El desarrollo y los complejos mecanismos de resistencia de S. aureus: una amenaza persistente en la era de los antibióticos

Introducción: S. aureus ha emergido como una amenaza persistente, demostrando una notable habilidad para desarrollar resistencia a lo largo de la evolución de los antibióticos. Desde los primeros enfrentamientos con la penicilina hasta los desafíos actuales con cepas resistentes a la vancomicina y la daptomicina, el estudio de los mecanismos de resistencia de este patógeno ha adquirido una importancia crítica. Objetivos: documentar los cambios en los patrones de resistencia de S. aureus a lo largo del tiempo, además de identificar las etapas críticas en el desarrollo de la resistencia a diferentes antibióticos. Materiales y métodos: el proceso de selección de artículos revisados se llevó a cabo identificando artículos publicados entre 2010 y 2023. Se utilizaron varias bases de datos relevantes, incluyendo PubMed, Scopus, Embase, Cochrane Library y Scielo. Se incluyeron estudios observacionales, artículos de revisión y guías clínicas. Se desarrollaron estrategias de búsqueda específicas para cada base de datos utilizando palabras clave y términos de búsqueda relacionados con S. aureus y su resistencia antimicrobiana, así como los tipos de estudios de interés. Se extrajeron datos relevantes de los estudios seleccionados, incluyendo información sobre los patrones de resistencia, mecanismos de resistencia, impacto clínico y estrategias terapéuticas. Los datos recopilados se analizaron y sintetizaron para documentar los cambios en los patrones de resistencia de S. aureus a lo largo del tiempo y para identificar las etapas críticas en el desarrollo de la resistencia a diferentes antibióticos. Resultados: se incluyeron 100 artículos donde se evidencia una evolución temporal de la resistencia, desde las primeras cepas resistentes a la penicilina hasta las actuales cepas resistentes a la vancomicina y la daptomicina. Estos estudios proporcionaron un análisis detallado de los mecanismos moleculares clave que impulsan la resistencia antimicrobiana, tales como la producción de beta-lactamasas, las alteraciones en las proteínas de unión a penicilina y las modificaciones en la membrana celular. Los hallazgos destacan una evolución significativa en la capacidad de S. aureus para adaptarse a diferentes antibióticos a lo largo del tiempo, subrayando la complejidad y la diversidad de los mecanismos de resistencia desarrollados por esta bacteria. Conclusiones: la evolución de la resistencia de S. aureus ha seguido un patrón marcado por etapas críticas, desde la aparición de cepas productoras de penicilinasa tras la introducción de la penicilina, hasta el surgimiento de MRSA con la meticilina y de VISA y VRSA con la vancomicina. Estos cambios destacan la capacidad de adaptación de S. aureus a nuevas presiones antibióticas. La revisión subraya la necesidad urgente de desarrollar estrategias antimicrobianas innovadoras y sostenibles para controlar esta creciente amenaza. Comprender los mecanismos de resistencia es crucial para desarrollar enfoques más efectivos y personalizados en el tratamiento de las infecciones por este germen.

Introduction: S. aureus has emerged as a persistent threat, demonstrating a remarkable ability to develop resistance throughout the evolution of antibiotics. From the first confrontations with penicillin to the current challenges with strains resistant to vancomycin and daptomycin, the study of the resistance mechanisms of this pathogen has acquired critical importance. Objectives: To document changes in S. aureus resistance patterns over time and identify critical stages in the development of resistance to different antibiotics. Materials and methods: The reviewed articles were selected by identifying articles published between 2010 and 2023. Several relevant databases were used, including PubMed, Scopus, Embase, Cochrane Library, and SciELO. Observational studies, review articles, and clinical guidelines were included. Specific search strategies were developed for each database using keywords and search terms related to S. aureus and its antimicrobial resistance as well as the types of studies of interest. Relevant data were extracted from the selected studies, including information on resistance patterns, resistance mechanisms, clinical impact, and therapeutic strategies. The collected data were analyzed and synthesized to document changes in S. aureus resistance patterns over time and identify critical stages in the development of resistance to different antibiotics. Results: One hundred articles were included where a temporal evolution of resistance is evident, from the first strains resistant to penicillin to the current strains resistant to vancomycin and daptomycin. These studies provided a detailed analysis of the key molecular mechanisms driving antimicrobial resistance, such as beta-lactamase production, alterations in penicillin-binding proteins, and cell membrane modifications. The findings highlight a significant evolution in the ability of S. aureus to adapt to different antibiotics over time, underscoring the complexity and diversity of resistance mechanisms developed by this bacterium. Conclusions: The evolution of S. aureus resistance has followed a pattern marked by critical stages, from the appearance of penicillinase-producing strains after the introduction of penicillin to the emergence of MRSA with methicillin and of VISA and VRSA with vancomycin. These changes highlight the ability of S. aureus to adapt to new antibiotic pressures. The review highlights the urgent need to develop innovative and sustainable antimicrobial strategies to control this growing threat. Understanding resistance mechanisms is crucial to developing more effective and personalized approaches for the treatment of infections caused by this germ.

