KPC-2 allelic variants in Klebsiella pneumoniae isolates resistant to ceftazidime-avibactam from Argentina: blaKPC-80, blaKPC-81, blaKPC-96 and blaKPC-97.

Ceftazidime-avibactam (CZA) therapy has significantly improved survival rates for patients infected by carbapenem-resistant bacteria, including KPC producers. However, resistance to CZA is a growing concern, attributed to multiple mechanisms. In this study, we characterized four clinical CZA-resistant Klebsiella pneumoniae isolates obtained between July 2019 and December 2020. These isolates expressed novel allelic variants of blaKPC-2 resulting from changes in hotspots of the mature protein, particularly in loops surrounding the active site of KPC. Notably, KPC-80 had an K269_D270insPNK mutation near the Lys270-loop, KPC-81 had a del_I173 mutation within the Ω-loop, KPC-96 showed a Y241N substitution within the Val240-loop and KPC-97 had an V277_I278insNSEAV mutation within the Lys270-loop. Three of the four isolates exhibited low-level resistance to imipenem (4 µg/mL), while all remained susceptible to meropenem. Avibactam and relebactam effectively restored carbapenem susceptibility in resistant isolates. Cloning mutant blaKPC genes into pMBLe increased imipenem MICs in recipient Escherichia coli TOP10 for blaKPC-80, blaKPC-96, and blaKPC-97 by two dilutions; again, these MICs were restored by avibactam and relebactam. Frameshift mutations disrupted ompK35 in three isolates. Additional resistance genes, including blaTEM-1, blaOXA-18 and blaOXA-1, were also identified. Interestingly, three isolates belonged to clonal complex 11 (ST258 and ST11) and one to ST629. This study highlights the emergence of CZA resistance including unique allelic variants of blaKPC-2 and impermeability. Comprehensive epidemiological surveillance and in-depth molecular studies are imperative for understanding and monitoring these complex resistance mechanisms, crucial for effective antimicrobial treatment strategies. IMPORTANCE: The emergence of ceftazidime-avibactam (CZA) resistance poses a significant threat to the efficacy of this life-saving therapy against carbapenem-resistant bacteria, particularly Klebsiella pneumoniae-producing KPC enzymes. This study investigates four clinical isolates exhibiting resistance to CZA, revealing novel allelic variants of the key resistance gene, blaKPC-2. The mutations identified in hotspots surrounding the active site of KPC, such as K269_D270insPNK, del_I173, Y241N and V277_I278insNSEAV, prove the adaptability of these pathogens. Intriguingly, low-level resistance to imipenem and disruptions in porin genes were observed, emphasizing the complexity of the resistance mechanisms. Interestingly, three of four isolates belonged to clonal complex 11. This research not only sheds light on the clinical significance of CZA resistance but also shows the urgency for comprehensive surveillance and molecular studies to inform effective antimicrobial treatment strategies in the face of evolving bacterial resistance.

Secuelas cognitivas en encefalitis inmunomediadas: cohorte de pacientes en Argentina / Cognitive sequelae in immunomediated encephalitis: cohort of patients in Argentina

Resumen Introducción: Las encefalitis inmunomediadas son un desorden neurológico de origen autoinmune. Actual mente es escasa la descripción de las secuelas cognitivas crónicas. El objetivo del presente trabajo fue caracterizar la secuela cognitiva de diferentes tipos de encefalitis inmunomediadas en una cohorte de un centro único de Argentina. Métodos: Estudio prospectivo, observacional, trans versal, de pacientes en seguimiento en un hospital de la Ciudad de Buenos Aires, con diagnóstico de encefalitis inmunomediada probable y definitiva. Se evaluaron variables epidemiológicas, clínicas, paraclínicas y tra tamiento. Se determinó la secuela cognitiva a través de una evaluación neurocognitiva realizada a partir del año de la presentación clínica. Resultados: Fueron incluidos 15 pacientes, todos con resultado disminuido en al menos un test. La memoria fue el dominio más afectado. Aquellos que se encon traban bajo tratamiento inmunosupresor al momento de evaluarse presentaron menores resultados en el aprendizaje seriado (media -2.94; desvío estándar 1.54) versus los que se encontraban sin tratamiento (media -1.18; desvío estándar 1.40; p = 0.05) y en la prueba de reconocimiento (media -10.34; desvío estándar 8.02) ver sus sin tratamiento (media -1.39; desvío estándar 2.21; p = 0.003). Los pacientes con estatus epiléptico tuvieron resultados deficitarios en la prueba de reconocimiento (media -7.2; desvío estándar 7.91) en comparación a los que no lo tenían (media -1.47; desvío estándar 2.34; p = 0.05). Conclusión: Nuestros resultados demuestran que, a pesar del curso monofásico de la enfermedad, todos los pacientes presentan daño cognitivo persistente más allá del año del inicio del cuadro. Estudios prospectivos de mayor envergadura serían necesarios para confirmar nuestros hallazgos.

