Ceftazidime-Avibactam plus Aztreonam for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria.

This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.

[A real-world study to evaluate adherence and flavor of a high-protein hypercaloric oral nutritional supplement in patients with malnutrition in a hospital]. / Estudio en vida real para evaluar la adherencia y el sabor de un suplemento oral nutricional hipercalórico e hiperproteico en pacientes con desnutrición en un hospital.

Introduction: Aim: the objective of our real-life study was to evaluate adherence and taste preferences of a hypercaloric and hyperprotein oral nutritional supplement (ONS) in malnourished hospitalized patients. Methods: a total of 34 in patients with recent weight loss were included in this study. One flavor (coffe, vanilla or strawberry) was administered each day in a random way to each patient during three consecutive days. In the first three days, patients were asked to fulfill two questionnaires intended to reflect ONS (Renutryl®) tolerance and acceptance. Adherence to the ONS was measured during hospital stay. Results: the sweet flavor was higher for strawberry (4.54 ± 0.2 points) than for the vanilla flavor (3.13 ± 0.1 points; p < 0.03) and coffee flavor (3.03 ± 0.1 points; p <0.02). When analyzing the total number of patients who took supplements after choosing the flavor, the patients who chose coffee took a total of 13.3 ± 1.1 packages on average during hospitalization (0.91 ± 0.2 per day), the patients who chose strawberry took 13.4 ± 1.3 packages (0.92 ± 0.1 per day), and finally the patients who chose vanilla packages took 8.3 ± 0, 9 packages during admission (0.61 ± 0.1 per day), with significant differences in favor of the strawberry and coffee flavors versus vanilla. The ONS chosen mostly by the patients at hospital discharge was the multiflavor pack (n = 20; 50 %). Conclusions: taste preferences for the three flavored ONSs are similar, although adherence was higher during admission to the coffee- and strawberry-flavored ONS. Sweetness may have influenced this finding, especially with the strawberry flavor, with a good tolerance of all three flavors.

Introducción: Objetivo: el objetivo de nuestro estudio en vida real fue evaluar en pacientes ingresados desnutridos la adherencia y las preferencias de sabor de un suplemento oral nutricional (SON) hipercalórico e hiperproteico. Métodos: se incluyeron en este estudio en vida real un total de 34 pacientes ingresados con pérdida de peso reciente. Se administró un sabor (café, vainilla o fresa) cada día de forma aleatoria a cada paciente durante tres días consecutivos. En los primeros tres días se pidió a los pacientes que completaran dos cuestionarios destinados a reflejar la tolerancia y aceptación del SON (Renutryl®). La adherencia del SON fue evaluada durante el ingreso hospitalario. Resultados: el sabor dulce fue más elevado para el sabor fresa (4,54 ± 0,2 puntos) que para el sabor vainilla (3,13 ± 0,1 puntos; p < 0,03) y el sabor café (3,03 ± 0,1 puntos; p < 0,02). Al analizar a los pacientes que tomaron suplementos después de elegir el sabor, los pacientes que eligieron café tomaron un total de 13,3 ± 1,1 envases de promedio durante la hospitalización (0,91 ± 0,2 por día), los pacientes que eligieron fresa tomaron 13,4 ± 1,3 envases (0,92 ± 0,1 por día) y, finalmente, los pacientes que eligieron envases de vainilla tomaron 8,3 ± 0,9 envases durante el ingreso (0,61 ± 0,1 por día), con diferencias significativas a favor de los sabores de fresa y café frente al sabor de vainilla. Por otra parte, el SON elegido mayoritariamente por los pacientes al alta hospitalaria fue el pack multisabor (n = 20; 50 %). Conclusiones: las preferencias de sabor de los SON de tres sabores son similares, aunque la adherencia fue más elevada durante el ingreso con respecto a los SON con sabor a café y fresa. La dulzura puede haber influido en este hallazgo, sobre todo con el sabor fresa, con una buena tolerancia de los 3 sabores.

[Real-world study in oncological outpatients of an oral supplement enriched with ω-3 fatty acids - effect on quality of life and nutritional parameters]. / Estudio en vida real de un suplemento oral enriquecido con ácidos grasos ω-3 en pacientes ambulatorios oncológicos: efecto sobre la calidad de vida y los parámetros nutricionales.

