Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

BACKGROUND: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018 - 2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n= 10), mucormycosis (n= 8), histoplasmosis (n= 2), cryptococcosis (n= 2), and others (n= 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSIONS: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study.

OBJECTIVES: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. METHODS: BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. RESULTS: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases. CONCLUSIONS: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.

El trasplante de microbiota fecal es un tratamiento sencillo, efectivo y seguro en el manejo de la infección por C. difficile en la práctica clínica diaria / Faecal microbiota transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice

Introducción: El trasplante de microbiota fecal (TMF) es un tratamiento avalado por evidencia científica amplia y muy efectivo en el manejo de la infección por Clostridioides difficile (CD). El objetivo de este estudio es analizar su efectividad y seguridad en un ámbito de práctica clínica real. Métodos: Estudio observacional retrospectivo, unicéntrico y descriptivo, en el que se recogieron todos los TMF realizados entre mayo de 2016 y diciembre de 2020. Se definió como éxito técnico la administración exitosa del preparado fecal en el tracto gastrointestinal del receptor y éxito clínico la desaparición de la diarrea en las primeras 72 h tras el procedimiento y ausencia de recidiva a las ocho semanas. Resultados: Se realizaron 15 TMF a 13 pacientes. La edad media de los pacientes fue de 73 ± 19,4 años (rango: 40 a 98 años); siendo el 60% mujeres. La indicación del TMF fue la colitis recidivante por CD en el 84,6%. Todos los TMF se realizaron por colonoscopia y de donantes emparentados. Con un primer procedimiento, el TMF fue efectivo en 11 de 13 pacientes (84,61%; IC 95%; 54,55-98,07). El tiempo hasta la resolución de los síntomas fue menos de 48 h en todos los casos. El seguimiento postrasplante fue de 25,66 ± 17,5 meses. No se registraron complicaciones precoces ni tardías significativas en el seguimiento. Conclusión: El TMF es un procedimiento sencillo, eficaz y seguro en la infección por CD, incluso en pacientes de edad muy avanzada o con grandes comorbilidades.(AU)

Introduction: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile (CD) infection. The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. Methods: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the fecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started. Results: 15 FMT were performed in 13 patients. The mean age of the patients was 73 ± 19,4 years (range: 40–98 years); being 60% women. The indication for FMT was relapsing colitis due to CD in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the TMF was effective in 11 of 13 patients (84.61%; 95% CI; 54.55–98.07). Time until resolution of symptoms was less than 48h in all cases. Post-transplant follow-up was 25.66 ± 17.5 months. No significant short or long-term complications were recorded at follow-up. Conclusion: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.(AU)

Sequential oral antibiotic in uncomplicated Staphylococcus aureus bacteraemia: a propensity-matched cohort analysis.

OBJECTIVES: We aimed to analyse the efficacy and safety of oral sequential therapy (OST) in uncomplicated Staphylococcus aureus bacteraemia (SAB). METHODS: Single-centre observational cohort at a tertiary hospital in Spain, including all patients with the first SAB episode from January 2015 to December 2020. We excluded patients with complicated SAB and those who died during the first week. Patients were classified into the OST group (patients who received oral therapy after initial intravenous antibiotic therapy [IVT]), and IVT group (patients who received exclusively IVT). We performed a propensity-score matching to balance baseline differences. The primary composite endpoint was 90-day mortality or microbiological failure. Secondary endpoints included 90-day SAB relapse. RESULTS: Out of 407 SAB first episodes, 230 (56.5%) were included. Of these, 112 (n = 48.7%) received OST and 118 (51.3%) IVT exclusively. Transition to oral therapy was performed after 7 days (interquartile range, 4-11). The primary endpoint occurred in 10.7% (11/112) in OST vs. 30.5% (36/118) in IVT (p < 0.001). SAB relapses occurred in 3.6% (4/112) vs. 1.7% (2/118) (p 0.436). None of the deaths in OST were related to SAB or its complications. After propensity-score matching, the primary endpoint was not more frequent in the OST group (relative risk, 0.42; 95% CI, 0.22-0.79). Ninety-day relapses occurred similarly in both groups (relative risk, 1.35; 95% CI, 0.75-2.39). DISCUSSION: After an initial intravenous antibiotic, patients with uncomplicated SAB can safely be switched to oral antibiotics without apparent adverse outcomes. This strategy could save costs and complications of prolonged hospital stays. Prospective randomized studies are needed.

