Unresolved issues in the diagnosis of catheter related candidemia: A position paper.

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper.

Evaluación de la incidencia y tendencia de la enfermedad cerebrovascular en la región sanitaria de Lleida (España) en el periodo 2010-2014 / Assessment of incidence and trends in cerebrovascular disease in the healthcare district of Lleida (Spain) in the period 2010-2014

ObjetivoDeterminar la incidencia de la enfermedad cerebrovascular (ECV) y su tendencia en el área sanitaria de Lleida.Material y métodosEstudio de cohortes de base poblacional que incluyó a toda la población del área sanitaria de Lleida (440.000 personas). Se utilizaron los listados del Conjunto Mínimo Básico de Datos (CMBD) de urgencias y de las altas hospitalarias en el periodo comprendido entre enero de 2010 y diciembre de 2014. Se seleccionaron todos los episodios de ictus. Se evaluaron las tasas brutas y las tasas estandarizadas por edad utilizando la población mundial como referencia. Se excluyeron aquellos casos sin confirmación diagnóstica por neuroimagen.ResultadosSe incluyeron 4.397 casos, de los cuales 1.617 (36,8%) fueron ≥ 80 años; 3.969 (90,3%) sujetos sufrieron un ictus isquémico, mientras que 1.741 (39,6%) casos correspondieron a mujeres. La tasa de incidencia cruda osciló entre los 192 (intervalo de confianza [IC] del 95%: 179-205) en 2012 y los 211 (IC 95%: 197-224) en 2013 casos cada 100.000 habitantes. Las tasas estandarizadas por edad oscilaron entre los 93 (IC 95%: 86-100) en 2012 y los 104 (IC 95%: 96-111) en 2013 casos por cada 100.000 habitantes. En todos los años, las tasas de incidencia fueron significativamente mayores entre los varones en comparación con las mujeres; y se incrementaron con la edad.ConclusionesEl impacto de la ECV en Lleida es equiparable a otras regiones europeas, pero que el envejecimiento de la población se traduce en una incidencia bruta elevada que se mantiene estable en los 5 años analizados. (AU)

ObjectivesThis study aimed to determine the incidence and trends of cerebrovascular disease (CVD) in the healthcare district of Lleida.Material and methodsWe performed a population-based prospective cohort study including the entire population of the healthcare district of Lleida (440 000 people). Information was gathered from the minimum basic data set from the emergency department and hospital discharges for the period from January 2010 to December 2014. All types of stroke were included. We evaluated crude and age-standardised rates using the world population as a reference. Patients without neuroimaging confirmation of the diagnosis were excluded.ResultsWe identified 4397 patients: 1617 (36.8%) were aged 80 years or over; 3969 (90.3%) presented ischaemic stroke, and 1741 (39.6%) were women. The crude incidence rate ranged from 192 (95% confidence interval [CI], 179-205) to 211 (95% CI, 197-224) cases per 100 000 population, in 2012 and 2013, respectively. Age-standardised rates ranged from 93 (95% CI, 86-100) to 104 (95% CI, 96-111) cases per 100 000 population, in 2012 and 2013, respectively. For all years, incidence rates increased with age, and were significantly higher among men than among women.ConclusionThe impact of CVD in Lleida is comparable to that observed in other European regions. However, population ageing induces a high crude incidence rate, which remained stable over the five-year study period. (AU)

Assessment of incidence and trends in cerebrovascular disease in the healthcare district of Lleida (Spain) in the period 2010-2014. / Evaluación de la incidencia y tendencia de la enfermedad cerebrovascular en la región sanitaria de Lleida (España) en el periodo 2010-2014.

