Emergence of lineage III of Shigella sonnei ST152 belonging to a high-risk clone harboring the blaCTX-M-15 gene in Peru.

Multidrug-resistant Shigella sonnei ST152, global lineage III, is a high-risk clone, whose dissemination has limited therapeutic options for shigellosis. This study aimed to characterize two isolates of S. sonnei, which were recovered in Lima, Peru, during November 2019, exhibiting resistance to extended-spectrum cephalosporins and quinolones, and concurrently harboring blaCTX-M-15 and qnrS1 genes, in addition to mutations in gyrA-S83L. These isolates were resistant to ceftriaxone, ciprofloxacin and trimethoprim/sulfamethoxazole. The molecular analysis showed that both isolates belonged to lineage III, sublineages IIIa and IIIb. The blaCTX-M-15 gene was located in the same genetic platform as qnrS1, flanked upstream by ISKpn19, on a conjugative plasmid belonging to the IncI-γ group. To the best of our knowledge, this would be the first report on S. sonnei isolates carrying the blaCTX-M-15 gene in Peru. The global dissemination of S. sonnei ST152, co-resistant to ß-lactams and quinolones, could lead to a worrisome scenario in the event of potential acquisition of genetic resistance mechanisms to azithromycin.

Identificación y caracterización de herramientas para evaluar la alergia a las penicilinas: Revisión estructurada / Identification and characterization of tools used to assess penicillin allergy: structured review

Introducción: Las reacciones alérgicas son uno de los problemas de seguridad más graves asociadas al uso de medicamentos, siendo la alergia a los antibióticos betalactámicos la más prevalente. Las pruebas de alergia a las penicilinas pueden ayudar a identificar pacientes hospitalizados y ambulatorios que podrían tolerar y usar de manera segura este grupo de antibióticos y evitar rótulos que limiten el uso de antibióticos betalactámicos por tiempo indefinido. Objetivo: Identificar las herramientas disponibles en la literatura para valorar el antecedente de alergia a las penicilinas y proponer una herramienta que consolide la información extraída. Metodología: Revisión estructurada en PubMed/MEDLINE entre 1 junio 2015 hasta 30 noviembre 2022, utilizando los términos MeSH: (((“skin tests”[MeSH Terms]) OR (“skin irritancy tests”[MeSH Terms])) AND (“penicillins”[All Fields])) AND (“drug hypersensitivity”[MeSH Terms]). Publicaciones en inglés y español con acceso a texto completo y estudios realizados en humanos, sobre herramientas disponibles para evaluar la alergia a penicilinas fueron incluidos. Resultados: Se identificaron201 artículos, de los cuales se incluyeron 108. Dentro de las herramientas para evaluar la alergia a las penicilinas se identificaron: a) pruebas in vivo: pruebas cutáneas, pruebas de provocación oral, pruebas del parche; y b) pruebas in vitro: pruebas de IgE específica, determinación de triptasa, histamina. De los 1181 pacientes reportados con alergia a las penicilinas, sólo el 2 % de ellos se confirmó la presencia de alergia. Conclusión: Las pruebas cutáneas y de provocación oral sumado a algunas combinaciones in vivo/in vitro, fueron las herramientas más utilizadas para evaluar la alergia a las penicilinas. (AU)

Introduction: Allergic reactions are one of the most serious safety problems associated with the use of medications, with allergy to beta-lactam antibiotics being the most prevalent. In fact, the American Academy of Allergy, Asthma and Immunology (AAAAI) states that penicillin allergy testing can help identify inpatients and outpatients who could safely tolerate and use this group of antibiotics and avoid labels that limit the use of beta-lactam antibiotics indefinitely. Objective: To identify the tools available in the literature to assess the history of allergy to penicillins and propose a tool that consolidates the information extracted. Methodology: Structured review on PubMed/MEDLINE between June 1, 2015 until November 30, 2022; using the search terms MeSH: (((“skin tests”[MeSH Terms]) OR (“skin irritancy tests”[MeSH Terms])) AND (“penicillins”[All Fields])) AND (“drug hypersensitivity”[MeSH Terms]). Papers in English and Spanish with access to full text and human trials, regarding available tools used to evaluate penicillin allergies were included. Results: A total of 201 articles were identified, of which after an independent evaluation, 108 were included. Among the tools to evaluate penicillin allergy, in vivo tests were identified: skin tests, oral provocation tests, patch tests and in vitro tests: specific IgE tests, determination of tryptase, histamine, T lymphocytes and basophilic activation tests. Of the patients (1181) reported with penicillin allergy, 905 (77 %) had their allergy assessed with skin testing or oral challenge tests, and only 2 % of them had a confirmed allergic reaction. Conclusion: Skin tests and oral provocation tests added to some in vivo/in vitro combinations were the most used tools to evaluate penicillin allergy. (AU)

El farmacéutico clínico en el abordaje del paciente con sospecha de alergia a beta-lactámicos: una revisión sistemática / The role of clinical pharmacists in patients with suspected allergy to B-lactams: A systematic review

Objetivo analizar el papel desempeñado por el farmacéutico clínico y su impacto en el ámbito de los programas de optimización de antimicrobianos ante la sospecha de alergia a antibióticos beta-lactámicos.Método se realizaron 2 búsquedas bibliográficas independientes. Se encontraron un total de 35 artículos incluyéndose 12. Se analizaron los artículos incluidos y se recogieron variables de eficacia, seguridad y aplicabilidad de herramientas de evaluación a pacientes con sospecha de alergia a beta-lactámicos. Además, se analizó la variación en el consumo y en el perfil de prescripción de antibióticos alternativos. Resultados los estudios seleccionados analizaron cuestionarios, desetiquetado, test intradérmicos y pruebas de provocación oral realizados por farmacéuticos. Se hallaron diferencias significativas en la variable principal de eficacia en 4 estudios incluidos a favor de la intervención farmacéutica. En un estudio cuasi experimental, la utilización de cefazolina aumentó tras la intervención farmacéutica (65 vs. 28%; p < 0,01). En otro estudio cuasi experimental, la dosis diaria definida media de aztreonam y la media de días de terapéutica por 1.000 pacientes/día disminuyeron (21,23 vs. 9,05; p < 0,01) y (8,79–4,24; p = 0,016), pre y postintervención, respectivamente, aumentando las desescaladas antibióticas (p ≤ 0,01). En otro estudio, disminuyó la prescripción de antibióticos de uso restringido (42,5 vs. 17,9%; p < 0,01) y en otro, la utilización de antibióticos profilácticos prequirúrgicos alternativos a cefazolina (81,9 vs. 55,9%; p < 0,01). En otro estudio, el tiempo medio por entrevista fue de 5,2 minutos por paciente. No se reportaron eventos adversos en ningún estudio. Conclusiones la intervención del farmacéutico en la evaluación del paciente con sospecha de alergia a beta-lactámicos resulta eficaz, segura y aplicable a la práctica clínica (AU)

