Residual antibiotics, antibiotic resistant superbugs and antibiotic resistance genes in surface water catchments: Public health impact

NASA Astrophysics Data System (ADS)

Anthony A, Adegoke; Adekunle C, Faleye; Thor A, Stenstrӧm

2018-06-01

Antibiotics are released to the surface water through different routes, like for example the wastewater treatment plants, from human and animal metabolic waste, agriculture run off, industrial antibiotic waste. The release of the antibiotics to the water catchment and/or the environments in sub-lethal concentrations for the microorganisms lead to the emergence of antibiotic resistance (AR) and selection for antibiotic resistance genes (ARGs). The bacteria utilize their quorum sensing to form biofilm within which ARGs are transferred from antibiotic resistant bacteria (ARB) to the susceptible strains, conferring resistance on them. This has contributed substantially to the growing trend of resistance from multiple antibiotic resistance to extended spectrum resistance, extreme resistance and recently to total antibiotic resistance. The antibiotics, ARB, ARGs are sometimes internalized into the crops irrigated with the surface water returning the bacteria to human in a difficult to control form. While quorum quenching strategy is being advocated during treatment of wastewater to disrupt biofilm as well as the spread of resistance, intermittent check for effectiveness of treatment of wastewater before release into receiving water bodies is hereby advocated. To achieve this, there is the need for better measurements, surveillance and follow-up and thereby the further needs to incorporate more integrative (multidisciplinary) approaches and state of the art tools, for appropriate detection and action. This presentation is to critically review the effect of antibiotic release, ARGs, ARB in water catchment on other water related applications in Southern African countries in relation to other part of the world.

A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes.

PubMed

Sharma, Virender K; Johnson, Natalie; Cizmas, Leslie; McDonald, Thomas J; Kim, Hyunook

2016-05-01

Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG) in the aquatic environment have become an emerging contaminant issue, which has implications for human and ecological health. This review begins with an introduction to the occurrence of ARB and ARG in different environmental systems such as natural environments and drinking water resources. For example, ARG or ARB with resistance to ciprofloxacin, sulfamethoxazole, trimethoprim, quinolone, vancomycin, or tetracycline (e.g., tet(A), tet(B), tet(C), tet(G), tet(O), tet(M), tet(W), sul I, and sul II) have been detected in the environment. The development of resistance may be intrinsic, may be acquired through spontaneous mutations (de novo), or may occur due to horizontal gene transfer from donor bacteria, phages, or free DNA to recipient bacteria. An overview is also provided of the current knowledge regarding inactivation of ARB and ARG, and the mechanism of the effects of different disinfection processes in water and wastewater (chlorination, UV irradiation, Fenton reaction, ozonation, and photocatalytic oxidation). The effects of constructed wetlands and nanotechnology on ARB and ARG are also summarized. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antibiotics and Resistance: Glossary

MedlinePlus

... R S T U V W X Y Z Antibacterials (see Antibacterial agents ) Antibiotics (see About bacteria and antibiotics ) Antibiotic ... antibiotic resistance? When and how to take antibiotics Antibacterial agents Bioterrorism & stockpiling antibiotics The Cost of Resistance ...

Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy

PubMed Central

Wong, Michael; Daly, Seth M.; Greenberg, David E.; Toprak, Erdal

2016-01-01

The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene’s sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities. PMID:27631336

Characterization of Antibiotic Resistance Genes from Lactobacillus Isolated from Traditional Dairy Products.

PubMed

Guo, Huiling; Pan, Lin; Li, Lina; Lu, Jie; Kwok, Laiyu; Menghe, Bilige; Zhang, Heping; Zhang, Wenyi

2017-03-01

Lactobacilli are widely used as starter cultures or probiotics in yoghurt, cheese, beer, wine, pickles, preserved food, and silage. They are generally recognized as safe (GRAS). However, recent studies have shown that some lactic acid bacteria (LAB) strains carry antibiotic resistance genes and are resistant to antibiotics. Some of them may even transfer their intrinsic antibiotic resistance genes to other LAB or pathogens via horizontal gene transfer, thus threatening human health. A total of 33 Lactobacillus strains was isolated from fermented milk collected from different areas of China. We analyzed (1) their levels of antibiotic resistance using a standardized dilution method, (2) their antibiotic resistance gene profiles by polymerase chain reaction (PCR) using gene-specific primers, and (3) the transferability of some of the detected resistance markers by a filter mating assay. All Lactobacillus strains were found to be resistant to vancomycin, but susceptible to gentamicin, linezolid, neomycin, erythromycin, and clindamycin. Their susceptibilities to tetracycline, kanamycin, ciprofloxacin, streptomycin, quinupristin/dalfopristin, trimethoprim, ampicillin, rifampicin, and chloramphenicol was different. Results from our PCR analysis revealed 19 vancomycin, 10 ciprofloxacin, and 1 tetracycline-resistant bacteria that carried the van(X), van(E), gyr(A), and tet(M) genes, respectively. Finally, no transferal of the monitored antibiotic resistance genes was observed in the filter mating assay. Taken together, our study generated the antibiotic resistance profiles of some milk-originated lactobacilli isolates and preliminarily assessed their risk of transferring antibiotic gene to other bacteria. The study may provide important data concerning the safe use of LAB. © 2017 Institute of Food Technologists®.

Diversity and antibiotic resistance patterns of Sphingomonadaceae isolates from drinking water.

PubMed

Vaz-Moreira, Ivone; Nunes, Olga C; Manaia, Célia M

2011-08-15

Sphingomonadaceae (n = 86) were isolated from a drinking water treatment plant (n = 6), tap water (n = 55), cup fillers for dental chairs (n = 21), and a water demineralization filter (n = 4). The bacterial isolates were identified based on analysis of the 16S rRNA gene sequence, and intraspecies variation was assessed on the basis of atpD gene sequence analysis. The isolates were identified as members of the genera Sphingomonas (n = 27), Sphingobium (n = 28), Novosphingobium (n = 12), Sphingopyxis (n = 7), and Blastomonas (n = 12). The patterns of susceptibility to five classes of antibiotics were analyzed and compared for the different sites of isolation and taxonomic groups. Colistin resistance was observed to be intrinsic (92%). The highest antibiotic resistance prevalence values were observed in members of the genera Sphingomonas and Sphingobium and for beta-lactams, ciprofloxacin, and cotrimoxazole. In tap water and in water from dental chairs, antibiotic resistance was more prevalent than in the other samples, mainly due to the predominance of isolates of the genera Sphingomonas and Sphingobium. These two genera presented distinct patterns of association with antibiotic resistance, suggesting different paths of resistance development. Antibiotic resistance patterns were often related to the species rather than to the site or strain, suggesting the importance of vertical resistance transmission in these bacteria. This is the first study demonstrating that members of the family Sphingomonadaceae are potential reservoirs of antibiotic resistance in drinking water.

Diversity and Antibiotic Resistance Patterns of Sphingomonadaceae Isolates from Drinking Water▿

PubMed Central

Vaz-Moreira, Ivone; Nunes, Olga C.; Manaia, Célia M.

2011-01-01

Sphingomonadaceae (n = 86) were isolated from a drinking water treatment plant (n = 6), tap water (n = 55), cup fillers for dental chairs (n = 21), and a water demineralization filter (n = 4). The bacterial isolates were identified based on analysis of the 16S rRNA gene sequence, and intraspecies variation was assessed on the basis of atpD gene sequence analysis. The isolates were identified as members of the genera Sphingomonas (n = 27), Sphingobium (n = 28), Novosphingobium (n = 12), Sphingopyxis (n = 7), and Blastomonas (n = 12). The patterns of susceptibility to five classes of antibiotics were analyzed and compared for the different sites of isolation and taxonomic groups. Colistin resistance was observed to be intrinsic (92%). The highest antibiotic resistance prevalence values were observed in members of the genera Sphingomonas and Sphingobium and for beta-lactams, ciprofloxacin, and cotrimoxazole. In tap water and in water from dental chairs, antibiotic resistance was more prevalent than in the other samples, mainly due to the predominance of isolates of the genera Sphingomonas and Sphingobium. These two genera presented distinct patterns of association with antibiotic resistance, suggesting different paths of resistance development. Antibiotic resistance patterns were often related to the species rather than to the site or strain, suggesting the importance of vertical resistance transmission in these bacteria. This is the first study demonstrating that members of the family Sphingomonadaceae are potential reservoirs of antibiotic resistance in drinking water. PMID:21705522

Targeting Antibiotic Resistance

PubMed Central

Chellat, Mathieu F.; Raguž, Luka

2016-01-01

Abstract Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens. PMID:27000559

Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

PubMed Central

Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I.

2013-01-01

Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water. PMID:27029309

Fighting antibiotic resistance in the intensive care unit using antibiotics.

PubMed

Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

2015-01-01

Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

PubMed Central

Plésiat, Patrick

2015-01-01

SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps. PMID:25788514

Containing antibiotic resistance: decreased antibiotic-resistant coliform urinary tract infections with reduction in antibiotic prescribing by general practices

PubMed Central

Butler, Chris C; Dunstan, Frank; Heginbothom, Margaret; Mason, Brendan; Roberts, Zoë; Hillier, Sharon; Howe, Robin; Palmer, Stephen; Howard, Anthony

2007-01-01

Background GPs are urged to prescribe antibiotics less frequently, despite lack of evidence linking reduced antibiotic prescribing with reductions in resistance at a local level. Aim To investigate associations between changes in antibiotic dispensing and changes in antibiotic resistance at general-practice level. Design of study Seven-year study of dispensed antibiotics and antibiotic resistance in coliform isolates from urine samples routinely submitted from general practice. Setting General practices in Wales. Method Multilevel modelling of trends in resistance to ampicillin and trimethoprim, and changes in practice total antibiotic dispensing and amoxicillin and trimethoprim dispensing. Results The primary analysis included data on 164 225 coliform isolates from urine samples submitted from 240 general practices over the 7-year study period. These practices served a population of 1.7 million patients. The quartile of practices that had the greatest decrease in total antibiotic dispensing demonstrated a 5.2% reduction in ampicillin resistance over the 7-year period with changes of 0.4%, 2.4%, and −0.3% in the other three quartiles. There was a statistically significant overall decrease in ampicillin resistance of 1.03% (95% confidence interval [CI] = 0.37 to 1.67%) per decrease of 50 amoxicillin items dispensed per 1000 patients per annum. There were also significant reductions in trimethoprim resistance in the two quartiles of practices that reduced total antibiotic dispensing most compared with those that reduced it least, with an overall decrease in trimethoprim resistance of 1.08% (95% CI = 0.065 to 2.10%) per decrease of 20 trimethoprim items dispensed per 1000 patients per annum. Main findings were confirmed by secondary analyses of 256 370 isolates from 527 practices that contributed data at some point during the study period. Conclusion Reducing antibiotic dispensing at general-practice level is associated with reduced local antibiotic resistance

The multifaceted roles of antibiotics and antibiotic resistance in nature

PubMed Central

Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

2013-01-01

Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host–parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics

Rationalizing antibiotic use to limit antibiotic resistance in India+

PubMed Central

2011-01-01

Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

Strategies to Minimize Antibiotic Resistance

PubMed Central

Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

2013-01-01

Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

The Prehistory of Antibiotic Resistance.

PubMed

Perry, Julie; Waglechner, Nicholas; Wright, Gerard

2016-06-01

Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

The expression of antibiotic resistance genes in antibiotic-producing bacteria.

PubMed

Mak, Stefanie; Xu, Ye; Nodwell, Justin R

2014-08-01

Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance. © 2014 John Wiley & Sons Ltd.

The determinants of the antibiotic resistance process.

PubMed

Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

2009-01-01

The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. We conducted a MedLine search using the key words "determinants", "antibiotic", and "antibiotic resistance" to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals.

Antibiotic resistance increases with local temperature

NASA Astrophysics Data System (ADS)

MacFadden, Derek R.; McGough, Sarah F.; Fisman, David; Santillana, Mauricio; Brownstein, John S.

2018-06-01

Bacteria that cause infections in humans can develop or acquire resistance to antibiotics commonly used against them1,2. Antimicrobial resistance (in bacteria and other microbes) causes significant morbidity worldwide, and some estimates indicate the attributable mortality could reach up to 10 million by 20502-4. Antibiotic resistance in bacteria is believed to develop largely under the selective pressure of antibiotic use; however, other factors may contribute to population level increases in antibiotic resistance1,2. We explored the role of climate (temperature) and additional factors on the distribution of antibiotic resistance across the United States, and here we show that increasing local temperature as well as population density are associated with increasing antibiotic resistance (percent resistant) in common pathogens. We found that an increase in temperature of 10 °C across regions was associated with an increases in antibiotic resistance of 4.2%, 2.2%, and 2.7% for the common pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The associations between temperature and antibiotic resistance in this ecological study are consistent across most classes of antibiotics and pathogens and may be strengthening over time. These findings suggest that current forecasts of the burden of antibiotic resistance could be significant underestimates in the face of a growing population and climate change4.

Resistance diagnosis and the changing epidemiology of antibiotic resistance.

PubMed

McAdams, David

2017-01-01

Widespread adoption of point-of-care resistance diagnostics (POCRD) reduces ineffective antibiotic use but could increase overall antibiotic use. Indeed, in the context of a standard susceptible-infected epidemiological model with a single antibiotic, POCRD accelerates the rise of resistance in the disease-causing bacterial population. When multiple antibiotics are available, however, POCRD may slow the rise of resistance even as more patients receive antibiotic treatment, belying the conventional wisdom that antibiotics are "exhaustible resources" whose increased use necessarily promotes the rise of resistance. © 2017 New York Academy of Sciences.

Investigating the Antibiotic Resistance Problem.

ERIC Educational Resources Information Center

Lawson, Michael; Lawson, Amy L.

1998-01-01

Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

The Comprehensive Antibiotic Resistance Database

PubMed Central

McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

2013-01-01

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

Mechanisms of Antibiotic Resistance

PubMed Central

Munita, Jose M.; Arias, Cesar A.

2015-01-01

Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

The determinants of the antibiotic resistance process

PubMed Central

Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

2009-01-01

Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

Background antibiotic resistance patterns in antibiotic-free pastured poultry production

USDA-ARS?s Scientific Manuscript database

Antibiotic resistance (AR) is a significant public health issue, and agroecosystems are often viewed as major environmental sources of antibiotic resistant foodborne pathogens. While the use of antibiotics in agroecosystems can potentially increase AR, appropriate background resistance levels in th...

Bacterial cheating limits antibiotic resistance

NASA Astrophysics Data System (ADS)

Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

2012-02-01

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

Probiotic approach to prevent antibiotic resistance.

PubMed

Ouwehand, Arthur C; Forssten, Sofia; Hibberd, Ashley A; Lyra, Anna; Stahl, Buffy

2016-01-01

Probiotics are live microorganisms, mainly belonging to the genera Lactobacillus and Bifidobacterium, although also strain of other species are commercialized, that have a beneficial effect on the host. From the perspective of antibiotic use, probiotics have been observed to reduce the risk of certain infectious disease such as certain types of diarrhea and respiratory tract infection. This may be accompanied with a reduced need of antibiotics for secondary infections. Antibiotics tend to be effective against most common diseases, but increasingly resistance is being observed among pathogens. Probiotics are specifically selected to not contribute to the spread of antibiotic resistance and not carry transferable antibiotic resistance. Concomitant use of probiotics with antibiotics has been observed to reduce the incidence, duration and/or severity of antibiotic-associated diarrhea. This contributes to better adherence to the antibiotic prescription and thereby reduces the evolution of resistance. To what extent probiotics directly reduce the spread of antibiotic resistance is still much under investigation; but maintaining a balanced microbiota during antibiotic use may certainly provide opportunities for reducing the spread of resistances. Key messages Probiotics may reduce the risk for certain infectious diseases and thereby reduce the need for antibiotics. Probiotics may reduce the risk for antibiotic-associated diarrhea Probiotics do not contribute to the spread of antibiotic resistance and may even reduce it.