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice.

INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile infection (CDI). The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the faecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhoea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started. RESULTS: 15 FMT were performed in 13 patients. Median age was 79 years (range: 40-98 years); being 60% women and 33.3% depedent persons. The indication for FMT was recurrent CDI in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the FMT was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48 h in all cases. Post-transplant follow-up was 25.66 ±â€¯17.5 months. No significant short or long-term complications were recorded at follow-up. CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic.

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

Evidence of Fluconazole-Resistant Candida parapsilosis Genotypes Spreading across Hospitals Located in Madrid, Spain and Harboring the Y132F ERG11p Substitution.

We have been monitoring the antifungal resistance in Candida parapsilosis isolates collected from inpatients at Madrid metropolitan area hospitals for the last 3 years. The study aimed to elucidate the presence of fluconazole-resistant C. parapsilosis genotypes in Madrid. From January 2019 to December 2021, a total of 354 C. parapsilosis isolates (n = 346 patients) from blood (76.6%) or intraabdominal samples were collected and genotyped using species-specific microsatellite markers. Antifungal susceptibilities to amphotericin B, the triazoles, micafungin, anidulafungin, and ibrexafungerp were performed according to EUCAST E.Def 7.3.2; the ERG11 gene was sequenced in fluconazole-resistant isolates. A total of 13.6% (n = 48/354) isolates (one per patient) were found to be resistant to fluconazole and non-wild-type to voriconazole but fully susceptible to ibrexafungerp. Resistant isolates were mostly sourced from blood (n = 45/48, 93.8%) and were detected in five hospitals. Two hospitals accounted for a high proportion of resistant isolates (n = 41/48). Resistant isolates harbored either the Y132F ERG11p amino acid substitution (n = 43) or the G458S substitution (n = 5). Isolates harboring the Y132F substitution clustered into a clonal complex involving three genotypes (one genotype accounted for n = 39/43 isolates) that were found in four hospitals. Isolates harboring the G458S substitution clustered into another genotype found in a fifth hospital. C. parapsilosis genotypes demonstrating resistance to fluconazole have been spreading across hospitals in Madrid, Spain. Over the last 3 years, the frequency of isolation of such isolates and the number of hospitals affected is on the rise.

Impact of the COVID-19 Pandemic on the Clinical Profile of Candidemia and the Incidence of Fungemia Due to Fluconazole-Resistant Candida parapsilosis.

Severely ill COVID-19 patients are at high risk of nosocomial infections. The aim of the study was to describe the characteristics of candidemia during the pre-pandemic period (January 2019−February 2020) compared to the pandemic period (March 2020−September 2021). Antifungal susceptibilities were assessed using the EUCAST E.Def 7.3.2 broth dilution method. Fluconazole-resistant C. parapsilosis isolates (FRCP) were studied for sequencing of the ERG11 gene. The incidence of candidemia and C. parapsilosis bloodstream infection increased significantly in the pandemic period (p = 0.021). ICU admission, mechanical ventilation, parenteral nutrition and corticosteroids administration were more frequent in patients with candidemia who had been admitted due to COVID-19. Fifteen cases of FRCP fungemia were detected. The first case was recorded 10 months before the pandemic in a patient transferred from another hospital. The incidence of FRCP in patients admitted for COVID-19 was 1.34 and 0.16 in all other patients (p < 0.001). ICU admission, previous Candida spp. colonization, arterial catheter use, parenteral nutrition and renal function replacement therapy were more frequent in patients with candidemia due to FRCP. All FRCP isolates showed the Y132F mutation. In conclusion, the incidence of candidemia experienced an increase during the COVID-19 pandemic and FRCP fungemia was more frequent in patients admitted due to COVID-19.

Unreliability of Clinical Prediction Rules to Exclude without Echocardiography Infective Endocarditis in Staphylococcus aureus Bacteremia.

BACKGROUND: It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE, and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. METHODS: We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cutoff points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. RESULTS: Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE, and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95% CI 0.10-0.54, p = 0.001). CONCLUSION: PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

Effective definition of low humoral response to Clostridioides difficile infection.

