ANTIMICROBIAL RESISTANCE: REVIEW

Antimicrobial resistance (AMR) is resistance of a microorganism to an antimicrobial that was originally effective for treatment of infections caused by it. Increasing clinical incidence of antimicrobial resistance is a major global health care issue and the situation is perhaps aggravated in developing countries. Although, AMR is a major health care issue, there is a shortage of documented information on it. Therefore, the aim of this paper is to review the causes or risk factors, problems, mechanisms and control of antimicrobial resistance. The resistance problem can be seen simplistically as an equation with two main components: the antibiotic or antimicrobial drug, which inhibits susceptible organisms and selects the resistant ones; and the genetic resistance determinant in microorganisms selected by the antimicrobial drug. Antimicrobial resistance is associated with high mortality rates and high medical costs and has a significant impact on the effectiveness of antimicrobial agents. To appreciate the mechanisms of antimicrobial resistance, it is important to understand how antimicrobial agents act. The resistance mechanisms therefore depend on which specific pathways are inhibited by the drugs and the alternative ways available for those pathways that the organisms can modify to get a way around in order to survive. A comprehensive strategy is necessary to address the challenges that accompany the rising threat of antimicrobial resistance. Special vigilance must now be paid to appropriate selection and timing of antimicrobial agents as a major force in reducing the development of antimicrobial resistance. Prevention and control of these infections will require new antimicrobial agents, prudent use of existing agents, new vaccines, and enhanced public health efforts to reduce transmission.

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Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

BioMed Research International ◽

10.1155/2016/2475067 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 324

Author(s):

Sirijan Santajit ◽

Nitaya Indrawattana

Keyword(s):

Public Health ◽

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Global Public Health ◽

Drug Usage ◽

Inappropriate Use ◽

Public Health Challenges ◽

Eskape Pathogens

The ESKAPE pathogens (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.

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Antibiotic Resistance Surveillance and Control in the Mediterranean Region: report of the ARMed Consensus Conference

The Journal of Infection in Developing Countries ◽

10.3855/jidc.210 ◽

2009 ◽

Vol 3 (09) ◽

pp. 654-659 ◽

Cited By ~ 5

Author(s):

Michael A. Borg ◽

Barry D. Cookson ◽

Peter Zarb ◽

Elizabeth A. Scicluna ◽

ARMed Steering Group & Collaborators *

Keyword(s):

Health Care ◽

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Mediterranean Region ◽

Care Delivery ◽

Eastern Mediterranean ◽

Eastern Mediterranean Region ◽

Consensus Conference ◽

The Mediterranean ◽

And Control

Antimicrobial resistance has become a global threat to effective health care delivery. This is particularly the case within the Mediterranean region, where data from recent studies suggests the situation to be particularly acute. A better knowledge base, as well as a collaborative effort, is therefore required to address this ever increasing challenge to effective patient care. Over its four-year period, the Antibiotic Resistance Surveillance and Control in the Mediterranean Region (ARMed) project investigated the epidemiology of antimicrobial resistance, as well as its contributory factors, in a number of countries in the southern and eastern Mediterranean region through the collection of comparable and validated data. The project culminated in a consensus conference held in Malta in November 2006. The conference provided a forum for expert delegates to agree on a number of priority strategic recommendations that would be relevant to resistance containment efforts in the region. There was general agreement on the need for surveillance and audit to underpin any intervention to tackle antimicrobial resistance, both to monitor changing epidemiological trends in critical pathogens as well as to identify antibiotic consumption practices and effectiveness of prevention and control of health care associated infections. In addition, the importance to convey these data to key users was also stressed in all workshops, as was better education and training of health care workers. The recommendations also made it clear that ownership of the problem needs to be improved throughout the region and that resources, both financial as well as human, must be allocated by the respective policy makers in order to combat it.