Objective To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics. Method We performed two different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analysed the articles and collected variables of efficacy, safety and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed. Results The selected studies analysed questionnaires, allergy delabeling, intradermal tests and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favour of pharmaceutical intervention. In the study of Kwiatkowski et al, cefazolin use increased in surgical patients after pharmacist intervention (65 vs. 28%; p < 0.01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, p <0.01) and (8.79–4.24, p = 0.016), pre and post-intervention, respectively, increasing antibiotic de-escalations (p ≤ 0.01). In another quasi-experimental study, the prescription of restricted-use antibiotics decreased (42.5% vs. 17.9%, p < 0.01) and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, p<0.01) in another study. Other study showed that the mean time per interview was 5.2 minutes per patient. No adverse events were reported in any study. Conclusion The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe and feasible to implement on daily clinical practice (AU)

The role of clinical pharmacists in patients with suspected allergy to ß-lactams: A systematic review. / El farmacéutico clínico en el abordaje del paciente con sospecha de alergia a beta-lactámicos: una revisión sistemática.

OBJECTIVE: To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics. METHOD: We performed two different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analysed the articles and collected variables of efficacy, safety and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed. RESULTS: The selected studies analysed questionnaires, allergy delabeling, intradermal tests and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favour of pharmaceutical intervention. In the study of Kwiatkowski et al, cefazolin use increased in surgical patients after pharmacist intervention (65 vs. 28%; p < 0.01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, p <0.01) and (8.79-4.24, p = 0.016), pre and post-intervention, respectively, increasing antibiotic de-escalations (p ≤ 0.01). In another quasi-experimental study, the prescription of restricted-use antibiotics decreased (42.5% vs. 17.9%, p < 0.01) and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, p<0.01) in another study. Other study showed that the mean time per interview was 5.2 minutes per patient. No adverse events were reported in any study. CONCLUSION: The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe and feasible to implement on daily clinical practice. The standardization of protocols to clarify the history of allergies and development of evaluation tools represent simple screenings to perform delabelling or refer to the Immunoallergology service, improving penicilins use and reducing the need for second line antibiotics. More studies are needed to standardize the desensitization tests made by pharmacists. However, despite these results, the involvement and leadership of the pharmacist in this area is limited and constitutes a future challenge for the profession.

[Translated article] The role of clinical pharmacists in patients with suspected allergy to ß-lactams: A systematic review.

OBJECTIVE: To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics. METHOD: We performed 2 different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analyzed the articles and collected variables of efficacy, safety, and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed. RESULTS: The selected studies analyzed questionnaires, allergy delabeling, intradermal tests, and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favor of pharmaceutical intervention. In the study of Kwiatkowski et al., cefazolin use increased in surgical patients after pharmacist intervention (65% vs 28%; P < .01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, P <.01) and (8.79-4.24, P = .016), pre- and post-intervention, respectively, increasing antibiotic de-escalations (P = < .01). In another quasi-experimental study, the prescription of restricted use antibiotics decreased (42.5% vs 17.9%, P < .01)and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, P < .01)in another study. Other study showed that the mean time per interview was 5.2 min per patient. No adverse events were reported in any study. CONCLUSION: The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe, and feasible to implement on daily clinical practice. The standardization of protocols to clarify the history of allergies and development of evaluation tools represent simple screenings to perform delabeling or refer to the Immunoallergology service, improving penicilins use and reducing the need for second-line antibiotics. More studies are needed to standardize the desensitization tests made by pharmacists. However, despite these results, the involvement and leadership of the pharmacist in this area is limited and constitutes a future challenge for the profession.

Isolation of Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum ß-lactamases from dog urine of the Metropolitan Area of the Aburrá Valley (Antioquia, Colombia) / Aislamiento de Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido a partir de orina de perros del Área metropolitana del Valle de Aburrá (Antioquia, Colombia)

ABSTRACT Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing urinary tract infections in humans and animals. Close contact between humans and companion animals can facilitate the spread of multidrug resistant pathogens between both species. The objective of the research was to characterize extended-spectrum ß-lactamases (ESBL) -producing E. coli and K. pneumoniae isolated from dogs with urinary tract infections in the metropolitan area of Valle del Aburrá (Antioquia, Colombia). Three-hundred seventy-one urine samples collected from March 2018 to March 2019 in a veterinary clinical laboratory were analyzed. E. coli and K. pneumoniae isolates were detected in chromogenic agar and identified by biochemical tests. Susceptibility testing was performed by disc diffusion and ESBL production was evaluated by the double disk test in all isolates. MIC determination of ESBL-positive isolates were performed on the automated VITEK®2 system. Multiple PCR was used for the detection of CTX-M beta-lactamases (group 1, 2, 9 and 8/25), SHV, TEM, and AmpC of plasmid origin in ESBL-positive isolates. In total 22 out 371 isolates were positive for ESBL production by double disc test, 11 E. coli (ESBL-Ec) and 11 K. pneumoniae (ESBL-Kp). The multiple PCR detected CTX-M group 1 in the 22 ESBL-positive isolates. Multi-drug resistance was observed in all ESBL-producing isolates. In conclusion, a high frequency of antibiotic multi-resistance was found in ESBL-Ec and ESBL-Kp. The main ESBL detected was CTX-M group 1, which also prevails in human isolates.

