Genomic Surveillance Uncovers a 10-Year Persistence of an OXA-24/40 Acinetobacter baumannii Clone in a Tertiary Hospital in Northern Spain.

Infections caused by carbapenem-resistant Acinetobacter baumannii are a global threat causing a high number of fatal infections. This microorganism can also easily acquire antibiotic resistance determinants, making the treatment of infections a big challenge, and has the ability to persist in the hospital environment under a wide range of conditions. The objective of this work was to study the molecular epidemiology and genetic characteristics of two blaOXA24/40Acinetobacter baumannii outbreaks (2009 and 2020-21) at a tertiary hospital in Northern Spain. Thirty-six isolates were investigated and genotypically screened by Whole Genome Sequencing to analyse the resistome and virulome. Isolates were resistant to carbapenems, aminoglycosides and fluoroquinolones. Multi-Locus Sequence Typing analysis identified that Outbreak 1 was mainly produced by isolates belonging to ST3Pas/ST106Oxf (IC3) containing blaOXA24/40, blaOXA71 and blaADC119. Outbreak 2 isolates were exclusively ST2Pas/ST801Oxf (IC2) blaOXA24/40, blaOXA66 and blaADC30, the same genotype seen in two isolates from 2009. Virulome analysis showed that IC2 isolates contained genes for capsular polysaccharide KL32 and lipooligosacharide OCL5. A 8.9 Kb plasmid encoding the blaOXA24/40 gene was common in all isolates. The persistance over time of a virulent IC2 clone highlights the need of active surveillance to control its spread.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Outpatient management of children at low risk for bacterial meningitis.

OBJECTIVE: To determine the outcome of children aged 2-14 years with cerebrospinal fluid (CSF) pleocytosis and at very low risk for bacterial meningitis managed as outpatients without antibiotics. METHODS: Multicentre, prospective, observational study conducted at nine Spanish paediatric EDs. Patients were diagnosed with meningitis based on clinical suspicion of meningitis and CSF pleocytosis when evaluated in the ED. Children between 2 and 14 years of age with pleocytosis and very low-risk criteria for bacterial meningitis (well appearing, Bacterial Meningitis Score (BMS)=0, procalcitonin (PCT)<0.5 ng/mL and observation without deterioration for less than 24 hours in the ED) were treated as outpatients without antibiotics pending CSF cultures. The primary composite outcome was a final diagnosis of bacterial meningitis or return to the ED for clinical deterioration. RESULTS: Of 182 children between 2 and 14 years old diagnosed with meningitis, 56 met the very low-risk criteria and 45 were managed as outpatients. None was diagnosed with bacterial meningitis or returned due to clinical deterioration. Another 31 patients with BMS=1 (due to a peripheral absolute neutrophil count (ANC)>10 000/mm3) and PCT <0.5 ng/mL were managed as outpatients, diagnosed with aseptic meningitis and did well. BMS using PCT had the same sensitivity but greater specificity than classic BMS. CONCLUSIONS: This set of low-risk criteria appears safe for the outpatient management without antibiotics of children with CSF pleocytosis. Larger studies are needed to evaluate the predictive values of replacing peripheral ANC with PCT in the BMS.

Characteristics of children with microbiologically confirmed invasive bacterial infections in the emergency department.

BACKGROUND: Determination of the characteristics of paediatric invasive bacterial infections (IBI) is essential for early identification of children requiring immediate antibiotic therapy. The main objective is to characterize the emergency presentation of the IBI among children aged younger than 14 years. PATIENTS AND METHODS: A prospective registry-based cohort study including all patients aged younger than 14 years diagnosed with confirmed IBI (culture or genomic detection using the polymerase chain reaction) was carried out in a paediatric emergency department between 2008 and 2015. Severity criteria were as follows: death, sequelae or admission to the ICU. RESULTS: Of the 223 IBIs reported, 187 (83.9%) corresponded to previously healthy patients (median age=19 months) and 165 (74%) were well appearing. The most common diagnoses were occult bacteraemia [60 (26.9%)] and sepsis [56 (25.1%)]. The most frequent pathogens were Streptococcus pneumoniae [68 (30.5%)] and Neisseria meningitidis [42 (18.8%)]. Four (1.8) patients died (S. pneumoniae, 2) and eight (3.5%) had sequelae (S. pneumoniae, 5). The diagnoses and clinical characteristics of the children varied significantly depending on the isolated pathogen. Duration of fever less than 24 h, symptoms other than fever and not being well-appearing upon arrival to the emergency department were independent risk factors for greater severity (area under the receiver operating characteristics curve=0.805; 95% confidence interval: 0.741-0.868). CONCLUSION: IBIs are commonly diagnosed in previously healthy and well-appearing young children. S. pneumoniae was responsible for the majority of deaths or sequelae. Short duration of fever, symptoms other than fever and not being stable on arrival are associated with greater severity.

Dacryocystitis: Systematic Approach to Diagnosis and Therapy.

