Peptide-Resorcinarene Conjugates Obtained via Click Chemistry: Synthesis and Antimicrobial Activity.

Antimicrobial resistance (AMR) is one of the top ten threats to public health, as reported by the World Health Organization (WHO). One of the causes of the growing AMR problem is the lack of new therapies and/or treatment agents; consequently, many infectious diseases could become uncontrollable. The need to discover new antimicrobial agents that are alternatives to the existing ones and that allow mitigating this problem has increased, due to the rapid and global expansion of AMR. Within this context, both antimicrobial peptides (AMPs) and cyclic macromolecules, such as resorcinarenes, have been proposed as alternatives to combat AMR. Resorcinarenes present multiple copies of antibacterial compounds in their structure. These conjugate molecules have exhibited antifungal and antibacterial properties and have also been used in anti-inflammatory, antineoplastic, and cardiovascular therapies, as well as being useful in drug and gene delivery systems. In this study, it was proposed to obtain conjugates that contain four copies of AMP sequences over a resorcinarene core. Specifically, obtaining (peptide)4-resorcinarene conjugates derived from LfcinB (20-25): RRWQWR and BF (32-34): RLLR was explored. First, the synthesis routes that allowed obtaining: (a) alkynyl-resorcinarenes and (b) peptides functionalized with the azide group were established. These precursors were used to generate (c) (peptide)4-resorcinarene conjugates by azide-alkyne cycloaddition CuAAC, a kind of click chemistry. Finally, the conjugates' biological activity was evaluated: antimicrobial activity against reference strains and clinical isolates of bacteria and fungi, and the cytotoxic activity over erythrocytes, fibroblast, MCF-7, and HeLa cell lines. Our results allowed establishing a new synthetic route, based on click chemistry, for obtaining macromolecules derived from resorcinarenes functionalized with peptides. Moreover, it was possible to identify promising antimicrobial chimeric molecules that may lead to advances in the development of new therapeutic agents.

Consensus for the treatment of upper urinary tract infections during pregnancy / Consenso para el tratamiento de la infección de vías urinarias altas durante la gestación

Objectives: To generate evidence-based recommendations through formal consensus regarding the treatment of upper urinary tract infections during gestation. Materials and methods: Experts in microbiology, public health, internal medicine, infectious diseases, obstetrics, maternal fetal medicine and obstetric and gynecological infections participated in the consensus development group. The group also included professionals with training in clinical epidemiology, systematic data search, and representatives from the Health Secretariat and the Bogota Obstetrics and Gynecology Association. The participants disclosed their conflicts of interest. Starting with a clinical question, outcomes were graded and a systematic search was conducted in the Medline via PubMed, Embase, Lilacs, and Bireme databases. The search was expanded to include institutional repositories and antimicrobial resistance surveillance systems, with no language or date restrictions. The search was updated on October 1, 2022. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to assess the quality of the evidence and determine the strength of the recommendations. Finally, the RAND/UCLA (Research and Development/University of California Los Angeles) methodology was applied for the formal consensus. This document was reviewed by academic peers before publication. Results: The following are the consensus recommendations. Recommendation 1. The initial management of pregnant women with upper urinary tract infections (UTIs) should be approached in a hospital setting. Recommendation 2. The use of second generation cephalosporins is the suggested first option for empirical antimicrobial management in pregnant women with upper UTI in order to improve the rates of clinical and microbiological cure. Recommendation 3. Because of the risk-benefit balance, the use of aminoglycosides is suggested as a second option for empirical antimicrobial treatment in pregnant women presenting with upper UTIs in the second and third trimester. Recommendation 4. The use of third-generation cephalosporins is suggested as the third option for empirical antimicrobial treatment in pregnant women with upper UTIs given that the risk of inducing microbial resistance is high with this group of antibiotics. Recommendation 5. The use of carbapenems is suggested as a first option in pregnant women with upper UTIs and a history of infections caused by microorganisms with resistance to third or fourth-generation cephalosporins. Recommendation 6. The use of aminoglycosides or fourth-generation cephalosporins is suggested as a second option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third-generation cephalosporins, taking risk-benefit into account. Recommendation 7. The use of piperacillin/tazobactam is suggested as a third option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third or fourthgeneration cephalosporins. Recommendation 8. Getting a urine culture is recommended in pregnant women with upper UTIs before initiating empirical antimicrobial treatment. Recommendation 9. In pregnant women with upper UTIs, it is suggested to modify therapy in accordance with the results of the sensitivity test when the culture report shows resistance to the antimicrobial agent initiated empirically. Recommendation 10. In pregnant women hospitalized due to upper UTIs, it is suggested to switch to oral antimicrobial therapy after at least 48 hours of modulation of the systemic inflammatory response and the clinical signs of infection, and when tolerance to oral intake is adequate. Recommendation 11. In pregnant women with upper UTIs with no complications secondary to the primary infection, it is recommended to administer antibiotic therapy for a period of 7 to 10 days. Conclusions: It is expected that with this Colombian upper UTI consensus variability in clinical practice will be reduced. It is recommended that groups doing research in maternal fetal medicine assess the implementation and effectiveness of these recommendations.

