Antibiotic adjuvants: a promising approach to combat multidrug resistant bacteria

2021 ◽  
Vol 22 ◽  
Author(s):  
Namita Sharma ◽  
Anil K. Chhillar ◽  
Sweety Dahiya ◽  
Pooja Choudhary ◽  
Aruna Punia ◽  
...  
Keyword(s):  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibacterial Drugs ◽  
Effective Strategies ◽  
The Impact ◽  
Emergence Of Resistance

The escalating emergence and prevalence of infections caused by multi-drug resistant (MDR) pathogenic bacteria accentuate the crucial need to develop novel and effectual therapeutic strategies to control this threat. Recent past surprisingly indicates a staggering decline in effective strategies against MDR. Different approaches have been employed to minimize the effect of resistance but the question still lingers over the astounding number of drugs already tried and tested to no avail, furthermore, the detection of new drug targets and the action of new antibacterial agents against already existing drug targets also complicate the condition. Antibiotic adjuvants are considered as one such promising approach for overcoming the bacterial resistance. Adjuvants can potentiate the action of generally adopted antibacterial drugs against MDR bacterial pathogens either by minimizing the impact and emergence of resistance or improving the action of antibacterial drugs. This review provides an overview of mechanism of antibiotic resistance, main types of adjuvants and their mode of action, achievements and progression.

scholarly journals Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2

2015 ◽  
Vol 60 (3) ◽  
pp. 1194-1201 ◽  
Author(s):  
G. L. Drusano ◽  
William Hope ◽  
Alasdair MacGowan ◽  
Arnold Louie
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Regulatory Review ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Antibiotic Drug ◽  
New Chemical Entities

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens likePseudomonas aeruginosa,Acinetobacterspp., and multidrug-resistant (MDR)Enterobacteriaceae. These lessons need to be applied to our old drugs as well to preserve them and to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.

scholarly journals Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1

2015 ◽  
Vol 60 (3) ◽  
pp. 1183-1193 ◽  
Author(s):  
G. L. Drusano ◽  
Arnold Louie ◽  
Alasdair MacGowan ◽  
William Hope
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Regulatory Review ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Antibiotic Drug ◽  
New Chemical Entities

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens likePseudomonas aeruginosa,Acinetobacterspp., and multidrug-resistant (MDR)Enterobacteriaceae. These lessons need to be applied to our old drugs to preserve them as well and need to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a corresponding resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.

scholarly journals Antimicrobials and resistant bacteria in global fish farming and the possible risk for public health

2020 ◽  
Vol 87 ◽  
Author(s):  
Luís Eduardo de Souza Gazal ◽  
Kelly Cristina Tagliari de Brito ◽  
Renata Katsuko Takayama Kobayashi ◽  
Gerson Nakazato ◽  
Lissandra Souto Cavalli ◽  
...  
Keyword(s):  
Public Health ◽  
Infectious Diseases ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Public Health Problem ◽  
Fish Farming ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
The Impact ◽  
Selection Of

ABSTRACT: The use of antimicrobials in fish farming is a reflection of the fast aquaculture development worldwide. The intensification of aquaculture to achieve market demands could lead to an increase in infectious diseases by pathogenic bacteria. Consequently, antimicrobials act as controls for emerging infectious diseases, but their use must follow the rules and regulations of the country where the activity is performed. Although the regulations impose limits to the use of antimicrobials in fish farming, many studies show that resistant bacteria are isolated from this system. The selection of resistant bacteria is not limited only to the use of antimicrobials, but also to co-selection of resistance genes or even with cross-resistance processes. Resistant bacteria from fish farming are a serious concern because they can be acquired by humans with handling or food chain, which may represent a public health problem. In the present review, we present an overview of antimicrobials use in aquaculture, the antimicrobial resistance and the impact of antimicrobial and bacterial resistance from a public health perspective.

scholarly journals Antimicrobial Stewardship Program: Reducing Antibiotic’s Spectrum of Activity Is not the Solution to Limit the Emergence of Multidrug-Resistant Bacteria

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 70
Author(s):  
Rindala Saliba ◽  
Assaf Mizrahi ◽  
Péan de Ponfilly Gauthier ◽  
Le Monnier Alban ◽  
Jean-Ralph Zahar ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Stewardship Program ◽  
Intestinal Dysbiosis ◽  
Pharmacokinetic Properties ◽  
Multidrug Resistant Organisms ◽  
New Antibiotics ◽  
The Impact

