Bloodstream infections: trends and evolution of incidence and etiology in a 12-year period (2010-2021).

INTRODUCTION: The epidemiological evolution of bloodstream infections (BSIs) in the last decade is not clearly defined. Our aim was to analyze the changes in the workload in our institution and to describe the evolution of the incidence and etiology of BSIs in a 12-year period, including the COVID-19 pandemic. METHODS: All blood cultures received in the laboratory of a tertiary general hospital between 2010 and 2021 were analyzed. Bloodstream infection episodes refer to each episode of bacteremia or fungemia in each patient. Incidence rates per 1000 admissions and per 100,000 population were calculated. RESULTS: No significant changes in the incidence of BSI episodes/1000 admissions were observed (mean, 31.1), while estimated population-based incidences showed declining trends (mean, 182.8/100,000 inhabitants). There was a slight increase in BSI episodes per 1000 admissions caused by Gram-negatives (mean, 16.6/1000 admissions) and E. coli was the most frequent pathogen (mean, 8.5/1000 admissions). There was no significant rise in episodes caused by ESBL- and carbapenemase-producing E. coli or K. pneumoniae, with a decline in those caused by methicillin-resistant S. aureus. A spike in BSI episodes, fungal BSIs and catheter-related infections was detected in 2020, during the COVID-19 outbreak. CONCLUSIONS: No clear increase in the incidence of BSI episodes was detected in our center over this period. Gram-negatives are the most frequent etiology, with no clear rise in antimicrobial resistance phenotypes. The COVID-19 pandemic accounted for a small increase in BSI episodes in 2020, probably related to the increase of catheter-related infections.

Comparative study of the etiology of nosocomial bacteremic pneumonia in ventilated and non-ventilated patients: a 10-year experience in an institution.

IMPORTANCE: This study on bacteremic nosocomial pneumonia (bNP) demonstrates the importance of this condition both in patients undergoing and not undergoing mechanical ventilation. Staphylococcus aureus, Enterobacterales, and non-fermenting Gram-negative bacilli are all causative agents in ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP), with a predominance of S. aureus in HAP and of Pseudomonas aeruginosa in VAP. Mortality in this condition is very high. Therefore, new therapeutic and preventive approaches should be sought.

Antifungal resistance in Candida spp within the intra-abdominal cavity: study of resistance acquisition in patients with serial isolates.

OBJECTIVES: Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden echinocandin-resistant C. glabrata reservoir, we assessed whether testing sequential isolates from a given patient might increase the chances of detecting antifungal resistance. METHODS: Intra-abdominal initial and sequential isolates from the same species from patients included in the CANDIdaemia in MADrid study (January 2019 to June 2022) were studied. We assessed antifungal susceptibility to amphotericin B, azoles, anidulafungin, micafungin, and ibrexafungerp using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and molecularly characterized resistant isolates. RESULTS: We collected 308 isolates (C. albicans [n = 179/308; 58.1%], C. glabrata [n = 101/308; 32.8%], C. tropicalis [n = 17/308; 5.5%], and C. parapsilosis [n = 11/308; 3.6%]) from 112 patients distributed as incident (n = 125/308) and sequential (n = 183/308). Per patient resistance rates of fluconazole (13.4% [15/112] vs. 8% [9/112]); 5.4% proportions difference (95% CI, -2.7% to 13.5%, p 0.09) and echinocandins (8.9% [10/112] vs. 1.8% [2/112]); 7.1% proportions difference (95% CI; 1.2-12.9%; p 0.01) were higher when considering all available isolates than only incident isolates. Resistance was detected in 18 of 112 patients and would have been overlooked in 11 of 18 (61.1%) patients if only incident isolates had been studied. Of the patients who harboured fluconazole or echinocandin-resistant isolates, 14 of 15 and 8 of 10 had received or were receiving fluconazole or echinocandins, respectively. DISCUSSION: Testing sequential Candida isolates from intra-abdominal samples is required to detect antifungal resistance, particularly to echinocandins, in patients whose incident isolates turned out to be susceptible. Furthermore, patients with echinocandin-resistant infections had frequently used echinocandins and had common secondary resistance acquisition.