OBJECTIVES: This study aimed to determine the incidence and trends of cerebrovascular disease (CVD) in the healthcare district of Lleida. MATERIAL AND METHODS: We performed a population-based prospective cohort study including the entire population of the healthcare district of Lleida (440 000 people). Information was gathered from the minimum basic data set from the emergency department and hospital discharges for the period from January 2010 to December 2014. All types of stroke were included. We evaluated crude and age-standardised rates using the world population as a reference. Patients without neuroimaging confirmation of the diagnosis were excluded. RESULTS: We identified 4397 patients: 1617 (36.8%) were aged 80 years or over; 3969 (90.3%) presented ischaemic stroke, and 1741 (39.6%) were women. The crude incidence rate ranged from 192 (95% confidence interval [CI], 179-205) to 211 (95% CI, 197-224) cases per 100 000 population, in 2012 and 2013, respectively. Age-standardised rates ranged from 93 (95% CI, 86-100) to 104 (95% CI, 96-111) cases per 100 000 population, in 2012 and 2013, respectively. For all years, incidence rates increased with age, and were significantly higher among men than among women. CONCLUSION: The impact of CVD in Lleida is comparable to that observed in other European regions. However, population ageing induces a high crude incidence rate, which remained stable over the five-year study period.

Assessment of incidence and trends in cerebrovascular disease in the healthcare district of Lleida (Spain) in the period 2010-2014.

OBJECTIVES: This study aimed to determine the incidence and trends of cerebrovascular disease (CVD) in the healthcare district of Lleida. MATERIAL AND METHODS: We performed a population-based prospective cohort study including the entire population of the healthcare district of Lleida (440 000 people). Information was gathered from the minimum basic data set from the emergency department and hospital discharges for the period from January 2010 to December 2014. All types of stroke were included. We evaluated crude and age-standardised rates using the world population as a reference. Patients without neuroimaging confirmation of the diagnosis were excluded. RESULTS: We identified 4397 patients: 1617 (36.8%) were aged 80 years or over; 3969 (90.3%) presented ischaemic stroke, and 1741 (39.6%) were women. The crude incidence rate ranged from 192 (95% confidence interval [CI], 179-205) to 211 (95% CI, 197-224) cases per 100 000 population, in 2012 and 2013, respectively. Age-standardised rates ranged from 93 (95% CI, 86-100) to 104 (95% CI, 96-111) cases per 100 000 population, in 2012 and 2013, respectively. For all years, incidence rates increased with age, and were significantly higher among men than among women. CONCLUSION: The impact of CVD in Lleida is comparable to that observed in other European regions. However, population ageing induces a high crude incidence rate, which remained stable over the five-year study period.

Enfermedad de Fox-Fordyce en edad infantil / Fox-Fordyce Disease in a Pediatric Patient

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Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.

Antifungal susceptibility testing in Candida, Aspergillus and Cryptococcus infections: are the MICs useful for clinicians?

BACKGROUND: Invasive fungal infections (IFIs) represent a global issue and affect various patient populations. In recent years, resistant fungal isolates showing increased azole or echinocandin MICs have been reported, and their potential clinical impact has been investigated. AIMS: To provide an update on the epidemiology of resistance among fungi (e.g., Candida spp., Aspergillus spp., and Cryptococcus spp.) and to offer a critical appraisal of the relevant literature regarding the impact of MICs on clinical outcome in patients with IFI. SOURCES: PubMed search with relevant keywords along with a personal collection of relevant publications. CONTENT: Although antifungal resistance has been associated with a poorer response to antifungal therapy in various studies, other factors such as comorbidities, septic shock and source of infection appear to be key determinants affecting the clinical outcome of patients with IFI. IMPLICATIONS: Future international collaborative studies are required to tease out the relative contribution of in vitro antifungal resistance on patient outcomes, thus enabling the optimization of IFI management.

[A systematic review of the characteristics and prognosis of subjects who suffer an embolic stroke of undetermined source]. / Revision sistematica de las caracteristicas y pronostico de los sujetos que sufren un ictus criptogenico no lacunar de mecanismo embolico.