BACKGROUND: Determination of the humoral response to Clostridioides difficile (CD) toxins could be of great value in the management of patients with CD infection (CDI). METHODS: A prospective study was conducted on the clinical characteristics and humoral response in patients with CDI. Determination of ELISA IgG CD anti-toxin B (tgcBiomics, Germany) was performed. The following dilutions were planned for each patient, 1:100, 1: 200, 1: 400, 1: 800: 1: 1600. A significant concentration of antibody was considered to be present in each dilution if an optical density 0.2 units higher than the negative control of the technique was evident. RESULTS: Eighty-five patients were included during the study period, November 2018-February 2020. The median age was 73 years (interquartile range: 62.5-85 years), with female predominance (45 patients, 52.9%). Thirty-nine patients (45.9%) had a severe infection. Seven patients (8.2%) had suffered an episode of CDI in the previous three months. Seventeen patients (20%) had one or more recurrent episodes during the three-month follow-up: No patient died during admission or required surgery for severe-complicated infection. The incidence of recurrence in patients with no antibody detected at 1:400 dilution was 25.4% (16 patients) while it was 4.3% (one patient) in patients with antibody present at that dilution (p = 0.03). Liver cirrhosis was associated with higher humoral response against CD. CONCLUSIONS: Antibodies IgG CD anti-toxin B detection at a dilution of 1:400, using a B ELISA technique, effectively identified patients at increased risk of recurrence. This information could help assist in the management of patients.

A retrospective validation of different scores of guideline adherence and infectious diseases consultation on candidaemia: The higher, the better.

BACKGROUND: Recently, several scores to quantify compliance with the guidelines in candidaemia management (EQUAL, GEMICOMED, Valerio) have been developed. Evidence supporting the association of these scores to the prognosis is scarce. We aim to evaluate the performance of these candidaemia guideline adherence scores to predict candidaemia outcome. METHODS: We recorded retrospectively data from candidaemia episodes (January 2017-December 2018). We analysed adherence to guidelines for candidaemia management according to EQUAL, GEMICOMED and Valerio scores, and we correlated those to outcome. RESULTS: Fifty-four first episodes of candidaemia were retrieved. Five patients who died in the first 48 hours after blood cultures were not included. Thirty-day mortality in evaluable patients was 18.4%. Median adherence to guidelines according to EQUAL score was 17 (interquartile range [IQR]: 15-19), and according to GEMICOMED was 86% (IQR: 72.5%-100%). According to Valerio score, adequacy of antifungal prescription was 8.5/10 (SD: 1.9). A cut-off of ≥17 for EQUAL or compliance >70% for GEMICOMED was associated with inferior 30-day mortality (7.1% vs 33.3%, P = .028 and 7.9% vs 54.5%, P = .002, respectively). Infectious diseases (ID) evaluated cases obtained a better EQUAL score (>17; 82.1% vs 42.9%, P = .006), had inferior 30-day mortality (9.4% vs 35.3%, P = .049) and a better antifungal prescription adequacy (Valerio score 9.0 vs 7.5, P = .011). CONCLUSION: Adherence to guidelines for candidaemia management evaluated by means of EQUAL and GEMICOMED score was associated with a decreased 30-day mortality. Adequacy of antifungal prescription can be ameliorated. ID consultation improved guideline adherence and was associated with decreased 30-day mortality.

PET/TC con 18F-FDG en la sospecha de infección asociada a dispositivos intracardiacos: rendimiento y utilidad diagnóstica / PET/CT with 18F-FDG in suspected intracardiac device-related infections: analysis of performance and diagnostic usefulness