Objetivos: generar recomendaciones informadas en la evidencia, a través de un consenso formal, orientadas al tratamiento de la infección de vías urinarias altas durante la gestación. Materiales y métodos: en el grupo desarrollador participaron expertos temáticos en microbiología, salud pública, medicina interna, infectología, obstetricia, medicina materno-fetal e infectología ginecobstétrica. También hicieron parte profesionales con entrenamiento en epidemiología clínica, búsqueda sistemática de la información, representantes de la Secretaría de Salud y la Asociación Bogotana de Obstetricia y Ginecología. Los participantes presentaron sus conflictos de interés. A partir de una pregunta clínica se realizó la graduación de los desenlaces y una búsqueda sistemática que abarcó las bases de datos Medline vía PubMed, Embase, Lilacs, Bireme. La pesquisa se amplió a repositorios institucionales y reportes de vigilancia de resistencia antimicrobiana, sin restricción de idioma o fecha, la búsqueda se actualizó el 1 de octubre de 2022. Se utilizó la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) para valorar la calidad de la evidencia y establecer la fuerza de las recomendaciones.Finalmente, se utilizó la metodología RAND/ UCLA (Research and Development/University of California Los Angeles) para el consenso formal. Este documento fue revisado por pares académicos previo a su publicación. Resultados: el consenso formuló las siguientes recomendaciones. Recomendación 1. Se sugiere que el manejo inicial de la gestante con infección de vías urinarias (IVU) altas se realice de forma intrahospitalaria. Recomendación 2. Como primera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de segunda generación con el fin de mejorar la tasa de cura clínica y microbiológica. Recomendación 3. Como segunda opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas en el segundo y tercer trimestre se realice con aminoglucósidos dado su balance riesgo-beneficio. Recomendación 4. Como tercera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de tercera generación, debido a que el riesgo de inducción de resistencia microbiana es alto con este grupo de antibióticos. Recomendación 5. Como primera opción, en mujeres gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de carbapenémicos. Recomendación 6. Como segunda opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera generación se sugiere el uso de aminoglucósidos o cefalosporinas de cuarta generación teniendo en cuenta el riesgo-beneficio. Recomendación 7. Como tercera opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de piperacilina/tazobactam. Recomendación 8. En gestantes con IVU altas se recomienda realizar urocultivo previo al inicio de tratamiento antimicrobiano empírico. Recomendación 9. En gestantes con IVU altas, cuando el urocultivo reporte resistencia al antimicrobiano iniciado de forma empírica, se sugiere modificar la terapia guiada por los resultados del antibiograma. Recomendación 10. En la gestante hospitalizada por IVU altas se sugiere realizar el cambio de terapia antimicrobiana a vía oral cuando la paciente tenga, al menos, 48 horas de modulación de respuesta inflamatoria sistémica y de los signos clínicos de infección, así como adecuada tolerancia a vía oral. Recomendación 11. En gestantes con IVU altas, sin complicaciones secundarias a la infección primaria, se recomienda que la terapia antibiótica se administre de 7 a 10 días. Conclusiones: se espera que este consenso colombiano de IVU altas reduzca la variabilidad en la práctica clínica. Se recomienda a los grupos de investigación en medicina materno fetal e infectología evaluar la implementación y efectividad de las recomendaciones emitidas.

