An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004-2020).

Objectives: To describe and analyse erythromycin resistance trends in blood isolates of Staphylococcus aureus (EARS-Net Spain, 2004-2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates. Materials and methods: We collected antibiotic susceptibility data for all first-blood S. aureus isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLSB antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008-2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis. Results: For the 36,612 invasive S. aureus isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible S. aureus (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (p < 0.001); however, it decreased from 68.7 to 61.8% (p < 0.0001) in methicillin-resistant S. aureus (MRSA). Total consumption of MLSB antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were erm (59.8%), msrA (46%), and mphC (45.2%). The erm genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the erm genes identified in MSSA after 2013 differed from the predominant ermC gene (17/22, 77.3%), largely because ermT was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 ermT isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces. Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLSB antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with ermT-mediated resistance to erythromycin may be involved in this trend.

The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018).

Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts’ view / Resistencia a antimicrobianos en bacilos gramnegativos en España: una visión de expertos

Background: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. Objectives: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. Methodology: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. Results and conclusions: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them. (AU)

Contexto: La resistencia a los antibióticos en bacilos gramnegativos representa un grave problema de salud pública. En el hospital, además de unas elevadas tasas de mortalidad, la aparición y propagación de resistencias a la práctica totalidad de los antibióticos limita las opciones terapéuticas frente a infecciones graves y frecuentes. Objetivos: Este trabajo tiene por objetivo dar a conocer la visión de un grupo de expertos en los siguientes aspectos respecto a la resistencia a agentes antimicrobianos en bacilos gramnegativos: 1) la epidemiología actual en España, 2) su relación con la práctica clínica local y 3) las novedades terapéuticas en este ámbito, fundamentada en la evidencia actualmente disponible. Metodología: Tras la revisión de la evidencia más destacada, los datos más relevantes de estos 3 aspectos fueron presentados en una reunión nacional ante 99 expertos en enfermedades infecciosas, microbiología clínica, medicina interna, medicina intensiva, anestesiología y farmacia hospitalaria. Resultados y conclusiones: De debates locales posteriores entre estos expertos se extrajeron conclusiones al respecto entre las que se destacan que la aprobación de nuevos antibióticos hace necesaria la formación de los especialistas implicados para optimizar su uso y mejorar los resultados en salud; los laboratorios de Microbiología de los hospitales deben estar disponibles en horario continuado; todos los antibióticos deben estar disponibles para cuando sean necesarios y se debe aprender a usarlos de forma correcta; y los Programas de Optimización del Uso de Antimicrobianos (PROA) desempeñan una labor clave en ubicar de forma ágil los nuevos antibióticos en las guías y asegurar un uso apropiado de los mismos. (AU)

Diagnóstico microbiológico de la bacteriemia y la fungemia: hemocultivos y métodos moleculares / Microbiological diagnosis of bacteraemia and fungaemia: Blood cultures and molecular methods

OBJETIVO: En esta revisión se pretende actualizar los nuevos procedimientos aplicables en el diagnóstico microbiológico de las bacteriemias y fungemias. MÉTODO: Revisión de la literatura científica. RESULTADOS Y CONCLUSIONES: Tras definir el proceso e indicar sus principios fundamentales, se revisan los principales biomarcadores utilizados en la práctica clínica. Posteriormente, se resaltan las particularidades de la fase preanalítica (recogida y transporte de las muestras) y se detallan los pasos a seguir para la identificación microbiológica por métodos clásicos, basados en el cultivo de las muestras de sangre. En el siguiente apartado, se revisan los métodos diagnósticos no basados en el cultivo, incluyendo los que detectan la presencia del genoma del microorganismo y los basados en el estudio del proteoma mediante espectrometría de masas. En el último apartado se describen los procedimientos a seguir para el estudio de la sensibilidad antibiótica, tanto por métodos fenotípicos como genotípicos

OBJETIVE: In this review we try to update the new procedures applicable in the microbiological diagnosis of bacteriemia and fungemias. METHOD: Review of scientific literature. RESULTS AND CONCLUSIONS: After defining the process and indicating its fundamental principles, the main biomarkers used in clinical practice are reviewed. Subsequently, the particularities of the pre-analytical phase (collection and transport of samples) are highlighted and the steps to follow for the microbiological identification by classical methods are detailed, based on the culture of the blood samples. In the following section, we review the diagnostic methods not culture based, including those that detect the presence of the genome of the microorganism and those based on the study of proteome by mass spectrometry. The last section describes the procedures more frecuently used for the study of antibiotic susceptibility, both by phenotypic and genotypic methods

Microbiological diagnosis of bacteraemia and fungaemia: Blood cultures and molecular methods. / Diagnóstico microbiológico de la bacteriemia y la fungemia: hemocultivos y métodos moleculares.

OBJETIVE: In this review we try to update the new procedures applicable in the microbiological diagnosis of bacteriemia and fungemias. METHOD: Review of scientific literature. RESULTS AND CONCLUSIONS: After defining the process and indicating its fundamental principles, the main biomarkers used in clinical practice are reviewed. Subsequently, the particularities of the pre-analytical phase (collection and transport of samples) are highlighted and the steps to follow for the microbiological identification by classical methods are detailed, based on the culture of the blood samples. In the following section, we review the diagnostic methods not culture based, including those that detect the presence of the genome of the microorganism and those based on the study of proteome by mass spectrometry. The last section describes the procedures more frecuently used for the study of antibiotic susceptibility, both by phenotypic and genotypic methods.