Introducción y objetivos Las infecciones relacionadas con dispositivos intracardiacos (i-DIC) son potencialmente graves y requieren un diagnóstico precoz y certero. Los objetivos del estudio son analizar el rendimiento de la tomografía por emisión de positrones con tomografía computarizada (PET/TC) ante sospecha de i-DIC y los cambios que induce sobre el diagnóstico inicial e identificar el escenario con mayor beneficio de uso. Métodos Estudio retrospectivo de pacientes valorados mediante PET/TC por sospecha de i-DIC desde 2011 a 2018. Se calcularon valores de rendimiento diagnóstico de la PET/TC y la concordancia entre diagnóstico inicial y post-PET y el diagnóstico definitivo. Se analizaron los cambios diagnósticos considerando la sospecha clínica inicial para identificar a los pacientes con mayor beneficio. Resultados Se incluyó a 44 pacientes. La prevalencia de endocarditis fue del 57%. La sensibilidad y la especificidad de la 18F-FDG-PET/TC para el diagnóstico de endocarditis fueron 0,84 y 0,95. El diagnóstico tras la PET mejoró el inicial un 45%. De los pacientes con sospecha de infección local, la PET/TC reclasificó adecuadamente al 57% por detección de infección profunda. Conclusiones La PET/TC muestra elevado rendimiento diagnóstico ante la sospecha de i-DIC y mejora significativamente el diagnóstico convencional, sobre todo en el grupo de pacientes con sospecha de infección limitada al bolsillo. (AU)

Introduction and objectives Cardiac device-related infections (CDRI) may be life-threatening and require early and accurate diagnosis. The aims of this study were to analyze the performance of positron emission tomography-computed tomography (PET/CT) in suspected CDRI, to assess changes to the initial diagnosis, and to identify a clinical subgroup deriving the greatest benefit from this imaging modality. Methods Retrospective study including patients evaluated by PET/CT for suspected CDRI from 2011 to 2018. We assessed PET/CT performance and the agreement between the initial, post-PET and definitive diagnoses. We also assessed changes in the diagnosis, depending on initial clinical suspicion, to identify patients deriving the greatest benefit from PET/CT. Results We included 44 patients. The prevalence of endocarditis was 57%. The sensitivity and specificity of PET/CT for the diagnosis of infective endocarditis were 0.84 and 0.95, respectively. Post-PET diagnosis improved the initial diagnosis by 45%. PET/CT correctly reclassified 57% of patients with initial suspicion of generator pocket infection by detecting lead infection. Conclusions PET/CT showed high diagnostic performance in suspected of CDRI and significantly improved the conventional diagnostic approach, especially in patients with initial suspicion of focal infection. (AU)

PET/CT with 18F-FDG in suspected intracardiac device-related infections: analysis of performance and diagnostic usefulness.

INTRODUCTION AND OBJECTIVES: Cardiac device-related infections (CDRI) may be life-threatening and require early and accurate diagnosis. The aims of this study were to analyze the performance of positron emission tomography-computed tomography (PET/CT) in suspected CDRI, to assess changes to the initial diagnosis, and to identify a clinical subgroup deriving the greatest benefit from this imaging modality. METHODS: Retrospective study including patients evaluated by PET/CT for suspected CDRI from 2011 to 2018. We assessed PET/CT performance and the agreement between the initial, post-PET and definitive diagnoses. We also assessed changes in the diagnosis, depending on initial clinical suspicion, to identify patients deriving the greatest benefit from PET/CT. RESULTS: We included 44 patients. The prevalence of endocarditis was 57%. The sensitivity and specificity of PET/CT for the diagnosis of infective endocarditis were 0.84 and 0.95, respectively. Post-PET diagnosis improved the initial diagnosis by 45%. PET/CT correctly reclassified 57% of patients with initial suspicion of generator pocket infection by detecting lead infection. CONCLUSIONS: PET/CT showed high diagnostic performance in suspected of CDRI and significantly improved the conventional diagnostic approach, especially in patients with initial suspicion of focal infection.

Primera encuesta nacional sobre el diagnóstico de la infección por Helicobacter pylori en los laboratorios de microbiología clínica en España / First national survey of the diagnosis of Helicobacter pylori infection in Clinical Microbiology Laboratories in Spain