Significant increase of CTX-M-15-ST131 and emergence of CTX-M-27-ST131 Escherichia coli high-risk clones causing healthcare-associated bacteraemia of urinary origin in Spain (ITUBRAS-2 project).

OBJECTIVES: To assess the microbiological characteristics of Escherichia coli causing healthcare-associated bacteraemia of urinary origin (HCA-BUO) in Spain (ITUBRAS-2 project), with particular focus on ESBL producers and isolates belonging to ST131 high-risk clone (HiRC). Clinical characteristics and outcomes associated with ST131 infection were investigated. METHODS: A total of 222 E. coli blood isolates were prospectively collected from patients with HCA-BUO from 12 tertiary-care hospitals in Spain (2017-19). Antimicrobial susceptibility and ESBL/carbapenemase production were determined. ST131 subtyping was performed. A subset of 115 isolates were selected for WGS to determine population structure, resistome and virulome. Clinical charts were reviewed. RESULTS: ESBL-producing E. coli prevalence was 30.6% (68/222). ST131 represented 29.7% (66/222) of E. coli isolates and accounted for the majority of ESBL producers (46/68, 67.6%). The C2/H30-Rx subclone accounted for most ST131 isolates (44/66) and was associated with CTX-M-15 (37/44) and OXA-1 enzymes (27/44). Cluster C1-M27 was identified in 4/10 isolates belonging to subclade C1/H30-R1 and associated with CTX-M-27. Additionally, ST131 isolates showed a high content of other acquired resistance genes, and clade C/ST131 isolates carried characteristic QRDR mutations. They were categorized as uropathogenic E. coli and had higher aggregate virulence scores. ST131 infection was associated with more complex patients, prior use of cephalosporins and inadequate empirical treatment but was not associated with worse clinical outcomes. CONCLUSIONS: ST131 HiRC is the main driver of ESBL-producing E. coli causing HCA-BUO in Spain, mainly associated with the expansion of subclade CTX-M-15-C2/H30-Rx and the emergence of CTX-M-27-C1/H30-R1 (Cluster C1-M27).

Yeasts from blood cultures in the wake of the COVID-19 pandemic in a tertiary care hospital: Shift in species epidemiology, steady low antifungal resistance and full in vitro ibrexafungerp activity.

Several institutions reported a rise not only in fungemia incidence but also in the number of cases caused by Candida auris or fluconazole-resistant C. parapsilosis during the COVID-19 pandemic. Since the pandemic broke out in early 2020, we studied its impact on fungemia incidence, species epidemiology, potential patient-to-patient transmission, and antifungal resistance in 166 incident yeast isolates collected from January 2020 to December 2022. Isolates were molecularly identified, and their antifungal susceptibilities to amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp were studied following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method, and genotyped. The fungemia incidence (episodes per 1000 admissions) tended to decrease over time (2020 = 1.60, 2021 = 1.36, 2022 = 1.16); P > .05). Species distribution was C. albicans (50.6%, n = 84), C. parapsilosis (18.7%, n = 31), C. glabrata (12.0%, n = 20), C. tropicalis (11.4%, n = 19), C. krusei (3.0%, n = 5), other Candida spp. (1.2%, n = 2), and non-Candida yeasts (3.0%, n = 5). The highest and lowest proportions of C. albicans and C. parapsilosis were detected in 2020. The proportion of isolates between 2020 and 2022 decreased in C. albicans (60.3% vs. 36.7%) and increased in C. parapsilosis (10.3% vs. 28.6%; P < .05) and C. tropicalis (8.8% vs. 16.3%; P > .05). Only three C. albicans intra-ward clusters involving two patients each were detected, and the percentages of patients involved in intra-ward clusters reached 9.8% and 8.0% in 2020 and 2021, respectively, suggesting that clonal spreading was not uncontrolled. Fluconazole resistance (5%) exhibited a decreasing trend (P > .05) over time (2020 = 7.6%; 2021 = 4.2%; and 2022 = 2.1%). Ibrexafungerp showed high in vitro activity.