RESUMEN Escherichia coli y Klebsiella pneumoniae son los patógenos más comunes causantes de infecciones en tracto urinario en humanos y animales. El contacto estrecho con los animales de compañía puede favorecer la diseminación de patógenos multiresistentes entre ambas especies. El objetivo de la investigación fue caracterizar E. coli (Ec -BLEE) y K. pneumo-niae (Kp -BLEE) productores de betalactamasas de espectro extendido provenientes de aislados de caninos con infecciones del tracto urinario del Área Metropolitana del Valle de Aburrá. 371 muestras de orina de caninos colectadas entre marzo de 2018 y marzo 2019 en un laboratorio clínico veterinario fueron analizadas. E. coli y K. pneumoniae se detectaron en agar cromogénico y se identificaron mediante pruebas bioquímicas. La prueba de susceptibilidad se realizó por difusión en disco y la producción de BLEE se evaluó por test de doble disco en todos los aislados. La determinación de la CIM en aislados positivos a BLEE se realizó en el sistema automatizado VITEK®2. Se utilizó PCR múltiple para la detección de betalactamasas tipo CTX-M (grupo 1, 2, 9 y 8/25), SHV, TEM y AmpC de origen plasmídico en aislados positivos a BLEE. Un total de 22 de 371 aislados fueron positivos a BLEE por test de doble disco, 11 E. coli (Ec -BLEE) y 11 K. pneumoniae (Kp-BLEE). La PCR detectó CTX-M grupo 1 en los 22 aislados positivos a BLEE. Se observó multirresistencia en todos los aislamientos productores de BLEE. En conclusión, se encontró una alta frecuencia de multirresistencia en Ec-BLEE y Kp-BLEE. La principal BLEE detectada fue CTX-M grupo 1, que también predomina en aislados humanos.

Filogenia y resistencia de cepas de Escherichia coli productoras de betalactamasas de espectro extendido a los antibióticos en pacientes con cáncer hospitalizados en Perú / Phylogeny and antimicrobial resistance of extended-spectrum beta-lactamase- producing Escherichia coli from hospitalized oncology patients in Perú

Introducción. Las infecciones asociadas con la atención en salud constituyen un problema de salud pública porque aumentan la morbimortalidad de los pacientes, sobre todo de aquellos con factores de riesgo, como la inmunosupresión debida a enfermedades oncológicas. Es importante conocer la diversidad genética de los principales microorganimos causantes de infecciones hospitalarias mediante la vigilancia epidemiológica tradicional y la epidemiología molecular, para hacer un mejor seguimiento y detectar brotes tempranamente. Objetivo. Determinar el grupo filogenético y la resistencia a antibióticos de las cepas de Escherichia coli aisladas de pacientes con cáncer hospitalizados. Materiales y métodos. Se hizo un estudio de tipo transversal que incluyó 67 cepas de Escherichia coli productoras de betalactamasas de espectro extendido (BLEE). Se determinó el grupo filogenético, el perfil de resistencia a los antibióticos, los genes de resistencia a betalactámicos, el tipo de las muestras y los servicios de hospitalización de donde fueron recuperadas. Resultados. El grupo filogenético más frecuente fue el B2 (36 %). El 57 % de las cepas B2 fueron aisladas de muestras de orina y el 33 % provenía del servicio de urología. La resistencia a ciprofloxacino y gentamicina fue de 91 y 53 %, respectivamente, y el 79 % de las cepas tenía el gen blaCTX-M. Se encontró una relación significativa (p<0,05) entre los grupos filogenéticos y la resistencia a ciprofloxacina, así como a la edad del paciente. Conclusión. El filogrupo de E. coli predominante fue el B2. Se evidenció una gran resistencia a ciprofloxacina y gentamicina, una proporción elevada de cepas BLEE con el blaCTX-M, y una relación entre el grupo filogenético y la resistencia a ciprofloxacino.

Introduction: Healthcare-associated infections are a public health problem due to the increased morbimortality of patients, especially those with risk factors such as immunosuppression due to oncological diseases. It is essential to determine the genetic diversity of the main microorganisms causing healthcare infections by combining traditional epidemiological surveillance and molecular epidemiology for better outbreak follow-up and early detection. Objective: To determine the phylogenetic group and antibiotic resistance of Escherichia coliisolated from hospitalized oncologic patients. Materials and methods: We conducted a cross-sectional study of 67 strains of ESBL-producing Escherichia coli to determine their phylogenetic group and described their antibiotic resistance profile, beta-lactam resistance genes, as well as the type of sample and the hospitalization areas from which they were recovered. Results: The most frequent phylogenetic group was B2 (36%); 57% of B2 strains were isolated from urine and 33% came from the urology department. Resistance to ciprofloxacin and gentamicin was 92% and 53%, respectively, and 79% of the strains had the blaCTX-Mgene. A significant association (p<0.05) was found between the phylogenetic groups, ciprofloxacin resistance, and the age of the patients. Conclusion: The predominant E. coli phylogroup was B2. We evidenced high resistance to ciprofloxacin and gentamicin, a high proportion of ESBL strains with the blaCTX-M gene, and a significant association between the phylogenetic group and the resistance to ciprofloxacin.

Farmacocinética y farmacodinámica de los antibióticos betalactámicos en pacientes críticos / Pharmacokinetics and pharmacodynamics of beta-lactam antibiotics in critically ill patients

La terapia antibiótica óptima en los pacientes en estado crítico puedecomplicarse por la alteración de la fisiología asociada a esta etapa de laenfermedad. La farmacocinética y la exposición a los antibióticos puedenverse alteradas por la enfermedad crítica subyacente y las intervencionesmédicas que reciben estos pacientes en la unidad de cuidados intensivos.Además, las cepas que suelen encontrarse en la unidad de cuidados intensivossuelen ser menos susceptibles y “resistentes” a los antibióticos máshabituales. De hecho, una dosificación de antibióticos que no tenga encuenta estas diferencias únicas, probablemente fracasará y dará lugar aresultados clínicos deficientes y a la aparición de resistencia a los antibióticosen la unidad de cuidados intensivos. Los objetivos de esta revisión sondescribir la farmacocinética de los antibióticos betalactámicos en pacientescríticos, destacar los objetivos farmacocinéticos/farmacodinámicos paralos pacientes y exponer algunas estrategias importantes que pueden optimizarla dosificación de los antibióticos betalactámicos en pacientes críticosen la unidad de cuidados intensivos.

Optimal antibiotic therapy for critically ill patients can be complicated bythe altered physiology associated with critical illness. Antibiotic pharmacokinetics and exposures can be altered driven by the underlying critical illnessand medical interventions that critically ill patients receive in the intensivecare unit. Furthermore, pathogens that are usually isolated in the intensivecare unit are commonly less susceptible and “resistant” to common antibiotics. Indeed, antibiotic dosing that does not consider these unique differences will likely fail leading to poor clinical outcomes and the emergenceof antibiotic resistance in the intensive care unit. The aims of this narrativereview were to describe the pharmacokinetics of beta-lactam antibiotics incritically ill patients, to highlight pharmacokinetic/pharmacodynamic targetsfor both non-critically ill and critically ill patients, and to discuss importantstrategies that can be undertaken to optimize beta-lactam antibiotic dosingfor critically ill patients in the intensive care unit.