Consenso para el tratamiento de la infección de vías urinarias altas durante la gestación / Consensus for the treatment of upper urinary tract infections during pregnancy

Objetivos: Generar recomendaciones informadas en la evidencia, a través de un consenso formal, orientadas al tratamiento de la infección de vías urinarias altas durante la gestación. Materiales y métodos: En el grupo desarrollador participaron expertos temáticos en microbiología, salud pública, medicina interna, infectología, obstetricia, medicina materno-fetal e infectología ginecobstétrica. También hicieron parte profesionales con entrenamiento en epidemiología clínica, búsqueda sistemática de la información, representantes de la Secretaría de Salud y la Asociación Bogotana de Obstetricia y Ginecología. Los participantes presentaron sus conflictos de interés. A partir de una pregunta clínica se realizó la graduación de los desenlaces y una búsqueda sistemática que abarcó las bases de datos Medline vía PubMed, Embase, Lilacs, Bireme. La pesquisa se amplió a repositorios institucionales y reportes de vigilancia de resistencia antimicrobiana, sin restricción de idioma o fecha, la búsqueda se actualizó el 1 de octubre de 2022. Se utilizó la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) para valorar la calidad de la evidencia y establecer la fuerza de las recomendaciones. Finalmente, se utilizó la metodología RAND/ UCLA (Research and Development/University of California Los Angeles) para el consenso formal. Este documento fue revisado por pares académicos previo a su publicación. Resultados: El consenso formuló las siguientes recomendaciones. Recomendación 1. Se sugiere que el manejo inicial de la gestante con infección de vías urinarias (IVU) altas se realice de forma intrahospitalaria. Recomendación 2. Como primera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de segunda generación con el fin de mejorar la tasa de cura clínica y microbiológica. Recomendación 3. Como segunda opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas en el segundo y tercer trimestre se realice con aminoglucósidos dado su balance riesgo-beneficio. Recomendación 4. Como tercera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de tercera generación, debido a que el riesgo de inducción de resistencia microbiana es alto con este grupo de antibióticos. Recomendación 5. Como primera opción, en mujeres gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de carbapenémicos. Recomendación 6. Como segunda opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera generación se sugiere el uso de aminoglucósidos o cefalosporinas de cuarta generación teniendo en cuenta el riesgo-beneficio. Recomendación 7. Como tercera opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de piperacilina/tazobactam. Recomendación 8. En gestantes con IVU altas se recomienda realizar urocultivo previo al inicio de tratamiento antimicrobiano empírico. Recomendación 9. En gestantes con IVU altas, cuando el urocultivo reporte resistencia al antimicrobiano iniciado de forma empírica, se sugiere modificar la terapia guiada por los resultados del antibiograma. Recomendación 10. En la gestante hospitalizada por IVU altas se sugiere realizar el cambio de terapia antimicrobiana a vía oral cuando la paciente tenga, al menos, 48 horas de modulación de respuesta inflamatoria sistémica y de los signos clínicos de infección, así como adecuada tolerancia a vía oral. Recomendación 11. En gestantes con IVU altas, sin complicaciones secundarias a la infección primaria, se recomienda que la terapia antibiótica se administre de 7 a 10 días. Conclusiones: se espera que este consenso colombiano de IVU altas reduzca la variabilidad en la práctica clínica. Se recomienda a los grupos de investigación en medicina materno fetal e infectología evaluar la implementación y efectividad de las recomendaciones emitidas.

Objectives: To generate evidence-based recommendations through formal consensus regarding the treatment of upper urinary tract infections during gestation. Materials and methods: Experts in microbiology, public health, internal medicine, infectious diseases, obstetrics, maternal fetal medicine and obstetric and gynecological infections participated in the consensus development group. The group also included professionals with training in clinical epidemiology, systematic data search, and representatives from the Health Secretariat and the Bogota Obstetrics and Gynecology Association. The participants disclosed their conf licts of interest. Starting with a clinical question, outcomes were graded and a systematic search was conducted in the Medline via PubMed, Embase, Lilacs, and Bireme databases. The search was expanded to include institutional repositories and antimicrobial resistance surveillance systems, with no language or date restrictions. The search was updated on October 1, 2022. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to assess the quality of the evidence and determine the strength of the recommendations. Finally, the RAND/UCLA (Research and Development/University of California Los Angeles) methodology was applied for the formal consensus. This document was reviewed by academic peers before publication. Results: The following are the consensus recommendations. Recommendation 1. The initial management of pregnant women with upper urinary tract infections (UTIs) should be approached in a hospital setting. Recommendation 2. The use of second generation cephalosporins is the suggested first option for empirical antimicrobial management in pregnant women with upper UTI in order to improve the rates of clinical and microbiological cure. Recommendation 3. Because of the risk-benefit balance, the use of aminoglycosides is suggested as a second option for empirical antimicrobial treatment in pregnant women presenting with upper UTIs in the second and third trimester. Recommendation 4. The use of third-generation cephalosporins is suggested as the third option for empirical antimicrobial treatment in pregnant women with upper UTIs given that the risk of inducing microbial resistance is high with this group of antibiotics. Recommendation 5. The use of carbapenems is suggested as a first option in pregnant women with upper UTIs and a history of infections caused by microorganisms with resistance to third or fourth-generation cephalosporins. Recommendation 6. The use of aminoglycosides or fourth-generation cephalosporins is suggested as a second option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third-generation cephalosporins, taking risk-benefit into account. Recommendation 7. The use of piperacillin/tazobactam is suggested as a third option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third or fourth-generation cephalosporins. Recommendation 8. Getting a urine culture is recommended in pregnant women with upper UTIs before initiating empirical antimicrobial treatment. Recommendation 9. In pregnant women with upper UTIs, it is suggested to modify therapy in accordance with the results of the sensitivity test when the culture report shows resistance to the antimicrobial agent initiated empirically. Recommendation 10. In pregnant women hospitalized due to upper UTIs, it is suggested to switch to oral antimicrobial therapy after at least 48 hours of modulation of the systemic inflammatory response and the clinical signs of infection, and when tolerance to oral intake is adequate. Recommendation 11. In pregnant women with upper UTIs with no complications secondary to the primary infection, it is recommended to administer antibiotic therapy for a period of 7 to 10 days. Conclusions: It is expected that with this Colombian upper UTI consensus variability in clinical practice will be reduced. It is recommended that groups doing research in maternal fetal medicine assess the implementation and effectiveness of these recommendations.