Fungemia incidence increased during the COVID-19 pandemic in our hospital, however, clonal spreading was not uncontrolled. The proportion of C. parapsilosis and C. tropicalis cases constantly increased. Antifungal resistance remained very low, and fluconazole-resistant C. parapsilosis was undetected.

The Gastrointestinal Tract Is Pinpointed as a Reservoir of Candida albicans, Candida parapsilosis, and Candida tropicalis Genotypes Found in Blood and Intra-Abdominal Samples.

BACKGROUND: Candida spp., as part of the microbiota, can colonise the gastrointestinal tract. We hypothesised that genotyping Candida spp. isolates from the gastrointestinal tract could help spot genotypes able to cause invasive infections. MATERIALS/METHODS: A total of 816 isolates of C. albicans (n = 595), C. parapsilosis (n = 118), and C. tropicalis (n = 103) from rectal swabs (n = 754 patients) were studied. Genotyping was conducted using species-specific microsatellite markers. Rectal swab genotypes were compared with previously studied blood (n = 814) and intra-abdominal (n = 202) genotypes. RESULTS: A total of 36/754 patients had the same Candida spp. isolated from blood cultures, intra-abdominal samples, or both; these patients had candidemia (n = 18), intra-abdominal candidiasis (n = 11), both clinical forms (n = 1), and non-significant isolation (n = 6). Genotypes matching the rectal swab and their blood cultures (84.2%) or their intra-abdominal samples (92.3%) were found in most of the significant patients. We detected 656 genotypes from rectal swabs, 88.4% of which were singletons and 11.6% were clusters. Of these 656 rectal swab genotypes, 94 (14.3%) were also detected in blood cultures and 34 (5.2%) in intra-abdominal samples. Of the rectal swab clusters, 62.7% were previously defined as a widespread genotype. CONCLUSIONS: Our study pinpoints the gastrointestinal tract as a potential reservoir of potentially invasive Candida spp. genotypes.

Clinical impact of time to results from the microbiology laboratory in bloodstream infections caused by carbapenemase-producing Enterobacterales (TIME-CPE STUDY).

OBJECTIVES: To evaluate the impact of time to results (TTR) on the outcome of patients with carbapenemase-producing Enterobacterales bloodstream infections (CPE-BSI). METHODS: Times-series study conducted from January 2014 to December 2021, selecting patients with first CPE-BSI episodes. Periods of intervention were defined according to implementation of diagnostic bundle tests in the microbiology laboratory: pre-intervention (January 2014-December 2017) and post-intervention (January 2018-December 2021). TTR was defined as time elapsed from positivity time of the blood culture bottles to physicians' notification of CPE-BSI episodes, and was evaluated in patients who received inappropriate empirical and switched to appropriate targeted treatment (switch group). Analysis of a composite unfavourable outcome (mortality at Day 30 and/or persistent and/or recurrent bacteraemia) was performed for the total episodes and in the switch group. RESULTS: One hundred and nine episodes were analysed: 66 pre-intervention and 43 post-intervention. Compared with pre-intervention, patients in the post-intervention period were younger (68 versus 63 years, P = 0.04), had INCREMENT score > 7 (31.8% versus 53.5%, P = 0.02) and unfavourable outcome (37.9% versus 20.9%, P = 0.04). Proportion of TTR > 30 h was more frequent pre-intervention than post-intervention (61.7% versus 35.5%, P = 0.02). In multivariate analysis of the 109 episodes, source other than urinary or biliary (OR 2.76, 95% CI 1.11-6.86) was associated with unfavourable outcome, while targeted appropriate treatment trended to being protective (OR 0.17, 95% CI 0.03-1.00). Considering the switch group (n = 78), source other than urinary or biliary (OR 14.9, 95% CI 3.25-69.05) and TTR > 30 h (OR 4.72, 95% CI 1.29-17.22) were associated with unfavourable outcome. CONCLUSIONS: Decreased TTR in the post-intervention period was associated with the outcome in patients with CPE-BSI episodes.