Exantema intertriginoso y flexural simétrico por fármacos: presentación de un caso / Symmetrical drug-related intertriginous and flexural exanthema: a case report

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a benign, self-limited, immune-mediated, symmetric erythematous rash involving the buttocks and other intertriginous/flexural areas, observed after systemic exposure to a drug in an individual with or without prior sensitization. We present a 70-year old patient, who presented SDRIFE after the administration of piperacillin-tazobactam which improved rapidly after its suspension.

El exantema intertriginoso y flexural simétrico relacionado con fármacos (SDRIFE, por su sigla en inglés) es una erupción eritematosa simétrica, inmunomediada, benigna y autolimitada, que compromete glúteos y otras áreas intertriginosas, flexurales o ambas, y que se observa luego de la exposición sistémica a un fármaco en un individuo con sensibilización previa o sin ella. Se comenta el caso clínico de un paciente de 70 años de edad, que presentó SDRIFE posterior a la administración de piperacilina-tazobactam y que mejoró rápidamente luego de su suspensión.

Síndrome de intolerancia a múltiples medicamentos / Syndrome of intolerance to multiple medicines

El síndrome de intolerancia a múltiples medicamentos (MDIS, por sus siglas en inglés) se caracteriza por la intolerancia a dos o más medicamentos no relacionados. Tiene una prevalencia baja y es común en pacientes con polifarmacia. A pesar de que las reacciones adversas a los medicamentos son muy frecuentes, es raro que los pacientes debuten con este síndrome, el cual tiene implicaciones clínicas de leves a graves que afectan su vida; de acuerdo con esto varían el abordaje y su manejo. La sintomatología presentada varía desde síntomas gastrointestinales como reflujo gastroesofágico, dolores musculares y cefalea, hasta síntomas cutáneos; estos son los más frecuentes, tales como urticaria y erupciones maculopapulares o presentaciones menos comunes como el síndrome de Stevens-Johnson. El MDIS es causado por una amplia variedad de fármacos; por ello el conocimiento del síndrome, así como un adecuado interrogatorio de los antecedentes del paciente, es necesario para realizar un diagnóstico oportuno e instaurar un manejo adecuado y preventivo, evitando reacciones adversas que pongan en riesgo su vida. Con los hallazgos del cuadro clínico en la paciente, y basados en los antecedentes alérgicos presentados anteriormente a diferentes medicamentos no relacionados entre ellos, más la presentación de un rash maculopapular generalizado posterior a la administración de trimetoprim/sulfametoxazol se realiza el diagnóstico de MDIS. Se decide cambiar de medicamento por fosfomicina, con una consecuente evolución favorable. (AU)

Mecanismos de resistencia en aislados clínicos de Klebsiella pneumoniae

Resumen La bacteria Klebsiella pneumoniae es la causante de infecciones intrahospitalarias multirresistentes, posee diversos mecanismos de resistencia como la producción de enzimas betalactamasas cuya acción afecta a los antibióticos betalactámicos. Objetivo: Caracterizar los mecanismos de resistencia presentes en aislados clínicos con Klebsiella pneumoniae identificados mediante métodos fenotípicos en el Hospital Monte Sinai desde enero de 2018 hasta agosto de 2020. Materiales y métodos: Estudio positivista con un enfoque cuantitativo de corte transversal descriptivo de diseño documental. La población estuvo conformada por 274 datos de aislados clínicos identificados con Klebsiella pneumoniae. Los cuales conformaron la totalidad de la muestra con un muestreo por cobertura total. Mismos que fueron recopilados de fuentes secundarias ingresados en la base de datos del departamento de Microbiología. Para el análisis se utilizó estadística descriptiva. Resultados: Klebsiella pneumoniae mostró mayor frecuencia en el año 2020 con el 35%. Se identificó al mecanismo de resistencia BLEE con el 27,7% y carbapenemasas tipo KPC con el 7.7 %, con mayor presencia en el sexo masculino. Presentó una mayor resistencia a Penicilinas, una sensibilidad moderada a Cefalosporinas, Aminoglucósidos, Quinolonas y una alta sensibilidad a los Carbapenémicos, Tigeciclina y Colistina. Los aislados se clasificaron como multidrogorresistentes, con mayor frecuencia en Urocultivo, Aspirado bronquial, Líquido corporal, Punta de Catéter y Hemocultivo en áreas de Hospitalización, UCI y Neonatología. Conclusiones: Los mecanismos de resistencia de K. pneumoniae a los antibióticos son un hallazgo común en ambientes hospitalarios independientemente de sexo, servicio hospitalario o tipo de muestra, convirtiéndose en un problema de salud pública.

Abstract The bacterium Klebsiella pneumoniae is the cause of multiresistant intrahospital infections, it has various resistance mechanisms such as the production of beta-lactamase enzymes whose action affects beta-lactam antibiotics. Objective: To characterize the resistance mechanisms present in clinical isolates with Klebsiella pneumoniae identified by phenotypic methods at Monte Sinai Hospital from January 2018 to August 2020. Materials and methods: Positivist study with a descriptive cross-sectional quantitative approach to documentary design. The population consisted of 274 data from clinical isolates identified with Klebsiella pneumoniae. Which made up the entire sample with a total coverage sampling. The same ones that were collected from secondary sources entered in the database of the Microbiology department. Descriptive statistics were used for the analysis. Results: Klebsiella pneumoniae showed a higher frequency in 2020 with 35%. The ESBL resistance mechanism was identified with 27.7% and KPC-type carbapenemases with 7.7%, with a higher presence in males. It presented a greater resistance to Penicillins, a moderate sensitivity to Cephalosporins, Aminoglycosides, Quinolones and a high sensitivity to Carbapenems, Tigecycline and Colistin. The isolates were classified as multidrug resistant, more frequently in Urine culture, Bronchial aspirate, Body fluid, Catheter Tip and Blood culture in Hospitalization, ICU and Neonatology areas. Conclusions: The resistance mechanisms of K. pneumoniae to antibiotics are a common finding in hospital settings regardless of sex, hospital service or type of sample, becoming a public health problem.