INTRODUCCIÓN: El objetivo de este trabajo fue conocer, mediante una encuesta nacional, los métodos y técnicas empleados para el diagnóstico de Helicobacter pylori (Hp) en los distintos servicios/laboratorios de microbiología clínica en España, así como datos de resistencia antibiótica. MÉTODOS: En la encuesta se preguntaba sobre los métodos de diagnóstico realizados (serología, detección de antígeno en heces, cultivo de biopsias gástricas y PCR) y por la realización de pruebas de sensibilidad antibiótica. También fueron solicitados el número de muestras procesadas en 2016, la positividad de cada técnica empleada y porcentajes de resistencia antibiótica. La encuesta fue enviada por correo electrónico entre octubre y diciembre de 2017 a los responsables de 198 laboratorios de microbiología clínica. RESULTADOS: En total, 51 centros de 29 provincias respondieron a la encuesta y 48 de ellos realizaban algún tipo de técnica de diagnóstico de Hp en su laboratorio. En cuanto a las técnicas empleadas, el cultivo de biopsia gástrica fue el más utilizado (37/48), seguido de la detección de antígeno en heces (35/48), la serología (19/48) y la PCR (5/48). Respecto a la sensibilidad antibiótica, se observaron altas tasas de resistencia, especialmente a metronidazol y claritromicina (superiores al 33%). CONCLUSIÓN: El cultivo de biopsia gástrica fue la técnica diagnóstica de Hp utilizada por más centros, mientras que la detección de antígeno en heces mediante inmunocromatografía fue con la que se analizaron el mayor número de muestras. En España, en la actualidad, es preocupante el aumento de resistencia de Hp a antibióticos de «primera línea»

INTRODUCTION: The aim of this study was to know, through a national survey, the methods and techniques used for the diagnosis of Helicobacter pylori (Hp) in the different Clinical Microbiology Services/Laboratories in Spain, as well as antibiotic resistance data. METHODS: The survey requested information about the diagnostic methods performed for Hp detection in Clinical Microbiology laboratories, including serology, stool antigen, culture from gastric biopsies, and PCR. In addition, the performance of antibiotic susceptibility was collected. Data on the number of samples processed in 2016, positivity of each technique and resistance data were requested. The survey was sent by email (October-December 2017) to the heads of 198 Clinical Microbiology Laboratories in Spain. RESULTS: Overall, 51 centers from 29 regions answered the survey and 48/51 provided Hp microbiological diagnostic testing. Concerning the microbiological methods used to diagnose Hp infection, the culture of gastric biopsies was the most frequent (37/48), followed by stool antigen detection (35/48), serology (19/48) and biopsy PCR (5/48). Regarding antibiotic resistance, high resistance rates were observed, especially in metronidazole and clarithromycin (over 33%). CONCLUSION: Culture of gastric biopsies was the most frequent method for detection of Hp, but the immunochromatographic stool antigen test was the one with which the largest number of samples were analyzed. Nowadays, in Spain, it concerns the problem of increased antibiotic resistance to 'first-line' antibiotics

Azole and Amphotericin B MIC Values against Aspergillus fumigatus: High Agreement between Spectrophotometric and Visual Readings Using the EUCAST EDef 9.3.2 Procedure.

The EUCAST EDef 9.3.2 procedure recommends visual readings of azole and amphotericin B MICs against Aspergillus spp. Visual determination of MICs may be challenging. In this work, we aim to obtain and compare visual and spectrophotometric MIC readings of azoles and amphotericin B against Aspergillus fumigatussensu lato isolates. A total of 847 A. fumigatussensu lato isolates (A. fumigatus sensu stricto [n = 828] and cryptic species [n = 19]) were tested against amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole using the EUCAST EDef 9.3.2 procedure. Isolates were classified as susceptible or resistant/non-wild type according to the 2020 updated breakpoints. The area of technical uncertainty for the azoles was defined in the updated breakpoints. Visual and spectrophotometric (fungal growth reduction of >95% compared to the control, read at 540 nm) MICs were compared. Essential (±1 2-fold dilution) and categorical agreements were calculated. Overall, high essential (97.1%) and categorical (99.6%) agreements were found. We obtained 100% categorical agreements for amphotericin B, itraconazole, and posaconazole, and consequently, no errors were found. Categorical agreements were 98.7 and 99.3% for voriconazole and isavuconazole, respectively. Most of the misclassifications for voriconazole and isavuconazole were found to be associated with MIC results falling either in the area of technical uncertainty or within one 2-fold dilution above the breakpoint. The resistance rate was slightly lower when the MICs were obtained by spectrophotometric readings. However, all relevant cyp51A mutants were correctly classified as resistant. Spectrophotometric determination of azole and amphotericin B MICs against A. fumigatussensu lato isolates may be a convenient alternative to visual endpoint readings.