Correction: Díaz-García et al. Candida Genotyping of Blood Culture Isolates from Patients Admitted to 16 Hospitals in Madrid: Genotype Spreading during the COVID-19 Pandemic Driven by Fluconazole-Resistant C. parapsilosis. J. Fungi 2022, 8, 1228.

In the original publication [...].

Unresolved issues in the epidemiology and diagnosis of bacteremia: an opinion paper / Cuestiones no resueltas en la epidemiología y el diagnóstico de la bacteriemia: un documento de opinión

Bacteremia is an important cause of morbidity and mortality worldwide and, despite the diagnostic and therapeutic advances of the last decades, the evidence supporting many diagnostic aspects of bacteremia is scarce. Information on the epidemiological evolution of this entity is limited and many methodological aspects of blood culture collection and analysis are under discussion. Furthermore, the recommendations of the main scientific societies on many of these aspects are variable and, in many cases, have not been updated recently.In this scenario, we have arranged a series of questions on different aspects of bacteremia and reviewed the literature trying to find proper answers for them. We offer our opinion on the topics where the evidence was weak.The topics covered include epidemiological aspects of bacteremia, indications for blood culture extraction, methods for obtaining and incubating samples, or ways of transmitting results from the microbiology laboratory.We do not intend to summarize the current clinical practice guidelines, nor will we deal with the therapeutic management of this entity. The aim of this paper is to review the current perspective on the diagnosis of bacteremia with a critical approach, to point out the gaps in the literature, to offer the opinion of a team dedicated to infectious diseases and clinical microbiology, and to identify some areas of knowledge on which future studies should focus. (AU)

La bacteriemia es una causa importante de morbilidad y mortalidad en todo el mundo y, a pesar de los avances diagnósticos y terapéuticos de las últimas décadas, la evidencia que apoya muchos aspectos diagnósticos suele ser escasa. La información sobre la evolución epidemiológica de esta entidad es limitada y muchos aspectos metodológicos sobre la obtención y análisis de hemocultivos están en discusión. Además, las recomendaciones de las principales sociedades científicas sobre muchos de estos aspectos son variables y, en muchos casos, no se han actualizado recientemente.En este escenario, hemos preparado una serie de preguntas sobre diferentes aspectos de la bacteriemia y hemos revisado la literatura tratando de encontrar respuestas adecuadas para ellas. Ofrecemos nuestra opinión sobre los temas en los que la evidencia era débil.Los temas tratados incluyen los aspectos epidemiológicos de la bacteriemia, las indicaciones para la extracción de hemocultivos, los métodos de obtención e incubación de muestras o las formas de transmisión de los resultados desde el laboratorio de microbiología.No pretendemos resumir las guías de práctica clínica actuales, ni trataremos el manejo terapéutico de esta entidad. El objetivo de este trabajo es revisar la perspectiva actual sobre el diagnóstico de la bacteriemia con un enfoque crítico, señalar las carencias en la literatura, ofrecer la opinión de un equipo dedicado a las enfermedades infecciosas y a la microbiología clínica, e identificar algunas áreas de conocimiento en las que deberían centrarse futuros estudios. (AU)

Candida Genotyping of Blood Culture Isolates from Patients Admitted to 16 Hospitals in Madrid: Genotype Spreading during the COVID-19 Pandemic Driven by Fluconazole-Resistant C. parapsilosis.