Abstract Introduction: Autoimmune encephalitis represents a group of immune-mediated neurological disorders. At present, the description of the chronic cognitive sequela is scarce. The objective of this study was to characterize the cognitive after effects of different types of autoimmune encephalitis in a cohort from a single center in Argentina. Methods: Prospective, observational, cross-sectional study of patients under follow-up at a hospital in Buenos Aires city, with a diagnosis of probable and definitive immune-mediated encephalitis. Epidemiological, clini cal, paraclinical and treatment related variables were evaluated. Cognitive sequela was determined through a neurocognitive evaluation performed at least a year after the clinical presentation. Results: Fifteen patients were included. All had di minished results in at least one test. Memory was the most affected domain. Patients who were under im munosuppressive treatment at the time of evaluation presented lower results in serial learning (mean -2.94; standard deviation 1.54) versus those who weren't under treatment (mean -1.18; standard deviation 1.40; p = 0.05). The same pattern was observed on the recognition test of treatment group (mean -10.34; standard deviation 8.02) versus treatment-free group (mean -1.39; standard deviation 2.21; p =0.003). Patients with status epilepticus had poorer results in the recognition test (mean -7.2; standard deviation 7.91) compared to those without it (mean -1.47; standard deviation 2.34; p = 0.05). Conclusion: Our results show that, despite the mo nophasic course of this disease, all patients had persis tent cognitive damage beyond the year of onset. Larger prospective studies are required to confirm our findings.

[Cognitive sequelae in immunomediated encephalitis: cohort of patients in Argentina]. / Secuelas cognitivas en encefalitis inmunomediadas: cohorte de pacientes en Argentina.

INTRODUCTION: Autoimmune encephalitis represents a group of immune-mediated neurological disorders. At present, the description of the chronic cognitive sequela is scarce. The objective of this study was to characterize the cognitive after effects of different types of autoimmune encephalitis in a cohort from a single center in Argentina. METHODS: Prospective, observational, cross-sectional study of patients under follow-up at a hospital in Buenos Aires city, with a diagnosis of probable and definitive immune-mediated encephalitis. Epidemiological, clinical, paraclinical and treatment related variables were evaluated. Cognitive sequela was determined through a neurocognitive evaluation performed at least a year after the clinical presentation. RESULTS: Fifteen patients were included. All had diminished results in at least one test. Memory was the most affected domain. Patients who were under immunosuppressive treatment at the time of evaluation presented lower results in serial learning (mean -2.94; standard deviation 1.54) versus those who weren't under treatment (mean -1.18; standard deviation 1.40; p = 0.05). The same pattern was observed on the recognition test of treatment group (mean -10.34; standard deviation 8.02) versus treatment-free group (mean -1.39; standard deviation 2.21; p =0.003). Patients with status epilepticus had poorer results in the recognition test (mean -7.2; standard deviation 7.91) compared to those without it (mean -1.47; standard deviation 2.34; p = 0.05). CONCLUSION: Our results show that, despite the monophasic course of this disease, all patients had persistent cognitive damage beyond the year of onset. Larger prospective studies are required to confirm our findings.

