Action and resistance mechanisms of antibiotics: A guide for clinicians
01 Jul 2017-Journal of Anaesthesiology Clinical Pharmacology (Medknow Publications)-Vol. 33, Iss: 3, pp 300-305
TL;DR: The mechanism of action and resistance development in commonly used antimicrobials is discussed and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful.
Abstract: Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.
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TL;DR: The mechanisms by which nanomaterials can be used to target antibiotic-resistant bacterial infections are discussed, design elements and properties of nanomMaterials that can be engineered to enhance potency are highlighted, and recent progress and remaining challenges for clinical implementation are explored.
Abstract: Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative 'outside of the box' therapeutics Nanomaterial-based therapies are promising tools to combat bacterial infections that are difficult to treat, featuring the capacity to evade existing mechanisms associated with acquired drug resistance In addition, the unique size and physical properties of nanomaterials give them the capability to target biofilms, overcoming recalcitrant infections In this Review, we highlight the general mechanisms by which nanomaterials can be used to target bacterial infections associated with acquired antibiotic resistance and biofilms We emphasize design elements and properties of nanomaterials that can be engineered to enhance potency Lastly, we present recent progress and remaining challenges for widespread clinical implementation of nanomaterials as antimicrobial therapeutics
418 citations
TL;DR: In this article, the major sources responsible for emergence of antibiotic resistance are elucidated and a variety of introductory sources and fate of PPCPs in aquatic environment including human and veterinary wastes, aquaculture and agriculture related wastes, and other anthropogenic activities have been discussed.
198 citations
TL;DR: In this paper, both the mode of action and the mechanisms of resistance of commonly used antimicrobials are examined and the current state of AMR in the most critical resistant bacteria as determined by the WHO's global priority pathogens list.
Abstract: Antibiotics have made it possible to treat bacterial infections such as meningitis and bacteraemia that, prior to their introduction, were untreatable and consequently fatal. Unfortunately, in recent decades overuse and misuse of antibiotics as well as social and economic factors have accelerated the spread of antibiotic-resistant bacteria, making drug treatment ineffective. Currently, at least 700,000 people worldwide die each year due to antimicrobial resistance (AMR). Without new and better treatments, the World Health Organization (WHO) predicts that this number could rise to 10 million by 2050, highlighting a health concern not of secondary importance. In February 2017, in light of increasing antibiotic resistance, the WHO published a list of pathogens that includes the pathogens designated by the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) to which were given the highest “priority status” since they represent the great threat to humans. Understanding the resistance mechanisms of these bacteria is a key step in the development of new antimicrobial drugs to tackle drug-resistant bacteria. In this review, both the mode of action and the mechanisms of resistance of commonly used antimicrobials will be examined. It also discusses the current state of AMR in the most critical resistant bacteria as determined by the WHO’s global priority pathogens list.
150 citations
TL;DR: The paper suggests that AMR presents an opportunity to take seriously connections, scale and systems but that this effort is undermined by the prevailing tendency to reduce health issues to matters for individual responsibility.
Abstract: Antimicrobial resistance (AMR) is one of the latest issues to galvanise political and financial investment as an emerging global health threat. This paper explores the construction of AMR as a problem, following three lines of analysis. First, an examination of some of the ways in which AMR has become an object for action—through defining, counting and projecting it. Following Lakoff’s work on emerging infectious diseases, the paper illustrates that while an ‘actuarial’ approach to AMR may be challenging to stabilise due to definitional and logistical issues, it has been successfully stabilised through a ‘sentinel’ approach that emphasises the threat of AMR. Second, the paper draws out a contrast between the way AMR is formulated in terms of a problem of connectedness—a ‘One Health’ issue—and the frequent solutions to AMR being focused on individual behaviour. The paper suggests that AMR presents an opportunity to take seriously connections, scale and systems but that this effort is undermined by the prevailing tendency to reduce health issues to matters for individual responsibility. Third, the paper takes AMR as a moment of infrastructural inversion (Bowker and Star) when antimicrobials and the work they do are rendered more visible. This leads to the proposal of antibiotics as infrastructure—part of the woodwork that we take for granted, and entangled with our ways of doing life, in particular modern life. These explorations render visible the ways social, economic and political frames continue to define AMR and how it may be acted upon, which opens up possibilities for reconfiguring AMR research and action.
150 citations
TL;DR: In this paper, the authors discuss evidence that vaccines can have a major role in fighting antimicrobial resistance (AMR), and describe the current state of development of vaccines against resistant bacterial pathogens that cause a substantial disease burden both in high-income countries and in low- and medium income countries, discuss possible obstacles that hinder progress in vaccine development and speculate on the impact of next-generation vaccines against bacterial infectious diseases on AMR.