Epidemiological characteristics and serotype distribution of culture-confirmed pediatric pneumococcal pneumonia before and after PCV 10 introduction, a multicenter study in Bogota, Colombia, 2008-2019.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have decreased pneumonia in children. Colombia introduced mass vaccination with PCV10 in 2012. METHODS: Cases of pneumococcal pneumonia from 10 hospitals were included. Two periods were compared: pre-PCV10: 2008-2011 and post-PCV10: 2014-2019. The objective was to compare epidemiological and clinical characteristics before and after PCV10 vaccination. RESULTS: A total of 370 cases were included. Serotypes 1 (15, 11.2%) and 14 (33, 24.6%) were the most frequent in the pre-PCV10 period, with only 4 (3%) cases of serotype 19A and 1 case (0.7%) serotype 3. From the pre-PCV10 period to the post-PCV10 period, cases of serotypes 1 (6, 3.1%) and 14 (1, 7.8%) decreased, while cases of serotypes 19A (58, 30.2%), serotype 3 (32, 16.7%) and 6A (7, 3.6%) increased (p < 0.001); complicated pneumonia (CP) increased significantly (13.4% to 31.8%) (p < 0.001); hospitalizations increased from 8 (5.5-15) to 12 (7-22) days (p < 0.001); and the frequency of PICU admission increased from 32.8% to 51.6% (p = 0.001). The use of ampicillin-sulbactam (0.7% to 24%) and ceftriaxone/clindamycin (0.7% to 5.7%) increased in the post-PCV10 period. The duration of empirical antibiotic treatment was 7 (4-11) days in the pre-PCV10 period and increased to 10 (6-17) days (p < 0.001) in the post-PCV10 period. Lethality showed a slight nonsignificant increase (7.5% vs. 9.9%; p = 0.57) in the post-PCV10 period. CONCLUSIONS: PCV10 significantly decreased cases of serotypes 1 and 14, with an increase in cases of serotypes 19A, 3 and 6A, which were the predominant serotypes and had greater severity (e.g., admission to the PICU, CP and more resistance, with an increase in the use of broad-spectrum antibiotics and longer hospitalization) and subsequently included in PCV13. Current data support national and regional evidence on the importance of replacing PCV10 with a higher valence that includes 19A, such as PCV13, with the aim of reducing circulation, particularly of this serotype.

Designing Chimeric Peptides: A Powerful Tool for Enhancing Antibacterial Activity.