Introducción: Las encefalitis inmunomediadas son un desorden neurológico de origen autoinmune. Actualmente es escasa la descripción de las secuelas cognitivas crónicas. El objetivo del presente trabajo fue caracterizar la secuela cognitiva de diferentes tipos de encefalitis inmunomediadas en una cohorte de un centro único de Argentina. Métodos: Estudio prospectivo, observacional, transversal, de pacientes en seguimiento en un hospital de la Ciudad de Buenos Aires, con diagnóstico de encefalitis inmunomediada probable y definitiva. Se evaluaron variables epidemiológicas, clínicas, paraclínicas y tratamiento. Se determinó la secuela cognitiva a través de una evaluación neurocognitiva realizada a partir del año de la presentación clínica. Resultados: Fueron incluidos 15 pacientes, todos con resultado disminuido en al menos un test. La memoria fue el dominio más afectado. Aquellos que se encontraban bajo tratamiento inmunosupresor al momento de evaluarse presentaron menores resultados en el aprendizaje seriado (media -2.94; desvío estándar 1.54) versus los que se encontraban sin tratamiento (media -1.18; desvío estándar 1.40; p = 0.05) y en la prueba de reconocimiento (media -10.34; desvío estándar 8.02) versus sin tratamiento (media -1.39; desvío estándar 2.21; p = 0.003). Los pacientes con estatus epiléptico tuvieron resultados deficitarios en la prueba de reconocimiento (media -7.2; desvío estándar 7.91) en comparación a los que no lo tenían (media -1.47; desvío estándar 2.34; p = 0.05). Conclusión: Nuestros resultados demuestran que, a pesar del curso monofásico de la enfermedad, todos los pacientes presentan daño cognitivo persistente más allá del año del inicio del cuadro. Estudios prospectivos de mayor envergadura serían necesarios para confirmar nuestros hallazgos.

Genomic Comparative Analysis of Two Multi-Drug Resistance (MDR) Acinetobacter baumannii Clinical Strains Assigned to International Clonal Lineage II Recovered Pre- and Post-COVID-19 Pandemic.

BACKGROUND: After the emergence of COVID-19, numerous cases of A. baumannii/SARS-CoV-2 co-infection were reported. Whether the co-infecting A. baumannii strains have distinctive characteristics remains unknown. METHODS AND RESULTS: A. baumannii AMA_NO was isolated in 2021 from a patient with COVID-19. AMA166 was isolated from a mini-BAL used on a patient with pneumonia in 2016. Both genomes were similar, but they possessed 337 (AMA_NO) and 93 (AMA166) unique genes that were associated with biofilm formation, flagellar assembly, antibiotic resistance, secretion systems, and other functions. The antibiotic resistance genes were found within mobile genetic elements. While both strains harbored the carbapenemase-coding gene blaOXA-23, only the strain AMA_NO carried blaNDM-1. Representative functions coded for by virulence genes are the synthesis of the outer core of lipooligosaccharide (OCL5), biosynthesis and export of the capsular polysaccharide (KL2 cluster), high-efficiency iron uptake systems (acinetobactin and baumannoferrin), adherence, and quorum sensing. A comparative phylogenetic analysis including 239 additional sequence type (ST) 2 representative genomes showed high similarity to A. baumannii ABBL141. Since the degree of similarity that was observed between A. baumannii AMA_NO and AMA166 is higher than that found among other ST2 strains, we propose that they derive from a unique background based on core-genome phylogeny and comparative genome analysis. CONCLUSIONS: Acquisition or shedding of specific genes could increase the ability of A. baumannii to infect patients with COVID-19.

[The "Tortoni effect" in prosopagnosia]. / El "efecto Tortoni" en la prosopagnosia.

Proposapnosia is a type of visual agnosia characterized by the inability to recognize people's faces. There are basically two variants, apperceptive and associative. The "Tortoni effect" is a phenomenon described by Bekinschtein et al a few years ago in waiters from Buenos Aires, who used this tool to remember the orders of each member of a table. We present a case of prosopagnosia associated with bilateral temporo-occipital injury secondary to head trauma, initially manifested by the lack of face recognition with the use of an associative strategy similar to that described in the "Tortoni effect" as compensation, in a 62-year-old female who suffered a severe head injury. A few months after this event, the patient had difficulty in recognizing familiar people, a fact evidenced by her relatives when at a restaurant table, they changed their seats, remained silent momentarily, and right after the patient kept naming them by their previous location. The magnetic resonance imaging of the brain revealed blunt sequelae lesions in the bilateral temporo-occipital region. Acquired prosopagnosia due to focal lesions in the temporo-occipital region, generally bilateral and right, and less frequently left, is a rare condition. The strategy used in the "Tortoni effect" was one of the initial manifestations of the condition in our patient. Carrying out an ecological neuropsychological test that considers this strategy could be useful in the screening and early detection of this entity.