BACKGROUND: Candidaemia and invasive candidiasis are typically hospital-acquired. Genotyping isolates from patients admitted to different hospitals may be helpful in tracking clones spreading across hospitals, especially those showing antifungal resistance. METHODS: We characterized Candida clusters by studying Candida isolates (C. albicans, n = 1041; C. parapsilosis, n = 354, and C. tropicalis, n = 125) from blood cultures (53.8%) and intra-abdominal samples (46.2%) collected as part of the CANDIMAD (Candida in Madrid) study in Madrid (2019-2021). Species-specific microsatellite markers were used to define the genotypes of Candida spp. found in a single patient (singleton) or several patients (cluster) from a single hospital (intra-hospital cluster) or different hospitals (widespread cluster). RESULTS: We found 83 clusters, of which 20 were intra-hospital, 49 were widespread, and 14 were intra-hospital and widespread. Some intra-hospital clusters were first detected before the onset of the COVID-19 pandemic, but the number of clusters increased during the pandemic, especially for C. parapsilosis. The proportion of widespread clusters was significantly higher for genotypes found in both compartments than those exclusively found in either the blood cultures or intra-abdominal samples. Most C. albicans- and C. tropicalis-resistant genotypes were singleton and presented exclusively in either blood cultures or intra-abdominal samples. Fluconazole-resistant C. parapsilosis isolates belonged to intra-hospital clusters harboring either the Y132F or G458S ERG11p substitutions; the dominant genotype was also widespread. CONCLUSIONS: the number of clusters-and patients involved-increased during the COVID-19 pandemic mainly due to the emergence of fluconazole-resistant C. parapsilosis genotypes.

Production of biofilm by Staphylococcus aureus: Association with infective endocarditis?

OBJECTIVES: Staphylococcus aureus is a well-known biofilm-producing pathogen that is capable of causing chronic infections owing to its ability to resist antibiotic treatment and obstruct the immune response. However, the possible association between high biofilm production and infective endocarditis (IE) has not been assessed. Our objective was to compare production of biofilm by S. aureus strains isolated from patients with bacteremia and IE, catheter-related bloodstream infection (C-RBSI), or non-device associated bacteremia. METHODS: We isolated 260 S. aureus strains from the blood of patients with bacteremia who were diagnosed during hospital admission between 2012 and 2015. Patients were divided into 3 groups according to whether they had IE, C-RBSI, or non-device associated bacteremia. Biofilm production was measured in terms of biomass and metabolic activity using the crystal violet and XTT assays, respectively. High biomass and metabolic activity rates (based on tertile ranks classification) were compared between the 3 groups. RESULTS: The high biomass and metabolic activity rates of each group were 41.9% and 37.2% for IE, 32.5% and 35.0%, for C-RBSI, and 29.0% and 33.3% for non-device associated bacteremia (p=0.325 and p=0.885, respectively). CONCLUSIONS: High biomass and metabolic activity levels for S. aureus isolates from IE were similar to those of S. aureus isolates from C-RBSI or non-device associated bacteremia.

Production of biofilm by Staphylococcus aureus: Association with infective endocarditis? / Producción de biofilm en Staphylococcus aureus: ¿Asociación con endocarditis infecciosa?

Objectives: Staphylococcus aureus is a well-known biofilm-producing pathogen that is capable of causing chronic infections owing to its ability to resist antibiotic treatment and obstruct the immune response. However, the possible association between high biofilm production and infective endocarditis (IE) has not been assessed. Our objective was to compare production of biofilm by S. aureus strains isolated from patients with bacteremia and IE, catheter-related bloodstream infection (C-RBSI), or non-device associated bacteremia. Methods: We isolated 260 S. aureus strains from the blood of patients with bacteremia who were diagnosed during hospital admission between 2012 and 2015. Patients were divided into 3 groups according to whether they had IE, C-RBSI, or non-device associated bacteremia. Biofilm production was measured in terms of biomass and metabolic activity using the crystal violet and XTT assays, respectively. High biomass and metabolic activity rates (based on tertile ranks classification) were compared between the 3 groups. Results: The high biomass and metabolic activity rates of each group were 41.9% and 37.2% for IE, 32.5% and 35.0%, for C-RBSI, and 29.0% and 33.3% for non-device associated bacteremia (p=0.325 and p=0.885, respectively). Conclusions: High biomass and metabolic activity levels for S. aureus isolates from IE were similar to those of S. aureus isolates from C-RBSI or non-device associated bacteremia.(AU)