Chimeric peptides containing short sequences derived from bovine Lactoferricin (LfcinB) and Buforin II (BFII) were synthetized using solid-phase peptide synthesis (SPPS) and characterized via reversed-phase liquid chromatography and mass spectrometry. The chimeras were obtained with high purity, demonstrating their synthetic viability. The chimeras' antibacterial activity against Gram-positive and Gram-negative strains was evaluated. Our results showed that all the chimeras exhibited greater antibacterial activity against the evaluated strains than the individual sequences, suggesting that chemical binding of short sequences derived from AMPs significantly increased the antibacterial activity. For each strain, the chimera with the best antibacterial activity exerted a bacteriostatic and/or bactericidal effect, which was dependent on the concentration. It was found that: (i) the antibacterial activity of a chimera is mainly influenced by the linked sequences, the palindromic motif RLLRRLLR being the most relevant one; (ii) the inclusion of a spacer between the short sequences did not significantly affect the chimera's synthesis process; however, it enhanced its antibacterial activity against Gram-negative and Gram-positive strains; on the other hand, (iii) the replacement of Arg with Lys in the LfcinB or BFII sequences improved the chimeras' synthesis process without significantly affecting their antibacterial activity. These results illustrate the great importance of the synthesis of chimeric peptides for the generation of promising antibacterial peptides.

Short peptides conjugated to non-peptidic motifs exhibit antibacterial activity.

Short peptides derived from buforin and lactoferricin B were conjugated with other antimicrobial molecules of different chemical natures. The sequences RLLR, RLLRLLR, RWQWRWQWR, and RRWQWR were conjugated at their N-terminal end with non-peptidic molecules such as 6-aminohexanoic acid, ferrocene, caffeic acid, ferulic acid, and oxolinic acid. Peptide conjugates and unmodified peptides were synthesized by means of solid-phase peptide synthesis using the Fmoc/tBu strategy (SPPS-Fmoc/tBu), purified via RP-SPE, and characterized via RP-HPLC and MS. The peptides' antibacterial activity against bacterial strains E. coli ATCC 25922 and S. aureus ATCC 25923 was evaluated, and the results showed that the peptide conjugates exhibited higher antibacterial activity than the original unconjugated peptides. Conjugation of AMPs is a promising strategy for designing and identifying new drugs for treating bacterial infections.

Synergistic bactericide and antibiotic effects of dimeric, tetrameric, or palindromic peptides containing the RWQWR motif against Gram-positive and Gram-negative strains.

Dimeric and tetrameric peptides derived from LfcinB (20-25): RRWQWR, LfcinB (20-30): RRWQWRMKKLG, LfcinB (17-31): FKARRWQWRMKKLGA, or the palindromic sequence LfcinB (21-25)Pal: RWQWRWQWR were obtained by means of the SPPS-Fmoc/tBu methodology. The antibacterial activity of these molecules was evaluated against Escherichia coli (ATCC 25922 and ATCC 11775), Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), and Pseudomonas aeruginosa (ATCC 27853). The dimer LfcinB (20-25)2: (RRWQWR)2K-Ahx, the tetramer LfcinB (20-25)4: (RRWQWR)4K2-Ahx2-C2, and the palindromic sequence LfcinB (21-25)Pal exhibited the highest antibacterial activity against the tested bacterial strains. In all cases, the antibacterial activity was dependent on peptide concentration. The polyvalent molecules LfcinB (20-25)2 and LfcinB (20-25)4 exhibited bacteriostatic and bactericidal activity against E. coli, P. aeruginosa, and S. aureus strains; additionally, this dimer and this tetramer combined with ciprofloxacin exhibited a synergistic antibacterial effect against E. coli ATCC 25922 and P. aeruginosa, respectively. Furthermore, the peptides LfcinB (20-30)4, LfcinB (20-25)4, and LfcinB (21-25)Pal combined with vancomycin exhibited a synergistic antibacterial effect against S. aureus and E. faecalis, respectively. This study showed that polyvalent peptides derived from LfcinB exhibit significant antibacterial activity, suggesting that these peptides could have a therapeutic application. Furthermore, our results suggest that polyvalent peptide synthesis could be considered as an innovative and viable strategy for obtaining promising antimicrobial molecules.

Anti-microbial sensitivity of enterobacteria identified in community-acquired urinary tract infection in pregnant women in 9 Colombian hospitals / Susceptibilidad antimicrobiana de enterobacterias identificadas en infección urinaria adquirida en la comunidad, en gestantes en nueve hospitales de Colombia