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Antimicrobial Resistance and Association with Class 1 Integrons in Escherichia coli Isolated from Turkey Meat Products

Journal of Food Protection ◽

10.4315/0362-028x-71.8.1679 ◽

2008 ◽

Vol 71 (8) ◽

pp. 1679-1684 ◽

Cited By ~ 5

Author(s):

M. L. KHAITSA ◽

J. OLOYA ◽

D. DOETKOTT ◽

R. KEGODE

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Population Attributable Fraction ◽

Meat Products ◽

Resistance Mechanisms ◽

E Coli ◽

Class 1 Integrons ◽

Turkey Meat ◽

Class 1

The objective of this study was to quantify the role of class 1 integrons in antimicrobial resistance in Escherichia coli isolated from turkey meat products purchased from retail outlets in the Midwestern United States. Of 242 E. coli isolates, 41.3% (102 of 242) tested positive for class 1 integrons. A significant association was shown between presence of class 1 integrons in E. coli isolates and the resistance to tetracycline, ampicillin, streptomycin, gentamicin, sulfisoxazole, and trimethoprim-sulfamethoxazole. Attributable risk analysis revealed that for every 100 E. coli isolates carrying class 1 integrons, resistance was demonstrated for ampicillin (22%), gentamycin (48%), streptomycin (29%), sulfisoxazole (40%), trimethoprimsulfamethoxazole (7%), and tetracycline (26%). Non–integron-related antimicrobial resistance was demonstrated for ampicillin (65%), gentamycin (16.9%), streptomycin (42.1%), sulfisoxazole (35.8%), and tetracycline (49.7%). Population-attributable fraction analysis showed that class 1 integrons accounted for the following resistances: gentamycin, 71% (50 of 71), amoxicillin–clavulanic acid, 19.6% (6 of 33), nalidixic acid, 34% (7 of 21), streptomycin, 28% (30 of 107), sulfisoxazole, 38% (40 of 106), and tetracycline, 14%, (26 of 185). In conclusion, although class 1 integrons have been implicated in resistance to antimicrobial agents, other non–integron resistance mechanisms seem to play an important part.

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Struggle To Survive: the Choir of Target Alteration, Hydrolyzing Enzyme, and Plasmid Expression as a Novel Aztreonam-Avibactam Resistance Mechanism

mSystems ◽

10.1128/msystems.00821-20 ◽

2020 ◽

Vol 5 (6) ◽

Author(s):

Ke Ma ◽

Yu Feng ◽

Alan McNally ◽

Zhiyong Zong

Keyword(s):

Antimicrobial Resistance ◽

Antisense Rna ◽

Antimicrobial Agents ◽

Binding Protein ◽

Resistance Mechanism ◽

Resistance Mechanisms ◽

Penicillin Binding Protein ◽

Plasmid Copy ◽

Copy Numbers

ABSTRACT Aztreonam-avibactam is a promising antimicrobial combination against multidrug-resistant organisms, such as carbapenemase-producing Enterobacterales. Resistance to aztreonam-avibactam has been found, but the resistance mechanism remains poorly studied. We recovered three Escherichia coli isolates of an almost identical genome but exhibiting varied aztreonam-avibactam resistance. The isolates carried a cephalosporinase gene, blaCMY-42, on IncIγ plasmids with a single-nucleotide variation in an antisense RNA-encoding gene, inc, of the replicon. The isolates also had four extra amino acids (YRIK) in penicillin-binding protein 3 (PBP3) due to a duplication of a 12-nucleotide (TATCGAATTAAC) stretch in pbp3. By cloning and plasmid-curing experiments, we found that elevated CMY-42 cephalosporinase production or amino acid insertions in PBP3 alone mediated slightly reduced susceptibility to aztreonam-avibactam, but their combination conferred aztreonam-avibactam resistance. We show that the elevated CMY-42 production results from increased plasmid copy numbers due to mutations in inc. We also verified the findings using in vitro mutation assays, in which aztreonam-avibactam-resistant mutants also had mutations in inc and elevated CMY-42 production compared with the parental strain. This choir of target modification, hydrolyzing enzyme, and plasmid expression represents a novel, coordinated, complex antimicrobial resistance mechanism and also reflects the struggle of bacteria to survive under selection pressure imposed by antimicrobial agents. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) is a serious global challenge with limited therapeutic options. Aztreonam-avibactam is a promising antimicrobial combination with activity against CPE producing serine-based carbapenemases and metallo-β-lactamases and has the potential to be a major option for combatting CPE. Aztreonam-avibactam resistance has been found, but resistance mechanisms remain largely unknown. Understanding resistance mechanisms is essential for optimizing treatment and developing alternative therapies. Here, we found that either penicillin-binding protein 3 modification or the elevated expression of cephalosporinase CMY-42 due to increased plasmid copy numbers does not confer resistance to aztreonam-avibactam, but their combination does. We demonstrate that increased plasmid copy numbers result from mutations in antisense RNA-encoding inc of the IncIγ replicon. The findings reveal that antimicrobial resistance may be due to concerted combinatorial effects of target alteration, hydrolyzing enzyme, and plasmid expression and also highlight that resistance to any antimicrobial combination will inevitably emerge.