Abstract: The use of antibiotics has enabled the successful treatment of bacterial infections, saving the lives and improving the health of many patients worldwide. However, the emergence and spread of antimicrobial resistance (AMR) has been highlighted as a global threat by different health organizations, and pathogens resistant to antimicrobials cause substantial morbidity and death. As resistance to multiple drugs increases, novel and effective therapies as well as prevention strategies are needed. In this Review, we discuss evidence that vaccines can have a major role in fighting AMR. Vaccines are used prophylactically, decreasing the number of infectious disease cases, and thus antibiotic use and the emergence and spread of AMR. We also describe the current state of development of vaccines against resistant bacterial pathogens that cause a substantial disease burden both in high-income countries and in low- and medium-income countries, discuss possible obstacles that hinder progress in vaccine development and speculate on the impact of next-generation vaccines against bacterial infectious diseases on AMR.
146 citations
References
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TL;DR: 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.
1,697 citations
"Action and resistance mechanisms of..." refers background in this paper
...AG’s bind to the 30S ribosomal subunit,[13] whereas chloramphenicol, macrolides, lincosamides, and streptogramin B bind to the 50S ribosomal subunit to suppress protein synthesis[14] b....
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TL;DR: They were initially reported in the second half of the 1980s, and their rate of dissemination among bacteria and in most parts of the world has increased dramatically since 1995, with the CTX-M β-lactamases being the most widespread enzymes.
Abstract: The production of β-lactamases is the predominant cause of resistance to β-lactam antibiotics in gram-negative bacteria. These enzymes cleave the amide bond in the β-lactam ring, rendering β-lactam antibiotics harmless to bacteria. They are classified according to the scheme of Ambler et al. (2) into four classes, designated classes A to D, on the basis of their amino acid sequences, with classes A and C being the most frequently occurring among bacteria. Oxyimino-cephalosporins such as cefotaxime and ceftazidime, which are inherently less susceptible to β-lactamases, were introduced in the early 1980s to treat infections caused by gram-negative bacilli that were resistant to established β-lactams and that produced class A, C, and D β-lactamases. Their repetitive and increased use induced the appearance of resistant strains, which overproduced class C enzymes (42, 72) and/or which produced extended-spectrum β-lactamases (ESBLs), mainly those of class A but also those of class D (19, 61).
Class A ESBLs hydrolyze oxyimino-cephalosporins and aztreonam but not 7-α-substituted β-lactams. They are generally susceptible to β-lactamase inhibitors (clavulanate, sulbactam, tazobactam). According to the functional classification scheme of Bush et al. (23), class A ESBLs are therefore clustered in group 2be, which can be subdivided on the basis of their activities against ceftazidime and cefotaxime as ceftazidimases (higher levels of hydrolytic activity against ceftazidime than against cefotaxime) and cefotaximases (higher levels of hydrolytic activity against cefotaxime than against ceftazidime), respectively (48).
However, class A ESBLs form a heterogeneous molecular cluster comprising β-lactamases sharing 20 to >99% identity. The earliest class A ESBLs, which were reported from 1985 to 1987, differed from widespread plasmid-mediated TEM-1/2 and SHV-1 penicillinases by one to four point mutations, which extend their hydrolytic spectra (51, 90, 91). TEM and SVH ESBLs now comprise at least 130 members and have a worldwide distribution. Most of them are ceftazidimases, and only a few are cefotaximases.
More recently, non-TEM and non-SHV plasmid-mediated class A ESBLs have been reported: ceftazidimases of the PER, VEB, TLA-1, and GES/IBC types and cefotaximases of the SFO-1, BES-1, and CTX-M types (8, 12, 13, 16, 31, 58, 62, 75, 76, 79, 81, 88, 96). The CTX-M β-lactamases are the most widespread enzymes. They were initially reported in the second half of the 1980s, and their rate of dissemination among bacteria and in most parts of the world has increased dramatically since 1995. This review focuses on the origin, epidemiology, clinical impact, enzymatic properties, and structural relationships of the CTX-M-type ESBLs.
1,547 citations
Additional excerpts
..., clavulanic acid, sulbactam, or tazobactam[21-23] b....
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TL;DR: The intrinsic mechanisms not commonly specified by mobile elements, such as efflux pumps that expel multiple kinds of antibiotics, are now recognized as major contributors to multidrug resistance in bacteria.
1,446 citations
"Action and resistance mechanisms of..." refers background in this paper
...β-lactamases are broadly prevalent enzymes that are classified using two main classification systems: Ambler (structural) and Bush–Jacoby–Medeiros (functional).[15] Ambler classification system is described below: a....
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...aureus that contains resistance gene mec A.[4,15,16] mec A gene encodes PBP2a protein, a new penicillin-binding protein, that is required to change a native staphylococcal PBP....
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TL;DR: In this article, the authors describe how Staphylococcus aureus can acquire resistance against all classes of antibiotics by mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium.
1,099 citations
TL;DR: Recent epidemiological data imply that MRSA has embarked on another evolutionary path as a community pathogen, as at least one novel SCCmec element seems to have been successful in converting S. aureus strains from the normal human flora into MRSA.
850 citations
"Action and resistance mechanisms of..." refers background in this paper
...aureus that contains resistance gene mec A.[4,15,16] mec A gene encodes PBP2a protein, a new penicillin-binding protein, that is required to change a native staphylococcal PBP....
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