Objetivos: Staphylococcus aureus es un conocido microorganismo productor de biofilm, capaz de causar infecciones crónicas debido a su capacidad de resistir el tratamiento antibiótico y dificultar la respuesta inmunitaria. Sin embargo, no se ha evaluado la posible asociación entre una elevada producción de biofilm y la endocarditis infecciosa (EI). Nuestro objetivo fue comparar la producción de biofilm por parte de cepas de S.aureus aisladas de pacientes con bacteriemia y EI, bacteriemia relacionada con el catéter (BRC) o bacteriemia no asociada a dispositivos. Métodos: Se aislaron 260 cepas de S.aureus de sangre de pacientes con bacteriemia que fueron diagnosticados durante su ingreso hospitalario entre 2012 y 2015. Los pacientes se dividieron en tres grupos según tuvieran EI, BRC o bacteriemia no asociada a dispositivos. La producción de biofilm se midió en términos de biomasa y de actividad metabólica utilizando los ensayos de cristal violeta y XTT, respectivamente. Se compararon los índices de alta biomasa y actividad metabólica (basadas en clasificación por terciles) entre los tres grupos. Resultados: Los índices altos de biomasa y actividad metabólica de cada grupo fueron del 41,9 y del 37,2% para EI, del 32,5 y del 35,0% para BRC, y del 29,0 y del 33,3% para bacteriemia no asociada a dispositivos (p=0,325 y p=0,885, respectivamente). Conclusiones: Los niveles altos de biomasa y actividad metabólica de los aislados de S.aureus procedentes de EI fueron similares a los de los aislados de BRC o de bacteriemia no asociada a dispositivos.(AU)

Abiotrophia spp. and Granulicatella spp. Infective Endocarditis: A Contemporary Perspective.

BACKGROUND: Abiotrophia spp. and Granulicatella spp. are Gram-positive cocci, formerly known as nutritionally variant or deficient Streptococcus. Their role as causative agents of infective endocarditis (IE) is numerically uncertain, as well as diagnostic and clinical management of this infection. The aim of our study is to describe the clinical, microbiological, therapeutic, and prognosis of patients with IE caused by these microorganisms in a large microbiology department. METHODS: Retrospective analysis of all the patients with Abiotrophia spp. and Granulicatella spp. IE registered in our centre in the period 2004-2021. RESULTS: Of the 822 IE in the study period, 10 (1.2%) were caused by Abiotrophia spp. (7) or Granulicatella spp. (3). The species involved were A.defectiva (7), G.adiacens (2) and G.elegans (1). Eight patients were male, their mean age was 46 years and four were younger than 21 years. The most frequent comorbidities were congenital heart disease (4; 40%) and the presence of intracardiac prosthetic material (5; 50%). IE occurred on 5 native valves and 5 prosthetic valve or material. Blood cultures were positive in 8/10 patients, within a mean incubation period of 18.07 hours. In the other two patients, a positive 16SPCR from valve or prosthetic material provided the diagnosis. Surgery for IE was performed in seven patients (70%) and in all cases positive 16S rRNA PCR and sequencing from valve or prosthetic material was demonstrated. Valves and/or prosthetic removed material cultures were positive in four patients. Nine patients received ceftriaxone (4 in monotherapy and 5 in combination with other antibiotics). The mean length of treatment was 6 weeks and IE-associated mortality was 20% at one year follow-up. CONCLUSIONS: Abiotrophia spp. or Granulicatella spp. IE were infrequent but not exceptional in our environment and particularly affected patients with congenital heart disease or prosthetic material. Blood cultures and molecular methods allowed the diagnosis. Most of them required surgery and the associated mortality, in spite of a mean age of 46 years, was high.

Blood and intra-abdominal Candida spp. from a multicentre study conducted in Madrid using EUCAST: emergence of fluconazole resistance in Candida parapsilosis, low echinocandin resistance and absence of Candida auris.