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Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition

Antibiotics ◽

10.3390/antibiotics10121502 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1502

Author(s):

Abolfazl Dashtbani-Roozbehani ◽

Melissa H. Brown

Keyword(s):

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Efflux Pump ◽

Current Knowledge ◽

Efflux Pumps ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Multidrug Efflux Pump ◽

New Antibiotics ◽

Efflux Pump Inhibitors

The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with increased use of sanitisers and disinfectants due to the ongoing COVID-19 pandemic can further aggravate the problem of antimicrobial resistance. Staphylococci utilise multiple mechanisms to circumvent the effects of antimicrobials. One of these resistance mechanisms is the export of antimicrobial agents through the activity of membrane-embedded multidrug efflux pump proteins. The use of efflux pump inhibitors in combination with currently approved antimicrobials is a promising strategy to potentiate their clinical efficacy against resistant strains of staphylococci, and simultaneously reduce the selection of resistant mutants. This review presents an overview of the current knowledge of staphylococcal efflux pumps, discusses their clinical impact, and summarises compounds found in the last decade from plant and synthetic origin that have the potential to be used as adjuvants to antibiotic therapy against multidrug resistant staphylococci. Critically, future high-resolution structures of staphylococcal efflux pumps could aid in design and development of safer, more target-specific and highly potent efflux pump inhibitors to progress into clinical use.

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Molecular Characteristics and Antimicrobial Susceptibility Profile of Pseudomonas aeruginosa isolated from patients attending Healthcare Facilities in Mthatha, South Africa

10.21203/rs.3.rs-16668/v1 ◽

2020 ◽

Author(s):

Mojisola C. Hosu ◽

Sandeep D. Vasaikar ◽

Grace E. Okuthe ◽

teke apalata

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Resistance Mechanisms ◽

High Rate ◽

Infection Prevention And Control ◽

Molecular Characteristics ◽

Mortality And Morbidity ◽

Resistance Patterns

Abstract Background: Pseudomonas aeruginosa is a common pathogen causing healthcare-associated infections most especially in critically ill and immunocompromised patients. This pathogen poses a public health threat due to its innate resistance to many antimicrobial agents and its ability to acquire new resistance mechanisms under pressure. Infections with Extended spectrum β-lactamases (ESBL)‑producing isolates result into outbreaks that lead to serious antibiotic management concerns with higher mortality and morbidity and significant economic causatives. In this study, we evaluated the antimicrobial resistance patterns and characterized genetically the ESBLs and Metallo- β-lactamases (MBL) produced by this pathogen. Methods: Isolates of P. aeruginosa cultured from patients who attended Nelson Mandela Academic Hospital and other clinics in the four district municipalities of the Eastern Cape between August 2017 and May 2019 were identified; and their antibiotic resistance patterns were tested against amikacin, aztreonam, cefepime, ceftazidime, ciprofloxacin, doripenem, gentamicin, imipenem, levofloxacin, meropenem, piperacillin, piperacillin/tazobactam and tobramycin using the bioMérieux VITEK® 2 and confirmed by Beckman autoSCAN-4 System. Real-time PCR was done using Roche Light Cycler 2.0 to detect the presence of ESBLs; blaSHV, blaTEM and blaCTX-M genes; and MBLs; blaIMP, blaVIM. Results: High antibiotic resistance in decreasing order was observed in piperacillin (64.2%), aztreonam (57.8%), cefepime (51.5%), ceftazidime (51.0%), piperacillin/tazobactam (50.5%), and imipenem (46.6%). A total of 75 (36.8%) multidrug resistant (MDR) isolates were observed of the total pool of isolates. The blaTEM, blaSHV and blaCTX-M was detected in 79.3%, 69.5% and 31.7% isolates (n=82), respectively. The blaIMP was detected in 1.25% while no blaVIM was detected in any of the isolates tested. Conclusions: The study showed a high rate of MDR P. aeruginosa in our setting. The vast majority of these resistant isolates carried blaTEM and blaSHV genes. Continuous monitoring of antimicrobial resistance and strict compliance towards infection prevention and control practices are the best defence against spread of MDR P. aeruginosa.

