scholarly journals Exceptions to the rule: Why does resistance evolution not undermine antibiotic therapy in all bacterial infections?

2021 ◽  
Author(s):  
Amrita Bhattacharya ◽  
Anton Aluquin ◽  
David A Kennedy

Antibiotic resistance poses one of the greatest public health challenges of the 21st century. Yet not all pathogens are equally affected by resistance evolution. Why? Here we examine what underlies variation in antibiotic resistance across human bacterial pathogens and the drugs used to treat them. We document the observed prevalence of antibiotic resistance for ′pathogen x drug′ combinations across 57 different human bacterial pathogens and 53 antibiotics from 15 drug classes used to treat them. Using AIC-based model selection we analyze 14 different traits of bacteria and antibiotics that are believed to be important in resistance evolution. Using these data, we identify the traits that best explain observed variation in resistance evolution. Our results show that nosocomial pathogens and indirectly transmitted pathogens are significantly associated with increased prevalence of resistance whereas zoonotic pathogens, specifically those with wild animal reservoirs, are associated with reduced prevalence of resistance. We found partial support for associations between drug resistance and gram classification, human microbiome reservoirs, horizontal gene transfer, and documented human-to human transfer. Global drug use, time since drug discovery, mechanism of drug action, and environmental reservoirs did not emerge as statistically robust predictors of drug resistance in our analyses. To the best of our knowledge this work is the first systematic analysis of resistance across such a wide range of human bacterial pathogens, encompassing the vast majority of common bacterial pathogens. Insights from our study may help guide public health policies and future studies on resistance control.

1968 ◽  
Vol 6 (13) ◽  
pp. 49-51

Treatment with a single drug is appropriate for most bacterial infections. A combination of antimicrobial drugs is indicated only in a limited number of circumstances, of which the most clearly defined is the prevention of drug resistance, as in the therapy of tuberculosis. It may be necessary to use antibiotic combinations in mixed infections, or as a temporary measure in the treatment of severe infections before bacteriological findings are available; for example, in severe neonatal infections in which a wide range of potentailly pathogenic organisms have to be considered.


Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 688
Author(s):  
Shashi B. Kumar ◽  
Shanvanth R. Arnipalli ◽  
Ouliana Ziouzenkova

Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.


2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
C You ◽  
V Lissillour ◽  
A Lefébure

Abstract Background The increase of life expectancy creates critical health needs that developed countries health systems have to deal with. They are also confronted to persistent health inequalities. A common vision of these issues may not be shared by the health care professionals, decision-makers and citizens. In the context of the launch of new public health laws in France, the French School of Public Health (EHESP) decided to offer a MOOC entitled “Public Health and Health System: transition and transformation” (2019). Objectives The MOOC intends to raise awareness and increase understanding of public health challenges. It is designed for a wide audience of professionals, decision-makers and citizens in the French speaking world. The content was designed by a multidisciplinary team of academics from the EHESP (N = 50) and a network of health professionals (N = 21). The 6 modules address major themes of the recent health policies, e.g. social and territorial inequalities in health, health care security, health pathways, innovation or health democracy. Results Over the course of 6 consecutive weeks, almost 7800 people have enrolled in this e-learning. They are provided with short teaching videos (109 capsules of 4-5’) and webinars, have access to a number of supplementary reading material and a variety of self-assessment. Active learning is enhanced via forum involving peers and teaching staff. The full course represents around 20 hours of teaching. So far, completion rate has attained 13% which compares well with usual rate for MOOCs. Participants include a wide range of professionals, students and citizens from 87 different countries (72% from France) and 50% had a master or higher degree. The overall satisfaction rate is 98%. Conclusions This MOOC attracted the attention of a wide and diverse audience regarding the major public health issues. Some public health agencies have expressed interest in implementing the MOOC into their professional development program of their staff. Key messages Health system reforms are constantly implemented to face new public health challenges. A multidisciplinary MOOC can help raise awareness and understanding of the issue being addressed by new policies.


2009 ◽  
Vol 78 (2) ◽  
pp. 563-566 ◽  
Author(s):  
Ferric C. Fang ◽  
Arturo Casadevall

ABSTRACT The concept of translational research, which aims to facilitate the application of basic scientific discoveries in clinical and community settings, is currently in vogue. While there are powerful forces driving this trend, support for translational research must be accompanied by a robust investment in basic science, which provides the essential raw material for translation and continues to represent humanity's best hope to meet a wide range of public health challenges.