Resumo A bactéria Klebsiella pneumoniae é causa de infecções intra-hospitalares multirresistentes, possui diversos mecanismos de resistência como a produção de enzimas beta-lactamase cuja ação afeta os antibióticos beta-lactâmicos. Objetivo: Caracterizar os mecanismos de resistência presentes em isolados clínicos de Klebsiella pneumoniae identificados por métodos fenotípicos no Hospital Monte Sinai de janeiro de 2018 a agosto de 2020. Materiais e métodos: Estudo positivista com abordagem quantitativa transversal descritiva do design documental. A população consistia em 274 dados de isolados clínicos identificados com Klebsiella pneumoniae. O que constituiu toda a amostra com uma amostra de cobertura total. Os mesmos que foram coletados em fontes secundárias e cadastrados no banco de dados do departamento de Microbiologia. Estatísticas descritivas foram utilizadas para a análise. Resultados: Klebsiella pneumoniae apresentou maior frequência em 2020 com 35%. O mecanismo de resistência a ESBL foi identificado com 27,7% e carbapenemases do tipo KPC com 7,7%, com maior presença no sexo masculino. Apresentou maior resistência às Penicilinas, sensibilidade moderada às Cefalosporinas, Aminoglicosídeos, Quinolonas e alta sensibilidade aos Carbapenêmicos, Tigeciclina e Colistina. Os isolados foram classificados como multirresistentes, com maior frequência em Urocultura, Aspirado Brônquico, Fluido Corporal, Ponta de Cateter e Hemocultura em Hospitalização, UTI e Neonatologia. Conclusões: Os mecanismos de resistência de K. pneumoniae aos antibióticos são um achado comum em ambientes hospitalares independentemente do sexo, serviço hospitalar ou tipo de amostra, tornando-se um problema de saúde pública.

Reconstrucción ancestral de una beta-lactamasa y comparativa con sus homólogos actuales / Ancestral reconstruction of a beta-lactamase and comparison with its extant proteins

Las β-lactamasas son proteínas de origen bacteriano que se caracterizan por hidrolizar los antibióticos β-lactámicos, confiriendo resistencia microbiana ante estos. Son una familia heterogénea de proteínas muy relevantes desde el punto de vista sanitario debido a la facilidad que presentan para adquirir resistencia a nuevos fármacos por su alta capacidad de evolución. La evolución in vitro de estas proteínas ha servido, no solo para desarrollar su caracterización y mejorar su conocimiento, sino como una nueva línea de investigación que permite identificar de manera predictiva residuos implicados en la adquisición de resistencia frente antibióticos. Al mismo tiempo, el método de reconstrucción ancestral de proteínas se ha revelado como una herramienta novedosa y útil para comprender la evolución de las β- lactamasas y entender algunas de sus características como es su promiscuidad. En este trabajo, se ha realizado un estudio de β-lactamasas ancestrales reconstruidas a partir de la filogenia de β-lactamasas existentes de clase A. De las cuatro proteínas ancestrales estudiadas, se ha obtenido una que es funcional y se ha comparado su actividad hidrolítica con la de cuatro de sus homólogos actuales frente a ocho fármacos β-lactámicos. Se ha comprobado que esta proteína ancestral tiene una actividad frente a antibióticos más generalista que cualquier de las proteínas actuales estudiadas. Además, la proteína ancestral activa mostró más resistencia frente a uno de los fármacos utilizados que el resto de β-lactamasas existentes. Finalmente se han discutido estos resultados y a partir de ellos se argumenta por qué las secuencias ancestrales reconstruidas pueden ser un punto de partida muy atractivo a la hora de realizar evolución dirigida de proteínas para la obtención de proteínas de interés biotecnológico.(AU)

The β-lactamases are proteins of bacterial origin that are characterized by hydrolyzing antibiotics β-lactams, conferring microbial resistance against them. They are a heterogeneous family of proteins very relevant from a health point of view due to the ease they present to acquire resistance to new drugs due to their high capacity for evolution. The in vitro evolution of these proteins has served not only to develop their characterization and improve their knowledge, but as a new line of research that allows to predictively identify residues involved in the acquisition of antibiotic resistance. At the same time, the method of ancestral protein reconstruction has been revealed as a novel and useful tool to understand the evolution of β-lactamases and understand some of their characteristics such as their promiscuity. In this work, a study of ancestral β-lactamases reconstructed from the phylogeny of existing class A β-lactamases has been carried out. Of the four ancestral proteins studied, one has been obtained that is functional and has compared its hydrolytic activity with that of four of its current counterparts against eight β-lactam drugs. This ancestral protein has been shown to have a more generalistic antibiotic activity than any of the current proteins studied. In addition, the active ancestral protein showed more resistance to one of the drugs used than the rest of β-lactamases existing. Finally these results have been discussed and from them it is argued why reconstructed ancestral sequences can be a very attractive starting point when it comes to direct evolution of proteins for obtaining proteins of biotechnological interest.(AU)

Sensibilidad disminuida a los antibóticos Beta-Lactamicos en estreptococos Beta-Hemolíticos / Decreased sensitivity to beta-lactam antibiotics in beta-hemolytic streptococci

Últimamente, se están detectando mutaciones en las proteínas ligadoras de penicilina (PBP) de los estreptococos beta-hemolíticos que corresponden a sitios que en Streptococcus pneumoniae han determinado sensibilidad disminuida a los antibióticos beta-lactámicos. Primero, se describieron cepas con sensibilidad intermedia a penicilina en Streptococcus agalactiae (estreptococos del grupo B), luego en Streptococcus dysgalactiae subsp. equisimilis (mayormente grupos C y G) y, más recientemente, cepas con sensibilidad disminuida a aminopenicilinas y cefalosporinas de tercera generación en Streptococcus pyogenes (grupo A). El costo biológico de estas modificaciones nos permite pensar que los niveles de resistencia no han de ser tan elevados como para comprometer por ahora la efectividad clínica de los beta-lactámicos (AU)

Recently, mutations in penicillin-binding proteins (PBPs) of beta-hemolytic streptococci have been detected corresponding to sites that in Streptococcus pneumoniae have been determined to have decreased sensitivity to beta-lactam antibiotics. First, strains with intermediate sensitivity to penicillin were described in Streptococcus agalactiae (group B streptococci), subsequently in Streptococcus dysgalactiae subsp. equisimilis (mainly groups C and G) and, more recently, strains with decreased sensitivity to third-generation aminopenicillins and cephalosporins were found in Streptococcus pyogenes (group A). The biological cost of these modifications suggests that, for now, resistance levels are not high enough to compromise the clinical effectiveness of beta-lactams (AU)