INTRODUCTION: The concept of embolic stroke of undetermined source (ESUS) has recently appeared to better characterise patients with cryptogenic stroke. PATIENTS AND METHODS: A systematic review of studies published since 2014 was performed to evaluate the epidemiology, clinical features and prognosis of patients with ESUS and their proportion among patients with cryptogenic stroke. RESULTS: Ten studies were identified with a total of 14,810 patients. The frequency of ESUS varied between 6% and 42%. We observed a high percentage of patients with cryptogenic stroke who met ESUS criteria (37-82%). The mean age of these patients was 65-68 years. The mean severity of the stroke, as measured using the National Institutes of Health Stroke Scale, was found to be 3-7 points. A high degree of variability was seen in the proportion of atrial fibrillation (detected during follow-up) related to the electrocardiogram monitoring technique. In five studies, some minor source of cardioembolism was observed in one out of every two patients, the most frequent being the persistence of patent foramen ovale. The risk of recurrence was 5-14.5%. CONCLUSION: The application of the new ESUS criteria provides a better definition of patients with cryptogenic stroke. Applying the concept of ESUS requires not only adequate electrocardiogram monitoring, but also routine complementary examinations to rule out the presence of minor sources of cardioembolism and other sources of embolism other than atrial fibrillation.

TITLE: Revision sistematica de las caracteristicas y pronostico de los sujetos que sufren un ictus criptogenico no lacunar de mecanismo embolico.Introduccion. Recientemente ha surgido el concepto de ictus criptogenico no lacunar de mecanismo embolico ­del ingles embolic stroke of undetermined source (ESUS)­ para caracterizar mejor a los pacientes con ictus criptogenico. Pacientes y metodos. Se realiza una revision sistematica de los estudios publicados desde 2014 hasta la actualidad, valorando la epidemiologia, las caracteristicas clinicas y el pronostico de los pacientes con ESUS y su proporcion entre los pacientes con ictus criptogenico. Resultados. Se identificaron 10 estudios con un total de 14.810 pacientes. La frecuencia de ESUS vario entre el 6 y el 42%. Se observo un porcentaje elevado de pacientes con ictus criptogenico que cumplian los criterios de ESUS (37-82%). La edad media de estos pacientes era de 65-68 años. La gravedad media del ictus, medida por la National Institutes of Health Stroke Scale, se establecio en 3-7 puntos. Se observo una alta variabilidad en la proporcion de fibrilacion auricular (detectada durante el seguimiento) relacionada con la tecnica de monitorizacion del electrocardiograma. En cinco estudios, hasta en uno de cada dos pacientes se observo alguna fuente de cardioembolismo menor, la mas frecuente, la persistencia del foramen oval permeable. El riesgo de recurrencia fue del 5-14,5%. Conclusion. La aplicacion de los nuevos criterios de ESUS define mejor a los pacientes con ictus criptogenico. La aplicacion del concepto de ESUS exige no solo una monitorizacion de electrocardiograma adecuada, sino exploraciones complementarias de rutina para descartar la presencia de fuentes de cardioembolismo menor y de otras fuentes de embolismo diferentes a la fibrilacion auricular.

Is biofilm production a prognostic marker in adults with candidaemia?

OBJECTIVES: The role of biofilm production in the outcome of candidaemia remains under discussion. Current evidence relies on variable biofilm detection methods while evaluating distinct clinical end points. We aimed to determine the impact of biofilm production measured by metabolic activity (MA) and biomass (BM) on the prognosis of adults with candidaemia. METHODS: Retrospective cohort including 280 adults with candidaemia admitted from 2010 to 2016. BM was assessed using crystal violet binding stain and the XTT reduction assay was used to detect MA. Strains were classified as high and moderate-low biofilm producers according to published cut-offs. The primary outcome was overall mortality within 7 and 30 days. The secondary outcome was unfavourable prognosis defined as metastatic infection, admission to an intensive care unit due to the severity of candidaemia, or death within 30 days. RESULTS: High BM and high MA were detected in 90 (32.1%) and 114 (40.7%) of the 280 isolates, respectively. Comparison of high and moderate-low biofilm forming isolates revealed no correlation between biofilm production and 7-day mortality (BM high 15/90 (16.7%) versus moderate-low 24/190 (12.6%); MA high 12/114 (10.5%) versus moderate-low 27/166 (16.3%)), 30-day mortality (BM high 34/90 (37.8%) versus moderate-low 61/190 (32.1%); MA high 33/114 (28.9%) versus moderate-low 62/166 (37.3%)), or unfavourable prognosis (BM high 45/90 (50.0%) versus moderate-low 73/190 (38.4%); MA high 41/114 (36.0%) versus moderate-low 77/166 (46.4%)). CONCLUSIONS: Biofilm production was not a predictor of mortality or of unfavourable prognosis in adults with candidaemia.

Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model.

BACKGROUND: In mechanically ventilated, lung injured, patients without spontaneous breathing effort, atelectasis with shunt and desaturation may appear suddenly when ventilator pressures are decreased. It is not known how such a formation of atelectasis is related to transpulmonary pressure (PL ) during weaning from mechanical ventilation when the spontaneous breathing effort is increased. If the relation between PL and atelectasis were known, monitoring of PL might help to avoid formation of atelectasis and cyclic collapse during weaning. The main purpose of this study was to determine the relation between PL and atelectasis in an experimental model representing weaning from mechanical ventilation. METHODS: Dynamic transverse computed tomography scans were acquired in ten anaesthetized, surfactant-depleted pigs with preserved spontaneous breathing, as ventilator support was lowered by sequentially reducing inspiratory pressure and positive end expiratory pressure in steps. The volumes of gas and atelectasis in the lungs were correlated with PL obtained using oesophageal pressure recordings. Work of breathing (WOB) was assessed from Campbell diagrams. RESULTS: Gradual decrease in PL in both end-expiration and end-inspiration caused a proportional increase in atelectasis and decrease in the gas content (linear mixed model with an autoregressive correlation matrix; P < 0.001) as the WOB increased. However, cyclic alveolar collapse during tidal ventilation did not increase significantly. CONCLUSION: We found a proportional correlation between atelectasis and PL during the 'weaning process' in experimental mild lung injury. If confirmed in the clinical setting, a gradual tapering of ventilator support can be recommended for weaning without risk of sudden formation of atelectasis.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

The misleading effect of serum galactomannan testing in high-risk haematology patients receiving prophylaxis with micafungin.

OBJECTIVES: To investigate the performance of the routine serum galactomannan (sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk haematology patients receiving prophylaxis with micafungin. METHODS: Retrospective study including all haematological patients who received prophylaxis with micafungin during high-risk IA episodes (neutropenic patients after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome; allogeneic haematopoietic stem-cell transplantation during early neutropenic phase or graft-versus-host disease requiring high prednisone doses) and for whom at least one sGM result was available. Episodes were classified as follows: true-positive (positive GM in the context of IA), false-positive (positive GM result in patients who had no evidence of IA), true-negative (negative GM test results and no IA), or false-negative (negative GM test in the context of IA). Non-evaluable patients were excluded. RESULTS: Among 146 evaluable episodes, four were true-positive in the context of probable breakthrough IA (incidence of breakthrough IA, 2.7%); 111/146 high-risk episodes (76%) were considered true-negative and 31/146 (21.2%) were considered false-positive. No false-negative episodes were detected. All but one of the false-positive episodes were detected in surveillance GM tests, leading to high-resolution CT scans in eight cases (8/31; 25.8%), all of which were negative. The positive predictive and negative predictive values of sGM for surveillance and diagnostic approaches were 3.2% (1/31) and 100% (110/110) and 75% (3/4) and 100% (1/1), respectively. CONCLUSIONS: Surveillance of asymptomatic patients receiving prophylaxis with micafungin using sGM is unnecessary, because the results are either negative or false-positive. However, sGM remains useful in the diagnosis of breakthrough IA in symptomatic patients during prophylaxis.

No evidence of increased ocular involvement in candidemic patients initially treated with echinocandins.