2018 ◽  
Author(s):  
Alita R. Burmeister ◽  
Rose G. Bender ◽  
Abigail Fortier ◽  
Adam J. Lessing ◽  
Benjamin K. Chan ◽  
...  

AbstractBacterial pathogens are increasingly evolving drug resistance under natural selection from antibiotics in medicine, agriculture, and nature. Meanwhile, bacteria ubiquitously encounter bacteriophages and can rapidly evolve phage resistance. However, the role of phages in interacting with drug-resistant and drug-sensitive bacteria remains unclear. To gain insight into such relationships, we screened for and characterized phages that rely on the multi-drug efflux pump genetolC. First, we screened a collection of 33 environmental and commercialEscherichia coliphages for their ability to infect cells that lackedtolC. Our screen revealed two phages that had reduced efficiency of plating (EOP) on thetolCknockout compared to wild type. We further characterized these phages with bacterial growth curves, transmission electron microscopy, and analysis of phage-resistant mutants. Phage U136B is a curly-tailed virus in familySiphoviridaewith no ability to infect atolCknockout, suggesting TolC is the U136B receptor. Phage 132 is a contractile-tailed virus in familyMyoviridaewith reduced EOP on cells lackingompFand its positive regulatorstolCandompR. U136B and 132 differentially effect bacterial growth and lysis, and U136B-resistant mutants contain mutations of thetolCgene. Together, these results show that thetolCgene involved in drug resistance can modify bacteria-phage interactions in multiple ways, altering bacterial lysis and selection. These new phages offer utility for studying evolution, tradeoffs, and infection mechanisms.ImportanceBacteria face strong selection by antibiotics in medicine and agriculture, resulting in increasing levels of drug resistance among bacterial pathogens. Slowing this process will require an understanding of the environmental contexts in which drug resistance evolutionarily increases or decreases. In this study, we investigate two newly-isolated bacteriophages that rely on a bacterial antibiotic resistance gene. These bacteriophages vary in their interactions with drug-resistant bacteria, with one of the phages selecting for phage-resistant mutants that have mutations in the antibiotic resistance gene. Further study of these new phages will be useful to understanding evolutionary tradeoffs and how phages might be applied in natural settings to reverse the problem of drug resistance.


2021 ◽  
Vol 11 (4) ◽  
pp. 197-214
Author(s):  
Mousumi Saha ◽  
Agniswar Sarkar

With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.


mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Richard C. Allen ◽  
Katia R. Pfrunder-Cardozo ◽  
Dominik Meinel ◽  
Adrian Egli ◽  
Alex R. Hall

ABSTRACT The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approaches rely on or are impacted by associations among resistance phenotypes (where bacteria resistant to one antibacterial agent are also relatively susceptible or resistant to others). Experiments with laboratory strains have shown strong associations between some resistance phenotypes, but we lack a quantitative understanding of associations among antibiotic and phage resistance phenotypes in natural and clinical populations. To address this, we measured resistance to various antibiotics and bacteriophages for 94 natural and clinical Escherichia coli isolates. We found several positive associations between resistance phenotypes across isolates. Associations were on average stronger for antibacterial agents of the same type (antibiotic-antibiotic or phage-phage) than different types (antibiotic-phage). Plasmid profiles and genetic knockouts suggested that such associations can result from both colocalization of resistance genes and pleiotropic effects of individual resistance mechanisms, including one case of antibiotic-phage cross-resistance. Antibiotic resistance was predicted by core genome phylogeny and plasmid profile, but phage resistance was predicted only by core genome phylogeny. Finally, we used observed associations to predict genes involved in a previously uncharacterized phage resistance mechanism, which we verified using experimental evolution. Our data suggest that susceptibility to phages and antibiotics are evolving largely independently, and unlike in experiments with lab strains, negative associations between antibiotic resistance phenotypes in nature are rare. This is relevant for treatment scenarios where bacteria encounter multiple antibacterial agents. IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages. IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sophaphan Intahphuak ◽  
Tawatchai Apidechkul ◽  
Patita Kuipiaphum