INTRODUCTION: Background: cancer patients are a group at high nutritional risk. Oral nutritional supplementation (ONS) can improve nutritional status. Objective: the objective of our study was to evaluate the effectiveness on nutritional parameters and quality of life of a ω3-enriched ONS in oncology outpatients in a real-world study. Material and methods: a total of 35 outpatient cancer patients who received 2 ONS per day were recruited. Chemistry, anthropometric, impedance measurement, nutritional survey, malnutrition universal screening tool (MUST) test, and EQ5D quality of life test were all used before and after 3 months of intervention. Results: mean age was 65.4 ± 10.7 years (18 females/17 males). Mean completion of the group was 81.7 ± 7.2 %. During the intervention, total protein (1.5 ± 0.2 g/dL; p = 0.01), albumin (0.9 ± 0.1 mg/dL; p = 0.04), and transferrin (53.9 ± 21.1 mg/dL; p = 0.02) levels increased. At the beginning of the study, 100 % of the patients were in the high nutritional risk category according to MUST. After the intervention, 34.3 % (n = 12) were in the low nutritional risk category, 51.4 % (n = 18) in the moderate nutritional risk category, and only 14.3 % (n = 5) in the category of high nutritional risk; previously, 100 % of patients had high nutritional risk (p = 0.02). The total score in the quality of life test increased significantly (0.51 ± 0.06 vs 0.84 ± 0.03 points; p = 0.01), with improvement in 5 dimensions. Conclusions: the use of a ω3-enriched ONS in a real-world study with cancer outpatients showed a beneficial effect on nutritional parameters and quality of life.

INTRODUCCIÓN: Antecedentes: los pacientes oncológicos son un grupo de alto riesgo nutricional. Los suplementos orales nutricionales (SON) pueden ayudar a mejorar su situación nutricional. Objetivo: el objetivo de nuestro estudio fue evaluar en un estudio en vida real la efectividad sobre los parámetros nutricionales y la calidad de vida de un SON enriquecido con ω-3 en pacientes ambulatorios oncológicos. Material y métodos: se reclutaron 35 pacientes oncológicos ambulatorios que recibieron 2 SON al día. Se realizaron: valoración bioquímica y antropométrica, impedanciometría, encuesta nutricional, test Malnutrition Universal Screening Tool (MUST) y test de calidad de vida EQ5D, antes y a los 3 meses de intervención. Resultados: la edad media fue de 65,4 ± 10,7 años (18 mujeres/17 hombres). La cumplimentación media del grupo fue de un 81,7 ± 7,2 %. Durante la intervención aumentaron los niveles de proteínas totales (1,5 ± 0,2 g/dl; p = 0,01), albúmina (0,9 ± 0,1 mg/dl; p = 0,04) y transferrina (53,9 ± 21,1 mg/dl; p = 0,02). Al inicio del estudio, un 100 % de los pacientes presentaban en el test MUST la categoría de alto riesgo nutricional. Tras la intervención, un 34,3 % (n = 12) presentaban la categoría de bajo riesgo nutricional, un 51,4 % (n = 18) presentaban en el test MUST la categoría de moderado riesgo nutricional, y solo un 14,3 % (n = 5) presentaban la categoría de alto riesgo nutricional; previamente, el 100 % de los pacientes tenían la categoría alto riesgo (p = 0,02). La puntuación total del test de calidad de vida aumentó significativamente (0,51 ± 0,06 vs. 0,84 ± 0,03 puntos; p = 0,01), mejorando cualitativamente las 5 dimensiones. Conclusiones: la utilización de un SON enriquecido con ω-3 en pacientes oncológicos ambulatorios en condiciones de vida real muestra un efecto beneficioso sobre los parámetros nutricionales y la calidad de vida.

Circulation of multi-drug-resistant Shigella sonnei and Shigella flexneri among men who have sex with men in Barcelona, Spain, 2015-2019.