Reacciones adversas a betalactámicos: una revisión de tema / Adverse reactions to beta-lactams: a topic review / Reações adversas a beta-lactâmicos: uma revisão de tópico

Las reacciones adversas a medicamentos son una de las principales causas de muerte en el mundo, producen muchos ingresos hospitalarios y aumentan los costos de atención. Dentro de los medicamentos que más se asocian con estas reacciones están los antibióticos y de estos los más comunes son los betalactámicos, ampliamente utilizados en las instituciones de salud. Las manifestaciones más frecuentes de las reacciones adversas a betalactámicos son alérgicas, dermatológicas, gastrointestinales, renales, hepáticas y neurológicas. Se realiza una revisión general de las reacciones adversas de estos medicamentos, se mencionan los distintos antibióticos betalactámicos con su clasificación y espectro de acción y más precisamente se explican las distintas reacciones adversas por uso de betalactámicos según el sistema comprometido.

Adverse drug reactions are one of the leading causes of death in the world. They are also responsible for an increase in hospital admissions and higher care costs. Among the most associated drugs with these reactions are antibiotics and of these the most common are beta-lactams, which are widely used in health institutions. The most fre-quent manifestations of adverse reactions to beta-lactams are allergic, dermatological, gastrointestinal, renal, hepatic and neurological reactions. A general review of the adverse reactions to these drugs is carried out. Also, the different beta-lactam antibiotics are described along with their classification and spectrum of action, and an accurate explanation of the different adverse reactions due to the use of beta-lactams according to the compromised system is made.

As reações adversas a medicamentos são uma das principais causas de morte no mundo, resultam em muitas admissões hospitalares e aumentam os custos do atendimento. Entre os medicamentos que mais se associam a essas reações estão os antibióticos e, destes, os mais comuns são os beta-lactâmicos, amplamente utilizados em instituições de saúde. As manifestações mais frequentes de reações adversas aos beta-lactâmicos são alérgicas, dermatológicas, gastrointestinais, renais, hepáticas e neurológicas. Faz-se uma revisão geral das reações adversas desses medicamentos, são mencionados os diferentes antibióticos beta-lactâmicos com sua classificação e espectro de ação, e mais precisamente explicam as diferentes reações adversas devidas ao uso de beta-lactâmicos de acordo com o sistema comprometido

Proteomics characterization of Staphylococcus spp. from goat mastitis and phenogeno-typical assessment of resistance to beta-lactamics / Caracterização proteômica de Staphylococcus spp. oriundos de mastite caprina e avaliação fenogenotípica da resistência aos beta-lactâmicos

Mastitis occupies a prominent place among the diseases that affect dairy herds due to economic problems and public health. Staphylococcus spp. are infectious agents more involved in the etiology of caprine mastites, especially coagulase-negative Staphylococcus. Nineteen isolates of Staphylococcus spp. were obtained from subclinical caprine mastitis. All isolates were characterized by MALDI-TOF MS, being 47.36% (9/19) identified for S. epidermidis, 15.78% (3/19) for S. warneri, 10.52% (2/19) for S. aureus and S. caprae and 5.26% (1/19) for S. lugdunensis, S. simulans, and S. cohnii. All isolates characterized by MALDI-TOF were subjected a to polymerase chain reaction (PCR) for the 16S rRNA gene of Staphylococcus spp. to confirm the gender. After determining the species, tests for phenotypic detection of resistance to beta-lactams were carried out simple disk diffusion oxacillin, cefoxitin, penicillin G and amoxicillin + clavulanic acid, agar "screen" oxacillin and microdilution (MIC) cefoxitin. The disk diffusion test showed a strength of 58% (11/19) for penicillin G, 26.31% (5/19) for cefoxitin and 26.31% (5/19) for oxacillin. All strains were susceptible to amoxicillin + clavulanic acid and agar "screen" oxacillin. In the MIC, 63.15% (12/19) of the samples were cefoxitin resistant (MIC >4.0μg/ml). Then isolates were subjected to detection of the mecA resistance genes and regulators (mecl and mecRI), mecC and blaZ. Two samples of Staphylococcus epidermidis had the mecA gene. All isolates were negative for the mecA gene variant, mecl, mecRI, mecC and blaZ. These findings reinforce the importance of this group of microorganisms in the etiology of subclinical mastitis in goats and open perspectives for future research to investigate the epidemiology of the disease.(AU)

A mastite ocupa lugar de destaque entre as doenças que acometem o rebanho leiteiro, em virtude de problemas econômicos e de saúde pública. Staphylococcus spp. são os agentes infecciosos mais envolvidos na etiologia das mastites caprinas, principalmente Staphylococcus coagulase negativo. Dezenove isolados de Staphylococcus spp. foram obtidos a partir de mastite caprina subclínica. Todos os isolados foram caracterizados por MALDI-TOF MS, sendo 47,36% (9/19) identificadas como S. epidermidis, 15,78%(3/19) como S. warneri, 10,52% (2/19) como S. caprae e S. aureus e 5,26% (1/19) tanto para S. lugdunensis, como para S. simulans e S. cohnii. Todos os isolados caracterizados pelo MALDI-TOF foram submetidos a reação em cadeia da polimerase (PCR) para o gene 16rRNA de Staphylococcus spp. para a confirmação do gênero. Após a determinação da espécie, foram realizadas as provas para a detecção fenotípica de resistência aos beta-lactâmicos: difusão em disco simples de oxacilina, cefoxitina, penicilina G e amoxacilina +ácido clavulânico, ágar "screen" de oxacilina e microdiluição em caldo (MIC) de cefoxitina. O teste de difusão em disco demonstrou resistência de 58% (11/19) para penicilina G, 26,31% (5/19) para cefoxitina e 26,31% (5/19) para oxacilina. Todas as amostras foram sensíveis a amoxicilina + ácido clavulânico e ao ágar "screen" de oxacilina. Pelo MIC, 63,15% (12/19) das amostras foram resistentes a cefoxitina (MIC >4,0μg/ml). Em seguida os isolados foram submetidos a detecção dos genes de resistência mecA e seus reguladores (mecl e mecRI), mecC e blaZ. Duas amostras de S. epidermidis apresentaram o gene mecA. Todos os isolados foram negativos para a variante do gene mecA, mecl, mecRI, mecC e blaZ. Tais achados reforçam a importância deste grupo de microrganismos na etiologia da mastite subclínica em caprinos e abre perspectivas para futuras pesquisas para a investigação da epidemiologia da doença.(AU)

