Synergistic Combination of Antimicrobial Peptides and Cationic Polyitaconates in Multifunctional PLA Fibers.

Combining different antimicrobial agents has emerged as a promising strategy to enhance efficacy and address resistance evolution. In this study, we investigated the synergistic antimicrobial effect of a cationic biobased polymer and the antimicrobial peptide (AMP) temporin L, with the goal of developing multifunctional electrospun fibers for potential biomedical applications, particularly in wound dressing. A clickable polymer with pendent alkyne groups was synthesized by using a biobased itaconic acid building block. Subsequently, the polymer was functionalized through click chemistry with thiazolium groups derived from vitamin B1 (PTTIQ), as well as a combination of thiazolium and AMP temporin L, resulting in a conjugate polymer-peptide (PTTIQ-AMP). The individual and combined effects of the cationic PTTIQ, Temporin L, and PTTIQ-AMP were evaluated against Gram-positive and Gram-negative bacteria as well as Candida species. The results demonstrated that most combinations exhibited an indifferent effect, whereas the covalently conjugated PTTIQ-AMP displayed an antagonistic effect, potentially attributed to the aggregation process. Both antimicrobial compounds, PTTIQ and temporin L, were incorporated into poly(lactic acid) electrospun fibers using the supercritical solvent impregnation method. This approach yielded fibers with improved antibacterial performance, as a result of the potent activity exerted by the AMP and the nonleaching nature of the cationic polymer, thereby enhancing long-term effectiveness.

Listeria monocytogenes infections: Analysis of 41 patients / Infección por Listeria monocytogenes: análisis de 41 pacientes

OBJECTIVE: We describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections. METHODS: We performed a retrospective study using positive isolation of Listeria monocytogenes from blood, cerebrospinal fluid, and other organic fluids. Electronic health records were used to determine the epidemiological and clinical features of infections caused by L. monocytogenes. Mortality and sepsis were considered dependent variables in the statistical analyses. RESULTS: We included 41 patients in an observation period of 15 years (2003-2018), with an annual incidence rate of 1.3 cases per 100,000 population. Three main population profiles were identified: newborns, pregnant women, and other adults (17.1%, 12.2%, and 82.9%, respectively). Neuroinvasive infection was present in 17 patients (41.5%). In both univariate and multivariate analyses, neurological infections, whether meningoencephalitis, rhombencephalitis, or brain abscesses, were the main risk factors for severe forms of Listeria-related infections (odds ratio 1.8, 95% CI 1.52-2.14, p = 0.01). Malignancies, whether solid tumors or hematological neoplasms, immunosuppression, and chronic diseases were not related to either mortality or severe clinical syndromes. CONCLUSION: Infections caused by L. monocytogenes were uncommon but could cause severe sepsis and mortality, especially in susceptible populations. Our study focused on neurological involvement and severe invasive forms of listeriosis. Neuroinvasive forms were the most important risk factors for severe illness but not for mortality

INTRODUCCIÓN: Describir y analizar las características demográficas y clínicas de las infecciones por Listeria para determinar los factores predisponentes para infecciones severas. MÉTODOS: Diseñamos un estudio retrospectivo utilizando los aislamientos positivos de Listeria monocytogenes en sangre, líquido cefalorraquídeo u otros fluidos orgánicos. Se obtuvieron los registros electrónicos para conseguir las características clínicas y epidemiológicas de las infecciones causadas por L. monocytogenes. Mortalidad y sepsis fueron las variables dependientes en los análisis estadísticos. RESULTADOS: Se incluyeron 41 pacientes en un período de 15 años (2003-2018), con una incidencia anual de 1,3 casos por cada 100.000 habitantes. Identificamos tres perfiles de población: neonatos, mujeres embarazadas y resto de adultos (el 17,1%, el 12,2% y el 82,9%, respectivamente). Las formas neuroinvasivas se identificaron en 17 pacientes (41,5%). Tanto en los análisis univariados como en los multivariados, las infecciones neurológicas, bien meningoencefalitis, rombencefalitis o abscesos cerebrales, fueron los principales factores de riesgo para considerar formas severas de infección por Listeria (odds ratio 1,8; IC 1,52-2,14, p = 0,01). Las neoplasias sólidas o hematológicas, la inmunosupresión o las enfermedades crónicas no estuvieron relacionadas ni con la mortalidad ni con la presencia de severidad en la infección. CONCLUSIÓN: Las infecciones causadas por L. monocytogenes son infrecuentes, pero son causa de sepsis severa y mortalidad en poblaciones susceptibles. Nuestro estudio estuvo dirigido a la infección neuroinvasiva y otras formas graves. La forma neuroinvasiva fue el factor de riesgo más importante asociado a la infección severa, pero no a la mortalidad