Antibiotic Resistance and Antibiotic Resistance Genes in Escherichia coli Isolates from Hospital Wastewater in Vietnam

PubMed Central

Lan, Pham Thi; Chuc, Nguyen Thi Kim; Hoa, Nguyen Quynh; Nhung, Pham Hong; Thoa, Nguyen Thi Minh; Diwan, Vishal; Tamhankar, Ashok J.; Stålsby Lundborg, Cecilia

2017-01-01

The environmental spread of antibiotic-resistant bacteria has been recognised as a growing public health threat for which hospitals play a significant role. The aims of this study were to investigate the prevalence of antibiotic resistance and antibiotic resistance genes (ARGs) in Escherichia coli isolates from hospital wastewater in Vietnam. Wastewater samples before and after treatment were collected using continuous sampling every month over a year. Standard disk diffusion and E-test were used for antibiotic susceptibility testing. Extended-spectrum beta-lactamase (ESBL) production was tested using combined disk diffusion. ARGs were detected by polymerase chain reactions. Resistance to at least one antibiotic was detected in 83% of isolates; multidrug resistance was found in 32%. The highest resistance prevalence was found for co-trimoxazole (70%) and the lowest for imipenem (1%). Forty-three percent of isolates were ESBL-producing, with the blaTEM gene being more common than blaCTX-M. Co-harbouring of the blaCTX-M, blaTEM and qepA genes was found in 46% of isolates resistant to ciprofloxacin. The large presence of antibiotic-resistant E. coli isolates combined with ARGs in hospital wastewater, even post-treatment, poses a threat to public health. It highlights the need to develop effective processes for hospital wastewater treatment plants to eliminate antibiotic resistant bacteria and ARGs. PMID:28661465

Antibiotic Resistance and Antibiotic Resistance Genes in Escherichia coli Isolates from Hospital Wastewater in Vietnam.

PubMed

Lien, La Thi Quynh; Lan, Pham Thi; Chuc, Nguyen Thi Kim; Hoa, Nguyen Quynh; Nhung, Pham Hong; Thoa, Nguyen Thi Minh; Diwan, Vishal; Tamhankar, Ashok J; Stålsby Lundborg, Cecilia

2017-06-29

The environmental spread of antibiotic-resistant bacteria has been recognised as a growing public health threat for which hospitals play a significant role. The aims of this study were to investigate the prevalence of antibiotic resistance and antibiotic resistance genes (ARGs) in Escherichia coli isolates from hospital wastewater in Vietnam. Wastewater samples before and after treatment were collected using continuous sampling every month over a year. Standard disk diffusion and E-test were used for antibiotic susceptibility testing. Extended-spectrum beta-lactamase (ESBL) production was tested using combined disk diffusion. ARGs were detected by polymerase chain reactions. Resistance to at least one antibiotic was detected in 83% of isolates; multidrug resistance was found in 32%. The highest resistance prevalence was found for co-trimoxazole (70%) and the lowest for imipenem (1%). Forty-three percent of isolates were ESBL-producing, with the bla TEM gene being more common than bla CTX-M . Co-harbouring of the bla CTX-M , bla TEM and qepA genes was found in 46% of isolates resistant to ciprofloxacin. The large presence of antibiotic-resistant E. coli isolates combined with ARGs in hospital wastewater, even post-treatment, poses a threat to public health. It highlights the need to develop effective processes for hospital wastewater treatment plants to eliminate antibiotic resistant bacteria and ARGs.

Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants.

PubMed

Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra

2018-01-01

The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fluorescent Antibiotics: New Research Tools to Fight Antibiotic Resistance.

PubMed

Stone, M Rhia L; Butler, Mark S; Phetsang, Wanida; Cooper, Matthew A; Blaskovich, Mark A T

2018-05-01

Better understanding how multidrug-resistant (MDR) bacteria can evade current and novel antibiotics requires a better understanding of the chemical biology of antibiotic action. This necessitates using new tools and techniques to advance our knowledge of bacterial responses to antibiotics, ideally in live cells in real time, to selectively investigate bacterial growth, division, metabolism, and resistance in response to antibiotic challenge. In this review, we discuss the preparation and biological evaluation of fluorescent antibiotics, focussing on how these reporters and assay methods can help elucidate resistance mechanisms. We also examine the potential utility of such probes for real-time in vivo diagnosis of infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

PubMed Central

Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

2017-01-01

Abstract Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as “antibiotic cycling” and “antibiotic mixing.” However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to “cycle” between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. Key words: antibiotic cycling, antibiotic mixing, optimal control, stochastic models. PMID:28096304

Origins and Evolution of Antibiotic Resistance

PubMed Central

Davies, Julian; Davies, Dorothy

2010-01-01

Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

Empirical Mode Decomposition and k-Nearest Embedding Vectors for Timely Analyses of Antibiotic Resistance Trends

PubMed Central

Teodoro, Douglas; Lovis, Christian

2013-01-01

Background Antibiotic resistance is a major worldwide public health concern. In clinical settings, timely antibiotic resistance information is key for care providers as it allows appropriate targeted treatment or improved empirical treatment when the specific results of the patient are not yet available. Objective To improve antibiotic resistance trend analysis algorithms by building a novel, fully data-driven forecasting method from the combination of trend extraction and machine learning models for enhanced biosurveillance systems. Methods We investigate a robust model for extraction and forecasting of antibiotic resistance trends using a decade of microbiology data. Our method consists of breaking down the resistance time series into independent oscillatory components via the empirical mode decomposition technique. The resulting waveforms describing intrinsic resistance trends serve as the input for the forecasting algorithm. The algorithm applies the delay coordinate embedding theorem together with the k-nearest neighbor framework to project mappings from past events into the future dimension and estimate the resistance levels. Results The algorithms that decompose the resistance time series and filter out high frequency components showed statistically significant performance improvements in comparison with a benchmark random walk model. We present further qualitative use-cases of antibiotic resistance trend extraction, where empirical mode decomposition was applied to highlight the specificities of the resistance trends. Conclusion The decomposition of the raw signal was found not only to yield valuable insight into the resistance evolution, but also to produce novel models of resistance forecasters with boosted prediction performance, which could be utilized as a complementary method in the analysis of antibiotic resistance trends. PMID:23637796

Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

PubMed

Beardmore, Robert Eric; Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

2017-04-01

Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as "antibiotic cycling" and "antibiotic mixing." However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to "cycle" between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. : antibiotic cycling, antibiotic mixing, optimal control, stochastic models. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Fate of Antibiotic Resistant Bacteria and Genes during Wastewater Chlorination: Implication for Antibiotic Resistance Control

PubMed Central

Yuan, Qing-Bin; Guo, Mei-Ting; Yang, Jian

2015-01-01

This study investigated fates of nine antibiotic-resistant bacteria as well as two series of antibiotic resistance genes in wastewater treated by various doses of chlorine (0, 15, 30, 60, 150 and 300 mg Cl2 min/L). The results indicated that chlorination was effective in inactivating antibiotic-resistant bacteria. Most bacteria were inactivated completely at the lowest dose (15 mg Cl2 min/L). By comparison, sulfadiazine- and erythromycin-resistant bacteria exhibited tolerance to low chlorine dose (up to 60 mg Cl2 min/L). However, quantitative real-time PCRs revealed that chlorination decreased limited erythromycin or tetracycline resistance genes, with the removal levels of overall erythromycin and tetracycline resistance genes at 0.42 ± 0.12 log and 0.10 ± 0.02 log, respectively. About 40% of erythromycin-resistance genes and 80% of tetracycline resistance genes could not be removed by chlorination. Chlorination was considered not effective in controlling antimicrobial resistance. More concern needs to be paid to the potential risk of antibiotic resistance genes in the wastewater after chlorination. PMID:25738838

Non-antibiotic antimicrobial triclosan induces multiple antibiotic resistance through genetic mutation.

PubMed

Lu, Ji; Jin, Min; Nguyen, Son Hoang; Mao, Likai; Li, Jie; Coin, Lachlan J M; Yuan, Zhiguo; Guo, Jianhua

2018-06-11

Antibiotic resistance poses a major threat to public health. Overuse and misuse of antibiotics are generally recognized as the key factors contributing to antibiotic resistance. However, whether non-antibiotic, anti-microbial (NAAM) chemicals can directly induce antibiotic resistance is unclear. We aim to investigate whether the exposure to a NAAM chemical triclosan (TCS) has an impact on inducing antibiotic resistance on Escherichia coli. Here, we report that at a concentration of 0.2 mg/L TCS induces multi-drug resistance in wild-type Escherichia coli after 30-day TCS exposure. The oxidative stress induced by TCS caused genetic mutations in genes such as fabI, frdD, marR, acrR and soxR, and subsequent up-regulation of the transcription of genes encoding beta-lactamases and multi-drug efflux pumps, together with down-regulation of genes related to membrane permeability. The findings advance our understanding of the potential role of NAAM chemicals in the dissemination of antibiotic resistance in microbes, and highlight the need for controlling biocide applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antibiotic Resistance in Plant-Pathogenic Bacteria.

PubMed

Sundin, George W; Wang, Nian

2018-06-01

Antibiotics have been used for the management of relatively few bacterial plant diseases and are largely restricted to high-value fruit crops because of the expense involved. Antibiotic resistance in plant-pathogenic bacteria has become a problem in pathosystems where these antibiotics have been used for many years. Where the genetic basis for resistance has been examined, antibiotic resistance in plant pathogens has most often evolved through the acquisition of a resistance determinant via horizontal gene transfer. For example, the strAB streptomycin-resistance genes occur in Erwinia amylovora, Pseudomonas syringae, and Xanthomonas campestris, and these genes have presumably been acquired from nonpathogenic epiphytic bacteria colocated on plant hosts under antibiotic selection. We currently lack knowledge of the effect of the microbiome of commensal organisms on the potential of plant pathogens to evolve antibiotic resistance. Such knowledge is critical to the development of robust resistance management strategies to ensure the safe and effective continued use of antibiotics in the management of critically important diseases. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance.

PubMed

Alam, Md Kausar; Alhhazmi, Areej; DeCoteau, John F; Luo, Yu; Geyer, C Ronald

2016-03-17

Antibiotic resistance arises from the maintenance of resistance mutations or genes acquired from the acquisition of adaptive de novo mutations or the transfer of resistance genes. Antibiotic resistance is acquired in response to antibiotic therapy by activating SOS-mediated DNA repair and mutagenesis and horizontal gene transfer pathways. Initiation of the SOS pathway promotes activation of RecA, inactivation of LexA repressor, and induction of SOS genes. Here, we have identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response. These inhibitors potentiate the activity of bactericidal antibiotics, including members of the quinolone, β-lactam, and aminoglycoside families in both Gram-negative and Gram-positive bacteria. They reduce the ability of bacteria to acquire antibiotic resistance mutations and to transfer mobile genetic elements conferring resistance. This study highlights the advantage of including RecA inhibitors in bactericidal antibiotic therapies and provides a new strategy for prolonging antibiotic shelf life. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pneumococcal resistance to antibiotics.

PubMed Central

Klugman, K P

1990-01-01

The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

Overview: Global and Local Impact of Antibiotic Resistance.

PubMed

Watkins, Richard R; Bonomo, Robert A

2016-06-01

The rapid and ongoing spread of antibiotic resistance poses a serious threat to global public health. The indiscriminant use of antibiotics in agriculture and human medicine along with increasingly connected societies has fueled the distribution of antibiotic-resistant bacteria. These factors together have led to rising numbers of infections caused by multidrug-resistant and pan-resistant bacteria, with increases in morbidity and mortality. This article summarizes the trends in antibiotic resistance, discusses the impact of antibiotic resistance on society, and reviews the use of antibiotics in agriculture. Feasible ways to tackle antibiotic resistance to avert a post-antibiotic era are suggested. Copyright © 2016 Elsevier Inc. All rights reserved.

DEVELOPMENT OF AN ANTIBIOTIC OPTIONS INDEX FOR ANTIBIOTIC RESISTANCE MONITORING.

PubMed

Manomayitthikan, Taweesuk; Borlace, Glenn N; Kessomboon, Nusaraporn

2016-11-01

Using antibiogram data to indicate the overall antibiotic resistance of a pathogen is complicated by the multiple antibiotic susceptibilities reported in the antibiogram. The objectives of this study were to develop and determine the benefits of an Antibiotic Options Index (AOI); an index that summarizes antibiotic susceptibility data for a pathogen by presenting it as the availability of antibiotic treatment options. The AOI was calculated using antibiogram data for the seven most commonly isolated pathogens from the National Antimicrobial Resistance Surveillance Center of Thailand between 1998 and 2014 and was classified as acceptable (AOI ≥ 0.8) or unacceptable (AOI < 0.8) based on the availability of treatment options. The AOI identified two problematic pathogens: Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA). For A. baumannii, the probability of having at least two viable antibiotic treatment options (AOIm2) decreased from an acceptable level (0.93) in 1998 to an unacceptable level (0.53) in 2014 and for MRSA the AOIm2 decreased from an acceptable level (0.82) in 1998 to an unacceptable level (0.47) in 2014. By including the idea that the problem with increasing antibiotic resistance is a problem with treating infections, the AOI effectively compiles susceptibility data to present it as the probability of having effective antibiotic treatment. This index is calculated from widely available antibiogram data, making it more suitable to be used to monitor antibiotic resistance at the hospital, provincial and national levels.

Antibiotics and antibiotic resistance: a bitter fight against evolution.

PubMed

Rodríguez-Rojas, Alexandro; Rodríguez-Beltrán, Jerónimo; Couce, Alejandro; Blázquez, Jesús

2013-08-01

One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance. Copyright © 2013 Elsevier GmbH. All rights reserved.

Antibiotic-Resistant Bacteria.

ERIC Educational Resources Information Center

Longenecker, Nevin E.; Oppenheimer, Dan

1982-01-01

A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

The intrinsic resistome of bacterial pathogens

PubMed Central

Olivares, Jorge; Bernardini, Alejandra; Garcia-Leon, Guillermo; Corona, Fernando; B. Sanchez, Maria; Martinez, Jose L.

2013-01-01

Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice. PMID:23641241

The intrinsic resistome of bacterial pathogens.

PubMed

Olivares, Jorge; Bernardini, Alejandra; Garcia-Leon, Guillermo; Corona, Fernando; B Sanchez, Maria; Martinez, Jose L

2013-01-01

Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

Antibiotic-Resistant Gonorrhea

MedlinePlus

... Surveillance Project (GISP) Profiles 2015 (June 1, 2017) AR Investment Map This interactive tool shows CDC’s key investments to combat antibiotic resistance (AR), including resistant gonorrhea, across the nation. Blog by ...

Probing minority population of antibiotic-resistant bacteria.

PubMed

Huang, Tianxun; Zheng, Yan; Yan, Ya; Yang, Lingling; Yao, Yihui; Zheng, Jiaxin; Wu, Lina; Wang, Xu; Chen, Yuqing; Xing, Jinchun; Yan, Xiaomei

2016-06-15

The evolution and spread of antibiotic-resistant pathogens has become a major threat to public health. Advanced tools are urgently needed to quickly diagnose antibiotic-resistant infections to initiate appropriate treatment. Here we report the development of a highly sensitive flow cytometric method to probe minority population of antibiotic-resistant bacteria via single cell detection. Monoclonal antibody against TEM-1 β-lactamase and Alexa Fluor 488-conjugated secondary antibody were used to selectively label resistant bacteria green, and nucleic acid dye SYTO 62 was used to stain all the bacteria red. A laboratory-built high sensitivity flow cytometer (HSFCM) was applied to simultaneously detect the side scatter and dual-color fluorescence signals of single bacteria. By using E. coli JM109/pUC19 and E. coli JM109 as the model systems for antibiotic-resistant and antibiotic-susceptible bacteria, respectively, as low as 0.1% of antibiotic-resistant bacteria were accurately quantified. By monitoring the dynamic population change of a bacterial culture with the administration of antibiotics, we confirmed that under the antimicrobial pressure, the original low population of antibiotic-resistant bacteria outcompeted susceptible strains and became the dominant population after 5hours of growth. Detection of antibiotic-resistant infection in clinical urine samples was achieved without cultivation, and the bacterial load of susceptible and resistant strains can be faithfully quantified. Overall, the HSFCM-based quantitative method provides a powerful tool for the fundamental studies of antibiotic resistance and holds the potential to provide rapid and precise guidance in clinical therapies. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of antibiotic resistance in Listeria spp. isolated from slaughterhouse environments, pork and human infections.