Proteomics characterization of Staphylococcus spp. from goat mastitis and phenogeno-typical assessment of resistance to beta-lactamics

ABSTRACT: Mastitis occupies a prominent place among the diseases that affect dairy herds due to economic problems and public health. Staphylococcus spp. are infectious agents more involved in the etiology of caprine mastites, especially coagulase-negative Staphylococcus. Nineteen isolates of Staphylococcus spp. were obtained from subclinical caprine mastitis. All isolates were characterized by MALDI-TOF MS, being 47.36% (9/19) identified for S. epidermidis, 15.78% (3/19) for S. warneri, 10.52% (2/19) for S. aureus and S. caprae and 5.26% (1/19) for S. lugdunensis, S. simulans, and S. cohnii. All isolates characterized by MALDI-TOF were subjected a to polymerase chain reaction (PCR) for the 16S rRNA gene of Staphylococcus spp. to confirm the gender. After determining the species, tests for phenotypic detection of resistance to beta-lactams were carried out simple disk diffusion oxacillin, cefoxitin, penicillin G and amoxicillin + clavulanic acid, agar screen oxacillin and microdilution (MIC) cefoxitin. The disk diffusion test showed a strength of 58% (11/19) for penicillin G, 26.31% (5/19) for cefoxitin and 26.31% (5/19) for oxacillin. All strains were susceptible to amoxicillin + clavulanic acid and agar screen oxacillin. In the MIC, 63.15% (12/19) of the samples were cefoxitin resistant (MIC >4.0g/ml). Then isolates were subjected to detection of the mecA resistance genes and regulators (mecl and mecRI), mecC and blaZ. Two samples of Staphylococcus epidermidis had the mecA gene. All isolates were negative for the mecA gene variant, mecl, mecRI, mecC and blaZ. These findings reinforce the importance of this group of microorganisms in the etiology of subclinical mastitis in goats and open perspectives for future research to investigate the epidemiology of the disease.

RESUMO: A mastite ocupa lugar de destaque entre as doenças que acometem o rebanho leiteiro, em virtude de problemas econômicos e de saúde pública. Staphylococcus spp. são os agentes infecciosos mais envolvidos na etiologia das mastites caprinas, principalmente Staphylococcus coagulase negativo. Dezenove isolados de Staphylococcus spp. foram obtidos a partir de mastite caprina subclínica. Todos os isolados foram caracterizados por MALDI-TOF MS, sendo 47,36% (9/19) identificadas como S. epidermidis, 15,78%(3/19) como S. warneri, 10,52% (2/19) como S. caprae e S. aureus e 5,26% (1/19) tanto para S. lugdunensis, como para S. simulans e S. cohnii. Todos os isolados caracterizados pelo MALDI-TOF foram submetidos a reação em cadeia da polimerase (PCR) para o gene 16rRNA de Staphylococcus spp. para a confirmação do gênero. Após a determinação da espécie, foram realizadas as provas para a detecção fenotípica de resistência aos beta-lactâmicos: difusão em disco simples de oxacilina, cefoxitina, penicilina G e amoxacilina +ácido clavulânico, ágar screen de oxacilina e microdiluição em caldo (MIC) de cefoxitina. O teste de difusão em disco demonstrou resistência de 58% (11/19) para penicilina G, 26,31% (5/19) para cefoxitina e 26,31% (5/19) para oxacilina. Todas as amostras foram sensíveis a amoxicilina + ácido clavulânico e ao ágar screen de oxacilina. Pelo MIC, 63,15% (12/19) das amostras foram resistentes a cefoxitina (MIC >4,0g/ml). Em seguida os isolados foram submetidos a detecção dos genes de resistência mecA e seus reguladores (mecl e mecRI), mecC e blaZ. Duas amostras de S. epidermidis apresentaram o gene mecA. Todos os isolados foram negativos para a variante do gene mecA, mecl, mecRI, mecC e blaZ. Tais achados reforçam a importância deste grupo de microrganismos na etiologia da mastite subclínica em caprinos e abre perspectivas para futuras pesquisas para a investigação da epidemiologia da doença.

Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido en un hospital de La Habana

RESUMEN Introducción: En microorganismos gramnegativos la producción de enzimas betalactamasas es el mecanismo más común de resistencia. Las de espectro extendido constituyen un grupo importante por su capacidad de inactivar las cefalosporinas de tercera y cuarta generación y el aztreonam. Su detección es vital para indicar el tratamiento óptimo y las medidas de aislamiento que eviten la dispersión de los microorganismos que las portan. Objetivos: Determinar la incidencia y principales características de los aislados de Escherichiacoli y Klebsiellapneumoniae productores de betalactamasas de espectro extendido en muestras no urogenitales. Métodos: Estudio transversal realizado en el hospital "Salvador Allende" durante el año 2017. Se determinó la frecuencia de Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido, su procedencia según servicio del hospital, tipo de muestra clínica, y su sensibilidad antimicrobiana. La identificación de betalactamasas de espectro extendido se hizo por el método de doble disco de Jarlier. Resultados: Fueron productores de betalactamasas de espectro extendido 46 y 50 % de aislados de Escherichia coli y Klebsiella pneumoniae, respectivamente. La mayoría provenían de muestras de las salas del Instituto de Angiología, el antimicrobiano con mayor efectividad fue el meropenem, la sensibilidad al resto de los antimicrobianos estuvo por debajo de 80 % y no hubo aislados sensibles a las cefalosporinas de tercera generación. Conclusiones: Se demuestra una alta incidencia de aislados de Escherichia coli y Klebsiella pneumoniae productores de betalactamasas de espectro extendido en el Hospital "Salvador Allende" de La Habana, más marcada en las salas del Instituto de Angiología y en muestras de piel.