Actividad in vitro de la combinación de ceftarolina con otros antimicrobianos activos frente a Staphylococcus spp / In vitro activity of ceftaroline in combination with other antimicrobials active against Staphylococcus spp

INTRODUCCIÓN: Evaluamos la actividad in vitro de la combinación de ceftarolina con daptomicina, linezolid y vancomicina frente a aislados de Staphylococcus aureus (S. aureus) y Staphylococcus coagulasa negativa (SCN) resistentes a meticilina. MATERIAL Y MÉTODOS: Se analizaron 70 cepas de estafilococos (31 S. aureus y 39 SCN) utilizando el método de CMI: CMI ratio con Etest y cálculo de los índices de concentración inhibitoria fraccionaria. RESULTADOS: La combinación de ceftarolina con daptomicina resultó aditiva (53,2%) y sinérgica (6,6%) frente a S. aureus sensibles a meticilina y aditiva (81,2%) frente a S. aureus resistentes a meticilina (SARM). También resultó aditiva frente al 33% de SCN sensibles a linezolid y no hubo sinergia frente a SCN resistentes a linezolid. Ceftarolina con vancomicina mostró sinergia (87%) y ceftarolina con linezolid adición (37%) frente a SAMR. CONCLUSIONES: Las combinaciones de ceftarolina con daptomicina, vancomicina o linezolid presentan efectos aditivos o sinérgicos frente a Staphylococcus resistentes a meticilina

INTRODUCTION: We evaluated the in vitro activity of the combination of ceftaroline with daptomycin, linezolid and vancomycin against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus (CNS). MATERIAL AND METHODS: We analysed 70 staphylococcal strains (31 S. aureus and 39 CNS) with the Etest using the MIC: MIC ratio method and calculation of fractional inhibitory concentration indexes. RESULTS: The combination of ceftaroline with daptomycin showed an additive effect (53.2%) and synergy (6.6%) against methicillin-susceptible S. aureus, and an additive effect (81.2%) against methicillin-resistant S. aureus (MRSA). This combination also showed an additive effect against 33% of linezolid-susceptible CNS and was not synergistic against linezolid-resistant CNS. The combination of ceftaroline with vancomycin was synergistic (87%) and ceftaroline with linezolid was additive (37%) against MRSA. CONCLUSIONS: The combinations of ceftaroline with daptomycin, vancomycin or linezolid showed additive and/or synergistic effects against methicillin-resistant Staphylococcus

In vitro activity of ceftaroline in combination with other antimicrobials active against Staphylococcus spp. / Actividad in vitro de la combinación de ceftarolina con otros antimicrobianos activos frente a Staphylococcus spp.

INTRODUCTION: We evaluated the in vitro activity of the combination of ceftaroline with daptomycin, linezolid and vancomycin against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus (CNS). MATERIAL AND METHODS: We analysed 70 staphylococcal strains (31 S. aureus and 39 CNS) with the Etest using the MIC:MIC ratio method and calculation of fractional inhibitory concentration indexes. RESULTS: The combination of ceftaroline with daptomycin showed an additive effect (53.2%) and synergy (6.6%) against methicillin-susceptible S. aureus, and an additive effect (81.2%) against methicillin-resistant S. aureus (MRSA). This combination also showed an additive effect against 33% of linezolid-susceptible CNS and was not synergistic against linezolid-resistant CNS. The combination of ceftaroline with vancomycin was synergistic (87%) and ceftaroline with linezolid was additive (37%) against MRSA. CONCLUSIONS: The combinations of ceftaroline with daptomycin, vancomycin or linezolid showed additive and/or synergistic effects against methicillin-resistant Staphylococcus.

Listeria monocytogenes infections: Analysis of 41 patients.