Overconsumption of antibiotics in hospitals has led to policy implementation, including the control of antibiotic prescriptions. The impact of these policies on the evolution of antimicrobial resistance remains uncertain. In this work, we review the possible limits of such policies and focus on the need for a more efficient approach. Establishing a causal relationship between the introduction of new antibiotics and the emergence of new resistance mechanisms is difficult. Several studies have demonstrated that many resistance mechanisms existed before the discovery of antibiotics. Overconsumption of antibiotics has worsened the phenomenon of resistance. Antibiotics are responsible for intestinal dysbiosis, which is suspected of being the source of bacterial resistance. The complexity of the intestinal microbiota composition, the impact of the pharmacokinetic properties of antibiotics, and the multiplicity of other factors involved in the acquisition and emergence of multidrug-resistant organisms, lead us to think that de-escalation, in the absence of studies proving its effectiveness, is not the solution to limiting the spread of multidrug-resistant organisms. More studies are needed to clarify the ecological risk caused by different antibiotic classes. In the meantime, we need to concentrate our efforts on limiting antibiotic prescriptions to patients who really need it, and work on reducing the duration of these treatments.

scholarly journals Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Chih-Yuan Chiang ◽  
Ijeoma Uzoma ◽  
Richard T. Moore ◽  
Merle Gilbert ◽  
Allen J. Duplantier ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Small Molecule ◽  
Pathogenic Bacteria ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Pathogen Virulence ◽  
Fda Approval ◽  
Antibacterial Drug Resistance ◽  
The Impact

ABSTRACT Increasing incidences of multidrug resistance in pathogenic bacteria threaten our ability to treat and manage bacterial infection. The development and FDA approval of novel antibiotics have slowed over the past decade; therefore, the adoption and improvement of alternative therapeutic strategies are critical for addressing the threat posed by multidrug-resistant bacteria. Host-directed therapies utilize small-molecule drugs and proteins to alter the host response to pathogen infection. Here, we highlight strategies for modulating the host inflammatory response to enhance bacterial clearance, small-molecule potentiation of innate immunity, and targeting of host factors that are exploited by pathogen virulence factors. Application of state-of-the-art “omic” technologies, including proteomics, transcriptomics, and image-omics (image-based high-throughput phenotypic screening), combined with powerful bioinformatics tools will enable the modeling of key signaling pathways in the host-pathogen interplay and aid in the identification of host proteins for therapeutic targeting and the discovery of host-directed small molecules that will regulate bacterial infection. We conclude with an outlook on research needed to overcome the challenges associated with transitioning host-directed therapies into a clinical setting.

scholarly journals Bacterial Resistance to Antimicrobial Agents

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 593
Author(s):  
Manuel F. Varela ◽  
Jerusha Stephen ◽  
Manjusha Lekshmi ◽  
Manisha Ojha ◽  
Nicholas Wenzel ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Targets ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Health Sector ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Cellular Mechanisms ◽  
Causative Agents

Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness. This review briefly summarizes the various antimicrobial resistance mechanisms that are harbored within infectious bacteria.

scholarly journals Molecules that Inhibit Bacterial Resistance Enzymes

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 43 ◽  
Author(s):  
Yuan Liu ◽  
Ruichao Li ◽  
Xia Xiao ◽  
Zhiqiang Wang
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Resistance ◽  
Enzyme Inhibitors ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Clinical Challenge ◽  
Potential Inhibitors ◽  
The Impact ◽  
Emergence Of Resistance ◽  
Secreted Enzymes

Antibiotic resistance mediated by bacterial enzymes constitutes an unmet clinical challenge for public health, particularly for those currently used antibiotics that are recognized as “last-resort” defense against multidrug-resistant (MDR) bacteria. Inhibitors of resistance enzymes offer an alternative strategy to counter this threat. The combination of inhibitors and antibiotics could effectively prolong the lifespan of clinically relevant antibiotics and minimize the impact and emergence of resistance. In this review, we first provide a brief overview of antibiotic resistance mechanism by bacterial secreted enzymes. Furthermore, we summarize the potential inhibitors that sabotage these resistance pathways and restore the bactericidal activity of inactive antibiotics. Finally, the faced challenges and an outlook for the development of more effective and safer resistance enzyme inhibitors are discussed.

scholarly journals Multidrug Resistence Prevalence in COVID Area

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 601
Author(s):  
Caterina Aurilio ◽  
Pasquale Sansone ◽  
Antonella Paladini ◽  
Manlio Barbarisi ◽  
Francesco Coppolino ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Respiratory Infections ◽  
Prolonged Mechanical Ventilation ◽  
Viral Disease ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Infected People ◽  
Therapeutic Procedures ◽  
Viral Respiratory Infections