BACKGROUND: In high-income countries, shigellosis is mainly found in travellers to high-risk regions or in men who have sex with men (MSM). This study investigated the genomic characteristics and the features of antimicrobial resistance of MSM-associated Shigella flexneri and Shigella sonnei circulating in Barcelona, Spain, elucidating their connectivity with contemporaneous Shigella spp. from other countries. METHODS: Antimicrobial susceptibility, whole-genome sequencing, genomic characterization and phylogenetic analysis were performed in MSM-associated Shigella spp. recovered from 2015 to 2019. Reference genomes of MSM-associated Shigella spp. were included for contextualization and to determine their connection with international outbreaks. RESULTS: In total, 44 S. flexneri and 26 S. sonnei were identified among MSM. Overall, 80% showed resistance to azithromycin, 65.7% showed resistance to trimethoprim-sulphamethoxazole and 32.8% showed resistance to ciprofloxacin; 27.1% were resistant to all three antimicrobials. mphA and/or ermB, and qnrS and mutations in the quinolone resistance determining regions were found in the azithromycin- and ciprofloxacin-resistant isolates, respectively. Additionally, two isolates carried blaCTX-M-27. Single-nucleotide-polymorphism-based analysis revealed that the isolates were organized into different lineages, most of which were closely related to dominant MSM-associated lineages described previously in the UK and Australia. CONCLUSIONS: This study investigated the circulation of lineages of S. flexneri and S. sonnei among MSM in Spain that were mainly resistant to first-/second-line oral treatments, and closely related to dominant MSM-associated lineages described previously in the UK and Australia. These data reinforce the urgent need for the implementation of public health measures focusing on the early detection and prevention of transmission of this emerging pathogen, which is contributing to the antimicrobial resistance crisis in sexually transmitted infections.

Faecal phageome of healthy individuals: presence of antibiotic resistance genes and variations caused by ciprofloxacin treatment.

OBJECTIVES: Antimicrobial resistance genes (ARGs) can be transferred by means of mobile genetic elements, which play a critical role in the dissemination of resistance in the bacterial community. ARG transmission within mobile genetic elements has been reported in plasmids and transposons but less frequently in bacteriophages. Here, the bacteriophage fraction of seven human faecal samples was purified and deep-sequenced to detect the presence of ARGs in the phage particles. METHODS: Seven faecal samples (five from healthy individuals and two from a patient before and after receiving ciprofloxacin treatment) were used to extract phage DNA, which was purified and then sequenced in a MiSeq (Illumina). Generated reads were checked for quality and assembled, and then the generated contigs analysed with Kraken, PHASTER, VirSorter and Prokka. Some genes were also validated by quantitative PCR. RESULTS: Analysis of the purified phage DNA by Kraken identified from 4 to 266 viruses in the samples. The viral fraction corresponded mainly to the order Caudovirales, including phages from the Siphoviridae and Myoviridae families. Bacterial genes associated with antimicrobial resistance were detected in the viral DNA, as confirmed by quantitative PCR. Higher densities of ARG-carrying phage particles were observed in the post- versus pre-ciprofloxacin treatment sample. CONCLUSIONS: The finding of ARGs in phage particles supports the description of phages as mobile elements contributing to the dissemination of bacterial antibiotic resistance and suggests ciprofloxacin treatment may play a role in the release of ARG-carrying particles, thereby increasing resistance.

Teicoplanin for treating enterococcal infective endocarditis: A retrospective observational study from a referral centre in Spain.

This study aimed to evaluate the effectiveness and safety of teicoplanin for treating enterococcal infective endocarditis (EIE). A retrospective analysis of a prospective cohort of definite EIE patients treated with teicoplanin in a Spanish referral centre (2000-2017) was performed. The primary outcome was mortality during treatment. Secondary outcomes were mortality during 3-month follow-up, adverse effects and relapse. A total of 22 patients received teicoplanin, 9 (40.9%) as first-line (8 Enterococcus faecium and 1 Enterococcus faecalis) and 13 (59.1%) as salvage therapy (13 E. faecalis). Median (IQR) age was 71.5 (58.3-78) years and Charlson comorbidity index was 4.5 (3-7). Five (22.7%) affected prosthetic valves. Median duration of treatment in survivors was 53 (42.5-61) days for antibiotics and 27 (17-41.5) days for teicoplanin [median dose 10 (10-10.8) mg/kg/day]. Reasons for teicoplanin use were resistance to ß-lactams (40.9%), adverse events with previous regimens (31.8%) and outpatient parenteral antimicrobial therapy (OPAT) (27.3%). Teicoplanin was withdrawn due to adverse events in 2 patients (9.1%). Five patients (22.7%) died during treatment: four in the first-line (three with surgery indicated but not performed) and one in the salvage therapy group (surgery indicated but not performed). Two deaths (11.8%) occurred over the 3-month follow-up. There were no relapses during a median of 43.2 (22.1-69.1) months. Teicoplanin can be used as an alternative treatment for susceptible E. faecium IE and as a salvage therapy in selected patients with E. faecalis IE when adverse events develop with standard regimens or to allow OPAT.