ABSTRACT Objective: To identify sensitivity profiles of the main anti-microbial agents used in the management of community-acquired urinary tract infection in pregnant women, and to make the molecular characterisation in order to confirm the existence of bacterial resistance in this population group. Materials and methods: Descriptive crosssectional study that included pregnant women with community-acquired urinary tract infection requiring admission to hospital. They were part of a study conducted in the general population. The microbiological results of the urine cultures were analysed. Isolates of Escherichia coli, Klebsiella spp. And Proteus mirabilis were identified over a period of 12 months in 9 Colombian hospitals, and their sensitivity profiles were determined using microdilution broth and gradient diffusion tests, and the presence of extended spectrum beta-lactamases was characterised using microbiological and molecular methods.The sociodemographic and clinical characteristics of these patients are presented. Results: Overall, 74 isolates were collected (64 E. coli, 7 Klebsiella spp. and 3 P. mirabilis isolates) in 73 patients. Prior use of antibiotics was documented in 58% of the patients. Resistance to ampicillin/sulbactam, cefazolin and ceftriaxone was 15.6%, 17.2% and 4.7%, respectively. There was extended spectrum beta-lactamase expression in three of the isolates, 2 of E. coli and 1 of Klebsiella spp. (3.1% E. coli and 14.3% Klebsiella spp.) One E. coli isolate expressed enzymes of the AmpC type. Conclusion: The presence of resistant strains to antibiotics used as first-line empirical treatment and to third-generation cephalosporins was confirmed in enterobacteria responsible for community-acquired urinary tract infection in pregnant women, produced by type CTX M-15 and AmpC extended spectrum betalactamase enzymes.

RESUMEN Objetivo: determinar los perfiles de susceptibilidad a los principales agentes antimicrobianos utilizados en el manejo de infección de vías urinarias adquirida por gestantes en la comunidad, y caracterizarlos molecularmente para confirmar la existencia de resistencia bacteriana en este grupo poblacional. Materiales y métodos: Estudio de corte transversal, descriptivo, en el que se incluyeron gestantes con infección urinaria adquirida en la comunidad que requirieron hospitalización. Estas hacían parte de un estudio realizado en población general. Se analizaron los resultados microbiológicos de los urocultivos. Se identificaron los aislamientos de Escherichia coli, Klebsiella spp. y Proteus mirabilis durante 12 meses en 9 hospitales de Colombia, y se determinó su perfil de susceptibilidad por microdilución en caldo y pruebas de difusión por gradiente; se caracterizó la presencia de betalactamasas de espectro extendido, con métodos microbiológicos y moleculares. Se presentan las características sociodemográficas y clínicas de estas pacientes. Resultados: se recogieron 74 aislamientos (64 de E. coli, 7 de Klebsiella spp. y 3 de P. mirabilis) en 73 pacientes. En 58 % de las pacientes se reportó uso previo de antibióticos. La resistencia a ampicilina/sulbactam, cefazolina y ceftriaxona fue de 15,6, 17,2 y 4,7 %, respectivamente. Tres aislamientos, dos de E. coli y uno de Klebsiella spp., expresaron betalactamasas de espectro extendido (3,1 % en E. coli y 14,3 % Klebsiella spp.). Un aislamiento de E. coli expresó enzimas tipo AmpC. Conclusión: se confirmó la presencia de cepas resistentes a antibióticos utilizados de primera línea de manera empírica, y a cefalosporinas de tercera generación en enterobacterias responsables de infección del tracto urinario adquirida en la comunidad en embarazadas, producida por enzimas de tipo betalactamasas de espectro extendido tipo CTX M-15 y AmpC.

Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines.

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076.

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B-containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC 13636, and Salmonella enteritidis ATCC 13076 was evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The synthetic bovine lactoferricin exhibited antibacterial activity against E. coli ATCC 11775 and S. enteritidis ATCC 13076. The dimeric peptide (RRWQWR)2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strain. The monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif exhibited high and specific activity against E. coli ATCC 11775. The results suggest that short peptides derived from lactoferricin B could be considered as potential candidates for the development of antibacterial agents against infections caused by E. coli.

Etiología de la neumonía adquirida en la comunidad en un hospital de cuarto nivel en Bogotá: estudio descriptivo de un registro institucional durante los años 2007 a 2012 / Etiology of community acquired pneumonia in a fourth level attention hospital in Bogotá: Descriptive study of an institutional record during 2007 to 2012