Abstract Background Antibiotic resistance is often reported and great concerned as one of public health problems especially people living with poverty in developing countries including Thailand. The hill tribe people is defined as vulnerable population for antibiotic resistance in Thailand due to poor economic and education status particularly the Lahu people who is the second greatest group of the hill tribe people in Thailand. The study aimed to estimate the prevalence, factors associated with, and typing major species of bacteria with antibiotic drugs resistance among the Lahu hill tribe people in northern Thailand. Methods A cross-sectional study was conducted to gather the information from the participants. A validated questionnaire was used for data collection. Participants who presented an illness related to infectious diseases were eligible to participate the study and were asked to obtain specific specimen; sputum, urine or stool. Antibiotic susceptibility was tested by Kirbey Bauer’s disc diffusion test. Chi-square and logistic regression were used to detect the associations between variables at the significant level of α = 0.05. Results A total of 240 participants were recruited into the study. The majority had urinary tract infection (67.9%) with two major pathogenic species of the infection; Escherichia coli (12.8%), and Enterobacter cloacae (8.0%). The prevalence of antibiotic resistance was 16.0%. Escherichia coli and Klebsiella pneumoniae species were found to have multidrug resistance that was greater than that of other species, while ampicillin was found to have the greatest drug resistance. It was found that those who had poor knowledge of antibiotic use had a 2.56-fold greater chance (95% CI = 1.09–5.32) of having antibiotic resistance than did those who had good knowledge of antibiotic use, and those who had poor antibiotic use behaviors had a 1.79-fold greater chance (95% CI = 1.06–4.80) of having antibiotic resistance than did those who had good antibiotic use behaviors. Conclusion Effective public health interventions are urgently needed to reduce antibiotic drug resistance among the Lahu people by improving their knowledge and skills regarding the proper use of antibiotics and eventually minimizing antibiotic resistance. Moreover, health care professionals should strictly follow the standard guideline to prescribe antibiotics.


2020 ◽  
Author(s):  
SOPHAPHAN INTAHPHUAK ◽  
TAWATCHAI APIDECHKUL ◽  
PATITA KUIPIAPHUM

Abstract Background Antibiotic resistance is often reported and is of major concern as a public health problem. The hill tribe people in Thailand are considered populations vulnerable to antibiotic resistance due to their poor economic and educational status. The study aimed to estimate the prevalence of, the factors associated with, and the major species of bacteria involved in antibiotic drug resistance among the Lahu hill tribe people in northern Thailand. Methods A cross-sectional study was conducted to gather information from participants between March and September 2019. A validated questionnaire was used for data collection. Participants who presented an illness related to infectious diseases were eligible to participate in the study and were asked to obtain specific specimens. Antibiotic susceptibility was tested by the Kirbey-Bauer disk diffusion test. Chi-square tests and logistic regression were used to detect the associations between variables at the significance level of α = 0.05. Results A total of 240 participants were recruited into the study; 70.4% were females, 25.4% were aged 30–40 years. More than half worked in the agricultural sector (55.4%) and had an education level of less than primary school (45.8%). The majority had urinary tract infections (67.9%) with two major pathogenic species of the infection: Escherichia coli (12.8%) and Enterobacter cloacae (8.0%). The prevalence of antibiotic resistance was 16.0%. Escherichia coli and Klebsiella pneumoniae species were found to have multidrug resistance that was greater than that of other species, while ampicillin was found to have the greatest drug resistance. In the multivariate model, it was found that those who had poor knowledge of antibiotic use had a 2.56-fold greater chance (95% CI = 1.09–5.32) of having antibiotic resistance than did those who had good knowledge of antibiotic use, and those who had poor antibiotic use behaviors had a 1.79-fold greater chance (95% CI = 1.06–4.80) of having antibiotic resistance than did those who had good antibiotic use behaviors. Conclusion Effective public health interventions are urgently needed to reduce antibiotic drug resistance among the Lahu people by improving their knowledge and skills regarding the proper use of antibiotics and eventually minimizing antibiotic resistance.


2021 ◽  
Vol 14 (2) ◽  
pp. 087-097
Author(s):  
Shifa Begum ◽  
Tofa Begum ◽  
Naziza Rahman ◽  
Ruhul A. Khan

Antibiotics are widely used most effective medication since the twentieth century against bacterial infections (Tetanus, Strep Throat, Urinary Tract Infections, etc.) and thus save one’s life. Before 20th-century infectious disease played the main role in the death. Thus, antibiotics opened a revolutionary era in the field of medication. These cannot fight against viral infections. Antibiotics are also known as an antibacterial that kill or slow down bacterial growth and prohibit the bacteria to harm. Resistance comes as a curse with antibiotics that occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals or other agents designed to cure or prevent infections. It is now a significant threat to public health that is affecting humans worldwide outside the environment of the hospital. When a bacterium once become resistant to antibiotic then the bacterial infections cannot be cured with that antibiotic. Thus, the emergence of antibiotic-resistance among the most important bacterial pathogens causing more harm. In this context, the classification of antibiotics, mode of action of antibiotics, and mechanism of resistance and the process of overcoming antibiotic resistance are discussed broadly.


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