OBJECTIVES: We prospectively monitored the epidemiology and antifungal susceptibility of Candida spp. from blood cultures and intra-abdominal samples in patients admitted to hospitals in the Madrid area. METHODS: Between 2019 and 2021, we prospectively collected incident isolates [one per species, patient and compartment (blood cultures versus intra-abdominal samples)] from patients admitted to any of 16 hospitals located in Madrid. We studied the antifungal susceptibilities to amphotericin B, triazoles, micafungin, anidulafungin and ibrexafungerp following the EUCAST E.Def 7.3.2 procedure. RESULTS: A total of 2107 Candida spp. isolates (1895 patients) from blood cultures (51.7%) and intra-abdominal samples were collected. Candida albicans, the Candida glabrata complex, the Candida parapsilosis complex, Candida tropicalis and Candida krusei accounted for 96.9% of the isolates; in contrast, Candida auris was undetected. Fluconazole resistance in Candida spp. was higher in blood cultures than in intra-abdominal samples (9.1% versus 8.2%; P > 0.05), especially for the C. parapsilosis complex (16.6% versus 3.6%, P < 0.05), whereas echinocandin resistance tended to be lower in blood cultures (0.5% versus 1.0%; P > 0.05). Resistance rates have risen, particularly for fluconazole in blood culture isolates, which increased sharply in 2021. Ibrexafungerp showed in vitro activity against most isolates. Species distributions and resistance rates varied among hospitals. CONCLUSIONS: Whereas no C. auris isolates were detected, fluconazole-resistant C. parapsilosis isolates have been spreading across the region and this has pulled up the rate of fluconazole resistance. In contrast, the rate of echinocandin resistance continues to be low.

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.

[Recurrent Cupriavidus Pauculus catheter-related bacteremia]. / Bacteriemia recurrente relacionada con catéter por Cupriavidus pauculus.

Catheter-related bacteriemia by Cupriavidus spp. is a rare condition with very few cases reported in the literature. Most of them occurred in immunocompromised patients. OBJECTIVE: To report a case of recurrent catheter-related bacteriemia by Cupriavidus pauculus in an immunocompromised infant in order to analyze possible therapeutic options, especially in relation to the need or not for central venous catheter (CVC) removal. CLINICAL CASE: 22-month-old infant with B-cell acute lymphoblas tic leukemia (ALL) in reinduction phase, CVC carrier. He presented to the Emergency Room with fever without focus on examination. Blood tests were performed (without increase of acute phase reactants) and differential blood cultures (peripheral and CVC). He was hospitalized and empirical antibiotic therapy was started with intravenous fourth-generation cephalosporin (cefepime). After 24 hours, blood cultures were positive for Cupriavidus pauculus, growing first in the CVC culture. We maintained cefepime, adding catheter lock therapy with ciprofloxacin. Afterward, the infection was resolved, allowing us to keep the CVC. Seven months later, in the context of fever, Cupriavidus pauculus was again identified in CVC blood culture. We decided this time to remove the catheter, in addition to the administration of intravenous cefepime. The patient has not presented new episodes nine months after de removal of the CVC. CONCLUSION: Catheter-related bacteremia by Cupriavidus is a rare condition in children that usually occurs in immunocompromised patients. Catheter lock therapy associated with systemic antibiotics could be a safe option in patients with difficult CVC re moval. However, if persistent colonization of the CVC is suspected, it may be necessary to remove it.

ΔF659 and F659S substitutions at the HS1 of FKS2 gene, along with E655A and W715L upstream and downstream substitutions, correlate with high ibrexafungerp MICs against Candidaglabrata.