La prosopagnosia es un tipo de agnosia visual caracterizada por la incapacidad de reconocer los rostros de las personas. Existen básicamente dos variantes, aperceptivas y asociativas. El "efecto Tortoni" es un fenómeno descripto por Bekinschtein y col. hace unos años en mozos de café en Buenos Aires, quienes utilizaban esta herramienta para recordar los pedidos de cada integrante de una mesa. Presentamos un caso de prosopagnosia asociada a lesión temporo-occipital bilateral secundaria a traumatismo encefalocraneano, manifestada en forma inicial por la falta de reconocimiento de rostros, con la utilización de una estrategia asociativa similar a la descripta en el efecto "Tortoni" como compensación. Mujer de 62 años que sufrió un traumatismo encefalocraneano grave. Pocos meses después del evento, presentó dificultad para reconocer personas conocidas, hecho evidenciado por sus allegados cuando en una mesa los integrantes cambiaron su asiento, permanecieron callados por unos instantes, y posteriormente la paciente continuó nombrándolos por su ubicación previa. En la resonancia magnética de cerebro se objetivaron lesiones contusas de aspecto secuelar en región temporo-occipital bilateral. La prosopagnosia adquirida secundaria a lesiones focales en la región temporo-occipital generalmente bilateral, derecha, y raramente izquierda, es un cuadro poco frecuente. La estrategia utilizada en el "efecto Tortoni" fue en nuestra paciente una de las manifestaciones iniciales del cuadro. La realización de un test neuropsicológico ecológico que considere esta estrategia podría ser de utilidad en el rastreo y detección precoz de esta entidad.

El "efecto Tortoni" en la prosopagnosia / The "Tortoni effect" in prosopagnosia

Resumen La prosopagnosia es un tipo de agnosia visual caracterizada por la incapacidad de reconocer los rostros de las personas. Existen básicamente dos variantes, aperceptivas y asociativas. El "efecto Tortoni" es un fenómeno descripto por Bekinschtein y col. hace unos años en mozos de café en Buenos Aires, quienes utilizaban esta herramienta para recordar los pedidos de cada integrante de una mesa. Presentamos un caso de prosopagnosia asociada a lesión temporo-occipital bilateral secundaria a traumatismo encefalocra neano, manifestada en forma inicial por la falta de reconocimiento de rostros, con la utilización de una estra tegia asociativa similar a la descripta en el efecto "Tortoni" como compensación. Mujer de 62 años que sufrió un traumatismo encefalocraneano grave. Pocos meses después del evento, presentó dificultad para reconocer personas conocidas, hecho evidenciado por sus allegados cuando en una mesa los integrantes cambiaron su asiento, permanecieron callados por unos instantes, y posteriormente la paciente continuó nombrándolos por su ubicación previa. En la resonancia magnética de cerebro se objetivaron lesiones contusas de aspecto secuelar en región temporo-occipital bilateral. La prosopagnosia adquirida secundaria a lesiones focales en la región temporo-occipital generalmente bilateral, derecha, y raramente izquierda, es un cuadro poco frecuente. La es trategia utilizada en el "efecto Tortoni" fue en nuestra paciente una de las manifestaciones iniciales del cuadro. La realización de un test neuropsicológico ecológico que considere esta estrategia podría ser de utilidad en el rastreo y detección precoz de esta entidad.

Abstract Proposapnosia is a type of visual agnosia characterized by the inability to recognize people's faces. There are basically two variants, apperceptive and associative. The "Tortoni effect" is a phenomenon described by Bekinschtein et al a few years ago in waiters from Buenos Aires, who used this tool to remember the orders of each member of a table. We present a case of prosopagnosia associated with bilateral temporo-occipital injury secondary to head trauma, initially manifested by the lack of face recognition with the use of an associative strategy similar to that described in the "Tortoni effect" as compensation, in a 62-year-old female who suffered a severe head injury. A few months after this event, the patient had difficulty in recognizing familiar people, a fact evidenced by her relatives when at a restaurant table, they changed their seats, remained silent momentarily, and right after the patient kept naming them by their previous location. The magnetic resonance imaging of the brain revealed blunt sequelae lesions in the bilateral temporo-occipital region. Acquired prosopagnosia due to focal lesions in the temporo-occipital region, generally bilateral and right, and less frequently left, is a rare condition. The strategy used in the "Tortoni effect" was one of the initial manifestations of the condition in our patient. Carrying out an ecological neuropsychological test that considers this strategy could be useful in the screening and early detection of this entity.