Antimicrobial Peptides with Antibacterial Activity against Vancomycin-Resistant Staphylococcus aureus Strains: Classification, Structures, and Mechanisms of Action.

The emergence of bacteria resistant to conventional antibiotics is of great concern in modern medicine because it renders ineffectiveness of the current empirical antibiotic therapies. Infections caused by vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-intermediate S. aureus (VISA) strains represent a serious threat to global health due to their considerable morbidity and mortality rates. Therefore, there is an urgent need of research and development of new antimicrobial alternatives against these bacteria. In this context, the use of antimicrobial peptides (AMPs) is considered a promising alternative therapeutic strategy to control resistant strains. Therefore, a wide number of natural, artificial, and synthetic AMPs have been evaluated against VRSA and VISA strains, with great potential for clinical application. In this regard, we aimed to present a comprehensive and systematic review of research findings on AMPs that have shown antibacterial activity against vancomycin-resistant and vancomycin-intermediate resistant strains and clinical isolates of S. aureus, discussing their classification and origin, physicochemical and structural characteristics, and possible action mechanisms. This is the first review that includes all peptides that have shown antibacterial activity against VRSA and VISA strains exclusively.

Systematic review and meta-analysis of the epidemiology of vancomycin-resistance Staphylococcus aureus isolates.

BACKGROUND: Vancomycin­resistant Staphylococcus aureus (VRSA) is a serious public health challenging concern worldwide. OBJECTIVES: Therefore, the objective of present study of 62 published studies was to evaluate the prevalence of VRSA based on different years, areas, isolate source, antimicrobial susceptibility testing, and the genetic determinants. METHODS: We searched the relevant articles that focused on the prevalence rates of VRSA in PubMed, Scopus, Embase, and Web of Science from 2000 to 2019. Statistical analyses were conducted using STATA software (version 14.0). RESULTS: The prevalence of VRSA was 2% before 2006, 5% in 2006-2014, and 7% in 2015-2020 that showed a 3.5-fold increase in the frequency of VRSA between before 2006 and 2020 years. The prevalence of VRSA was 5% in Asia, 1% in Europe, 4% in America, 3% in South America, and 16% in Africa. The frequencies of VRSA isolated from clinical, non-clinical, and mixed samples were 6%, 7%, and 14%, respectively. The prevalence of VRSA was 12% using disk diffusion agar method, 7% using MIC-base methods, and 4% using mixed-methods. The prevalence of vanA, vanB, and vanC1 positive were 71%, 26%, and 4% among VRSA strains. The most prevalent genotype was staphylococcal cassette chromosomemec (SCCmec) II, which accounted for 57% of VRSA. The most prevalent staphylococcal protein A (spa) types were t002, t030, and t037. CONCLUSION: The prevalence of VRSA has been increasing in recent years particularly in Africa/Asia than Europe/America. The most prevalent of genetic determinants associated with VRSA were vanA and SCCmec II. This study clarifies that the rigorous monitoring of definite antibiotic policy, regular surveillance/control of nosocomial-associated infections and intensive surveillance of vancomycin-resistance are required for preventing emergence and further spreading of VRSA.