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Multidrug-resistant (MDR) Gram-negative pathogens remain an unmet public health threat. In recent times, increased rates of resistance have been reported not only to commonly used antibiotics, but also to the last-resort antibiotics, such as polymyxins. More worryingly, despite the current trends in resistance, there is a lack of new antibiotics in the drug-discovery pipeline. Hence, it is imperative that new strategies are developed to preserve the clinical efficacy of the current antibiotics, particularly the last-line agents. Combining conventional antibiotics such as polymyxins with non-antibiotics (or adjuvants), has emerged as a novel and effective strategy against otherwise untreatable MDR pathogens. This review explores the available literature detailing the latest polymyxin/non-antibiotic combinations, their mechanisms of action, and potential avenues to advance their clinical application. [ABSTRACT FROM AUTHOR]

The worldwide scenario of antibiotic resistance and the falling number of funds for the development of novel antibiotics have led research efforts toward the study of specific cost-effective strategies aimed at discovering drugs against microbial infections. Among the potential options, drug repositioning, which has already exhibited satisfactory results in other medical fields, came out as the most promising. It consists of finding new uses for previously approved medicines and, over the years, many "repurposed drugs" displayed some encouraging in vitro and in vivo results beyond their initial application. The principal theoretical justification for reusing already existing drugs is that they have known mechanisms of action and manageable side effects. Reuse of old drugs is now considered an interesting approach to overcome the drawbacks of conventional antibiotics. The purpose of this review is to offer the reader a panoramic view of the updated studies concerning the repositioning process of different classes of non-antibiotic drugs in the antimicrobial field. Several research works reported the ability of some non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, antipsychotics, and statins to counteract the growth of harmful microorganisms, demonstrating an interesting winning mode to fight infectious diseases caused by antimicrobial resistant bacteria. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) Gram-negative pathogens remain an unmet public health threat. In recent times, increased rates of resistance have been reported not only to commonly used antibiotics, but also to the last-resort antibiotics, such as polymyxins. More worryingly, despite the current trends in resistance, there is a lack of new antibiotics in the drug-discovery pipeline. Hence, it is imperative that new strategies are developed to preserve the clinical efficacy of the current antibiotics, particularly the last-line agents. Combining conventional antibiotics such as polymyxins with non-antibiotics (or adjuvants), has emerged as a novel and effective strategy against otherwise untreatable MDR pathogens. This review explores the available literature detailing the latest polymyxin/non-antibiotic combinations, their mechanisms of action, and potential avenues to advance their clinical application.

The worldwide scenario of antibiotic resistance and the falling number of funds for the development of novel antibiotics have led research efforts toward the study of specific cost-effective strategies aimed at discovering drugs against microbial infections. Among the potential options, drug repositioning, which has already exhibited satisfactory results in other medical fields, came out as the most promising. It consists of finding new uses for previously approved medicines and, over the years, many “repurposed drugs” displayed some encouraging in vitro and in vivo results beyond their initial application. The principal theoretical justification for reusing already existing drugs is that they have known mechanisms of action and manageable side effects. Reuse of old drugs is now considered an interesting approach to overcome the drawbacks of conventional antibiotics. The purpose of this review is to offer the reader a panoramic view of the updated studies concerning the repositioning process of different classes of non-antibiotic drugs in the antimicrobial field. Several research works reported the ability of some non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, antipsychotics, and statins to counteract the growth of harmful microorganisms, demonstrating an interesting winning mode to fight infectious diseases caused by antimicrobial resistant bacteria.

Although concerns have been raised about co-selection for antibiotic resistance and various antibiotics and non-antibiotic agents, the data on their association in urban sludge is still limited. In addition, antibiotic contamination can result in not only the toxicity but also the antibiotic resistance. In this study, the first large-scale identification of antibiotics and non-antibiotic agents concern for co-selection of resistance against antibiotics was conducted in urban sludge. Co-occurrence analysis showed that antibiotic resistance genes (ARGs) had no significant correlation with the corresponding antibiotics. Therefore, the results of co-occurrence analysis based on antibiotic concentration and ARG abundance were always ambiguous and difficult to interpret. However, antibiotic resistance was positively correlated with highly toxic compounds such as diclofenac, enrofloxacin and nicotine, suggesting that environmental contaminants might influence antibiotic resistance while exerting toxicity through mechanisms such as changes in microbial community and enzyme activity. The close correlation between class 1 integrase gene (intI 1) and diclofenac/enrofloxacin indicated that the co-selection scenario between environmental contaminants and ARGs was likely mediated via intI 1. In total, the derived co-occurrence patterns improve our understanding of the co-selection between ARGs, antibiotics and non-antibiotic agents, and also reaffirm the importance of potential role of non-antibiotic agents in the global spread of antibiotic resistance. [Display omitted] • The abundance of sulfonamide and tetracycline ARGs was the highest in sludge. • DCF, EN and NCT appeared to be the more hazardous compounds. • Positive correlation between toxicity and antibiotic resistance was found. • Co-selection between contaminants and ARGs was likely mediated via intI 1. • The role of non-antibiotic agents in the dissemination of ARGs was highlighted. [ABSTRACT FROM AUTHOR]