Epidemiología y clínica de las infecciones y colonizaciones causadas por enterobacterias productoras de carbapenemasas en un hospital de tercer nivel / Epidemiology and clinical of infections and colonizations caused by Enterobacterales producing carbapenemases in a tertiary hospital

OBJETIVOS: Describir la epidemiologia de las Enterobacterias portadoras de carbapenemasas (EPC) en un hospital de tercer nivel. MATERIAL Y MÉTODOS: Estudio observacional retrospectivo, se incluyeron todos los pacientes con muestra positiva para EPC atendidos en hospitalización o en el servicio de Urgencias, entre el 1 Enero de 2014 y el 31 de Diciembre de 2016. RESULTADOS: Se incluyeron 272 pacientes (316 muestras): 155 (57%) varones. Media de edad de 70,4 años (IC 95% 68,2-72,7). Media del índice de Charlson 3,6 (IC95% 3,4-3,8). En el 63,2% la adquisición fue nosocomial, en el 35,3% fue asociada a cuidados sanitarios (ACS). Presentaron infección el 55,1%, siendo la más frecuente la infección del tracto urinario (ITU) (58,7%). Las especies más frecuentes fueron Klebsiella pneumoniae (62,7%) y Enterobacter cloacae (10,1%). Los tipos de carbapenemasa más frecuente fueron OXA-48 (53,8%) y VIM (43%). La adquisición nosocomial se asoció con el género masculino, trasplante, inmunosupresión, ingreso en Unidad de Cuidados Intensivos (UCI) o Servicio Quirúrgico, tratamiento antibiótico previo, Enterobacter, VIM, infecciones respiratorias e intraabdominales. La adquisición ACS se asoció con mayor edad y comorbilidad, procedencia de residencia, sondaje vesical, mayor número de procedimientos ambulatorios, ingreso hospitalario previo, K. pneumoniae y E. coli, OXA-48, coproducción de betalactamasas de espectro extendido, ITU y sepsis. CONCLUSIONES: Los pacientes que adquieren la EPC en residencias presentan frecuentemente infección. Los pacientes con adquisición nosocomial se colonizan por EPC en la UCI, en relación a procedimientos invasivos y trasplante. Esta población presenta mayor mortalidad por desarrollar infecciones respiratorias por EPC

OBJECTIVE: To describe the epidemiology of Enterobacterales producing carbapenemases (EPC) in a tertiary hospital. MATERIAL AND METHODS: A retrospective observational study, all patients with a positive sample for EPC treated in hospitalization or in the Emergency Department were included, between January 1, 2014 and December 31, 2016. RESULTS: A total of 272 patients (316 samples) were included: 155 (57%) male. Mean age of 70.4 years (95% CI 68.2 -72.7). Mean Charlson index was 3.6 (95% CI 3.4-3.8). In 63.2% the acquisition was nosocomial, in 35.3% it was health-care associated (HA). 55.1% presented infection, the most frequent infection was urinary tract infection (UTI) (58.7%). The most frequent species were Klebsiella pneumoniae (62.7%) and Enterobacter cloacae (10.1%). The most frequent types of carbapenemase were OXA-48 (53.8%) and VIM (43%). The nosocomial acquisition was associated with the male gender, transplantation, immunosuppression, admission to the Intensive Care Unit (ICU) or surgical service, prior antibiotic treatment, Enterobacter, VIM, respiratory and intra-abdominal infections. The HA acquisition was associated with age and comorbidity, nursery home origin, bladder catheterization, greater number of outpatient procedures, previous hospital admission, K. pneumoniae and E. coli, OXA-48, coproduction of extended spectrum betalactamases, UTI and sepsis. CONCLUSIONS: Patients who acquire EPC in nursery homes frequently have an infection. Patients with nosocomial acquisition are colonized by EPC in the ICU, in relation to invasive procedures and transplantation. This population has a higher mortality due to developing respiratory infections by EPC

First national survey of the diagnosis of Helicobacter pylori infection in Clinical Microbiology Laboratories in Spain. / Primera encuesta nacional sobre el diagnóstico de la infección por Helicobacter pylori en los laboratorios de microbiología clínica en España.