Long-term follow-up of jaw osteomyelitis associated with bisphosphonate use in a tertiary-care center

OBJETIVES: This study reviews our experience in bisphosphonate-associated jaw osteomyelitis (BJOM), focusing on the incidence, etiology, treatment, and long-term outcome. Methods Retrospective review of the clinical histories adult patients diagnosed with BJOM (1995-2008) in a tertiary hospital. Results BJOM was found in 30 of 132 (22.7%) consecutive patients with jaw osteomyelitis. The percentage of BJOM cases increased from 8.7% (4/46) in 1995-2005 to 30.2% (26/86) in 2005-2008. Symptoms appeared in a median of 2.5 years after intravenous use, and 4.5 years after oral exposure. Viridans group streptococci were isolated in 83.3% of cases. Actinomyces spp. was found in 16 (39.0%) of 41 bone histologies. All included patients received a median of 6 months of appropiate antibiotic therapy and a surgical procedure (debridament and/or sequestrectomy). Thirteen of 27 cases (48.1%) with long-term follow-up (median 22 months, IQR 25-75 17-28) failed. Clinical failure defined as, persistent infection or relapse, was more frequent in patients receiving intravenous than oral bisphosphonates (11/16 [68.8%] vs. 2/11 [18.2%]; P < .05) and in cases with Actinomyces spp. (7/10 [70.0%] vs6/17 [35.3%]; P = .08).Conclusions Bisphosphonate therapy is now a frequent cause of JO. BJOM is difficult to cure and relapses are common, particularly in patients exposed to intravenous bisphosphonates

OBJETIVOS: Analizar la incidencia, la etiología, el tratamiento y la evolución clínica a largo plazo de la osteomielitis maxilar (OM) asociada al tratamiento con bifosfonatos (OMAB). MÉTODOS: Estudio retrospectivo de pacientes adultos con diagnóstico de OMAB (1995-2008) en un hospital universitario. RESULTADOS: Fueron diagnosticadas 30OMAB de un total de 132OM. Desde el año 1995 al 2004 fueron diagnosticadas 4OMAB de 46OM (8,7%), y desde el año 2005 al 2008, 26 de 86 (30,2%). Los síntomas de osteomielitis aparecieron en una mediana de 2,5años en los pacientes que recibieron el tratamiento con bifosfonatos por vía intravenosa y una mediana de 4,5 años en los pacientes que lo recibieron por vía oral. En el 83,3% se aislaron Streptococcus del grupo viridans. En 16 (39%) de 41muestras enviadas para estudio histológico se constató la presencia de Actinomyces spp. Todos los pacientes fueron sometidos a desbridamiento quirúrgico y/o secuestrectomía y recibieron una mediana de 6meses de tratamiento antibiótico. Trece de los 27casos (48,1%) con seguimiento a largo plazo (mediana 22meses, IQR25-75 17-28) presentaron fracaso terapéutico. Estos fueron más frecuentes en pacientes que recibieron bifosfonatos por vía intravenosa en comparación con los que los recibieron por vía oral (11/16 [68,8%] vs 2/11 [18,2%], p < 0,05) y en los casos con Actinomyces spp. (7/10 [70,0%] vs 6/17 [35,3%], p = 0,08). CONCLUSIONES: Actualmente el tratamiento con bifosfonatos es causa frecuente de OM. Las recidivas son frecuentes en las OMAB, especialmente en pacientes expuestos a los bifosfonatos por vía intravenosa

Long-term follow-up of jaw osteomyelitis associated with bisphosphonate use in a tertiary-care center.

OBJECTIVES: This study reviews our experience in bisphosphonate-associated jaw osteomyelitis (BJOM), focusing on the incidence, etiology, treatment, and long-term outcome. METHODS: Retrospective review of the clinical histories adult patients diagnosed with BJOM (1995-2008) in a tertiary hospital. RESULTS: BJOM was found in 30 of 132 (22.7%) consecutive patients with jaw osteomyelitis. The percentage of BJOM cases increased from 8.7% (4/46) in 1995-2005 to 30.2% (26/86) in 2005-2008. Symptoms appeared in a median of 2.5 years after intravenous use, and 4.5 years after oral exposure. Viridans group streptococci were isolated in 83.3% of cases. Actinomyces spp. was found in 16 (39.0%) of 41 bone histologies. All included patients received a median of 6 months of appropiate antibiotic therapy and a surgical procedure (debridament and/or sequestrectomy). Thirteen of 27 cases (48.1%) with long-term follow-up (median 22 months, IQR 25-75 17-28) failed. Clinical failure defined as, persistent infection or relapse, was more frequent in patients receiving intravenous than oral bisphosphonates (11/16 [68.8%] vs. 2/11 [18.2%]; P < .05) and in cases with Actinomyces spp. (7/10 [70.0%] vs6/17 [35.3%]; P = .08). CONCLUSIONS: Bisphosphonate therapy is now a frequent cause of JO. BJOM is difficult to cure and relapses are common, particularly in patients exposed to intravenous bisphosphonates.