos: Se analizaron un total de 2.053 garrapatas (1.333 Hyalomma marginatum, 680 Hyalomma lusitanicum y 40 Rhipicephalus bursa) mediante técnicas de biología molecular (PCR) para la detección del vFHCC. Se realizó la determinación de anticuerpos IgG específicos frente al vFHCC mediante inmunofluorescencia indirecta a 228 sueros de personas en contacto habitual con garrapatas, y por tanto, en riesgo de adquirir la infección. Resultados: No se amplificó el vFHCC en garrapatas ni se encontraron anticuerpos frente al mismo en los sueros analizados. Conclusión: La ausencia del vFHCC en las garrapatas estudiadas y de anticuerpos frente al mismo en personas expuestas a picaduras indica un riesgo bajo de adquisición de la infección por el vFHCC en humanos en España (AU)

Infecciones por enterobacterias productoras de betalactamasas de espectro extendido tras cirugía cardiaca: su impacto en la mortalidad / Extended-spectrum beta-lactamase-producing Enterobacteriaceae infections after cardiac surgery: their impact on mortality

Introducción: Las enterobacterias productoras de betalactamasas de espectro extendido (EP BLEE) causan infecciones nosocomiales de modo creciente. Es controvertido si se asocian a peor pronóstico. El objetivo de este trabajo fue analizar si las infecciones por EP BLEE tras cirugía cardiaca presentan peor pronóstico que las causadas por enterobacterias no multirresistentes. Material y método: Estudio retrospectivo de las infecciones postquirúrgicas por enterobacterias, diagnosticadas en el Servicio de Cirugía Cardiaca de un Hospital Universitario (1/12/2007-1/12/2012). Se analizó la presencia de BLEE, la idoneidad del tratamiento empírico y la mortalidad global y relacionada. Resultados: Se analizaron 61 pacientes (67,2 ± 10 años). En 16 (26,2%) se aislaron EP BLEE. Las especies más frecuentes fueron Escherichia coli (20 casos/9 BLEE), Enterobacter spp (18/1), Serratia marcescens (11/3), Proteus mirabilis (11/1) y Klebsiella spp (9/2). Las localizaciones más frecuentes fueron la sangre (54,1%), las vías respiratorias (31,1%) y la herida quirúrgica (19,7%). El tratamiento empírico inicial fue no idóneo en mayor proporción en las infecciones por EP BLEE (66,7% frente a 15,9%, p < 0,0001). Fallecieron 26 pacientes (42,6%). La mortalidad global se asoció a infección por EP BLEE (odds ratio 5,3; IC 95% 1,3-21,5). La mortalidad atribuida a enterobacterias (14 pacientes) fue mayor cuando hubo bacteriemia (75% frente a 22%, p < 0,02) y el tratamiento empírico fue no idóneo (87,5% frente a 43,7%, p = 0,05). Conclusiones: La infección por EP BLEE en la post-cirugía cardiaca puede asociarse a mayor mortalidad, especialmente cuando hay bacteriemia. Ante la sospecha de infección post-quirúrgica por enterobacterias, se debe ajustar el tratamiento empírico según la incidencia local de EP BLEE.

Introduction: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ES BLEE) increasingly cause nosocomial infections. It is controversial whether they are associated to a worse prognosis. The motivation for this study is to analyse if infections caused by ES BLEE after a cardiac surgery show a worse diagnosis that those caused by non-multidrug-resistant enterobacteriaceae. Material and methods: Retrospective study of postoperative infections caused by enterobacteriaceae, diagnosed at the Cardiac Surgery Department (1/12/2007-1/12/2012). The presence of BLEE, the adequacy of the empirical treatment and global and related mortality were analysed. Results: 61 patients were analysed (67.2 ± 10 years). In 16 (26.2%) ES BLEE were found. Most commonly found species were Escherichia coli (20 cases/9 BLEE), Enterobacter spp (18/1), Serratia marcescens (11/3), Proteus mirabilis (11/1) and Klebsiella spp (9/2). Most frequent locations were blood (54.1%), respiratory tract (31.1%) and surgical wound (19.7%). Initial empirical treatment was not adequate in greater proportion in infections for ES BLEE (66.7% versus 15.9%, p < 0,0001). 26 patients died (42.6%). Global mortality was associated to an ES BLEE infection (odds ratio 5.3; CI 95% 1.3-21.5). Mortality attributed to enterobacteriaceae (14 patients) was higher when bacteremia was present (75% versus 22%, p < 0,02) and empirical treatment was not adequate (87.5% versus 43.7%, p = 0,05). Conclusions: Infections caused by ES BLEE in the cardiac postoperative period can be associated to higher mortality, especially when there is bacteremia. In suspicion of postoperative enterobacteriaceae infection, empirical treatment must be adjusted according to the local incidence of ES BLEE