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Novel Strategiesto Combat the Emerging Drug Resistance in Human Pathogenic Microbes

Current Drug Targets ◽

10.2174/1389450121666201228123212 ◽

2020 ◽

Vol 21 ◽

Author(s):

Hafsa Qadri ◽

Abdul Haseeb ◽

Manzoor Mir

Keyword(s):

Drug Resistance ◽

Combination Therapy ◽

Antimicrobial Agents ◽

Resistance Mechanisms ◽

Antimicrobial Drug ◽

The Novel ◽

Host Defenses ◽

Bacteriophage Therapy ◽

Antimicrobial Drug Resistance ◽

Pathogenic Microbes

: The major health-care burden for the developing world are the Infectious diseases and antimicrobial agents prove to be the magical drugs to combat this. But the phenomenon of antimicrobial resistance (AMR) represents a global challenging issue, which requires to be addressed effectively. The antimicrobial treatment for the emerging multidrug-resistant bacterial (e.g. TB, Cholera) and fungal (e.g. Candidiasis) infections is very limited and there are multiple causes and reasons responsible for the evolution of such resistance. Considering the critical issues of increasing AMR, there is an urgent requirement of identification, development, validation, and progression of novel strategies and approaches that can easily be utilized for overcoming this serious issue. Immunotherapy represents a significant way to improve host defenses and combat the issue of antimicrobial drug resistance. Similarly, drug combination therapy represents another promising approach for reducing the evolution of resistance and enhancing the longevity of the antimicrobial agents. Bacteriophage therapy also acts as a novel therapeutic option to control the development of the multidrug resistance (MDR) phenomenon. Besides, CRISPR, an innovative genome editing technology offers multiple applications to safeguard host defenses to overcome different resistance challenges. The novel approaches/strategies like combination therapy, bacteriophage therapy, immunotherapy, and CRISPR/Cas discussed here presents an overview of some of the novel strategies/approaches to be adopted against the pathogenic microbes/microbial invasions along with advanced knowledge of different drug resistance mechanisms adopted by the microbial pathogens to gain resistance against different antimicrobial agents. Therefore, understanding the novel control plans/approaches and different drug resistance mechanisms will help achieve the goals of the successful development of potential antimicrobial drugs and their respective targets and eventually help curtail the problem of increasing antimicrobial drug resistance menace in various human pathogenic microbes.

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Relationship between the severity of acne vulgaris and antimicrobial resistance of bacteria isolated from acne lesions in a hospital in Japan

Journal of Medical Microbiology ◽

10.1099/jmm.0.067611-0 ◽

2014 ◽

Vol 63 (5) ◽

pp. 721-728 ◽

Cited By ~ 41

Author(s):

Keisuke Nakase ◽

Hidemasa Nakaminami ◽

Yuko Takenaka ◽

Nobukazu Hayashi ◽

Makoto Kawashima ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Acne Vulgaris ◽