PubMed

Moreno, Luisa Z; Paixão, Renata; Gobbi, Débora D S; Raimundo, Daniele C; Ferreira, Thais P; Moreno, Andrea M; Hofer, Ernesto; Reis, Cristhiane M F; Matté, Glavur R; Matté, Maria H

2014-04-15

Listeria species are susceptible to most antibiotics. However, over the last decade, increasing reports of multidrug-resistant Listeria spp. from various sources have prompted public health concerns. The objective of this study was to characterize the antibiotic susceptibility of Listeria spp. and the genetic mechanisms that confer resistance. Forty-six Listeria spp. isolates were studied, and their minimal inhibitory concentrations of antibiotics were determined by microdilution using Sensititre standard susceptibility MIC plates. The isolates were screened for the presence of gyrA, parC, lde, lsa(A), lnu(A), and mprF by PCR, and the amplified genes were sequenced. All isolates were susceptible to penicillin, ampicillin, tetracycline, erythromycin, and carbapenems. Resistance to clindamycin, daptomycin, and oxacillin was found among L. monocytogenes and L. innocua, and all species possessed at least intermediate resistance to fluoroquinolones. GyrA, parC, and mprF were detected in all isolates; however, mutations were found only in gyrA sequences. A high daptomycin MIC, as reported previously, was observed, suggesting an intrinsic resistance of Listeria spp. to daptomycin. These results are consistent with reports of emerging resistance in Listeria spp. and emphasize the need for further genotypic characterization of antibiotic resistance in this genus.

Tackling antibiotic resistance: the environmental framework.

PubMed

Berendonk, Thomas U; Manaia, Célia M; Merlin, Christophe; Fatta-Kassinos, Despo; Cytryn, Eddie; Walsh, Fiona; Bürgmann, Helmut; Sørum, Henning; Norström, Madelaine; Pons, Marie-Noëlle; Kreuzinger, Norbert; Huovinen, Pentti; Stefani, Stefania; Schwartz, Thomas; Kisand, Veljo; Baquero, Fernando; Martinez, José Luis

2015-05-01

Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.

Plant Growth, Antibiotic Uptake, and Prevalence of Antibiotic Resistance in an Endophytic System of Pakchoi under Antibiotic Exposure

PubMed Central

Zhang, Hao; Li, Xunan; Yang, Qingxiang; Sun, Linlin; Yang, Xinxin; Zhou, Mingming; Deng, Rongzhen; Bi, Linqian

2017-01-01

Antibiotic contamination in agroecosystems may cause serious problems, such as the proliferation of various antibiotic resistant bacteria and the spreading of antibiotic resistance genes (ARGs) in the environment or even to human beings. However, it is unclear whether environmental antibiotics, antibiotic resistant bacteria, and ARGs can directly enter into, or occur in, the endophytic systems of plants exposed to pollutants. In this study, a hydroponic experiment exposing pakchoi (Brassica chinensis L.) to tetracycline, cephalexin, and sulfamethoxazole at 50% minimum inhibitory concentration (MIC) levels and MIC levels, respectively, was conducted to explore plant growth, antibiotic uptake, and the development of antibiotic resistance in endophytic systems. The three antibiotics promoted pakchoi growth at 50% MIC values. Target antibiotics at concentrations ranging from 6.9 to 48.1 µg·kg−1 were detected in the treated vegetables. Additionally, the rates of antibiotic-resistant endophytic bacteria to total cultivable endophytic bacteria significantly increased as the antibiotics accumulated in the plants. The detection and quantification of ARGs indicated that four types, tetX, blaCTX-M, and sul1 and sul2, which correspond to tetracycline, cephalexin, and sulfamethoxazole resistance, respectively, were present in the pakchoi endophytic system and increased with the antibiotic concentrations. The results highlight a potential risk of the development and spread of antibiotic resistance in vegetable endophytic systems. PMID:29099753

Plant Growth, Antibiotic Uptake, and Prevalence of Antibiotic Resistance in an Endophytic System of Pakchoi under Antibiotic Exposure.

PubMed

Zhang, Hao; Li, Xunan; Yang, Qingxiang; Sun, Linlin; Yang, Xinxin; Zhou, Mingming; Deng, Rongzhen; Bi, Linqian

2017-11-03

Antibiotic contamination in agroecosystems may cause serious problems, such as the proliferation of various antibiotic resistant bacteria and the spreading of antibiotic resistance genes (ARGs) in the environment or even to human beings. However, it is unclear whether environmental antibiotics, antibiotic resistant bacteria, and ARGs can directly enter into, or occur in, the endophytic systems of plants exposed to pollutants. In this study, a hydroponic experiment exposing pakchoi ( Brassica chinensis L.) to tetracycline, cephalexin, and sulfamethoxazole at 50% minimum inhibitory concentration (MIC) levels and MIC levels, respectively, was conducted to explore plant growth, antibiotic uptake, and the development of antibiotic resistance in endophytic systems. The three antibiotics promoted pakchoi growth at 50% MIC values. Target antibiotics at concentrations ranging from 6.9 to 48.1 µg·kg -1 were detected in the treated vegetables. Additionally, the rates of antibiotic-resistant endophytic bacteria to total cultivable endophytic bacteria significantly increased as the antibiotics accumulated in the plants. The detection and quantification of ARGs indicated that four types, tet X, bla CTX-M , and sul 1 and sul 2, which correspond to tetracycline, cephalexin, and sulfamethoxazole resistance, respectively, were present in the pakchoi endophytic system and increased with the antibiotic concentrations. The results highlight a potential risk of the development and spread of antibiotic resistance in vegetable endophytic systems.

Antibiotic resistances of intestinal lactobacilli isolated from wild boars.

PubMed

Klose, Viviana; Bayer, Katharina; Kern, Corinna; Goelß, Florian; Fibi, Silvia; Wegl, Gertrude

2014-01-10

Acquired antibiotic resistances have been reported in lactobacilli of various animal and food sources, but there are no data from wild boar. The objective was a preliminary examination of the antibiotic resistance prevalence of intrinsically vancomycin-resistant lactobacilli isolated from wild boar intestines and analysis of the genetic determinants implicated. Out of three wild boars, 121 lactobacilli were recovered and grouped according to their whole cell protein patterns. Initial phenotypic screening revealed that all were susceptible to erythromycin (2 μg/ml), but 30 were resistant to tetracycline (32 μg/ml). Based on Randomly Amplified Polymorphic DNA-PCR clustering, 64 strains were selected as representative genotypes for identification and minimum inhibitory concentration (MIC) determination. Partial 16S rRNA gene sequencing identified four species: (i) L. mucosae (n=57), (ii) L. reuteri (n=47), (iii) L. fermentum (n=12), and (iv) L. murinus (n=5). Most heterofermentative strains displayed low MICs for ampicillin (AMP), chloramphenicol (CHL), streptomycin (STR), kanamycin (KAN), gentamicin (GEN), erythromycin (ERY), quinupristin/dalfopristin (Q/D), and clindamycin (CLI). Atypical MICs were found mainly in L. mucosae and L. reuteri for TET, KAN, STR, AMP and CHL, but except the TET MICs of L. mucosae mostly at low level. L. murinus strains revealed atypical MICs for aminoglycosides, and/or CHL, AMP, CLI. PCR screening detected tet(W) in 12 and tet(M) in one of heterofermentative strains, as well as the aph(3')-III kanamycin gene in L. murinus. This is the first report showing acquired antibiotic resistance determinants in intestinal lactobacilli of wild boar origin. Copyright © 2013 Elsevier B.V. All rights reserved.

[Antibiotic resistance : A challenge for society].

PubMed

Antão, Esther-Maria; Wagner-Ahlfs, Christian

2018-05-01

Without doubt, drug resistance is now one of the greatest health threats of our time. Not even 100 years after the discovery of the first antibiotics that saved human lives, we find ourselves threatened by the thought of a post-antibiotic era. Currently it is estimated that around 700,000 people die annually as a consequence of drug-resistant infections. Antibiotic resistance is a natural phenomenon with bacteria having devised several ways of combating the antibiotic attack. Rather than being a spontaneous event, resistance becomes an integral part of the microbe's genetic make-up, spreading further between and across species. However, the misuse and overuse of antibiotics over the years has in fact allowed for resistant bacteria to thrive, while slowly wiping out sensitive bacteria. Spreading awareness and proper information in the community about the risks and consequences of a rapidly developing antibiotic resistance is essential in tackling this global problem. In working together as an entire community, we can find long-lasting solutions. The One Health concept includes human and veterinary medical sectors, the environmental sector, as well as various decision-making bodies that include individual action as well as national and international policymakers. The role of stakeholders like pharmaceutical companies and agriculturists must be given importance, too, thinking all the while in a global context. Only this way will we find solutions for sustainable healthcare and together help slow down the process of antibiotic resistance.

Antibiotics involved in the occurrence of antibiotic-resistant bacteria: a nationwide multilevel study suggests differences within antibiotic classes.

PubMed

Gbaguidi-Haore, Houssein; Dumartin, Catherine; L'Hériteau, François; Péfau, Muriel; Hocquet, Didier; Rogues, Anne-Marie; Bertrand, Xavier

2013-02-01

To identify the antibiotics potentially the most involved in the occurrence of antibiotic-resistant bacteria from an ecological perspective in French healthcare facilities (HCFs). This study was based on data from the French antimicrobial surveillance network (ATB-RAISIN, 2007-09). Antibiotics were expressed in defined daily doses per 1000 patient-days. Antibiotic-resistant bacteria were considered as count data adjusted for patient-days. These were third-generation cephalosporin (3GC)- and ciprofloxacin-resistant Escherichia coli, cefotaxime-resistant Enterobacter cloacae, methicillin-resistant Staphylococcus aureus and ceftazidime-, imipenem- and ciprofloxacin-resistant Pseudomonas aeruginosa. Three-level negative binomial regression models were built to take into account the hierarchical structure of data: level 1, repeated measures each year (count outcome, time, antibiotics); level 2, HCFs (type and size); and level 3, regions (geographical area). A total of 701 HCFs from 20 French regions and up to 1339 HCF-years were analysed. The use of ceftriaxone, but not of cefotaxime, was positively correlated with incidence rates of 3GC- and ciprofloxacin-resistant E. coli. In contrast, both 3GCs were positively correlated with the incidence rate of cefotaxime-resistant E. cloacae. Higher levels of use of ciprofloxacin and/or ofloxacin, but not of levofloxacin, were associated with higher incidence rates of 3GC- and ciprofloxacin-resistant E. coli, cefotaxime-resistant E. cloacae, methicillin-resistant S. aureus and ceftazidime- and ciprofloxacin-resistant P. aeruginosa. Our study suggests differences within antibiotic classes in promoting antibiotic resistance. We identified ceftriaxone, ciprofloxacin and ofloxacin as priority targets in public health strategies designed to reduce antibiotic use and antibiotic-resistant bacteria in French HCFs.

CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database

PubMed Central

Jia, Baofeng; Raphenya, Amogelang R.; Alcock, Brian; Waglechner, Nicholas; Guo, Peiyao; Tsang, Kara K.; Lago, Briony A.; Dave, Biren M.; Pereira, Sheldon; Sharma, Arjun N.; Doshi, Sachin; Courtot, Mélanie; Lo, Raymond; Williams, Laura E.; Frye, Jonathan G.; Elsayegh, Tariq; Sardar, Daim; Westman, Erin L.; Pawlowski, Andrew C.; Johnson, Timothy A.; Brinkman, Fiona S.L.; Wright, Gerard D.; McArthur, Andrew G.

2017-01-01

The Comprehensive Antibiotic Resistance Database (CARD; http://arpcard.mcmaster.ca) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR. CARD is ontologically structured, model centric, and spans the breadth of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven and acquired resistance. It is built upon the Antibiotic Resistance Ontology (ARO), a custom built, interconnected and hierarchical controlled vocabulary allowing advanced data sharing and organization. Its design allows the development of novel genome analysis tools, such as the Resistance Gene Identifier (RGI) for resistome prediction from raw genome sequence. Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology and accompanying AMR detection models to power sequence analysis, new visualization tools, and expansion of the RGI for detection of emergent AMR threats. CARD curation is updated monthly based on an interplay of manual literature curation, computational text mining, and genome analysis. PMID:27789705

The role of outer membrane in Serratia marcescens intrinsic resistance to antibiotics.

PubMed

Sánchez, L; Ruiz, N; Leranoz, S; Viñas, M; Puig, M

1997-09-01

Three different porins from Serratia marcescens were described. They were named Omp1, Omp2 and Omp3 and their molecular weights were 42, 40 and 39 kDa respectively. Omp2 and Omp3 showed osmoregulation and thermoregulation in a similar way to OmpC and OmpF of Escherichia coli. Permeability coefficients of the outer membrane of this species were calculated following the Zimmermann and Rosselet method. P values were similar to those obtained in Escherichia coli, which suggests that the chromosomal beta-lactamase would play a major role in the resistance of Serratia marcescens to beta-lactam antibiotics. Both MIC values and permeabilities were modified by salycilates and acetylsalycilate. Synergism between the outer membrane and the beta-lactamase was also evaluated. When bacteria grew in the presence of a beta-lactam in the medium, the beta-lactamase accounted for most of the resistance.

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

PubMed

Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

2011-11-01

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

Fate and transport of veterinary antibiotics, antibiotic-resistant bacteria, and antibiotic resistance gene from fields receiving poultry manure during storm events

USDA-ARS?s Scientific Manuscript database

Antimicrobials are used in production agriculture to treat disease and promote animal growth, but the presence of antibiotics in the environment raises concern about widespread antibiotic resistance. This study documents the occurrence and transport of tylosin, tetracycline, enterococci resistant to...

[Antibiotic Consumption and the Development of Antibiotic Resistance in Surgical Units].

PubMed

Tammer, I; Geginat, G; Lange, S; Kropf, S; Lodes, U; Schlüter, D; Lippert, H; Meyer, F

2016-02-01

Antibiotic resistence is increasing worldwide. A longitudinal analysis of the influence of the density of antibiotic use on the development of resistance in surgical units was undertaken. Over five years the incidence of pathogens and the resistance rates of isolates from patients of normal surgical units and those of a surgical ICU at a university hospital were examined. The resistence rates were correlated with the density of antibiotic use - calculated from the antibiotic consumption (in DDD) and the number of patient-days. At both units, Enterobacteriaceae and Enterococci were mostly cultured. Among the Enterobacteriaceae, E. coli, Klebsiella spp., Proteus mirabilis and Enterobacter predominated. In the group of Enterococci, E. faecalis predominated at wards whereas at ICU E. faecium was the most frequent. Anaerobes ranked third at normal wards and Candida spp. at ICU. From 2007 to 2011, there was an increasing resistance against ciprofloxacin in P. mirabilis (r = 0.87; p = 0.054) and against imipenem (r = 0.86; p = 0.06) and piperacillin (r = 0.81; p = 0.09) in P. aeruginosa at normal wards. At ICU, the resistance rates of imipenem in P. aeruginosa rose (r = 0.88; p = 0.049). Resistance against ciprofloxacin in E. coli increased (r = 0.65; p = 0.23). Due to the increasing use of ciprofloxacin and meropenem at normal wards, the density of antibiotic usage rose 1.4 %/year (r = 0.94; p = 0.02). Despite the increase of meropenem use at ICU (r = 0.9; p = 0.035), the total antibiotic uptake rate remained almost constant. The antibiotic usage density was 3-fold higher at ICU than at normal wards. At normal wards, the ciprofloxacin usage correlated with the rate of resistance against ciprofloxacin in P. mirabilis P. m. At ICU, an association was detected between the uptake rate of ceftazidime and the rate of resistance against cefotaxime in the CES group. In P. aeruginosa, the use of piperacillin and the rate

Mechanisms of antibiotic resistance in Staphylococcus aureus.

PubMed

Pantosti, Annalisa; Sanchini, Andrea; Monaco, Monica

2007-06-01

Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus.

Knowledge of antibiotics and antibiotic resistance in patients followed by family physicians.