Candins are commonly used as initial therapy in patients with candidemia and are known to diffuse poorly into ocular tissue. The aim of our multicenter study was to assess whether eye involvement was more common in patients initially treated with echinocandins. We performed a post hoc analysis of a prospective, multicenter, population-based candidemic surveillance program implemented in Spain during 2010-2011 (CANDIPOP project). Eye involvement was detected in 13 of 168 patients with candidemia (7.7%) who underwent ophthalmoscopy. Two patients had endophthalmitis, while the remaining patients had chorioretinitis. The frequency of ocular candidiasis was similar in patients receiving initial therapy with candins (3/56; 5.4%) or with other regimens (10/112; 8.9%). At multivariate analysis, risk conditions for eye involvement were dialysis after candidemia (OR, 19.4; 95% CI, 1.7-218.4) and involvement of organs other than the eye (OR, 5.4; 95% CI, 1.1-25.7). In conclusion, eye involvement was not found to be more frequent in patients receiving initial therapy with echinocandins than in patients receiving other drugs.

Association between source control and mortality in 258 patients with intra-abdominal candidiasis: a retrospective multi-centric analysis comparing intensive care versus surgical wards in Spain.

Early empiric therapy and adequate resuscitation have been identified as main predictors of outcome in patients with candidemia or bacteremia. Moreover, source control is a major determinant in infectious sites when feasible, as a main technique to reduce microbiological burden. A retrospective, multicenter, cohort study was performed at surgical wards and intensive care units (ICU) of three University Hospitals in Spain between 2010 and 2014, with the aim of improving understanding of the interaction between source control, early antifungal therapy, and use of vasoactives in patients with intra-abdominal candidiasis (IAC). Source control was defined as all physical actions taken to control a focus of infection and reduce the favorable conditions that promote microorganism growth or that maintain the impairment of host defenses. Two hundred and fifty-eight patients with IAC were identified. Sixty-one patients were at ICU for diagnosis. Mortality was higher in the ICU group compared to what was documented for the non-ICU group (35 % vs 19.5 %, p = 0011). Adequate source control within 48 h of diagnosis was achieved in 60 % of the cohort. In multivariate analysis, inadequate source control was identified as the only common risk factor for 30-day mortality in both groups (ICU group OR: 13.78 (95% CI: 2.60-72.9, p = 0.002) and non-ICU group OR: 6.53 (95% CI: 2.56-16.61, p = <0.001). The population receiving both adequate source control and adequate antifungal treatment was the one associated with a higher survival rate, in both the ICU and surgical groups. Source control remains a key element in IAC, inside and outside the intensive care unit. Early antifungal treatment among ICU patients was associated with lower mortality.

Risk factors for late recurrent candidaemia. A retrospective matched case-control study.

Incidence, risk factors and clinical significance of late recurrent (LR) candidaemia (>1 month between episodes) remains unclear. The 1219 episodes of candidaemia detected from January 1985 to December 2014 were reviewed. We selected all cases with more than one episode separated by at least 30 days after clinical resolution in the interim (cases) and compared each of them with two controls (patients with single episodes of candidaemia). Clinical strains were genotyped to differentiate relapses from re-infection. Eighteen patients (1.48%) had 36 episodes of LR candidaemia (median 4 months). Independent risk factors for recurrence in the multivariate analysis were: underlying gastrointestinal disease (OR 67.16; 95% CI 5.23-861.71; p 0.001) and fungaemia due to Candida parapsilosis (OR 9.10; 95% 1.33-62.00; p 0.02). All episodes of LR candidaemia diagnosed during the first 3 months were due to an intravascular source of infection, whereas in those occurring after 3 months the main source of the disease was the abdomen, followed by endocarditis, and urinary tract. Molecular typing showed that 42.9% of LR candidaemias were relapses and 57.1% were re-infections. Neither time of recurrence nor clinical origin could predict type of recurrence. LR candidaemia is a relatively rare event that is more frequent in patients who have an initial episode of candidaemia due to C. parapsilosis or an underlying gastrointestinal disease. Episodes of LR candidaemia that occur within the first 3 months should prompt an attempt to exclude an intravascular source of infection, whereas those occurring later point to an intra-abdominal origin.

Analysis of allergy alerts registered in a hospital electronic health record system

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