ABSTRACT Introduction: Beta-lactamase production is the most common resistance mechanism in gram-negative microorganisms. Extended-spectrum beta-lactamases are an important group of enzymes capable of inactivating third- and fourth-generation cephalosporins and aztreonam. Their detection is important to indicate the optimum treatment as well as isolation measures aimed at preventing the spread of carrier microorganisms. Objectives: Determine the incidence and main characteristics of isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae from non-urogenital samples. Methods: A cross-sectional study was conducted at Salvador Allende hospital during the year 2017. Determination was made of the frequency of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae, their origin by hospital service, the type of clinical sample and their antimicrobial sensitivity. Identification of extended-spectrum beta-lactamases was based on the Jarlier double disc method. Results: Of the total Escherichia coli and Klebsiella pneumoniae isolates studied, 46% and 50%, respectively, were extended-spectrum beta-lactamase producers. Most had been obtained from samples taken in wards of the Institute of Angiology; the most effective antimicrobial was meropenem; sensitivity to the remaining antimicrobials was below 80%; no isolates were sensitive to third-generation cephalosporins. Conclusions: A high incidence was found of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates at Salvador Allende Hospital in Havana, more noticeably in Institute of Angiology wards and skin samples.

Confirmación diagnóstica de alergia a la amoxicilina en niños tratados en una sección de alergia pediátrica / Diagnostic confirmation of amoxicillin allergy in children treated at a division of Pediatric Allergy

La amoxicilina es un antibiótico betalactámico comúnmente indicado en pediatría y es la causa más frecuente de alergia a medicamentos.Objetivos. Determinar la proporción de alergia confirmada a amoxicilina en niños con sospecha diagnóstica, atendidos en una sección de alergia pediátrica.Población y métodos. Estudio descriptivo retrospectivo entre enero de 2009 y enero de 2017, en menores de 18 años con sospecha diagnóstica de alergia a amoxicilina. Se realizó el diagnóstico según interrogatorio y pruebas específicas.Resultados. Fueron incluidos 234 pacientes; se diagnosticó alergia a la amoxicilina en el 10,7 % (intervalo de confianza del 95 %: 7-15). Estos pacientes tenían mayor prevalencia de síntomas inmediatos (el 40 % vs. el 22 %, p = 0,048) y de exposición previa a betalactámicos (el 84 % vs. el 56 %, p = 0,007).Conclusión. La confirmación de alergia a la amoxicilina en niños derivados a especialistas fue del 10,7 %.

Amoxicillin is a beta-lactam antibiotic commonly indicated in pediatrics and the most frequent cause of drug allergies.Objectives. To determine the proportion of confirmed amoxicillin allergy in children with diagnostic suspicion seen at the Division of Pediatric Allergy.Population and methods. This descriptive, retrospective study was done between January 2009 and January 2017 in children younger than 18 years with diagnostic suspicion of amoxicillin allergy. The diagnosis was based on questions and specific tests.Results. A total of 234 patients were included; amoxicillin allergy was diagnosed in 10.7 % (95 % confidence interval: 7-15). These patients had a higher prevalence of immediate symptoms (40 % vs. 22 %, p = 0.048) and prior exposure to beta-lactams (84 % vs. 56 %, p = 0.007).Conclusion. Amoxicillin allergy in children referred to specialists was confirmed in 10.7 %.

¿Cumplimos el objetivo de farmacocinética y farmacodinamia en pacientes críticos que reciben antibióticos betalactámicos? / Do we meet the goal of pharmacokinetics and pharmacodynamics in critically ill patients receiving beta-lactam antibiotics?

Introducción: Los pacientes críticamente enfermos presentan cambios fisiopatológicos que alteran las concentraciones de antibióticos betalactámicos. El objetivo fue determinar si las dosis de uso habitual en pacientes críticos alcanzan las concentraciones asociadas con mayor actividad y establecer las variables de PK/PD que se asocian con concentraciones subóptimas de antibiótico.Métodos: Estudio prospectivo realizado en una terapia intensiva de adultos en un periodo de 13 meses. Se incluyeron pacientes que recibieron cefazolina, ceftriaxona, ceftazidima o meropenem. Se realizó dosaje de concentración de antibiótico en plasma en el 50% del intervalo de dosis. Se calculó la concentración de antibiótico libre y se comparó con el objetivo 50% fT>CIM y el objetivo 50% fT>CIM x 4 para los microorganismos susceptibles definidos, según criterios del CLSI. Se comparó el grupo de pacientes que cumplió el objetivo 50% fT>CIM x 4 con el que no, en términos de variables de PK/PD.Resultados: Se incluyeron 29 determinaciones y 55 comparaciones. En el 92,7% de los casos se alcanzó el objetivo 50% fT>CIM y en el 61,8% el objetivo 50% fT>CIM x 4. En el peor escenario, es decir considerando el germen susceptible con CIM más alta, solo el 48,3% de los pacientes cumplieron el objetivo 50% fT>CIM x 4. Los pacientes que no llegaron al objetivo 50% fT>CIM x 4 tuvieron mayor RESUMENARTÍCULO ORIGINALaclaramiento renal que los que sí lo hicieron (160 vs 108,5 ml/min/1,73m2, p= 0,01). Conclusiones: un gran porcentaje de pacientes críticos que recibe betalactámicos no alcanza las metas de PK/PD recomendadas en la actualidad

Introduction: critically ill patients have physiopathological changes that upset the concentrations of beta-lactam antibiotics. The aim was to determine if the doses of usual use in critically ill patients reach the concentrations associated with maximal activity and to establish the variables of PK/PD that are associated with suboptimal concentrations of antibiotic. Methods: prospective study conducted in an intensive therapy of adults in a period of 13 months. Patients who received cefazolin, ceftriaxone, ceftazidime or meropenem were included. Dosage of antibiotic concentration in plasma was performed at 50% of the dose interval. The concentration of free antibiotic was calculated and compared with the objective 50% fT>MIC and the objective 50% fT>MIC x 4 for susceptible microorganisms, according to CLSI criteria. The group of patients who met the 50% objective fT>MIC x 4 was compared with the one who did not, in terms of PK/PD variables. Results: 29 determinations and 55 comparisons were included. The objective 50% fT>MIC was reached in 92.7% of the cases and the target 50% fT>MIC x 4 was achieved in 61.8%. In the worst scenario, that is, considering the germ susceptible with MIC higher, only 48.3% of patients met the objective 50% fT>MIC x 4. Patients who did not reach the goal 50% fT>MIC x 4 had greater renal clearance than those who reached the goal (160 vs 108.5 ml/min/1.73m2, p=0.01). Conclusions: a large percentage of critically ill patients receiving beta-lactams do not reach the PK/PD goals recommended nowadays