PubMed

Robert, A; Nguyen, Y; Bajolet, O; Vuillemin, B; Defoin, B; Vernet-Garnier, V; Drame, M; Bani-Sadr, F

2017-03-01

We aimed to evaluate factors associated with knowledge of antibiotics and drug resistance. A questionnaire was handed out by 14 family physicians to their patients between December 20, 2014 and April 20, 2015 in Rethel (North-East of France). We conducted a cross-sectional study using a logistical regression model to assess factors associated with antibiotic knowledge. Three criteria were used to assess that knowledge. Overall, 293 questionnaires were analysed; 48% of patients had received antibiotics in the previous 12 months. Only 44% and 26% gave a correct answer for the statements "Antibiotics are effective against bacteria and ineffective against viruses" and "Antibiotic resistance decreases if the antibiotic use decreases", respectively. Characteristics such as female sex, age>30 years, high level of education, high professional categories, and having received antibiotic information by the media were associated with high level of knowledge about antibiotics and/or antibiotic resistance. In contrast, having received antibiotic information from family physicians was not associated with good knowledge. Although media awareness campaigns had an independent impact on a higher public knowledge of antibiotics, the overall public knowledge remains low. It would be necessary to strengthen antibiotic campaigns with clearer information on the relation between the excessive use of antibiotics and the increased risk of antibiotic resistance. Family physicians should be more involved to improve antibiotic knowledge among target groups such as men, young patients, and people from a poor social and cultural background. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Micromonospora resistence to definite antibiotics and their ability to produce structurally analogous antibiotics].

PubMed

Bibikova, M V; Ivanitskaia, L P; Tikhonova, A S

1980-01-01

Thirty six cultures of Micromonospora freshly isolated from soil samples were studied with respect to their sensitivity to a number of antibiotics of various structures and modes of action. It was found that all of them were highly sensitive to penicillin, ristomycin, tetracycline, rifampicin, streptomycin, olivomycin, carminomycin and dactinomycin. Significant differences in sensitivity of the Micromonospora cultures were revealed only with respect to gentamicin, tobramicin, erythromycin and lincomycin. Seven cultures were resistant to gentamicin and tobramicin and sensitive to all of the other antibiotics. Broad spectrum antibiotics were isolated from these cultures. The study of the antibiotic chemistry showed that they were 2-desoxystreptamine-containing aminoglycosides. Two cultures proved to be resistant to erythromycin and lincomycin. When identified with the use of antibiotic resistant staphylococcal strains, the crude antibiotic substances isolated from these cultures appeared to be not active against staphylococci resistant to erythromycin and lincomycin. By their chromatograpi- behaviour the antibiotics were close to macrolides. Therefore, it was found that production of aminoglycoside and macrolide antibiotics was most characteristic of Micromonospora. A certain correlation between resistance of Micromonospora to these 2 antibiotic groups and capacity for their production was shown.

Antibiotic Resistance in Pediatric Urinary Tract Infections.

PubMed

Stultz, Jeremy S; Doern, Christopher D; Godbout, Emily

2016-12-01

Urinary tract infections (UTIs) are a common problem in pediatric patients. Resistance to common antibiotic agents appears to be increasing over time, although resistance rates may vary based on geographic region or country. Prior antibiotic exposure is a pertinent risk factor for acquiring resistant organisms during a first UTI and recurrent UTI. Judicious prescribing of antibiotics for common pediatric conditions is needed to prevent additional resistance from occurring. Complex pediatric patients with histories of hospitalizations, prior antibiotic exposure, and recurrent UTIs are also at high risk for acquiring UTIs due to extended spectrum beta-lactamase-producing organisms. Data regarding the impact of in vitro antibiotic susceptibility testing interpretation on UTI treatment outcomes is lacking.

WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics.

PubMed

Carlet, Jean; Rambaud, Claude; Pulcini, Céline

2012-07-09

Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians.

Mechanisms of antibiotic resistance in enterococci

PubMed Central

Miller, William R; Munita, Jose M; Arias, Cesar A

2015-01-01

Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

Antibiotic Resistance in Sepsis Patients: Evaluation and Recommendation of Antibiotic Use

PubMed Central

Pradipta, Ivan Surya; Sodik, Dian Chairunnisa; Lestari, Keri; Parwati, Ida; Halimah, Eli; Diantini, Ajeng; Abdulah, Rizky

2013-01-01

Background: The appropriate selection of empirical antibiotics based on the pattern of local antibiotic resistance can reduce the mortality rate and increase the rational use of antibiotics. Aims: We analyze the pattern of antibiotic use and the sensitivity patterns of antibiotics to support the rational use of antibiotics in patients with sepsis. Materials and Methods: A retrospective observational study was conducted in adult sepsis patient at one of Indonesian hospital during January-December 2011. Data were collected from the hospital medical record department. Descriptive analysis was used in the processing and interpretation of data. Results: A total of 76 patients were included as research subjects. Lung infection was the highest source of infection. In the 66.3% of clinical specimens that were culture positive for microbes, Klebsiella pneumoniae, Escherichia coli, Staphylococcus hominis were detected with the highest frequency. The six most frequently used antibiotics, levofloxacin, ceftazidime, ciprofloxacin, cefotaxime, ceftriaxone, and erythromycin, showed an average resistance above 50%. Conclusions: The high use of antibiotic with a high level resistance requires a policy to support its rational use. Local microbial pattern based on site infection and pattern of antibiotics sensitivity test can be used as supporting data to optimize appropriateness of empirical antibiotics therapy in sepsis patients. PMID:23923107

Emergence of antibiotic-resistant extremophiles (AREs).

PubMed

Gabani, Prashant; Prakash, Dhan; Singh, Om V

2012-09-01

Excessive use of antibiotics in recent years has produced bacteria that are resistant to a wide array of antibiotics. Several genetic and non-genetic elements allow microorganisms to adapt and thrive under harsh environmental conditions such as lethal doses of antibiotics. We attempt to classify these microorganisms as antibiotic-resistant extremophiles (AREs). AREs develop strategies to gain greater resistance to antibiotics via accumulation of multiple genes or plasmids that harbor genes for multiple drug resistance (MDR). In addition to their altered expression of multiple genes, AREs also survive by producing enzymes such as penicillinase that inactivate antibiotics. It is of interest to identify the underlying molecular mechanisms by which the AREs are able to survive in the presence of wide arrays of high-dosage antibiotics. Technologically, "omics"-based approaches such as genomics have revealed a wide array of genes differentially expressed in AREs. Proteomics studies with 2DE, MALDI-TOF, and MS/MS have identified specific proteins, enzymes, and pumps that function in the adaptation mechanisms of AREs. This article discusses the molecular mechanisms by which microorganisms develop into AREs and how "omics" approaches can identify the genetic elements of these adaptation mechanisms. These objectives will assist the development of strategies and potential therapeutics to treat outbreaks of pathogenic microorganisms in the future.

Bacterial Cheating Limits the Evolution of Antibiotic Resistance

NASA Astrophysics Data System (ADS)

Yurtsev, Eugene; Xiao Chao, Hui; Datta, Manoshi; Artemova, Tatiana; Gore, Jeff

2012-02-01

The emergence of antibiotic resistance in bacteria is a significant health concern. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removal of the antibiotic. The presence of a cooperative mechanism of resistance suggests that a cheater strain - which does not contribute to breaking down the antibiotic - may be able to take advantage of resistant cells. We find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We use a simple model in conjunction with difference equations to explain the observed population dynamics as a function of cell density and antibiotic concentration. Our experimental difference equations resemble the logistic map, raising the possibility of oscillations or even chaotic dynamics.

Predictable Phenotypes of Antibiotic Resistance Mutations.

PubMed

Knopp, M; Andersson, D I

2018-05-15

Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain

Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics.

PubMed

González-Bello, Concepción

2017-09-15

Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Cooperation, competition and antibiotic resistance in bacterial colonies.

PubMed

Frost, Isabel; Smith, William P J; Mitri, Sara; Millan, Alvaro San; Davit, Yohan; Osborne, James M; Pitt-Francis, Joe M; MacLean, R Craig; Foster, Kevin R

2018-06-01

Bacteria commonly live in dense and genetically diverse communities associated with surfaces. In these communities, competition for resources and space is intense, and yet we understand little of how this affects the spread of antibiotic-resistant strains. Here, we study interactions between antibiotic-resistant and susceptible strains using in vitro competition experiments in the opportunistic pathogen Pseudomonas aeruginosa and in silico simulations. Selection for intracellular resistance to streptomycin is very strong in colonies, such that resistance is favoured at very low antibiotic doses. In contrast, selection for extracellular resistance to carbenicillin is weak in colonies, and high doses of antibiotic are required to select for resistance. Manipulating the density and spatial structure of colonies reveals that this difference is partly explained by the fact that the local degradation of carbenicillin by β-lactamase-secreting cells protects neighbouring sensitive cells from carbenicillin. In addition, we discover a second unexpected effect: the inducible elongation of cells in response to carbenicillin allows sensitive cells to better compete for the rapidly growing colony edge. These combined effects mean that antibiotic treatment can select against antibiotic-resistant strains, raising the possibility of treatment regimes that suppress sensitive strains while limiting the rise of antibiotic resistance. We argue that the detailed study of bacterial interactions will be fundamental to understanding and overcoming antibiotic resistance.

The role of healthcare strategies in controlling antibiotic resistance.

PubMed

Aziz, Ann-Marie

In an interview in March 2013, the Chief Medical Officer described antibiotic resistance as a 'ticking time bomb' and ranked it along with terrorism on a list of threats to the nation. Her report Infections and the Rise of Antimicrobial Resistance (Department of Health, 2011) highlighted that, while a new infectious disease has been discovered nearly every year over the past three decades, there have been very few new antibiotics developed, leaving our armoury nearly empty. Antibiotic resistance is a universal problem that needs to be tackled by a wide variety of strategies and players. Our approach to tackling resistance to antibiotic agents must therefore also be dynamic. As well as reducing environmental use, we also need to lower antibiotic use in the healthcare setting. Healthcare workers have a huge role to play in combating antibiotic resistance. This article focuses on several issues related to antibiotic resistance, including antibiotic modes of action and the properties that confer resistance on bacteria. It includes information on antibiotic usage and describes current healthcare strategies we can adopt to help reduce the development of resistance.

Emergence and dissemination of antibiotic resistance: a global problem.

PubMed

Choudhury, R; Panda, S; Singh, D V

2012-01-01

Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure.

Effects of temperature and antibiotics on persistence of antibiotic-resistant bacteria and antibiotic resistance genes in poultry litter

USDA-ARS?s Scientific Manuscript database

The effect of low, residual concentrations of antibiotics in manure and other environmental matrices is not well understood. It has been hypothesized that antibiotic concentrations below clinical MIC (minimal inhibitory concentrations) are still capable of selecting for resistance. The objective of ...

Spontaneous and evolutionary changes in the antibiotic resistance of Burkholderia cenocepacia observed by global gene expression analysis.

PubMed

Sass, Andrea; Marchbank, Angela; Tullis, Elizabeth; Lipuma, John J; Mahenthiralingam, Eshwar

2011-07-22

Burkholderia cenocepacia is a member of the Burkholderia cepacia complex group of bacteria that cause infections in individuals with cystic fibrosis. B. cenocepacia isolate J2315 has been genome sequenced and is representative of a virulent, epidemic CF strain (ET12). Its genome encodes multiple antimicrobial resistance pathways and it is not known which of these is important for intrinsic or spontaneous resistance. To map these pathways, transcriptomic analysis was performed on: (i) strain J2315 exposed to sub-inhibitory concentrations of antibiotics and the antibiotic potentiator chlorpromazine, and (ii) on spontaneous mutants derived from J2315 and with increased resistance to the antibiotics amikacin, meropenem and trimethoprim-sulfamethoxazole. Two pan-resistant ET12 outbreak isolates recovered two decades after J2315 were also compared to identify naturally evolved gene expression changes. Spontaneous resistance in B. cenocepacia involved more gene expression changes and different subsets of genes than those provoked by exposure to sub inhibitory concentrations of each antibiotic. The phenotype and altered gene expression in the resistant mutants was also stable irrespective of the presence of the priming antibiotic. Both known and novel genes involved in efflux, antibiotic degradation/modification, membrane function, regulation and unknown functions were mapped. A novel role for the phenylacetic acid (PA) degradation pathway genes was identified in relation to spontaneous resistance to meropenem and glucose was found to repress their expression. Subsequently, 20 mM glucose was found to produce greater that 2-fold reductions in the MIC of multiple antibiotics against B. cenocepacia J2315. Mutation of an RND multidrug efflux pump locus (BCAM0925-27) and squalene-hopene cyclase gene (BCAS0167), both upregulated after chlorpromazine exposure, confirmed their role in resistance. The recently isolated outbreak isolates had altered the expression of multiple genes

Antibiotic-non-antibiotic combinations for combating extremely drug-resistant Gram-negative 'superbugs'.

PubMed

Schneider, Elena K; Reyes-Ortega, Felisa; Velkov, Tony; Li, Jian

2017-02-28

The emergence of antimicrobial resistance of Gram-negative pathogens has become a worldwide crisis. The status quo for combating resistance is to employ synergistic combinations of antibiotics. Faced with this fast-approaching post-antibiotic era, it is critical that we devise strategies to prolong and maximize the clinical efficacy of existing antibiotics. Unfortunately, reports of extremely drug-resistant (XDR) Gram-negative pathogens have become more common. Combining antibiotics such as polymyxin B or the broad-spectrum tetracycline and minocycline with various FDA-approved non-antibiotic drugs have emerged as a novel combination strategy against otherwise untreatable XDR pathogens. This review surveys the available literature on the potential benefits of employing antibiotic-non-antibiotic drug combination therapy. The apex of this review highlights the clinical utility of this novel therapeutic strategy for combating infections caused by 'superbugs'. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

[Antibiotic resistance: A global crisis].

PubMed

Alós, Juan-Ignacio

2015-12-01

The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Fate of antibiotic resistant cultivable heterotrophic bacteria and antibiotic resistance genes in wastewater treatment processes.

PubMed

Zhang, Songhe; Han, Bing; Gu, Ju; Wang, Chao; Wang, Peifang; Ma, Yanyan; Cao, Jiashun; He, Zhenli

2015-09-01

Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants of environmental concern. Heterotrophic bacteria in activated sludge have an important role in wastewater treatment plants (WWTPs). However, the fate of cultivable heterotrophic ARB and ARGs in WWPTs process remains unclear. In the present study, we investigated the antibiotic-resistant phenotypes of cultivable heterotrophic bacteria from influent and effluent water of three WWTPs and analysed thirteen ARGs in ARB and in activated sludge from anoxic, anaerobic and aerobic compartments. From each influent or effluent sample of the three plants, 200 isolates were randomly tested for susceptibility to 12 antibiotics. In these samples, between 5% and 64% isolates showed resistance to >9 antibiotics and the proportion of >9-drug-resistant bacteria was lower in isolates from effluent than from influent. Eighteen genera were identified in 188 isolates from influent (n=94) and effluent (n=94) of one WWTP. Six genera (Aeromonas, Bacillus, Lysinibacillus, Microbacterium, Providencia, and Staphylococcus) were detected in both influent and effluent samples. Gram-negative and -positive isolates dominated in influent and effluent, respectively. The 13 tetracycline-, sulphonamide-, streptomycin- and β-lactam-resistance genes were detected at a higher frequency in ARB from influent than from effluent, except for sulA and CTX-M, while in general, the abundances of ARGs in activated sludge from two of the three plants were higher in aerobic compartments than in anoxic ones, indicating abundant ARGs exit in the excess sledges and/or in uncultivable bacteria. These findings may be useful for elucidating the effect of WWTP on ARB and ARGs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Listeria monocytogenes: antibiotic resistance in food production.

PubMed

Lungu, Bwalya; O'Bryan, Corliss A; Muthaiyan, Arunachalam; Milillo, Sara R; Johnson, Michael G; Crandall, Philip G; Ricke, Steven C

2011-05-01

Listeria monocytogenes is an opportunistic human pathogen that causes listeriosis, a disease that mainly affects the immunocompromised, the elderly, infants, and pregnant women. Listeriosis has become increasingly common in the last 25 years since the first foodborne outbreak was noted. Treatment for listeriosis currently consists primarily of supportive therapy in conjunction with the use of intravenous antibiotics. Antibiotics have been commercially available for over 60 years for treatment of a myriad of clinical diseases. Bacteria resistant to antibiotics have been developing over this same period. This review seeks to elucidate the extent of antibiotic resistance in L. monocytogenes, the possible transmission mechanisms, and contributing factors to distribution of antibiotic resistance among Listeria species, and possible control strategies.