Prevalencia en España de mecanismos de resistencia a quinolonas en enterobacterias productoras de betalactamasas de clase C adquiridas y/o carbapenemasas / Prevalence of quinolone resistance mechanisms in Enterobacteriaceae producing acquired AmpC Beta-lactamases and/or carbapenemases in Spain

Introducción: En los últimos años se ha observado un incremento de la resistencia a fluoroquinolonas en enterobacterias, estando asociado significativamente a la resistencia a betalactámicos. Nuestro objetivo fue conocer la prevalencia de mecanismos cromosómicos y plasmídicos de resistencia a quinolonas en aislados productores de betalactamasas de claseC adquiridas y/o carbapenemasas. Métodos: Se evaluó la presencia de mecanismos cromosómicos y plasmídicos de resistencia a quinolonas [mutaciones en la región determinante de resistencia a quinolonas de gyrA y parCy genes qnr, aac(6')-Ib-cr y qepA] en 289 aislados de enterobacterias productoras de betalactamasas de claseC adquiridas y/o carbapenemasas recogidos entre febrero y julio de 2009 en 35 hospitales españoles. Resultados: Se detectaron determinantes plasmídicos en 92 aislados (31,8%); en 83 aislados (28,7%) se detectó algún gen qnr, y en 20 (7%), la variante aac(6')-Ib-cr. El gen qnr más prevalente fue qnrB4 (20%), asociado en la mayoría de los casos a DHA-1. El 14,6% de los aislados con una CMI de ciprofloxacino superior a 0,25mg/l no presentaban mutaciones en gyrA ni parC, detectándose en el 90% de los mismos algún determinante plasmídico de resistencia a quinolonas. Conclusión: qnrB4 fue el determinante plasmídico más prevalente, claramente asociado a DHA-1. Los mecanismos plasmídicos en asociación con mecanismos cromosómicos diferentes a las mutaciones en los genes de las topoisomerasas (sobreexpresión de bombas de expulsión, alteración del lipopolisacárido o disminución de porinas) pueden dar lugar a valores de CMI de ciprofloxacino que superan los puntos de corte establecidos por los principales comités internacionales de definición de puntos de corte para interpretación de datos de sensibilidad (AU)

Background: Quinolone resistance in Enterobacteriaceae species has increased over the past few years, and is significantly associated to beta-lactam resistance. The aim of this study was to evaluate the prevalence of chromosomal- and plasmid-mediated quinolone resistance in acquired AmpC Beta-lactamase and/or carbapenemase-producing Enterobacteriaceae isolates. Methods: The presence of chromosomal- and plasmid-mediated quinolone resistance mechanisms [mutations in the quinolone resistance determining region (QRDR) of gyrA and parC and qnr, aac(6')-Ib-cr and qepA genes] was evaluated in 289 isolates of acquired AmpC Beta -lactamase- and/or carbapenemase-producing Enterobacteriaceae collected between February and July 2009 in 35 Spanish hospitals. Results: Plasmid mediated quinolone resistance (PMQR) genes were detected in 92 isolates (31.8%), qnr genes were detected in 83 isolates (28.7%), and the aac(6')-Ib-cr gene was detected in 20 isolates (7%). qnrB4 gene was the most prevalent qnr gene detected (20%), associated, in most cases, with DHA-1. Only 14.6% of isolates showed no mutations in gyrA or parC with a ciprofloxacin MIC of 0.5mg/L or higher, whereas PMQR genes were detected in 90% of such isolates. Conclusion: qnrB4 gene was the most prevalent PMQR gene detected, and was significantly associated with acquired AmpC Beta -lactamase DHA-1. PMQR determinants in association with other chromosomal-mediated quinolone resistance mechanisms, different to mutations in gyrA and parC (increased energy-dependent efflux, altered lipopolysaccharide or porin loss), could lead to ciprofloxacin MIC values that exceed breakpoints established by the main international committees to define clinical antimicrobial susceptibility breakpoints (AU)

Oral Nutritional Supplements and Taste Adherence in Malnourished Adults Inpatients, Effect on Adhesion during Hospital Stance.