Introducción: La neumonía adquirida en la comunidad (NAC) puede ser causada por diferentes gérmenes. En Latinoamérica la principal etiología es Streptococcus pneumoniae , aislado en aproximadamente el 35-40% de los casos. Objetivos: Describir las características de los pacientes hospitalizados con diagnóstico de NAC durante 6 años en la Fundación Santa Fe de Bogotá, los principales agentes etiológicos y el patrón de susceptibilidad antibiótica en los microorganismos más importantes. Materiales y métodos: Estudio descriptivo retrospectivo que incluyó a todos los pacientes mayores de 16 años hospitalizados con diagnóstico de NAC. Se revisaron variables demográficas y clínicas, presencia de pruebas diagnósticas para determinar etiología y los microorganismos aislados. Resultados: Se aisló un germen en 130 pacientes, siendo los más frecuentes Streptococcus pneumoniae , Haemophilus influenzae y Staphylococcus aureus . Encontramos mayor frecuencia de microorganismos atípicos en menores de 65 años y en pacientes sin comorbilidades, y de enterobacterias en mayores de 65 años y en pacientes con comorbilidades. Discusión: Los principales gérmenes aislados son similares a los reportados en otras series. Llama la atención la frecuencia de Staphylococcus aureus y la presencia de SAMR. Es importante conocer la etiología local para adaptar las guías de manejo de acuerdo a los gérmenes encontrados, la susceptibilidad a los antibióticos y la disponibilidad de recursos.

Introduction: Community acquired pneumonia (CAP) can be caused by different microorganisms. In Latin America the main cause is Streptococcus pneumoniae isolated in about 35-40% of cases. Objectives: To describe the characteristics of patients admitted with diagnosis of CAP at Fundación Santa Fe de Bogotá during a 6 years period, the etiological agents isolated and the pattern of antibiotic susceptibility in the most frequent microorganisms. Materials and methods: Retrospective descriptive study; all patients older than 16 years admitted with diagnosis of CAP were included. Demographic and clinical variables, diagnostic tests to evaluate etiology and the microorganisms isolated were reviewed. Results: At least one microorganism was isolated in 130 patients, being the most common Streptococcus pneumoniae , Haemophilus influenzae and Staphylococcus aureus . We found higher frequency of atypical microorganisms in patients under 65 years and without comorbidities, while enteric gram-negative rods were more frequent in patients with comorbidities or older than 65 years. Discussion: Our most common etiologies are similar to those reported in other series. Special attention is drawn to Staphylococcus aureus as one of the major etiologies and the presence of MRSA. It is important to know the local etiology to adjust guidelines according to the isolated microorganisms, antibiotics susceptibility and availability of resources.

Tendencias de los fenotipos de resistencia bacteriana en hospitales públicos y privados de alta complejidad de Colombia / Trends of bacterial resistance phenotypes in high-complexity public and private hospitals in Colombia

Objetivo. Describir y comparar las frecuencias de los fenotipos de resistencia bacteriana de microorganismos obtenidos de pacientes en unidades de cuidados intensivos (UCI) y otros servicios de hospitalización (no UCI) públicos y privados de alta complejidad de Colombia. Métodos. Estudio observacional, analítico, retrospectivo y multicéntrico, en el cual se consolidaron los registros de los aislamientos bacterianos y los fenotipos de resistencia bacteriana de los microorganismos obtenidos de pacientes atendidos en UCI y no UCI de 79 hospitales públicos y privados de alta complejidad en el período de enero de 2007 a diciembre de 2009. La información se analizó con el programa WHONET® versión 5.5 (OMS) de acuerdo con las recomendaciones del Instituto de Estándares Clínicos y de Laboratorio 2009 y se resumió en un formato de extracción de datos en Excel®. Se realizó un análisis descriptivo en el cual se calcularon proporciones. El análisis de tendencias se realizó mediante la prueba de correlación de rangos de Spearman. Resultados. Las tendencias de los fenotipos de resistencia bacteriana de 2007 a 2009 muestran un comportamiento incremental en la proporción de Enterococcus faecium resistente a vancomicina, Klebsiella pneumoniae resistente a imipenem y a ciprofloxacina, Escherichia coli resistente a ceftazidima, y Enterobacter cloacae resistente a cefotaxima (ρ = 1, P < 0,01) y una disminución de la proporción de los fenotipos E. coli resistente a ciprofloxacina, K. pneumoniae resistente a ceftazidima, Staphylococcus aureus resistente a oxacilina, y Pseudomonas aeruginosa resistente a ceftazidima y a ciprofloxacina (ρ = –1, P < 0,01). Conclusiones. El análisis de tendencias presentado en este estudio constituye la línea de base para el establecimiento de un subsistema nacional de vigilancia epidemiológica. Las tendencias observadas muestran que la resistencia bacteriana a los antimicrobianos en el ámbito hospitalario es un fenómeno dinámico en Colombia y son evidencia de la emergencia de los fenotipos Efa-van y Kpn-imp en los hospitales.