Antibiotic resistance shaping multi-level population biology of bacteria

PubMed Central

Baquero, Fernando; Tedim, Ana P.; Coque, Teresa M.

2013-01-01

Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent “population biologies.” Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of “clinical” antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

Antibiotic resistance shaping multi-level population biology of bacteria.

PubMed

Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

2013-01-01

Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

Antibiotic susceptibility patterns and resistance genes of starter cultures and probiotic bacteria used in food.

PubMed

Kastner, Sabine; Perreten, Vincent; Bleuler, Helen; Hugenschmidt, Gabriel; Lacroix, Christophe; Meile, Leo

2006-03-01

A survey of starter and probiotic cultures was carried out to determine the current antibiotic resistance situation in microbial food additives in Switzerland. Two hundred isolates from 90 different sources were typed by molecular and other methods to belong to the genera Lactobacillus (74 samples), Staphylococcus (33 samples), Bifidobacterium (6 samples), Pediococcus (5 samples), or were categorized as lactococci or streptococci (82 samples). They were screened for phenotypic resistances to 20 antibiotics by the disk diffusion method. Twenty-seven isolates exhibiting resistances that are not an intrinsic feature of the respective genera were further analyzed by microarray hybridization as a tool to trace back phenotypic resistances to specific genetic determinants. Their presence was finally verified by PCR amplification or Southern hybridization. These studies resulted in the detection of the tetracycline resistance gene tet(K) in 5 Staphylococcus isolates used as meat starter cultures, the tetracycline resistance gene tet(W) in the probiotic cultures Bifidobacterium lactis DSM 10140 and Lactobacillus reuteri SD 2112 (residing on a plasmid), and the lincosamide resistance gene lnu(A) (formerly linA) in L. reuteri SD 2112.

Resistance to antibiotics in the normal flora of animals.

PubMed

Sørum, H; Sunde, M

2001-01-01

The normal bacterial flora contains antibiotic resistance genes to various degrees, even in individuals with no history of exposure to commercially prepared antibiotics. Several factors seem to increase the number of antibiotic-resistant bacteria in feces. One important factor is the exposure of the intestinal flora to antibacterial drugs. Antibiotics used as feed additives seem to play an important role in the development of antibiotic resistance in normal flora bacteria. The use of avoparcin as a feed additive has demonstrated that an antibiotic considered "safe" is responsible for increased levels of antibiotic resistance in the normal flora enterococci of animals fed with avoparcin and possibly in humans consuming products from these animals. However, other factors like stress from temperature, crowding, and management also seem to contribute to the occurrence of antibiotic resistance in normal flora bacteria. The normal flora of animals has been studied with respect to the development of antibiotic resistance over four decades, but there are few studies with the intestinal flora as the main focus. The results of earlier studies are valuable when focused against the recent understanding of mobile genetics responsible for bacterial antibiotic resistance. New studies should be undertaken to assess whether the development of antibiotic resistance in the normal flora is directly linked to the dramatic increase in antibiotic resistance of bacterial pathogens. Bacteria of the normal flora, often disregarded scientifically, should be studied with the intention of using them as active protection against infectious diseases and thereby contributing to the overall reduction of use of antibioties in both animals and humans.

Water Disinfection Byproducts Induce Antibiotic Resistance-Role of Environmental Pollutants in Resistance Phenomena.

PubMed

Li, Dan; Zeng, Siyu; He, Miao; Gu, April Z

2016-03-15

The spread of antibiotic resistance represents a global threat to public health, and has been traditionally attributed to extensive antibiotic uses in clinical and agricultural applications. As a result, researchers have mostly focused on clinically relevant high-level resistance enriched by antibiotics above the minimal inhibitory concentrations (MICs). Here, we report that two common water disinfection byproducts (chlorite and iodoacetic acid) had antibiotic-like effects that led to the evolution of resistant E. coli strains under both high (near MICs) and low (sub-MIC) exposure concentrations. The subinhibitory concentrations of DBPs selected strains with resistance higher than those evolved under above-MIC exposure concentrations. In addition, whole-genome analysis revealed distinct mutations in small sets of genes known to be involved in multiple drug and drug-specific resistance, as well as in genes not yet identified to play role in antibiotic resistance. The number and identities of genetic mutations were distinct for either the high versus low sub-MIC concentrations exposure scenarios. This study provides evidence and mechanistic insight into the sub-MIC selection of antibiotic resistance by antibiotic-like environmental pollutants such as disinfection byproducts in water, which may be important contributors to the spread of global antibiotic resistance. The results from this study open an intriguing and profound question on the roles of large amount and various environmental contaminants play in selecting and spreading the antibiotics resistance in the environment.

Newly approved antibiotics and antibiotics reserved for resistant infections: Implications for emergency medicine.

PubMed

Mazer-Amirshahi, Maryann; Pourmand, Ali; May, Larissa

2017-01-01

Millions of patients are evaluated every year in the emergency department (ED) for bacterial infections. Emergency physicians often diagnose and prescribe initial antibiotic therapy for a variety of bacterial infections, ranging from simple urinary tract infections to severe sepsis. In life-threatening infections, inappropriate choice of initial antibiotic has been shown to increase morbidity and mortality. As such, initiation of appropriate antibiotic therapy on the part of the emergency physician is critical. Increasing rates of antibiotic resistance, drug allergies, and antibiotic shortages further complicates the choice of antibiotics. Patients may have a history of prior resistant infections or culture data indicating that common first-line antibiotics used in the ED may be ineffective. In recent years, there have been several new antibiotic approvals as well as renewed interest in second and third line antibiotics because of the aforementioned concerns. In addition, several newly approved antibiotics have the advantage of being administered once weekly or even as a single infusion, which has the potential to decrease hospitalizations and healthcare costs. This article reviews newly approved antibiotics and antibiotics used to treat resistant infections with a focus on implications for emergency medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Diverse Antibiotic Resistance Genes in Dairy Cow Manure

PubMed Central

Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

2014-01-01

ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

Bacterial cheating limits the evolution of antibiotic resistance

NASA Astrophysics Data System (ADS)

Chao, Hui Xiao; Datta, Manoshi; Yurtsev, Eugene; Gore, Jeff

2011-03-01

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain--which does not contribute to breaking down the antibiotic--may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we experimentally find that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors found in nature.

Interplay Between Antibiotic Resistance and Virulence During Disease Promoted by Multidrug-Resistant Bacteria

PubMed Central

Geisinger, Edward

2017-01-01

Abstract Diseases caused by antibiotic-resistant bacteria in hospitals are the outcome of complex relationships between several dynamic factors, including bacterial pathogenicity, the fitness costs of resistance in the human host, and selective forces resulting from interventions such as antibiotic therapy. The emergence and fate of mutations that drive antibiotic resistance are governed by these interactions. In this review, we will examine how different forms of antibiotic resistance modulate bacterial fitness and virulence potential, thus influencing the ability of pathogens to evolve in the context of nosocomial infections. We will focus on 3 important multidrug-resistant pathogens that are notoriously problematic in hospitals: Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. An understanding of how antibiotic resistance mutations shape the pathobiology of multidrug-resistant infections has the potential to drive novel strategies that can control the development and spread of drug resistance. PMID:28375515

[Antibiotic-resistant bacteria and new directions of antimicrobial chemotherapy].

PubMed

Tateda, Kazuhiro

2012-05-01

The emergence and spread of antibiotic-resistant organisms are becoming more and more serious and are a worldwide problem. Recent trends in new antibiotic-resistant organisms include multiple-drug resistant Pseudomonas aeruginosa (MDRP), MDR-Acinetobacter baumannii (MDR-AB) and New Deli metallo beta-lactamase-1 (NDM-1) -producing bacteria. Antibiotic combination therapy is an option to overcome these MDR organisms. A breakpoint checkerboard plate was created to measure antibiotic combination effects at breakpoint concentrations, making it possible to evaluate the synergy of antibiotic combination within 24 hours. In this article, recent topics regarding antibiotic-resistant organisms are briefly reviewed and the directions of antibiotic chemotherapy against these organisms are discussed.

Surveillance of antibiotic resistance

PubMed Central

Johnson, Alan P.

2015-01-01

Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439

Enterobacteriaceae Antibiotic Resistance in Ready-to-Eat Foods Collected from Hospital and Community Canteens: Analysis of Prevalence.

PubMed

Vincenti, Sara; Raponi, Matteo; Sezzatini, Romina; Giubbini, Gabriele; Laurenti, Patrizia

2018-03-01

Foodborne diseases and antibiotic resistance are serious widespread health problems in the contemporary world. In this study, we compared the microbiological quality of ready-to-eat (RTE) foods found in community canteens versus hospital canteens in Rome, Italy, focusing on detection and quantification of Enterobacteriaceae and the antibiotic resistance of these bacteria. Our findings show a remarkable difference in Enterobacteriaceae contamination between RTE foods distributed in community canteens (33.5% of samples) and those distributed in hospital canteens (5.3% of samples). This result highlights greater attention to good manufacturing practices and good hygiene practices by the food operators in hospitals compared with food operators in community canteens. As expected, a higher percentage of cold food samples (70.9%) than of hot food samples (10.8%) were positive for these bacteria. Excluding the intrinsic resistance of each bacterial strain, 92.3% of the isolated strains were resistant to at least one antibiotic, and about half of the isolated strains were classified as multidrug resistant. The prevalence of multidrug-resistant strains was 50% in the community samples and 33.3% in hospital canteens. Our results indicate that approximately 38% of RTE foods provided in community canteens is not compliant with microbiological food safety criteria and could be a special risk for consumers through spread of antibiotic-resistant strains. Hygienic processing and handling of foods is necessary for both hospital and community canteens.

Isolated cell behavior drives the evolution of antibiotic resistance

PubMed Central

Artemova, Tatiana; Gerardin, Ylaine; Dudley, Carmel; Vega, Nicole M; Gore, Jeff

2015-01-01

Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the collective inactivation of antibiotic by the bacterial population can cause the measured MIC to depend strongly on the initial cell density. In cases where this inoculum effect is strong, the relationship between MIC and bacterial fitness in the antibiotic is not well defined. Here, we demonstrate that the resistance of a single, isolated cell—which we call the single-cell MIC (scMIC)—provides a superior metric for quantifying antibiotic resistance. Unlike the MIC, we find that the scMIC predicts the direction of selection and also specifies the antibiotic concentration at which selection begins to favor new mutants. Understanding the cooperative nature of bacterial growth in antibiotics is therefore essential in predicting the evolution of antibiotic resistance. PMID:26227664

Antibiotic resistance among Ureaplasma spp. isolates: cause for concern?

PubMed

Beeton, M L; Spiller, O B

2017-02-01

There is growing global concern regarding the rise of antibiotic-resistant organisms. Many of these reports have focused on various Gram-positive and Gram-negative pathogens, with little attention to the genus Ureaplasma. Ureaplasma spp. are associated with numerous infectious diseases affecting pregnant women, neonates and the immunocompromised. Treatment options are extremely limited due to high levels of intrinsic resistance resulting from the unique physiology of these organisms and further restricted in cases of the developing fetus or neonate, often limiting therapeutic options to predominantly macrolides or rarely fluoroquinolones. The increasing presence of macrolide- and fluoroquinolone-resistant strains among neonatal infections may result in pan-drug resistance and potentially untreatable conditions. Here, we review the requirements for accurate measurement of antimicrobial susceptibility, provide a comprehensive review of the antimicrobial resistance (AMR) for Ureaplasma species in the literature and contextualize these results relative to some investigators' reliance on commercial kits that are not CLSI compliant when determining AMR. The dramatic variation in the resistance patterns and impact of high levels of AMR amongst neonatal populations suggests the need for continued surveillance. Commercial kits represent an excellent tool for initial antibiotic susceptibility determination and screening. However, AMR reporting must utilize internationally standardized methods, as high-titre samples, or Mycoplasma hominis-contaminated samples routinely give false AMR results. Furthermore, there is a requirement for future reports to determine the underlying AMR mechanisms and determine whether expanding AMR is due to spontaneous mutation, transmission of resistance genes on mobile elements or selection and expansion of resistant clones. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy

Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

PubMed Central

Coelho, Tatiane; Machado, Diana; Couto, Isabel; Maschmann, Raquel; Ramos, Daniela; von Groll, Andrea; Rossetti, Maria L.; Silva, Pedro A.; Viveiros, Miguel

2015-01-01

Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates. PMID:25972842

Genomics of antibiotic-resistance prediction in Pseudomonas aeruginosa.

PubMed

Jeukens, Julie; Freschi, Luca; Kukavica-Ibrulj, Irena; Emond-Rheault, Jean-Guillaume; Tucker, Nicholas P; Levesque, Roger C

2017-06-02

Antibiotic resistance is a worldwide health issue spreading quickly among human and animal pathogens, as well as environmental bacteria. Misuse of antibiotics has an impact on the selection of resistant bacteria, thus contributing to an increase in the occurrence of resistant genotypes that emerge via spontaneous mutation or are acquired by horizontal gene transfer. There is a specific and urgent need not only to detect antimicrobial resistance but also to predict antibiotic resistance in silico. We now have the capability to sequence hundreds of bacterial genomes per week, including assembly and annotation. Novel and forthcoming bioinformatics tools can predict the resistome and the mobilome with a level of sophistication not previously possible. Coupled with bacterial strain collections and databases containing strain metadata, prediction of antibiotic resistance and the potential for virulence are moving rapidly toward a novel approach in molecular epidemiology. Here, we present a model system in antibiotic-resistance prediction, along with its promises and limitations. As it is commonly multidrug resistant, Pseudomonas aeruginosa causes infections that are often difficult to eradicate. We review novel approaches for genotype prediction of antibiotic resistance. We discuss the generation of microbial sequence data for real-time patient management and the prediction of antimicrobial resistance. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Does antifouling paint select for antibiotic resistance?

PubMed

Flach, Carl-Fredrik; Pal, Chandan; Svensson, Carl Johan; Kristiansson, Erik; Östman, Marcus; Bengtsson-Palme, Johan; Tysklind, Mats; Larsson, D G Joakim

2017-07-15

There is concern that heavy metals and biocides contribute to the development of antibiotic resistance via co-selection. Most antifouling paints contain high amounts of such substances, which risks turning painted ship hulls into highly mobile refuges and breeding grounds for antibiotic-resistant bacteria. The objectives of this study were to start investigate if heavy-metal based antifouling paints can pose a risk for co-selection of antibiotic-resistant bacteria and, if so, identify the underlying genetic basis. Plastic panels with one side painted with copper and zinc-containing antifouling paint were submerged in a Swedish marina and biofilms from both sides of the panels were harvested after 2.5-4weeks. DNA was isolated from the biofilms and subjected to metagenomic sequencing. Biofilm bacteria were cultured on marine agar supplemented with tetracycline, gentamicin, copper sulfate or zinc sulfate. Biofilm communities from painted surfaces displayed lower taxonomic diversity and enrichment of Gammaproteobacteria. Bacteria from these communities showed increased resistance to both heavy metals and tetracycline but not to gentamicin. Significantly higher abundance of metal and biocide resistance genes was observed, whereas mobile antibiotic resistance genes were not enriched in these communities. In contrast, we found an enrichment of chromosomal RND efflux system genes, including such with documented ability to confer decreased susceptibility to both antibiotics and biocides/heavy metals. This was paralleled by increased abundances of integron-associated integrase and ISCR transposase genes. The results show that the heavy metal-based antifouling paint exerts a strong selection pressure on marine bacterial communities and can co-select for certain antibiotic-resistant bacteria, likely by favoring species and strains carrying genes that provide cross-resistance. Although this does not indicate an immediate risk for promotion of mobile antibiotic resistance, the

Fighting antibiotic resistance in Portuguese hospitals: Understanding antibiotic prescription behaviours to better design antibiotic stewardship programmes.