OBJECTIVE: We describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections. METHODS: We performed a retrospective study using positive isolation of Listeria monocytogenes from blood, cerebrospinal fluid, and other organic fluids. Electronic health records were used to determine the epidemiological and clinical features of infections caused by L. monocytogenes. Mortality and sepsis were considered dependent variables in the statistical analyses. RESULTS: We included 41 patients in an observation period of 15 years (2003-2018), with an annual incidence rate of 1.3 cases per 100,000 population. Three main population profiles were identified: newborns, pregnant women, and other adults (17.1%, 12.2%, and 82.9%, respectively). Neuroinvasive infection was present in 17 patients (41.5%). In both univariate and multivariate analyses, neurological infections, whether meningoencephalitis, rhombencephalitis, or brain abscesses, were the main risk factors for severe forms of Listeria-related infections (odds ratio 1.8, 95% CI 1.52-2.14, p=0.01). Malignancies, whether solid tumors or hematological neoplasms, immunosuppression, and chronic diseases were not related to either mortality or severe clinical syndromes. CONCLUSION: Infections caused by L. monocytogenes were uncommon but could cause severe sepsis and mortality, especially in susceptible populations. Our study focused on neurological involvement and severe invasive forms of listeriosis. Neuroinvasive forms were the most important risk factors for severe illness but not for mortality.

Actividad sinérgica y eficacia clínica de la asociación fosfomicina-ciprofloxacino en el tratamiento de una infección de malla quirúrgica con absceso de partes blandas por Enterobacter cloacae productor de carbapenemasa / Synergistic activity and clinical efficacy of fosfomycin and ciprofloxacin combination treatment for soft tissue infection caused by carbapenemase-producing Enterobacter cloacae

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Valoración de 2 técnicas automatizadas de microdilución frente a dilución en agar en la determinación de la sensibilidad a fosfomicina en cepas de Pseudomonas aeruginosa resistentes a carbapenémicos / Assessment of 2 automated microdilution techniques compared to an agar dilution method in determining sensitivity to fosfomycin in strains of carbapenem-resistant Pseudomonas aeruginosa

Los aislamientos de Pseudomonas aeruginosa resistentes a carbapenémicos se producen cada vez con más frecuencia, haciendo conveniente establecer tratamientos combinados de los que fosfomicina puede formar parte. Los criterios para establecer la sensibilidad de Pseudomonas aeruginosa a fosfomicina han sido aprobados utilizando un método de dilución en agar. Sin embargo, los sistemas de microdilución comercializados son los más utilizados en la práctica diaria. Los resultados de este estudio indican que estos métodos resultan aceptables cuando se quiera conocer el comportamiento de estos microorganismos frente a fosfomicina

Carbapenems-resistance in Pseudomonas aeruginosa isolates has been widely reported. Fosfomycin has been shown to act synergistically with other antimicrobials. The agar dilution method was approved for susceptibility testing for fosfomycin and Pseudomonas aeruginosa. However, broth microdilution methods are the basis of systems currently used in clinical microbiology laboratories. The results of this study indicate that these methods are acceptable as susceptibility testing methods for fosfomycin against these organisms

Actividad in-vitro de fosfomicina, sola o en combinaciones, frente a aislamientos clínicos de Pseudomonas aeruginosa resistentes a carbapenémicos / In vitro activity of fosfomycin, alone or in combination, against clinical isolates of carbapenem resistant Pseudomonas aeruginosa

INTRODUCCIÓN: En la actualidad asistimos a un progresivo aumento de aislamientos de microorganismos con patrones de multirresistencia y aun de panresistencia. Fosfomicina (FO) es un antimicrobiano activo frente a una gran variedad de microorganismos, incluyendo cepas de Pseudomonas aeruginosa (P. aeruginosa), que es susceptible de actuar sinérgicamente con otras moléculas. MÉTODOS: El objetivo de este estudio consiste en evaluar la actividad in-vitro de FO frente a 120 cepas de P. aeruginosa resistentes a carbapenémicos, utilizando un método de dilución en agar y otro de difusión en gradiente y, además, explorar, mediante el método de E-test y curvas de muerte, la posible sinergia de FO/amikacina y FO/ciprofloxacino, asociaciones potencialmente eficaces frente a P. aeruginosa resistentes a carbapenémicos. RESULTADOS: Para FO, partiendo de los valores de corte epidemiológicos (ECOFF) que publica European Committee on Antimicrobial Susceptibility Testing (EUCAST), más de las 3 cuartas partes de las cepas serían susceptibles de poder ser tratadas con este antimicrobiano, especialmente en combinación con otro agente. La asociación FO/ciprofloxacino presentó un efecto sinérgico en casi la mitad de los aislamientos (40%), mientras que la asociación FO/amikacina solo alcanzó este efecto sinérgico en el 12% de los casos. CONCLUSIÓN: La aparición de cepas de P. aeruginosa resistentes a carbapenémicos hace necesaria la valoración de tratamientos combinados. Este trabajo sugiere que la combinación FO/ciprofloxacino puede ser útil, presentando un efecto sinérgico en el 40% de los aislamientos estudiados