Objective. Describe and compare the frequency of bacterial resistance phenotypes of microorganisms obtained from patients in intensive care units (ICU) and other (non- ICU) high-complexity public and private hospital services in Colombia. Methods. A retrospective observational, analytical, multicenter study was conducted. The records from January 2007 to December 2009 on bacterial isolates and bacterial resistance phenotypes of microorganisms obtained from ICU and non- ICU patients in 79 high-complexity public and private hospitals were consolidated. The information was analyzed with the WHONET® 5.5 (WHO) software, following the 2009 recommendations of the Clinical and Laboratory Standards Institute, and summarized on an Excel® spreadsheet. A descriptive analysis with the calculation of proportions was performed. The trends were analyzed with Spearman rank correlation. Results. The 2007–2009 trends for bacterial resistance phenotypes show increased percentages of vancomycin-resistant Enterococcus faecium, imipenem-resistant Klebsiella pneumoniae, ciprofloxacin-resistant K. pneumoniae, ceftazidime-resistant Escherichia coli and cefotaxime-resistant Enterobacter cloacae (r = 1, P < 0.01), and reduced percentages of ciprofloxacin-resistant E. coli, ceftazidime-resistant K. pneumoniae, oxacillinresistant Staphylococcus aureus, ceftazidime-resistant Pseudomonas aeruginosa, and ciprofloxacin-resistant P. aeruginosa (r = –1, P < 0.01). Conclusions. The trend analysis presented in this study is the baseline for establishing a national epidemiological surveillance subsystem. The trends observed reveal that bacterial resistance to antimicrobial drugs in hospitals in Colombia is a dynamic phenomenon, with evidence of the emergence of vancomycin-resistant E. faecium and imipenem-resistant K. pneumoniae phenotypes in the hospitals.

[Trends of bacterial resistance phenotypes in high-complexity public and private hospitals in Colombia]. / Tendencias de los fenotipos de resistencia bacteriana en hospitales públicos y privados de alta complejidad de Colombia.

OBJECTIVE: Describe and compare the frequency of bacterial resistance phenotypes of microorganisms obtained from patients in intensive care units (ICU) and other (non-ICU) high-complexity public and private hospital services in Colombia. METHODS: A retrospective observational, analytical, multicenter study was conducted. The records from January 2007 to December 2009 on bacterial isolates and bacterial resistance phenotypes of microorganisms obtained from ICU and non-ICU patients in 79 high-complexity public and private hospitals were consolidated. The information was analyzed with the WHONET(®) 5.5 (WHO) software, following the 2009 recommendations of the Clinical and Laboratory Standards Institute, and summarized on an Excel(®) spreadsheet. A descriptive analysis with the calculation of proportions was performed. The trends were analyzed with Spearman rank correlation. RESULTS: The 2007-2009 trends for bacterial resistance phenotypes show increased percentages of vancomycin-resistant Enterococcus faecium, imipenem-resistant Klebsiella pneumoniae, ciprofloxacin-resistant K. pneumoniae, ceftazidime-resistant Escherichia coli and cefotaxime-resistant Enterobacter cloacae (r = 1, P < 0.01), and reduced percentages of ciprofloxacin-resistant E. coli, ceftazidime-resistant K. pneumoniae, oxacillin-resistant Staphylococcus aureus, ceftazidime-resistant Pseudomonas aeruginosa, and ciprofloxacin-resistant P. aeruginosa (r = -1, P < 0.01). CONCLUSIONS: The trend analysis presented in this study is the baseline for establishing a national epidemiological surveillance subsystem. The trends observed reveal that bacterial resistance to antimicrobial drugs in hospitals in Colombia is a dynamic phenomenon, with evidence of the emergence of vancomycin-resistant E. faecium and imipenem-resistant K. pneumoniae phenotypes in the hospitals.

El caso de infecciosas: candidiasis urinaria revisión de 25 casos / The infectious case: urinary candidiasis review of 25 cases

Se revisaron los resultados de 63 muestras de orina enviadas para cultivo al Laboratorio de Micología de la Corporación para Investigaciones Biológicas, durante el período comprendido entre Enero de 1987 y Octubre de 1992.

El diagnóstico de candidiasis urinaria se comprobó en 25 casos, siendo más frecuente en mujeres. 17 casos (68%) y en mayores de 60 años. 14 casos (56%). Las condiciones asociadas fueron: procedimientos quirúrgicos. 14 casos (56%).diabetes mellitus. 9 casos (36%). uso de antibióticos de amplio espectro. 24 casos (96%) y presencia de catéter en el tracto urinario. 23 casos (92%). Candida albicans fue la especie aislada con mayor frecuencia. 18 casos (72%).