OBJECTIVES: Ibrexafungerp is a new inhibitor of Candida spp glucan synthase. We previously set the ibrexafungerp wild-type upper limit (wtUL) against Candida glabrata. We here assessed which FKS2 gene substitutions confer an ibrexafungerp non-wild-type phenotype in C. glabrata isolates. METHODS: We studied a set of C. glabrata (n = 34) isolates showing resistance to micafungin and anidulafungin (n = 28) or only to anidulafungin (n = 6) and harbouring 10 different FKS2 gene substitutions. Antifungal susceptibility to ibrexafungerp was tested according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) E.Def 7.3.2 procedure and isolates were considered ibrexafungerp non-wild type according to the statistical wtUL (minimum inhibitory concentration [MIC] ≥2) or visual wtUL (MIC ≥4). RESULTS: Ibrexafungerp MICs against the isolates ranged from 0.06 to 4 mg/L. Four FKS2 gene substitutions (ΔF659, F659S, E655A, and W715L) were exclusively found in isolates showing an ibrexafungerp MIC above the statistical wtUL (≥2 mg/L) whereas isolates harbouring other substitutions were found to be ibrexafungerp wild type. The use of the visual wtUL (MIC ≥4 mg/L) bisected the population of isolates harbouring such substitutions. DISCUSSION: C. glabrata isolates showing an ibrexafungerp MIC ≥2 mg/L may be considered non-wild type and are prone to harbour ΔF659, F659S, E655A, and W715L substitutions at the FKS2 gene. It is worth noting that substitutions ΔF659 and F659S were located at the beginning of the HS1 of FKS2 gene of C. glabrata. The role of other substitutions on conferring a non-wild-type phenotype to ibrexafungerp is not well elucidated.

Incidence of Candidemia Is Higher in COVID-19 versus Non-COVID-19 Patients, but Not Driven by Intrahospital Transmission.

There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared them with those without COVID-19 (2020 vs. 2019 and 2020, respectively). We also genotyped all C. albicans, C. parapsilosis, and C. tropicalis isolates (n = 88), causing candidemia in both groups, providing for the first time a genotypic characterization of isolates gathered in patients with either COVID-19 or non-COVID-19. Incidence of candidemia was higher in patients with COVID-19 than non-COVID-19 (4.73 vs. 0.85 per 1000 admissions; 3.22 vs. 1.14 per 10,000 days of stay). No substantial intergroup differences were found, including mortality. Genotyping proved the presence of a low number of patients involved in clusters, allowing us to rule out rampant patient-to-patient Candida transmission. The four patients, involved in two clusters, had catheter-related candidemia diagnosed in the first COVID-19 wave, which demonstrates breaches in catheter management policies occurring in such an overwhelming situation. In conclusion, the incidence of candidemia in patients with COVID-19 is significantly higher than in those without COVID-19. However, genotyping shows that this increase is not due to uncontrolled intrahospital transmission.

Prevalence and clinical features of secondary skin lesions in septic patients with bloodstream infections.

Cutaneous manifestations developed in the course of sepsis are poorly documented in the medical literature beyond those related to specific pathogens or classical clinical pictures such as purpura fulminans or ecthyma gangrenosum. The objective of this study was to determine the overall prevalence of sepsis-related skin findings and evaluate their possible impact on the prognosis of septic patients. Single-centre, retrospective study of septic patients with documented bloodstream infections admitted in a tertiary hospital during 2019. Primary skin and soft tissue infections, and non-sepsis-related skin conditions diagnosed during hospital admission were excluded. Unselected sample of 320 episodes of sepsis in 265 patients. Secondary skin lesions were documented in 57 sepsis episodes (17.8%) in 47 patients. Purpura (petechiae/ecchymosis) was the most frequent cutaneous finding in septic patients (35.5%), with non-acral involvement in more than one-third of the episodes (38.5%), followed by skin and soft tissue erythema/oedema (25.8%) and maculopapular rashes (11.3%). Secondary skin lesions occurred more frequently in sepsis of respiratory (p = 0.027) and skin and soft tissue (p = 0.018) origin, as well as in sepsis caused by Pseudomonas aeruginosa and Stenotrophomonas maltophilia (p = 0.001). Mean hospital stay was 38.58 days and sepsis-related mortality 21.1%. Our results suggest that cutaneous involvement in the course of sepsis is frequent, with purpura being the main clinical sign. The semiology described in this study, easily identifiable by non-dermatologists, should alert clinicians to the potential unfavourable course of these patients.