INTRODUCTION: The aim of this study was to know, through a national survey, the methods and techniques used for the diagnosis of Helicobacter pylori (Hp) in the different Clinical Microbiology Services/Laboratories in Spain, as well as antibiotic resistance data. METHODS: The survey requested information about the diagnostic methods performed for Hp detection in Clinical Microbiology laboratories, including serology, stool antigen, culture from gastric biopsies, and PCR. In addition, the performance of antibiotic susceptibility was collected. Data on the number of samples processed in 2016, positivity of each technique and resistance data were requested. The survey was sent by email (October-December 2017) to the heads of 198 Clinical Microbiology Laboratories in Spain. RESULTS: Overall, 51 centers from 29 regions answered the survey and 48/51 provided Hp microbiological diagnostic testing. Concerning the microbiological methods used to diagnose Hp infection, the culture of gastric biopsies was the most frequent (37/48), followed by stool antigen detection (35/48), serology (19/48) and biopsy PCR (5/48). Regarding antibiotic resistance, high resistance rates were observed, especially in metronidazole and clarithromycin (over 33%). CONCLUSION: Culture of gastric biopsies was the most frequent method for detection of Hp, but the immunochromatographic stool antigen test was the one with which the largest number of samples were analyzed. Nowadays, in Spain, it concerns the problem of increased antibiotic resistance to 'first-line' antibiotics.

Hospital-acquired infective endocarditis during Covid-19 pandemic.

BACKGROUND: The COVID pandemic has had a major impact on healthcare in hospitals, including the diagnosis and treatment of infections. Hospital-acquired infective endocarditis (HAIE) is a severe complication of medical procedures that has shown a progressive increase in recent years. OBJECTIVES: To determine whether the incidence of HAIE during the first two months of the epidemic (March-April 2020) was higher than previously observed and to describe the clinical characteristics of these cases. The probability of the studied event (HAIE) during the study period was calculated by Poisson distribution. RESULTS: Four cases of HAIE were diagnosed in our institution during the study period. The incidence of HAIE during the study period was 2/patient-month and 0.3/patient-month during the same calender months in the previous 5 years (p=0.033). Two cases presented during admission for COVID-19 with pulmonary involvement treated with methylprednisolone and tocilizumab. The other two cases were admitted to the hospital during the epidemic. All cases underwent central venous and urinary catheterization during admission. The etiology of HAIE was Enterococcus faecalis (2 cases), Staphylococcus aureus and Candida albicans (one case each). A source of infection was identified in three cases (central venous catheter, peripheral venous catheter, sternal wound infection, respectively). One patient was operated on. Two patients died during hospital admission. CONCLUSIONS: The incidence of HAIE during COVID-19 pandemic in our institution was higher than usual. In order to reduce the risk of this serious infection, optimal catheter care and early treatment of every local infection should be prioritized during coronavirus outbreaks.

Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization.

The pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients admitted in two Spanish hospitals with a resistant profile against echinocandins associated with different mutations in hot-spot 1 of FKS2 gene. For two of these patients susceptible FKS wild-type isolates obtained prior to resistant ones were also investigated. Isolates were genotyped using multilocus sequence typing and microsatellite length polymorphism techniques, which yielded comparable results. Susceptible and resistant isolates from the same patient had the same genotype, being sequence type (ST) 3 the most prevalent among them. Isolates with different FKS mutations but the same ST were present in the same patient. MSH2 gene alterations were also studied to investigate their correlation with antifungal resistance acquisition but no association was found with antifungal resistance nor with specific genotypes. In vitro exposure to increasing concentrations of micafungin to susceptible isolates developed colonies carrying FKS mutations in agar plates containing a minimum concentration of 0.06 mg/L of micafungin after less than 48 h of exposure. We investigated the correlation between development of resistance and genotype in a set of susceptible strains after being in vitro exposed to micafungin and anidulafungin but no correlation was found. Mutant prevention concentration values and spontaneous growth frequencies after selection with both echinocandins were statistically similar, although FKS mutant colonies were more abundant after micafungin exposure (p < 0.001). Mutation S663P and F659 deletion were the most common ones found after selection with both echinocandins.