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is often complicated by severe acute respiratory syndrome. The new coronavirus outbreak started in China in December 2019 and rapidly spread around the world. The high diffusibility of the virus was the reason for the outbreak of the pandemic viral disease, reaching more than 100 million infected people globally by the first three months of 2021. In the various treatments used up to now, the use of antimicrobial drugs for the management, especially of bacterial co-infections, is very frequent in patients admitted to intensive care. In addition, critically ill patients with SARS-CoV-2 infection are subjected to prolonged mechanical ventilation and other therapeutic procedures often responsible for developing hospital co-infections due to multidrug-resistant bacteria. Co-infections contribute to the increase in the morbidity–mortality of viral respiratory infections. We performed this study to review the recent articles published on the antibiotic bacterial resistance and viruses to predict risk factors of coronavirus disease 2019 and to assess the multidrug resistance in patients hospitalized in the COVID-19 area.

scholarly journals Gold Nanoparticles: Can They Be the Next Magic Bullet for Multidrug-Resistant Bacteria?

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 312
Author(s):  
Mohammad Okkeh ◽  
Nora Bloise ◽  
Elisa Restivo ◽  
Lorenzo De Vita ◽  
Piersandro Pallavicini ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
World Health ◽  
Resistant Bacteria ◽  
Magic Bullet ◽  
Global Challenge ◽  
Gold Silver ◽  
Inorganic Nanomaterials ◽  
Health Organization

In 2017 the World Health Organization (WHO) announced a list of the 12 multidrug-resistant (MDR) families of bacteria that pose the greatest threat to human health, and recommended that new measures should be taken to promote the development of new therapies against these superbugs. Few antibiotics have been developed in the last two decades. Part of this slow progression can be attributed to the surge in the resistance acquired by bacteria, which is holding back pharma companies from taking the risk to invest in new antibiotic entities. With limited antibiotic options and an escalating bacterial resistance there is an urgent need to explore alternative ways of meeting this global challenge. The field of medical nanotechnology has emerged as an innovative and a powerful tool for treating some of the most complicated health conditions. Different inorganic nanomaterials including gold, silver, and others have showed potential antibacterial efficacies. Interestingly, gold nanoparticles (AuNPs) have gained specific attention, due to their biocompatibility, ease of surface functionalization, and their optical properties. In this review, we will focus on the latest research, done in the field of antibacterial gold nanoparticles; by discussing the mechanisms of action, antibacterial efficacies, and future implementations of these innovative antibacterial systems.

scholarly journals Management of superficial and deep surgical site infection: an international multidisciplinary consensus

2021 ◽  
Author(s):  
Gabriele Sganga ◽  
Mohamed Baguneid ◽  
Pascal Dohmen ◽  
Evangelos J. Giamarellos-Bourboulis ◽  
Emilio Romanini ◽  
...  
Keyword(s):  
Length Of Hospital Stay ◽  
Surgical Site Infections ◽  
Early Discharge ◽  
Multidrug Resistant ◽  
Steering Committee ◽  
Resistant Bacteria ◽  
Modified Delphi ◽  
Hospital Stays ◽  
New Treatment ◽  
The Impact

AbstractSurgical site infections represent a considerable burden for healthcare systems. To obtain a consensus on the impact and future clinical and economic needs regarding SSI management in an era of multidrug resistance. A modified Delphi method was used to obtain consensus among experts from five European countries. The Delphi questionnaire was assembled by a steering committee, verified by a panel of experts and administered to 90 experts in 8 different surgical specialities (Abdominal, Cancer, Cardiac, General surgery, Orthopaedic, Thoracic, Transplant and Vascular and three other specialities (infectious disease, internal medicine microbiology). Respondents (n = 52) reached consensus on 62/73 items including that resistant pathogens are an increasing matter of concern and increase both treatment complexity and the length of hospital stay. There was strong positive consensus on the cost-effectiveness of early discharge (ED) programs, improvement of quality of life with ED and association between increased length of stay and economic burden to the hospital. However, established ED protocols were not widely available in their hospitals. Respondents expressed a positive consensus on the usefulness of antibiotics that allow ED. Surgeons are aware of their responsibility in an interdisciplinary team for the treatment of SSI, and of the impact of multidrug-resistant bacteria in the context of SSI. Reducing the length of hospital stays by applying ED protocols and implementing new treatment alternatives is crucial to reduce harm to patients and costs for the hospital.

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