Normal Skin ◽

Resistance Mechanisms ◽

University Hospital ◽

23S Rrna ◽

Rrna Gene ◽

Severe Acne ◽

23S Rrna Gene

Propionibacterium acnes and Staphylococcus epidermidis are normal skin inhabitants that are frequently isolated from lesions caused by acne, and these micro-organisms are considered to contribute to the inflammation of acne. In the present study, we examined the antimicrobial susceptibilities and resistance mechanisms of P. acnes and S. epidermidis isolated from patients with acne vulgaris in a university hospital in Japan from 2009 to 2010. Additionally, we analysed the relationship between the antimicrobial resistance of P. acnes and the severity of acne vulgaris. Some P. acnes strains (18.8 %; 13/69) were resistant to clindamycin. All strains had a mutation in the 23S rRNA gene, except for one strain that expressed erm(X) encoding a 23S rRNA methylase. Tetracycline-resistant P. acnes strains were found to represent 4.3 % (3/69) of the strains, and this resistance was caused by a mutation in the 16S rRNA gene. Furthermore, three strains with reduced susceptibility to nadifloxacin (MIC = 16 µg ml−1) were detected. When analysing the correlation between the antimicrobial resistance of P. acnes and S. epidermidis, more than 80 % of the patients who carried clindamycin-resistant P. acnes also carried clindamycin-resistant S. epidermidis. However, no epidemic strain that exhibited antimicrobial resistance was detected in the P. acnes strains when analysed by PFGE. Therefore, our results suggest that the antimicrobial resistance of P. acnes is closely related to antimicrobial therapy. Additionally, those P. acnes strains tended to be frequently found in severe acne patients rather than in mild acne patients. Consequently, the data support a relationship between using antimicrobial agents and the emergence of antimicrobial resistance.

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An overview of antimicrobial resistance surveillance among healthcare-associated pathogens in South Africa

African Journal of Laboratory Medicine ◽

10.4102/ajlm.v7i2.741 ◽

2018 ◽

Vol 7 (2) ◽

Cited By ~ 2

Author(s):

Ashika Singh-Moodley ◽

Husna Ismail ◽

Olga Perovic

Keyword(s):

Antimicrobial Resistance ◽

Treatment Guidelines ◽

Resistance Mechanisms ◽

Health Concern ◽

Infection Prevention And Control ◽

Surveillance Systems ◽

African Countries ◽

Lack Of Information ◽

Healthcare Associated ◽

And Control

Healthcare-associated infections are a serious public health concern resulting in morbidity and mortality particularly in developing countries. The lack of information from Africa, the increasing rates of antimicrobial resistance and the emergence of new resistance mechanisms intensifies this concern warranting the need for vigorous standardised surveillance platforms that produce reliable and accurate data which can be used for addressing these concerns. The implementation of national treatment guidelines, policies, antimicrobial stewardship programmes and infection prevention and control practices within healthcare institutions require a platform from which it can draw information and direct its approach. In this review, the importance of standardised surveillance systems, the challenges faced in the application of a surveillance system and the condition (existence and nonexistence) of such systems in African countries is discussed. This review also reports on some South African data.

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Antibiotic Cycling and Marketing Into the 21st Century: A Perspective From the Pharmaceutical Industry

Infection Control and Hospital Epidemiology ◽

10.1086/503171 ◽

2000 ◽

Vol 21 (S1) ◽

pp. S32-S35 ◽

Cited By ~ 13

Author(s):

Bruce S. Lavin

Keyword(s):

Antimicrobial Resistance ◽

Pharmaceutical Industry ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Resistance Mechanisms ◽

Medical Community ◽

Resistant Bacteria ◽

Environmental Pressures ◽

Development Of Resistance ◽

Antibiotic Cycling

AbstractBefore the development of the first antimicrobial agents, bacteria already had demonstrated an ability to adapt to stress in the environment, resulting in the development of resistance that often makes the prevailing antibiotic treatment ineffective. The response to antimicrobial resistance in the medical community has been to use new or alternative antibiotics not previously used against the resistant bacteria. The pharmaceutical industry has responded to the resistance problem by producing newer antibiotics, either as modifications of currently existing compounds or as combinations of compounds that may inhibit or bypass the bacterial resistance mechanisms. The development of new antibiotics is a lengthy and costly process. To be successful, the pharmaceutical industry must anticipate the changing needs of the medical community, as well as the dynamic process of antimicrobial resistance. The marketing of new antimicrobial agents must be adaptable to the potential environmental pressures that induce bacterial resistance in order to ensure the longevity of the agents.

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