PubMed

Simões, Alexandra S; Alves, Daniela A; Gregório, João; Couto, Isabel; Dias, Sónia; Póvoa, Pedro; Viveiros, Miguel; Gonçalves, Luzia; Lapão, Luís V

2018-06-01

Since physicians play an important role in antibiotic usage, it is vital to understand their antibiotic-prescribing behaviour and knowledge on antimicrobial resistance in order to develop and implement effective antibiotic stewardship interventions. The aim of this study was to evaluate Portuguese physicians' knowledge and to understand prescription behaviours, difficulties and barriers in their antibiotic prescription process in order to promote better and well-adapted antibiotic stewardship policies. This study was conducted in 2016 using a self-administered questionnaire to physicians in two tertiary public hospitals from two different regions in Portugal. Participating physicians [response rate 47.6% (30/63)] identified antibiotic resistance as a global problem; however, one-third did not recognise antibiotic resistance as a major problem on their own hospital. Factors that most influenced antibiotic prescription were 'microbiology laboratory results', 'patient clinical situation' and patient 'co-morbidities'. On the other hand, 'colleagues' opinion' and 'costs control' were considered as less determining factors. Regarding difficulties and bottlenecks in the antibiotic prescription process, participant physicians reported 'lack of (or delayed) microbiological results' and 'no access to antibiotic susceptibility patterns' as major barriers. 'Education and training' was considered the most effective intervention to improve antibiotic prescription. These results suggest that the design and implementation of antibiotic stewardship interventions should provide better data management and sharing tools between physicians and the microbiology laboratory, especially through the creation of antimicrobial prescribing guidelines according to hospital epidemiology, and easy access to hospital antibiotic susceptibility patterns and epidemiological data. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights

Antibiotic-resistant genes and antibiotic-resistant bacteria in the effluent of urban residential areas, hospitals, and a municipal wastewater treatment plant system.

PubMed

Li, Jianan; Cheng, Weixiao; Xu, Like; Strong, P J; Chen, Hong

2015-03-01

In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet, 2 sul), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene (intI1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8% tetracyclines, 66.8% sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria (R (2) = 0.330, P < 0.05), there was no significant correlation between antibiotics and the corresponding resistant bacteria (P > 0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes (P < 0.05). Tet (A) and tet (B) displayed noticeable relationships with both tetracycline and combined antibiotic-resistant bacteria (P < 0.01).

Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting

PubMed Central

Brandtzaeg, Petter; Høiby, E. Arne; Bohlin, Jon; Samuelsen, Ørjan; Steinbakk, Martin; Abrahamsen, Tore G.; Müller, Fredrik; Gammelsrud, Karianne Wiger

2017-01-01

We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the

Persistence of antibiotic resistance: evaluation of a probiotic approach using antibiotic-sensitive Megasphaera elsdenii strains to prevent colonization of swine by antibiotic-resistant strains.

PubMed

Stanton, Thad B; Humphrey, Samuel B

2011-10-01

Megasphaera elsdenii is a lactate-fermenting, obligately anaerobic bacterium commonly present in the gastrointestinal tracts of mammals, including humans. Swine M. elsdenii strains were previously shown to have high levels of tetracycline resistance (MIC=64 to >256 μg/ml) and to carry mosaic (recombinant) tetracycline resistance genes. Baby pigs inherit intestinal microbiota from the mother sow. In these investigations we addressed two questions. When do M. elsdenii strains from the sow colonize baby pigs? Can five antibiotic-sensitive M. elsdenii strains administered intragastrically to newborn pigs affect natural colonization of the piglets by antibiotic-resistant (AR) M. elsdenii strains from the mother? M. elsdenii natural colonization of newborn pigs was undetectable (<10(4) CFU/g [wet weight] of feces) prior to weaning (20 days after birth). After weaning, all pigs became colonized (4 × 10(5) to 2 × 10(8) CFU/g feces). In a separate study, 61% (76/125) of M. elsdenii isolates from a gravid sow never exposed to antibiotics were resistant to chlortetracycline, ampicillin, or tylosin. The inoculation of the sow's offspring with mixtures of M. elsdenii antibiotic-sensitive strains prevented colonization of the offspring by maternal AR strains until at least 11 days postweaning. At 25 and 53 days postweaning, however, AR strains predominated. Antibiotic susceptibility phenotypes and single nucleotide polymorphism (SNP)-based identities of M. elsdenii isolated from sow and offspring were unexpectedly diverse. These results suggest that dosing newborn piglets with M. elsdenii antibiotic-sensitive strains delays but does not prevent colonization by maternal resistant strains. M. elsdenii subspecies diversity offers an explanation for the persistence of resistant strains in the absence of antibiotic selection.

Molecular typing of antibiotic-resistant Staphylococcus aureus in Nigeria.

PubMed

O'Malley, S M; Emele, F E; Nwaokorie, F O; Idika, N; Umeizudike, A K; Emeka-Nwabunnia, I; Hanson, B M; Nair, R; Wardyn, S E; Smith, T C

2015-01-01

Antibiotic-resistant Staphylococcus aureus including methicillin-resistant strains (MRSA) are a major concern in densely populated urban areas. Initial studies of S. aureus in Nigeria indicated existence of antibiotic-resistant S. aureus strains in clinical and community settings. 73 biological samples (40 throat, 23 nasal, 10 wound) were collected from patients and healthcare workers in three populations in Nigeria: Lagos University Teaching Hospital, Nigerian Institute of Medical Research, and Owerri General Hospital. S. aureus was isolated from 38 of 73 samples (52%). Of the 38 S. aureus samples, 9 (24%) carried the Panton-Valentine leukocidin gene (PVL) while 16 (42%) possessed methicillin resistance genes (mecA). Antibiotic susceptibility profiles indicated resistance to several broad-spectrum antibiotics. Antibiotic-resistant S. aureus isolates were recovered from clinical and community settings in Nigeria. Insight about S. aureus in Nigeria may be used to improve antibiotic prescription methods and minimize the spread of antibiotic-resistant organisms in highly populated urban communities similar to Lagos, Nigeria. Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides.

PubMed

Lázár, Viktória; Martins, Ana; Spohn, Réka; Daruka, Lejla; Grézal, Gábor; Fekete, Gergely; Számel, Mónika; Jangir, Pramod K; Kintses, Bálint; Csörgő, Bálint; Nyerges, Ákos; Györkei, Ádám; Kincses, András; Dér, András; Walter, Fruzsina R; Deli, Mária A; Urbán, Edit; Hegedűs, Zsófia; Olajos, Gábor; Méhi, Orsolya; Bálint, Balázs; Nagy, István; Martinek, Tamás A; Papp, Balázs; Pál, Csaba

2018-06-01

Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.

Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture.

PubMed

Chuah, Li-Oon; Effarizah, M E; Goni, Abatcha Mustapha; Rusul, Gulam

2016-06-01

Catfish is one of the most cultivated species worldwide. Antibiotics are usually used in catfish farming as therapeutic and prophylactic agents. In the USA, only oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and florfenicol are approved by the Food Drug Administration for specific fish species (e.g., catfish and salmonids) and their specific diseases. Misuse of antibiotics as prophylactic agents in disease prevention, however, is common and contributes in the development of antibiotic resistance. Various studies had reported on antibiotic residues and/or resistance in farmed species, feral fish, water column, sediments, and, in a lesser content, among farm workers. Ninety percent of the world aquaculture production is carried out in developing countries, which lack regulations and enforcement on the use of antibiotics. Hence, efforts are needed to promote the development and enforcement of such a regulatory structure. Alternatives to antibiotics such as antibacterial vaccines, bacteriophages and their lysins, and probiotics have been applied to curtail the increasing emergence of antibiotic-resistant bacteria due to the imprudent application of antibiotics in aquaculture.

Antibiotic-resistant bacteria: a challenge for the food industry.

PubMed

Capita, Rosa; Alonso-Calleja, Carlos

2013-01-01

Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed.

Antibiotic resistance: a primer and call to action.

PubMed

Smith, Rachel A; M'ikanatha, Nkuchia M; Read, Andrew F

2015-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention, 2013; World Health Organization, 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral, and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices.

Antibiotic resistance: a physicist’s view

NASA Astrophysics Data System (ADS)

Allen, Rosalind; Waclaw, Bartłomiej

2016-08-01

The problem of antibiotic resistance poses challenges across many disciplines. One such challenge is to understand the fundamental science of how antibiotics work, and how resistance to them can emerge. This is an area where physicists can make important contributions. Here, we highlight cases where this is already happening, and suggest directions for further physics involvement in antimicrobial research.

A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

PubMed Central

2014-01-01

Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. Conclusions Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other

Antibiotic Resistance: A Primer and Call to Action

PubMed Central

Smith, Rachel A.; M’ikanatha, Nkuchia M.; Read, Andrew F.

2014-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention [CDC], 2013; World Health Organization [WHO], 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices. PMID:25121990

Aquaculture changes the profile of antibiotic resistance and mobile genetic element associated genes in Baltic Sea sediments.

PubMed

Muziasari, Windi I; Pärnänen, Katariina; Johnson, Timothy A; Lyra, Christina; Karkman, Antti; Stedtfeld, Robert D; Tamminen, Manu; Tiedje, James M; Virta, Marko

2016-04-01

Antibiotics are commonly used in aquaculture and they can change the environmental resistome by increasing antibiotic resistance genes (ARGs). Sediment samples were collected from two fish farms located in the Northern Baltic Sea, Finland, and from a site outside the farms (control). The sediment resistome was assessed by using a highly parallel qPCR array containing 295 primer sets to detect ARGs, mobile genetic elements and the 16S rRNA gene. The fish farm resistomes were enriched in transposon and integron associated genes and in ARGs encoding resistance to antibiotics which had been used to treat fish at the farms. Aminoglycoside resistance genes were also enriched in the farm sediments despite the farms not having used aminoglycosides. In contrast, the total relative abundance values of ARGs were higher in the control sediment resistome and they were mainly genes encoding efflux pumps followed by beta-lactam resistance genes, which are found intrinsically in many bacteria. This suggests that there is a natural Baltic sediment resistome. The resistome associated with fish farms can be from native ARGs enriched by antibiotic use at the farms and/or from ARGs and mobile elements that have been introduced by fish farming. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genomic and metagenomic diversity of antibiotic resistance in dairy animals

USDA-ARS?s Scientific Manuscript database

Antibiotic resistance in food animals has received increased scrutiny in recent years due to the increased prevalence of antibiotic resistant infections in the human clinical setting. The extent to which antibiotic usage in food animals is responsible for the burden of antibiotic resistance in human...

Antibiotic resistance in hospitals: a ward-specific random effect model in a low antibiotic consumption environment.

PubMed

Aldrin, Magne; Raastad, Ragnhild; Tvete, Ingunn Fride; Berild, Dag; Frigessi, Arnoldo; Leegaard, Truls; Monnet, Dominique L; Walberg, Mette; Müller, Fredrik

2013-04-15

Association between previous antibiotic use and emergence of antibiotic resistance has been reported for several microorganisms. The relationship has been extensively studied, and although the causes of antibiotic resistance are multi-factorial, clear evidence of antibiotic use as a major risk factor exists. Most studies are carried out in countries with high consumption of antibiotics and corresponding high levels of antibiotic resistance, and currently, little is known whether and at what level the associations are detectable in a low antibiotic consumption environment. We conduct an ecological, retrospective study aimed at determining the impact of antibiotic consumption on antibiotic-resistant Pseudomonas aeruginosa in three hospitals in Norway, a country with low levels of antibiotic use. We construct a sophisticated statistical model to capture such low signals. To reduce noise, we conduct our study at hospital ward level. We propose a random effect Poisson or binomial regression model, with a reparametrisation that allows us to reduce the number of parameters. Inference is likelihood based. Through scenario simulation, we study the potential effects of reduced or increased antibiotic use. Results clearly indicate that the effects of consumption on resistance are present under conditions with relatively low use of antibiotic agents. This strengthens the recommendation on prudent use of antibiotics, even when consumption is relatively low. Copyright © 2012 John Wiley & Sons, Ltd.

Antibiotics and antibiotic resistance in agroecosystems: State of the science

USDA-ARS?s Scientific Manuscript database

We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly su...

Resistance Elasticity of Antibiotic Demand in Intensive Care.

PubMed

Heister, Thomas; Hagist, Christian; Kaier, Klaus

2017-07-01

The emergence and spread of antimicrobial resistance (AMR) is still an unresolved problem worldwide. In intensive care units (ICUs), first-line antibiotic therapy is highly standardized and widely empiric while treatment failure because of AMR often has severe consequences. Simultaneously, there is a limited number of reserve antibiotics, whose prices and/or side effects are substantially higher than first-line therapy. This paper explores the implications of resistance-induced substitution effects in ICUs. The extent of such substitution effects is shown in a dynamic fixed effect regression analysis using a panel of 66 German ICUs with monthly antibiotic use and resistance data between 2001 and 2012. Our findings support the hypothesis that demand for reserve antibiotics substantially increases when resistance towards first-line agents rises. For some analyses the lagged effect of resistance is also significant, supporting the conjecture that part of the substitution effect is caused by physicians changing antibiotic choices in empiric treatment by adapting their resistance expectation to new information on resistance prevalence. The available information about resistance rates allows physicians to efficiently balance the trade-off between exacerbating resistance and ensuring treatment success. However, resistance-induced substitution effects are not free of charge. These effects should be considered an indirect burden of AMR. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Research progress on distribution, migration, transformation of antibiotics and antibiotic resistance genes (ARGs) in aquatic environment.

PubMed

Shao, Sicheng; Hu, Yongyou; Cheng, Jianhua; Chen, Yuancai

2018-05-28

Antimicrobial and antibiotics resistance caused by misuse or overuse of antibiotics exposure is a growing and significant threat to global public health. The spread and horizontal transfer of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) by the selective pressure of antibiotics in an aquatic environment is a major public health issue. To develop a better understanding of potential ecological risks die to antibiotics and ARGs, this study mainly summarizes research progress about: (i) the occurrence, concentration, fate, and potential ecological effects of antibiotics and ARGs in various aquatic environments, (ii) the threat, spread, and horizontal gene transfer (HGT) of ARGs, and (iii) the relationship between antibiotics, ARGs, and ARB. Finally, this review also proposes future research direction on antibiotics and ARGs.

The role of biofilms as environmental reservoirs of antibiotic resistance.

PubMed

Balcázar, José L; Subirats, Jéssica; Borrego, Carles M

2015-01-01

Antibiotic resistance has become a significant and growing threat to public and environmental health. To face this problem both at local and global scales, a better understanding of the sources and mechanisms that contribute to the emergence and spread of antibiotic resistance is required. Recent studies demonstrate that aquatic ecosystems are reservoirs of resistant bacteria and antibiotic resistance genes as well as potential conduits for their transmission to human pathogens. Despite the wealth of information about antibiotic pollution and its effect on the aquatic microbial resistome, the contribution of environmental biofilms to the acquisition and spread of antibiotic resistance has not been fully explored in aquatic systems. Biofilms are structured multicellular communities embedded in a self-produced extracellular matrix that acts as a barrier to antibiotic diffusion. High population densities and proximity of cells in biofilms also increases the chances for genetic exchange among bacterial species converting biofilms in hot spots of antibiotic resistance. This review focuses on the potential effect of antibiotic pollution on biofilm microbial communities, with special emphasis on ecological and evolutionary processes underlying acquired resistance to these compounds.

Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

EPA Science Inventory

Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world.

PubMed

Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

2013-01-01

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem.

Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world

PubMed Central

Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

2013-01-01

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem. PMID:23404545

Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India

PubMed Central

2010-01-01

Background Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies on antibiotic prescription quantity in a hospital and antibiotic residue levels and resistant bacteria in the effluent of the same hospital are few. Therefore, we quantified antibiotic residues in waters associated with a hospital in India and assessed their association, if any, with quantities of antibiotic prescribed in the hospital and the susceptibility of Escherichia coli found in the hospital effluent. Methods This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics - amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin - were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints. Results Ciprofloxacin was the highest prescribed antibiotic in the hospital and its residue levels in the hospital wastewater were also the highest. In samples of the municipal water supply and the groundwater, no antibiotics were detected. There was a positive correlation between the quantity of antibiotics prescribed in the hospital and antibiotic residue levels in the hospital wastewater

Fate and transport of antibiotic residues and antibiotic resistance genes following land application of manure waste.

