Antibióticos que inhiben la síntesis de dTMP; adyuvantes; estrategias de heterogeneidad

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1. Antibióticos que inhiben la síntesis de dTMP; adyuvantes; estrategias de heterogeneidad Tópico selecto "Mecanismo de acción de antibióticos, resistencia y perspectivas" Programa de Doctorado en Ciencias Biomédicas y Licenciatura en Ciencias Genómicas UNAM 2019
2. La síntesis de dTMP requiere folato y sólo las bacterias producen este último (Sanchez et al., 2012)⁠
3. La síntesis de folato: blanco de antibióticos (Kırmusaoğlu, Gareayaghi, & S. Kocazeybek, 2019; Tacic, Nikolic, Nikolic, & Savic, 2017) https://basicmedicalkey.com/trimethoprim/
4. Los adyuvantes aumentan o rescatan la acción del antibiótico (Melander & Melander, 2017)⁠ CLASE IA. Contra resist. activa CLASE IB. Contra barreras fisiológicas Inhibit antibiotic modification Inhibit target modification (Erm methylases inhibition) facilitate membrane penetration inhibit biofilm formation inhibit signaling pathways of resist. mechanisms *En uso
5. Hay otras aproximaciones para bajar la toxicidad y proteger al microbioma del hospedero (Johnson et al., 2018; Peck et al., 2019)⁠ https://clipart.wpblink.com/sites/default/files/styles/225x120/public/wallpaper/virus-clipart/94065/virus-clipart-bacteriophage-94065-4718871.png?itok=DIlVmAHb Localized targeting Biological adyuvants
6. Recomendaciones terapia combinada y monoterapia Combination therapy •Immunosuppressed patient •Severly ill patient •Virulent bacteria • Pseudomonas aeruginosa • Kleibsiella spp. • Enterobacter spp. Monotherapy •Immunocompetent patient •Well, stable patient •Less virulent bacteria • Escherichia coli • Serratia spp. • Citrobacter spp. • Providencia spp. (ref)
7. Cycling vs mixing: ¿Cuál es la mejor estrategia ? (Plantinga, Wittekamp, van Duijn, & Bonten, 2015) Alternating antibiotic therapy per time unit Podríamos seleccionar clonas resistentes; se espera que no sobrevivan al siguiente ciclo Alternating antibiotic therapy per patient Se espera reducir la presión selectiva sobre clonas resistentes
8. Cycling vs mixing: ¿Cuál es la mejor estrategia ? (Beardmore, Pena-Miller, Gori, & Iredell, 2017)
10. Beardmore, R. E., Pena-Miller, R., Gori, F., & Iredell, J. (2017). Antibiotic Cycling and Antibiotic Mixing: which one best mitigates antibiotic resistance? Molecular Biology and Evolution, msw292. https://doi.org/10.1093/molbev/msw292 Johnson, C. T., Wroe, J. A., Agarwal, R., Martin, K. E., Guldberg, R. E., Donlan, R. M., … García, A. J. (2018). Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing. Proceedings of the National Academy of Sciences, 115(22), E4960–E4969. https://doi.org/10.1073/pnas.1801013115 Kırmusaoğlu, S., Gareayaghi, N., & S. Kocazeybek, B. (2019). Introductory Chapter: The Action Mechanisms of Antibiotics and Antibiotic Resistance. In Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods [Working Title]. IntechOpen. https://doi.org/10.5772/intechopen.85211 Melander, R. J., & Melander, C. (2017). The Challenge of Overcoming Antibiotic Resistance: An Adjuvant Approach? ACS Infectious Diseases, 3(8), 559–563. https://doi.org/10.1021/acsinfecdis.7b00071 Peck, M., Rothenberg, M. E., Deng, R., Lewin-Koh, N., She, G., Kamath, A. V., … Tavel, J. A. (2019). A phase 1, randomized, single ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti- Staphylococcus aureus THIOMABTM antibody-antibiotic conjugate, in healthy volunteers. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/AAC.02588-18 Plantinga, N. L., Wittekamp, B. H., van Duijn, P. J., & Bonten, M. J. (2015). Fighting antibiotic resistance in the intensive care unit using antibiotics. Future Microbiology, 10(3), 391–406. https://doi.org/10.2217/fmb.14.146 Sanchez, A., Sharma, S., Rozenzhak, S., Roguev, A., Krogan, N. J., Chabes, A., & Russell, P. (2012). Replication Fork Collapse and Genome Instability in a Deoxycytidylate Deaminase Mutant. Molecular and Cellular Biology, 32(21), 4445–4454. https://doi.org/10.1128/MCB.01062-12 Tacic, A., Nikolic, V., Nikolic, L., & Savic, I. (2017). Antimicrobial sulfonamide drugs. Advanced Technologies, 6(1), 58–71. https://doi.org/10.5937/savteh1701058T