INTRODUCTION: The increase in microorganisms showing patterns of multi-drug resistance or even pan-drug resistance is of growing concern. Fosfomycin (FO) is well known to be active against a wide variety of microorganisms, including highly resistant strains of Pseudomonas aeruginosa (P. aeruginosa), and can also synergistically act with other molecules. METHODS: This study examines the in vitro activity shown by FO against 120 strains of carbapenem-resistant P. aeruginosa using an agar dilution and a gradient diffusion test. Possible synergistic effects of the combinations of FO/amikacin and FO/ciprofloxacin were also examined using E-test and time-kill techniques. RESULTS: According to the epidemiological cut-off value (ECOFF) issued by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), our results indicate that over three-quarters of the strains tested would be susceptible to FO treatment, especially if combined with another antimicrobial. The FO/ciprofloxacin combination had a synergistic effect on 40% of the clinical isolates, while for FO/amikacin this effect was only observed in 12% of the isolates. CONCLUSION: The appearance of carbapenem-resistant P. aeruginosa strains requires the evaluation by combination therapy. This report suggests that the FO/ciprofloxacin combination can be useful, showing a synergistic effect in 40% of the isolates

[Assessment of 2 automated microdilution techniques compared to an agar dilution method in determining sensitivity to fosfomycin in strains of carbapenem-resistant Pseudomonas aeruginosa]. / Valoración de 2 técnicas automatizadas de microdilución frente a dilución en agar en la determinación de la sensibilidad a fosfomicina en cepas de Pseudomonas aeruginosa resistentes a carbapenémicos.

Carbapenems-resistance in Pseudomonas aeruginosa isolates has been widely reported. Fosfomycin has been shown to act synergistically with other antimicrobials. The agar dilution method was approved for susceptibility testing for fosfomycin and Pseudomonas aeruginosa. However, broth microdilution methods are the basis of systems currently used in clinical microbiology laboratories. The results of this study indicate that these methods are acceptable as susceptibility testing methods for fosfomycin against these organisms.

[In vitro activity of fosfomycin, alone or in combination, against clinical isolates of carbapenem resistant Pseudomonas aeruginosa]. / Actividad in-vitro de fosfomicina, sola o en combinaciones, frente a aislamientos clínicos de Pseudomonas aeruginosa resistentes a carbapenémicos.

INTRODUCTION: The increase in microorganisms showing patterns of multi-drug resistance or even pan-drug resistance is of growing concern. Fosfomycin (FO) is well known to be active against a wide variety of microorganisms, including highly resistant strains of Pseudomonas aeruginosa (P. aeruginosa), and can also synergistically act with other molecules. METHODS: This study examines the in vitro activity shown by FO against 120 strains of carbapenem-resistant P. aeruginosa using an agar dilution and a gradient diffusion test. Possible synergistic effects of the combinations of FO/amikacin and FO/ciprofloxacin were also examined using E-test and time-kill techniques. RESULTS: According to the epidemiological cut-off value (ECOFF) issued by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), our results indicate that over three-quarters of the strains tested would be susceptible to FO treatment, especially if combined with another antimicrobial. The FO/ciprofloxacin combination had a synergistic effect on 40% of the clinical isolates, while for FO/amikacin this effect was only observed in 12% of the isolates. CONCLUSION: The appearance of carbapenem-resistant P. aeruginosa strains requires the evaluation by combination therapy. This report suggests that the FO/ciprofloxacin combination can be useful, showing a synergistic effect in 40% of the isolates.