[Cognitive dysfunction in systemic lupus erythematosus in relation to disease activity and damage]. / Disfunción cognitiva en lupus eritematoso sistémico y su asociación con actividad y daño.

Systemic lupus erythematosus (SLE) is a rheumatic disease, which during its evolution may present neurocognitive dysfunction with fronto-subcortical compromise. However, there is no enough published evidence regarding the relationship between cognitive dysfunction and SLE activity and SLE induced damage. The objective of the study was to analyze this association. We designed an observational cross-sectional study including 84 patients with SLE. We used the SLEDAI index to evaluate activity and the SLICC index to evaluate cumulative damage. We used neuropsychological tests to assess the presence of cognitive symptoms, global cognitive function, verbal and visual memory, visual-construction, semantic verbal fluency, processing speed and working memory. Scores more than 1.5 standard deviations below adjusted normal values were considered as cognitive dysfunction. We observed a statistically significant association between the higher value of SLEDAI and working memory impairment and a higher value of SLICC and viso-construction and semantic verbal fluency impairment. The association observed in SLE patients between disease activity or damage and some cognitive domains may be involving different pathophysiological brain mechanisms of different areas with different degrees of severity and vulnerability.

Disfunción cognitiva en lupus eritematoso sistémico y su asociación con actividad y daño / Cognitive dysfunction in systemic lupus erythematosus in relation to disease activity and damage

El lupus eritematoso sistémico (LES), es una enfermedad reumatológica, que puede presentar en su evolución alteraciones neurocognitivas, con importante compromiso fronto-subcortical. Sin embargo, existe escasa evidencia publicada sobre la relación entre la disfunción cognitiva y la actividad y daño de la enfermedad sistémica. El objetivo del trabajo fue analizar dicha asociación. Se realizó un estudio observacional de corte transversal, incluyendo 84 pacientes con LES. Se evaluó la actividad con el índice de SLEDAI y el daño acumulado con el índice de SLICC. Mediante pruebas neuropsicológicas se evaluó la presencia de síntomas cognitivos, función cognitiva global, memoria verbal y visual, viso-construcción, fluencia verbal semántica, velocidad de procesamiento y memoria de trabajo. Se consideró disfunción en un área cognitiva a un rendimiento de más de 1.5 desvíos estándares por debajo de los valores normales del test neuropsicológico. Se observó asociación estadísticamente significativa entre un mayor valor de SLEDAI y la alteración en la memoria de trabajo, y un mayor valor de SLICC y el compromiso de la viso-construcción y la fluencia verbal semántica. La asociación observada en los pacientes con LES entre el grado de actividad o daño de la enfermedad con algunos dominios cognitivos podría estar involucrando diferentes mecanismos fisiopatogénicos de la disfunción cerebral de cada área con distinto grado de afectación o vulnerabilidad.

Systemic lupus erythematosus (SLE) is a rheumatic disease, which during its evolution may present neurocognitive dysfunction with fronto-subcortical compromise. However, there is no enough published evidence regarding the relationship between cognitive dysfunction and SLE activity and SLE induced damage. The objective of the study was to analyze this association. We designed an observational cross-sectional study including 84 patients with SLE. We used the SLEDAI index to evaluate activity and the SLICC index to evaluate cumulative damage. We used neuropsychological tests to assess the presence of cognitive symptoms, global cognitive function, verbal and visual memory, visual-construction, semantic verbal fluency, processing speed and working memory. Scores more than 1.5 standard deviations below adjusted normal values were considered as cognitive dysfunction. We observed a statistically significant association between the higher value of SLEDAI and working memory impairment and a higher value of SLICC and viso-construction and semantic verbal fluency impairment. The association observed in SLE patients between disease activity or damage and some cognitive domains may be involving different pathophysiological brain mechanisms of different areas with different degrees of severity and vulnerability.