The objective of this paper is to review the main findings of the largest studies on the etiopathogenesis and microbiology of the development of dacryocystitis and to formulate clinical and surgical guidelines based on said studies and on our experience at Cruces Hospital, the Basque Country, Spain. The most common sign of this entity is the distal nasolacrimal duct obstruction, and this should be treated to prevent clinical relapse. The time when surgery should be indicated mainly depends on the clinical signs and symptoms, age and general status of a patient. Given the germs isolated in cases of dacryocystitis, antibiotic therapy against Gram positive (S. aureus, S. pneumoniae, S. epidermidis) and Gram negative bacteria (H. influenzae, P. aeruginosa) should be administered, orally in adults and intravenously in pediatric patients, prior to surgery. Gentamicin and amoxicillin-clavulanic acid have been found to be effective against the bacteria commonly implicated in the etiopathogenesis of this entity.

Invasive bacterial infections in a paediatric emergency department in the era of the heptavalent pneumococcal conjugate vaccine.

OBJECTIVE: To describe the characteristics of patients diagnosed with invasive bacterial infections (IBIs) in a Paediatric Emergency Department (PED) following the introduction of the heptavalent pneumococcal conjugated vaccine (PCV7). METHODS: Descriptive retrospective study of children under 14 years of age diagnosed with IBIs in a PED of a tertiary hospital between January 2008 and December 2009. RESULTS: In this period we registered 123 396 episodes and 59 patients who were diagnosed with IBIs (22 patients under 1 year of age, 37.2%). Of these, 11 (18.6%) had some severe underlying condition and 38 (64.4%) were stable on arrival. The most common diagnoses were sepsis with/without meningitis (23, 38.9%) and bacteraemia (14, 23.7%), while the pathogens most frequently isolated were Streptococcus pneumoniae (23, 38.9%) and Neisseria meningitidis (18, 30.5%). Pathogens were isolated from blood in 57 patients and from the cerebrospinal fluid in eight (in these, the same bacterial species was isolated in the blood, except for two cases with S. pneumoniae). Of the pneumococci isolated, 80% corresponded to serotypes included in the 13-valent PCV13. In seven cases, pathogens were detected using only PCR analysis (N. meningitidis, four; S. pneumoniae, three). Twenty-five patients were admitted to the Paediatric Intensive Care Unit. No patient died but two had sequelae. CONCLUSION: In the era of PCV7, pneumococcus is the leading cause of IBI in PED. The introduction of PCV13 may lead to a very significant decrease in the IBI rate and meningococcus may become the leading cause of IBI.

HIV-1 transmission cluster with T215D revertant mutation among newly diagnosed patients from the Basque Country, Spain.

OBJECTIVE: To determine the introduction of HIV-1 genetic forms and to examine transmission clusters and resistance to antiretroviral inhibitors among newly diagnosed patients from the Basque Country, Spain, during 2004-2007. METHODS: A total of 261 samples, corresponding to 47.5% heterosexuals, 37.9% men who have sex with men (MSM), and 11.1% intravenous drug users were analyzed in protease and reverse transcriptase to examine phylogenetic relationships and drug resistance-associated mutations. RESULTS: Subtype B was detected in 220 (84.3%) samples and non-B subtype variants in 41 (15.7%) samples. Nearly half (47%) of the sequences grouped in transmission clusters. One of these comprised 14 individuals, 12 of them MSM, with the T215D revertan mutation. In largest transmission clusters, the percentage of MSM was higher than heterosexuals (P < 0.001). Resistance mutations were detected in 29 (11.1%) patients: 20 (7.6%) of them to nucleoside reverse transcriptase inhibitor; 6 (2.3%) to nonnucleoside reverse transcriptase inhibitor (NNRTI); and 1 each to protease inhibitors, protease inhibitor plus NNRTI, and nucleoside reverse transcriptase inhibitor plus NNRTI, respectively. CONCLUSIONS: Our findings underscore recommendations for HIV-1 genotyping in newly diagnosed patients not only to provide information on transmitted drug resistance as an issue in public health and as a guide to future therapy but also to document transmission clusters and to increase the necessary preventive measures.

Modificaciones en la masa osea y en la homeostasis de la glucosa en residentes de la zona de Bahia Blanca con alta ingesta espontanea de fluor / Modifications in bone mass and in glucose homeostasis in subjects with high spontaneous fluoride intake

Se estudiaron 24 mujeres y 2 hombres de 44 a 66 años de edad, ex-residentes en una zona de fluorosis endémica carcana a Bahía Blanca. Las fluoremias de ayuno (0,5 a 9,2 muM) y fluorurias diarias (> 60 mumoles/día) corresponden a las de habitantes de un área de fluorosis endémica. La densidad mineral ósea (DMO) de la columna lumbar (L2-L4: 1330 + 41 mg/cm2) y del cuello femoral (1045 + 10 mg/cm2) fueron significativamente superiores al promedio de sujetos normales del mismo sexo y edad. La fluoruria y la DMO L2-4 se hallaron correlacionadas (r = 0,43, P < 0,05). Durante una prueba estándar de sobrecarga de glucosa, el Area Bajo la Curva de insulinemia mostró una relación inversa con la fluoremia, en coincidencia con experimentos que indican que concentraciones de fluoruro en plasma superiores a 5 muM perturban la homeostasis de la glucosa.