PubMed

Chee-Sanford, Joanne C; Mackie, Roderick I; Koike, Satoshi; Krapac, Ivan G; Lin, Yu-Feng; Yannarell, Anthony C; Maxwell, Scott; Aminov, Rustam I

2009-01-01

Antibiotics are used in animal livestock production for therapeutic treatment of disease and at subtherapeutic levels for growth promotion and improvement of feed efficiency. It is estimated that approximately 75% of antibiotics are not absorbed by animals and are excreted in waste. Antibiotic resistance selection occurs among gastrointestinal bacteria, which are also excreted in manure and stored in waste holding systems. Land application of animal waste is a common disposal method used in the United States and is a means for environmental entry of both antibiotics and genetic resistance determinants. Concerns for bacterial resistance gene selection and dissemination of resistance genes have prompted interest about the concentrations and biological activity of drug residues and break-down metabolites, and their fate and transport. Fecal bacteria can survive for weeks to months in the environment, depending on species and temperature, however, genetic elements can persist regardless of cell viability. Phylogenetic analyses indicate antibiotic resistance genes have evolved, although some genes have been maintained in bacteria before the modern antibiotic era. Quantitative measurements of drug residues and levels of resistance genes are needed, in addition to understanding the environmental mechanisms of genetic selection, gene acquisition, and the spatiotemporal dynamics of these resistance genes and their bacterial hosts. This review article discusses an accumulation of findings that address aspects of the fate, transport, and persistence of antibiotics and antibiotic resistance genes in natural environments, with emphasis on mechanisms pertaining to soil environments following land application of animal waste effluent.

The role of biofilms as environmental reservoirs of antibiotic resistance

PubMed Central

Balcázar, José L.; Subirats, Jéssica; Borrego, Carles M.

2015-01-01

Antibiotic resistance has become a significant and growing threat to public and environmental health. To face this problem both at local and global scales, a better understanding of the sources and mechanisms that contribute to the emergence and spread of antibiotic resistance is required. Recent studies demonstrate that aquatic ecosystems are reservoirs of resistant bacteria and antibiotic resistance genes as well as potential conduits for their transmission to human pathogens. Despite the wealth of information about antibiotic pollution and its effect on the aquatic microbial resistome, the contribution of environmental biofilms to the acquisition and spread of antibiotic resistance has not been fully explored in aquatic systems. Biofilms are structured multicellular communities embedded in a self-produced extracellular matrix that acts as a barrier to antibiotic diffusion. High population densities and proximity of cells in biofilms also increases the chances for genetic exchange among bacterial species converting biofilms in hot spots of antibiotic resistance. This review focuses on the potential effect of antibiotic pollution on biofilm microbial communities, with special emphasis on ecological and evolutionary processes underlying acquired resistance to these compounds. PMID:26583011

Antibiotic resistance in the wild: an eco-evolutionary perspective.

PubMed

Hiltunen, Teppo; Virta, Marko; Laine, Anna-Liisa

2017-01-19

The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Authors.

Antibiotic resistance in the wild: an eco-evolutionary perspective

PubMed Central

Virta, Marko

2017-01-01

The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences'. PMID:27920384

Phenotypic and genotypic characterisation of multiple antibiotic-resistant Staphylococcus aureus exposed to subinhibitory levels of oxacillin and levofloxacin.

PubMed

Jo, Ara; Ahn, Juhee

2016-07-29

The emergence and spread of multidrug resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA) has serious health consequences in the presence of sub-MIC antibiotics. Therefore, this study was designed to evaluate β-lactamase activity, efflux activity, biofilm formation, and gene expression pattern in Staphylococcus aureus KACC 10778, S. aureus ATCC 15564, and S. aureus CCARM 3080 exposed to sublethal concentrations of levofloxacin and oxacillin. The decreased MICs were observed in S. aureus KACC and S. aureus ATCC when exposed to levofloxacin and oxacillin, while and S. aureus CCARM remained resistance to streptomycin (512 μg/mL) in the presence of levofloxacin and imipenem (>512 μg/mL) in the presence of oxacillin. The considerable increase in extracellular and membrane-bound β-lactamase activities was observed in S. aureus ATCC exposed to oxacillin (>26 μmol/min/mL). The antibiotic susceptibility of all strains exposed to EPIs (CCCP and PAβN) varied depending on the classes of antibiotics. The relative expression levels of adhesion-related genes (clfA, clfB, fnbA, fnnB, and icaD), efflux-related genes (norB, norC, and qacA/B), and enterotoxin gene (sec) were increased more than 5-fold in S. aureus CCARM. The eno and qacA/B genes were highly overexpressed by more than 12- and 9-folds, respectively, in S. aureus CCARM exposed to levofloxacin. The antibiotic susceptibility, lactamase activity, biofilm-forming ability, efflux activity, and gene expression pattern varied with the intrinsic antibiotic resistance of S. aureus KACC, S. aureus ATCC, and S. aureus CCARM exposed to levofloxacin and oxacillin. This study would provide useful information for better understating of combination therapy related to antibiotic resistance mechanisms and open the door for designing effective antibiotic treatment protocols to prevent excessive use of antibiotics in clinical practice.

Occurrence and Distribution of Antibiotic-resistant Bacteria and Transfer of Resistance Genes in Lake Taihu

PubMed Central

Yin, Qian; Yue, Dongmei; Peng, Yuke; Liu, Ying; Xiao, Lin

2013-01-01

The overuse of antibiotics has accelerated antibiotic resistance in the natural environment, especially fresh water, generating a potential risk for public health around the world. In this study, antibiotic resistance in Lake Taihu was investigated and this was the first thorough data obtained through culture-dependent methods. High percentages of resistance to streptomycin and ampicillin among bacterial isolates were detected, followed by tetracycline and chloramphenicol. Especially high levels of ampicillin resistance in the western and northern regions were illustrated. Bacterial identification of the isolates selected for further study indicated the prevalence of some opportunistic pathogens and 62.0% of the 78 isolates exhibited multiple antibiotic resistance. The presence of ESBLs genes was in the following sequence: blaTEM > blaSHV > blaCTMX and 38.5% of the isolates had a class I integrase gene. Of all tested strains, 80.8% were able to transfer antibiotic resistance through conjugation. We also concluded that some new families of human-associated ESBLs and AmpC genes can be found in natural environmental isolates. The prevalence of antibiotic resistance and the dissemination of transferable antibiotic resistance in bacterial isolates (especially in opportunistic pathogens) was alarming and clearly indicated the urgency of realizing the health risks of antibiotic resistance to human and animal populations who are dependent on Lake Taihu for water consumption. PMID:24240317

Detection of antibiotic resistance in probiotics of dietary supplements.

PubMed

Wong, Aloysius; Ngu, Davey Yueh Saint; Dan, Lydia Annabel; Ooi, Amanda; Lim, Renee Lay Hong

2015-09-14

Probiotics are live microorganisms that confer nutrition- and health-promoting benefits if consumed in adequate amounts. Concomitant with the demand for natural approaches to maintaining health is an increase in inclusion of probiotics in food and health products. Since probiotic bacteria act as reservoir for antibiotic resistant determinants, the transfer of these genes to pathogens sharing the same intestinal habitat is thus conceivable considering the fact that dietary supplements contain high amounts of often heterogeneous populations of probiotics. Such events can confer pathogens protection against commonly-used drugs. Despite numerous reports of antibiotic resistant probiotics in food and biological sources, the antibiogram of probiotics from dietary supplements remained elusive. Here, we screened five commercially available dietary supplements for resistance towards antibiotics of different classes. Probiotics of all batches of products were resistant towards vancomycin while batch-dependent resistance towards streptomycin, aztreonam, gentamycin and/or ciprofloxacin antibiotics was detected for probiotics of brands Bi and Bn, Bg, and L. Isolates of brand Cn was also resistant towards gentamycin, streptomycin and ciprofloxacin antibiotics. Additionally, we also report a discrepancy between the enumerated viable bacteria amounts and the claims of the manufacturers. This short report has highlighted the present of antibiotic resistance in probiotic bacteria from dietary supplements and therefore serves as a platform for further screenings and for in-depth characterization of the resistant determinants and the molecular machinery that confers the resistance.

The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics.

PubMed

Krawczyk-Balska, A; Markiewicz, Z

2016-02-01

Intrinsic resistance to antibiotics is a serious therapeutic problem in the case of many bacterial species. The Gram-positive human pathogen Listeria monocytogenes is intrinsically resistant to broad spectrum cephalosporin antibiotics, which are commonly used in therapy of bacterial infections. Besides three penicillin-binding proteins the intrinsic cephalosporin resistome of L. monocytogenes includes multidrug resistance transporter transporters, proteins involved in peptidoglycan biosynthesis and modification, cell envelope proteins with structural or general detoxification function, cytoplasmic proteins with unknown function and regulatory proteins. Analysis of the regulation of the expression of genes involved in the intrinsic resistance of L. monocytogenes to cephalosporins highlights the high complexity of control of the intrinsic resistance phenotype. The regulation of the transcription of the intrinsic resistome determinants involves the activity of eight regulators, namely LisR, CesR, LiaR, VirR, σ(B) , σ(H) , σ(L) and PrfA, of which the most prominent role play LisR, CesR and σ(B) . Furthermore, the vast majority of the intrinsic resistome determinants contribute to the tolerance of different stress conditions and virulence. A study indicates that O-acetyltransferase OatA is the most promising candidate for co-drug development since an agent targeting OatA should sensitize L. monocytogenes to certain antibiotics, therefore improving the efficacy of listeriosis treatment as well as food preservation measures. © 2015 The Society for Applied Microbiology.

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

PubMed Central

Pamer, Eric G.

2016-01-01

The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria. PMID:27126035

Epidemiological Interpretation of Studies Examining the Effect of Antibiotic Usage on Resistance

PubMed Central

Schechner, Vered; Temkin, Elizabeth; Harbarth, Stephan; Carmeli, Yehuda

2013-01-01

SUMMARY Bacterial resistance to antibiotics is a growing clinical problem and public health threat. Antibiotic use is a known risk factor for the emergence of antibiotic resistance, but demonstrating the causal link between antibiotic use and resistance is challenging. This review describes different study designs for assessing the association between antibiotic use and resistance and discusses strengths and limitations of each. Approaches to measuring antibiotic use and antibiotic resistance are presented. Important methodological issues such as confounding, establishing temporality, and control group selection are examined. PMID:23554418

The scourge of antibiotic resistance: the important role of the environment.

PubMed

Finley, Rita L; Collignon, Peter; Larsson, D G Joakim; McEwen, Scott A; Li, Xian-Zhi; Gaze, William H; Reid-Smith, Richard; Timinouni, Mohammed; Graham, David W; Topp, Edward

2013-09-01

Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.

Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology.

PubMed

Gibson, Molly K; Forsberg, Kevin J; Dantas, Gautam

2015-01-01

Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.

The hidden societal cost of antibiotic resistance per antibiotic prescribed in the United States: an exploratory analysis.

PubMed

Michaelidis, Constantinos I; Fine, Michael J; Lin, Chyongchiou Jeng; Linder, Jeffrey A; Nowalk, Mary Patricia; Shields, Ryan K; Zimmerman, Richard K; Smith, Kenneth J

2016-11-08

Ambulatory antibiotic prescribing contributes to the development of antibiotic resistance and increases societal costs. Here, we estimate the hidden societal cost of antibiotic resistance per antibiotic prescribed in the United States. In an exploratory analysis, we used published data to develop point and range estimates for the hidden societal cost of antibiotic resistance (SCAR) attributable to each ambulatory antibiotic prescription in the United States. We developed four estimation methods that focused on the antibiotic-resistance attributable costs of hospitalization, second-line inpatient antibiotic use, second-line outpatient antibiotic use, and antibiotic stewardship, then summed the estimates across all methods. The total SCAR attributable to each ambulatory antibiotic prescription was estimated to be $13 (range: $3-$95). The greatest contributor to the total SCAR was the cost of hospitalization ($9; 69 % of the total SCAR). The costs of second-line inpatient antibiotic use ($1; 8 % of the total SCAR), second-line outpatient antibiotic use ($2; 15 % of the total SCAR) and antibiotic stewardship ($1; 8 %). This apperars to be an error.; of the total SCAR) were modest contributors to the total SCAR. Assuming an average antibiotic cost of $20, the total SCAR attributable to each ambulatory antibiotic prescription would increase antibiotic costs by 65 % (range: 15-475 %) if incorporated into antibiotic costs paid by patients or payers. Each ambulatory antibiotic prescription is associated with a hidden SCAR that substantially increases the cost of an antibiotic prescription in the United States. This finding raises concerns regarding the magnitude of misalignment between individual and societal antibiotic costs.

The evolution of antibiotic resistance in a structured host population.

PubMed

Blanquart, François; Lehtinen, Sonja; Lipsitch, Marc; Fraser, Christophe

2018-06-01

The evolution of antibiotic resistance in opportunistic pathogens such as Streptococcus pneumoniae , Escherichia coli or Staphylococcus aureus is a major public health problem, as infection with resistant strains leads to prolonged hospital stay and increased risk of death. Here, we develop a new model of the evolution of antibiotic resistance in a commensal bacterial population adapting to a heterogeneous host population composed of untreated and treated hosts, and structured in different host classes with different antibiotic use. Examples of host classes include age groups and geographic locations. Explicitly modelling the antibiotic treatment reveals that the emergence of a resistant strain is favoured by more frequent but shorter antibiotic courses, and by higher transmission rates. In addition, in a structured host population, localized transmission in host classes promotes both local adaptation of the bacterial population and the global maintenance of coexistence between sensitive and resistant strains. When transmission rates are heterogeneous across host classes, resistant strains evolve more readily in core groups of transmission. These findings have implications for the better management of antibiotic resistance: reducing the rate at which individuals receive antibiotics is more effective to reduce resistance than reducing the duration of treatment. Reducing the rate of treatment in a targeted class of the host population allows greater reduction in resistance, but determining which class to target is difficult in practice. © 2018 The Authors.

Antibiotic-Impregnated Central Venous Catheters Do Not Change Antibiotic Resistance Patterns.

PubMed

Turnbull, Isaiah R; Buckman, Sara A; Horn, Christopher B; Bochicchio, Grant V; Mazuski, John E

2018-01-01

Antibiotic-impregnated central venous catheters (CVCs) decrease the incidence of infection in high-risk patients. However, use of these catheters carries the hypothetical risk of inducing antibiotic resistance. We hypothesized that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a single intensive care unit (ICU) would change the resistance profile for Staphylococcus aureus. We reviewed antibiotic susceptibilities of S. aureus isolates obtained from blood cultures in a large urban teaching hospital from 2002-2015. Resistance patterns were compared before and after implementation of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients, in whom MR-CVCs were not used. Data for rifampin, oxacillin, and clindamycin were available for 9,703 cultures; tetracycline resistance data were available for 4,627 cultures. After implementation of MR-CVC use in the SICU, rifampin resistance remained unchanged, with rates the same as in other ICU and non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR-CVCs was not associated with any change in S. aureus oxacillin-resistance rates in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus clindamycin resistance (59% vs. 34%; p < 0.05) in SICU patients. Routine use of rifampin-minocycline-impregnated CVCs in the SICU was not associated with increased resistance of S. aureus isolates to rifampin or tetracyclines.

Antibiotic resistance and virulence genes in coliform water isolates.

