The issue of antibiotic resistance represents a significant threat that extends beyond human health, encompassing animal welfare and the sustainability of the natural environment. The inappropriate use of antibiotics, poor sanitation and inadequate control measures, have contributed to the emergence of drug-resistant bacteria, which can spread at the human-animal-environment interface. The documented presence of antimicrobials in agriculture, veterinary medicine and human medicine has convinced all stakeholders of the need to contribute to the development of a "One Health" approach, which recognises the interrelationships between animals, humans and their environment and the need to adopt a common strategy encompassing these sectors to limit the spread of antimicrobial resistance (AMR). Although a number of countries have implemented integrated surveillance systems to monitor antibiotic use and antimicrobial resistance, available data suggest that the use of antibiotics in humans, animals and the environment is increasing worldwide. Consequently, the emergence of antibiotic-resistant pathogens is becoming a recurring concern. This review provides a comprehensive overview of the measures that are necessary to be taken and implemented in order to guarantee global health security.

Antibiotics have played a crucial role in the reduction of TB incidence globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline of antibiotic development, and different economic and social conditions. In this review, we summarise recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasise that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throught the community.

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multiresistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.