AIM: The aim of our study was to evaluate a hypercaloric sweet milk-based oral nutrition supplement in a prospective 3-day study designed to assess the taste preferences of this oral nutritional supplement (ONS) in malnourished inpatients and the influence on adherence in daily intake. METHODS: A total of 46 in patients with recent weight loss were included in this study. One flavor (chocolate, vanilla or strawberry) was administered each day in a random way to each patient during 3 consecutive days. In the first 3 days, patients were asked to fill 2 questionnaires intended for reflecting ONS tolerance and acceptance. RESULTS: Sweet was better for chocolate flavor (3.9 ± 2.4 points) than for vanilla flavor (2.7 ± 2.3 points; p < 0.02) and strawberry flavor (3.1 ± 2.3 points; p < 0.01). Chocolate flavored ONSs were rated as having more aftertaste (3.4 ± 2.1 points) than vanilla (2.4 ± 2.1 points; p < 0.01) and strawberry (2.6 ± 1.5 points; p < 0.03). Patients who chose chocolate took a total of 20.7 ± 20.9 average bricks during hospitalization (1.95 ± 0.2 per day), patients who chose vanilla took 18.6 ± 21.0 bricks (1.90 ± 0.7 per day) and finally patients who chose strawberry took 14.5 ± 13.5 bricks during admission (1.78 ± 0.1 per day; p < 0.01). CONCLUSIONS: The taste preferences of all the ONSs are similar although the consumption is high in chocolate flavored ONS during hospitalization. Sweetness may have influenced this finding.

[Neisseria gonorrhoeae: antimicrobial resistance and study of population dynamics. Situation in Barcelona in 2011]. / Neisseria gonorrhoeae: resistencias antimicrobianas y estudio de la dinámica poblacional. Situación en 2011 en Barcelona.

BACKGROUND: Due to the high rates of antimicrobial resistance to certain antibiotics, together with the emergence of Neisseria gonorrhoeae (NG) with reduced susceptibility and resistance to third-generation cephalosporins, gonococcal infection is becoming a public health problem. The objectives of the study were: To keep track of the antimicrobial susceptibility of NG strains obtained from January to August 2011. To study the population dynamics. METHODS: The antimicrobial susceptibility was studied by disk-diffusion and E-test. The genotyping was performed by NG-MAST method. RESULTS: Of a total of 100strains studied, 59% showed intermediate sensitivity to penicillin and 9% were resistant. According to EUCAST, we detected 3gonococci with reduced susceptibility to ceftriaxone, 10 to cefixime and one with high-level resistance to both antibiotics (MIC 1.5µg/ml). MIC50 and MIC90 to cefixime were 0.016 and 0.125µg/ml, respectively, whereas to ceftriaxone they were <0.016 and 0.064µg/ml, respectively. Almost all (99%) of the strains were resistant to doxycycline, 53% to ciprofloxacin, 3% to azithromycin, and 1% to spectinomycin. The most prevalent ST was ST1407, predominantly associated to resistance or reduced sensitivity to cephalosporins or macrolides. CONCLUSIONS: NG has developed significant rates of resistance to various antibiotics. One strain has been detected with high level resistance to third generation cephalosporins, and several strains with reduced susceptibility. An increase in MIC50 and MIC90 to these antibiotics has also been observed. NG population structure remains stable and common to the rest of Europe, although two new ST (ST7226 and ST7227) have been identified that could be selected and acquire high levels of resistance to cephalosporins.

A propósito de un paciente con infección por Salmonella enterica serotipo Typhi resistente al ácido nalidíxico. Indicación terapéutica / About a patient with nalidixic acid-resistant Salmonella enterica serotype Typhi infection. Therapeutic management

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Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy.

PURPOSE: The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin-->CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel-->CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate. METHODS: A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C. RESULTS: Grade 3 or 4 National Cancer Institute toxicities were low (<5%) in all arms. Neuropathy was more frequent in the paclitaxel-containing arms (grade 2, 20.5% versus 5.0%; grade 3, 1.3% versus 0.2%). At 31 months of follow-up, asymptomatic drop of left ventricular ejection fraction was similar in all arms, whereas symptomatic cardiotoxicity was recorded in three patients (0.5%) in A and in three patients (0.3%) in B plus C. PST induced clinical complete plus partial remission in 78%, with an in-breast pathologic complete response rate of 23% and an in-breast plus axilla pathologic complete response rate of 20%. In the multivariate analysis, only estrogen receptor (ER) status was significantly associated with pathologic complete response (odds ratio for ER negative, 5.77; 95% confidence interval, 3.49-9.52; P<0.0001). PTS induced a significant axillary downstaging (P<0.001), and breast sparing surgery was feasible in 65% versus 34% (P<0.001). CONCLUSIONS: Doxorubicin/paclitaxel-->CMF is feasible, safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing surgery in a large fraction of patients.