PubMed

Stange, C; Sidhu, J P S; Tiehm, A; Toze, S

2016-11-01

Widespread fecal pollution of surface water may present a major health risk and a significant pathway for dissemination of antibiotic resistance bacteria. The River Rhine is one of the longest and most important rivers in Europe and an important raw water source for drinking water production. A total of 100 coliform isolates obtained from River Rhine (Germany) were examined for their susceptibility to seven antimicrobial agents. Resistances against amoxicillin, trimethoprim/sulfamethoxazole and tetracycline were detected in 48%, 11% and 9% of isolates respectively. The antibiotic resistance could be traced back to the resistance genes bla TEM , bla SHV , ampC, sul1, sul2, dfrA1, tet(A) and tet(B). Whereby, the ampC gene represents a special case, because its presence is not inevitably linked to a phenotypic antibiotic resistance. Multiple antibiotics resistance was often accompanied by the occurrence of class 1 or 2 integrons. E. coli isolates belonging to phylogenetic groups A and B1 (commensal) were more predominant (57%) compared to B2 and D groups (43%) which are known to carry virulent genes. Additionally, six E. coli virulence genes were also detected. However, the prevalence of virulence genes in the E. coli isolates was low (not exceeding 4.3% per gene) and no diarrheagenic E. coli pathotypes were detected. This study demonstrates that surface water is an important reservoir of ARGs for a number of antibiotic classes such as sulfonamide, trimethoprim, beta-lactam-antibiotics and tetracycline. The occurrence of antibiotic resistance in coliform bacteria isolated from River Rhine provides evidence for the need to develop management strategies to limit the spread of antibiotic resistant bacteria in aquatic environment. Copyright © 2016 Elsevier GmbH. All rights reserved.

Antibiotic and antiseptic resistance: impact on public health.

PubMed

Levy, S B

2000-10-01

More and more we are moving patients from hospitals to homes for continued treatment. Vancomycin and triclosan were used for 30 years before any resistance emerged, because their applications were strictly limited. Today, after greatly increased use, resistance to both antibiotics and antibacterials has appeared. Of importance there are genetic links between resistance to antibiotics and to antibacterials. Health professionals and the public need to be educated about the rational use of drugs that affect the microbial world. The Alliance for the Prudent Use of Antibiotics, an international organization established in 1981 with members in more than 100 countries, has adopted education as its prime mission. Via its web site (www.apua.org) and linked information on reservoirs of antibiotic resistance (ROAR) among nonpathogenic bacteria, it reaches both providers and consumers. The message is simple: bacteria are needed for our survival. The vast majority of bacteria perform important functions that are crucial for our lives. Prudent use of both antibiotics and antibacterials must be championed to achieve and maintain the balanced microbial environment in which we have entered and evolved.

Impact of dairy manure pre-application treatment on manure composition, soil dynamics of antibiotic resistance genes, and abundance of antibiotic-resistance genes on vegetables at harvest.

PubMed

Tien, Yuan-Ching; Li, Bing; Zhang, Tong; Scott, Andrew; Murray, Roger; Sabourin, Lyne; Marti, Romain; Topp, Edward

2017-03-01

Manuring ground used for crop production is an important agricultural practice. Should antibiotic-resistant enteric bacteria carried in the manure be transferred to crops that are consumed raw, their consumption by humans or animals will represent a route of exposure to antibiotic resistance genes. Treatment of manures prior to land application is a potential management option to reduce the abundance of antibiotic resistance genes entrained with manure application. In this study, dairy manure that was untreated, anaerobically digested, mechanically dewatered or composted was applied to field plots that were then cropped to lettuce, carrots and radishes. The impact of treatment on manure composition, persistence of antibiotic resistance gene targets in soil following application, and distribution of antibiotic resistance genes and bacteria on vegetables at harvest was determined. Composted manure had the lowest abundance of antibiotic resistance gene targets compared to the other manures. There was no significant difference in the persistence characteristics of antibiotic resistance genes following land application of the various manures. Compared to unmanured soil, antibiotic resistance genes were detected more frequently in soil receiving raw or digested manure, whereas they were not in soil receiving composted manure. The present study suggests that vegetables grown in ground receiving raw or digested manure are at risk of contamination with manure-borne antibiotic resistant bacteria, whereas vegetables grown in ground receiving composted manure are less so. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Inhaled antibiotics: the new era of personalized medicine?

PubMed

Biller, Julie A

2015-11-01

Treatment options for individuals with cystic fibrosis (CF) have improved survival significantly over the past two decades. One important treatment modality is inhaled antibiotics to treat chronic infection of the airways. This review includes those antibiotics that are currently in use, those that are in clinical trials. It also includes review of nonantibiotic antimicrobials, a growing area of investigation in CF. There are currently three inhaled antibiotics that are approved for use in patients with cystic fibrosis: tobramycin, aztreonam, and colistimethate. Tobramycin and colistimethate now are available as solution and new dry powder formulations, which are helping the treatment burden which has increased in CF. New antibiotics are in trial, although recently two did not meet primary outcomes in large clinical trials. Of particular interest is the development of nonantibiotic antimicrobials, which may allow treatment of intrinsically antibiotic resistant organisms. Inhaled antibiotics remain an important treatment option in cystic fibrosis due to chronic airway infection as a hallmark of the disease. Although there are now multiple options for treatment, improvements in this treatment class are needed to treat intrinsically resistant organisms. New formulation of antibiotics and nonantibiotic antimicrobials are being evaluated to add to our armamentarium.

Antibiotic-Resistant Escherichia coli in Migratory Birds Inhabiting Remote Alaska.

PubMed

Ramey, Andrew M; Hernandez, Jorge; Tyrlöv, Veronica; Uher-Koch, Brian D; Schmutz, Joel A; Atterby, Clara; Järhult, Josef D; Bonnedahl, Jonas

2017-12-11

We explored the abundance of antibiotic-resistant Escherichia coli among migratory birds at remote sites in Alaska and used a comparative approach to speculate on plausible explanations for differences in detection among species. At a remote island site, we detected antibiotic-resistant E. coli phenotypes in samples collected from glaucous-winged gulls (Larus glaucescens), a species often associated with foraging at landfills, but not in samples collected from black-legged kittiwakes (Rissa tridactyla), a more pelagic gull that typically inhabits remote areas year-round. We did not find evidence for antibiotic-resistant E. coli among 347 samples collected primarily from waterfowl at a second remote site in western Alaska. Our results provide evidence that glaucous-winged gulls may be more likely to be infected with antibiotic-resistant E. coli at remote breeding sites as compared to sympatric black-legged kittiwakes. This could be a function of the tendency of glaucous-winged gulls to forage at landfills where antibiotic-resistant bacterial infections may be acquired and subsequently dispersed. The low overall detection of antibiotic-resistant E. coli in migratory birds sampled at remote sites in Alaska is consistent with the premise that anthropogenic inputs into the local environment or the relative lack thereof influences the prevalence of antibiotic-resistant bacteria among birds inhabiting the area.

Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria

PubMed Central

Yosef, Ido; Manor, Miriam; Kiro, Ruth

2015-01-01

The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones. PMID:26060300

Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria.

PubMed

Yosef, Ido; Manor, Miriam; Kiro, Ruth; Qimron, Udi

2015-06-09

The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones.

A new antibiotic kills pathogens without detectable resistance.

PubMed

Ling, Losee L; Schneider, Tanja; Peoples, Aaron J; Spoering, Amy L; Engels, Ina; Conlon, Brian P; Mueller, Anna; Schäberle, Till F; Hughes, Dallas E; Epstein, Slava; Jones, Michael; Lazarides, Linos; Steadman, Victoria A; Cohen, Douglas R; Felix, Cintia R; Fetterman, K Ashley; Millett, William P; Nitti, Anthony G; Zullo, Ashley M; Chen, Chao; Lewis, Kim

2015-01-22

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment

PubMed Central

Pruden, Amy; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K.; Graham, David W.; Lazorchak, James M.; Suzuki, Satoru; Silley, Peter; Snape, Jason R.; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

2013-01-01

Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. PMID:23735422

Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

PubMed Central

SOARES, Geisla Mary Silva; FIGUEIREDO, Luciene Cristina; FAVERI, Marcelo; CORTELLI, Sheila Cavalca; DUARTE, Poliana Mendes; FERES, Magda

2012-01-01

Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections. PMID:22858695

Marine bacteria: potential sources for compounds to overcome antibiotic resistance.

PubMed

Eom, Sung-Hwan; Kim, Young-Mog; Kim, Se-Kwon

2013-06-01

Methicillin-resistant Staphylococcus aureus (MRSA) is the most problematic Gram-positive bacterium in the context of public health due to its resistance against almost all available antibiotics except vancomycin and teicoplanin. Moreover, glycopeptide-resistant S. aureus have been emerging with the increasing use of glycopeptides. Recently, resistant strains against linezolid and daptomycin, which are alternative drugs to treat MRSA infection, have also been reported. Thus, the development of new drugs or alternative therapies is clearly a matter of urgency. In response to the antibiotic resistance, many researchers have studied for alternative antibiotics and therapies. In this review, anti-MRSA substances isolated from marine bacteria, with their potential antibacterial effect against MRSA as potential anti-MRSA agents, are discussed and several strategies for overcoming the antibiotic resistance are also introduced. Our objective was to highlight marine bacteria that have potential to lead in developing novel antibiotics or clinically useful alternative therapeutic treatments.

Current perspectives on the dynamics of antibiotic resistance in different reservoirs.

PubMed

Caniça, Manuela; Manageiro, Vera; Jones-Dias, Daniela; Clemente, Lurdes; Gomes-Neves, Eduarda; Poeta, Patrícia; Dias, Elsa; Ferreira, Eugénia

2015-09-01

Antibiotic resistance consists of a dynamic web. In this review, we describe the path by which different antibiotic residues and antibiotic resistance genes disseminate among relevant reservoirs (human, animal, and environmental settings), evaluating how these events contribute to the current scenario of antibiotic resistance. The relationship between the spread of resistance and the contribution of different genetic elements and events is revisited, exploring examples of the processes by which successful mobile resistance genes spread across different niches. The importance of classic and next generation molecular approaches, as well as action plans and policies which might aid in the fight against antibiotic resistance, are also reviewed. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Photodynamic UVA-riboflavin bacterial elimination in antibiotic-resistant bacteria.

PubMed

Makdoumi, Karim; Bäckman, Anders

2016-09-01

To evaluate the bactericidal effect of clinical ultraviolet A (UVA) settings used in photoactivated chromophore for infectious keratitis (PACK)-collagen cross-linking (CXL) in antibiotic-resistant and non-resistant bacterial strains. Well-characterized bacterial strains from clinical isolates, without and with antibiotic resistance, were studied in a pairwise comparison. The evaluated pathogens were Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacteria were dispersed in PBS and diluted to a concentration of approximately 4 × 10 5 /ml. Riboflavin was added to a concentration of 0.01%. By spreading the solution on a microscope slide, a fluid film layer, with a thickness of around 400 mm, was formed and UVA exposure followed. Eight separate exposures were made for each strain (n = 8). The degree of elimination in resistant and non-resistant pathogens was compared. The bactericidal efficacy of exposure differed between the tested microorganisms, and the mean elimination ranged between 60 and 92%, being most extensive in both of the evaluated Pseudomonas strains and least in the E. faecalis strains. Similar reductions were seen in antibiotic-resistant and non-resistant strains, with the exception of S. aureus, in which the resistant strain metchicillin-resistant Staphylococcus aureus (MRSA) was eradicated in a greater extent than the non-resistant strain (P = 0.030). UVA-riboflavin settings used in PACK-CXL are effective in reducing both antibiotic-resistant and non-resistant bacteria. Antibiotic resistance does not appear to be protective against the photooxidative exposure. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Impact of Manure Fertilization on the Abundance of Antibiotic-Resistant Bacteria and Frequency of Detection of Antibiotic Resistance Genes in Soil and on Vegetables at Harvest

PubMed Central

Marti, Romain; Scott, Andrew; Tien, Yuan-Ching; Murray, Roger; Sabourin, Lyne; Zhang, Yun

2013-01-01

Consumption of vegetables represents a route of direct human exposure to bacteria found in soil. The present study evaluated the complement of bacteria resistant to various antibiotics on vegetables often eaten raw (tomato, cucumber, pepper, carrot, radish, lettuce) and how this might vary with growth in soil fertilized inorganically or with dairy or swine manure. Vegetables were sown into field plots immediately following fertilization and harvested when of marketable quality. Vegetable and soil samples were evaluated for viable antibiotic-resistant bacteria by plate count on Chromocult medium supplemented with antibiotics at clinical breakpoint concentrations. DNA was extracted from soil and vegetables and evaluated by PCR for the presence of 46 gene targets associated with plasmid incompatibility groups, integrons, or antibiotic resistance genes. Soil receiving manure was enriched in antibiotic-resistant bacteria and various antibiotic resistance determinants. There was no coherent corresponding increase in the abundance of antibiotic-resistant bacteria enumerated from any vegetable grown in manure-fertilized soil. Numerous antibiotic resistance determinants were detected in DNA extracted from vegetables grown in unmanured soil. A smaller number of determinants were additionally detected on vegetables grown only in manured and not in unmanured soil. Overall, consumption of raw vegetables represents a route of human exposure to antibiotic-resistant bacteria and resistance determinants naturally present in soil. However, the detection of some determinants on vegetables grown only in freshly manured soil reinforces the advisability of pretreating manure through composting or other stabilization processes or mandating offset times between manuring and harvesting vegetables for human consumption. PMID:23851089

Impact of manure fertilization on the abundance of antibiotic-resistant bacteria and frequency of detection of antibiotic resistance genes in soil and on vegetables at harvest.

PubMed

Marti, Romain; Scott, Andrew; Tien, Yuan-Ching; Murray, Roger; Sabourin, Lyne; Zhang, Yun; Topp, Edward

2013-09-01

Consumption of vegetables represents a route of direct human exposure to bacteria found in soil. The present study evaluated the complement of bacteria resistant to various antibiotics on vegetables often eaten raw (tomato, cucumber, pepper, carrot, radish, lettuce) and how this might vary with growth in soil fertilized inorganically or with dairy or swine manure. Vegetables were sown into field plots immediately following fertilization and harvested when of marketable quality. Vegetable and soil samples were evaluated for viable antibiotic-resistant bacteria by plate count on Chromocult medium supplemented with antibiotics at clinical breakpoint concentrations. DNA was extracted from soil and vegetables and evaluated by PCR for the presence of 46 gene targets associated with plasmid incompatibility groups, integrons, or antibiotic resistance genes. Soil receiving manure was enriched in antibiotic-resistant bacteria and various antibiotic resistance determinants. There was no coherent corresponding increase in the abundance of antibiotic-resistant bacteria enumerated from any vegetable grown in manure-fertilized soil. Numerous antibiotic resistance determinants were detected in DNA extracted from vegetables grown in unmanured soil. A smaller number of determinants were additionally detected on vegetables grown only in manured and not in unmanured soil. Overall, consumption of raw vegetables represents a route of human exposure to antibiotic-resistant bacteria and resistance determinants naturally present in soil. However, the detection of some determinants on vegetables grown only in freshly manured soil reinforces the advisability of pretreating manure through composting or other stabilization processes or mandating offset times between manuring and harvesting vegetables for human consumption.

Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis.

PubMed

Tacconelli, Evelina; Carrara, Elena; Savoldi, Alessia; Harbarth, Stephan; Mendelson, Marc; Monnet, Dominique L; Pulcini, Céline; Kahlmeter, Gunnar; Kluytmans, Jan; Carmeli, Yehuda; Ouellette, Marc; Outterson, Kevin; Patel, Jean; Cavaleri, Marco; Cox, Edward M; Houchens, Chris R; Grayson, M Lindsay; Hansen, Paul; Singh, Nalini; Theuretzbacher, Ursula; Magrini, Nicola

2018-03-01

The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier. Future development strategies should focus on

A potent synthetic inorganic antibiotic with activity against drug-resistant pathogens.

PubMed

Hubick, Shelby; Jayaraman, Arumugam; McKeen, Alexander; Reid, Shelby; Alcorn, Jane; Stavrinides, John; Sterenberg, Brian T

2017-02-06

The acronymously named "ESKAPE" pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to "eskape" antibiotic treatment. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). We show that this potent antibiotic is bactericidal, and exhibits low toxicity in an acute dose assay in mice. As a synthetic compound that does not occur naturally, phosphopyricin would be evolutionarily foreign to microbes, thereby slowing the evolution of resistance. In addition, it loses antibiotic activity upon exposure to light, meaning that the active antibiotic will not accumulate in the general environment where strong selective pressures imposed by antibiotic residuals are known to accelerate resistance. Phosphopyricin represents an innovation in antimicrobials, having a synthetic core, and a photosensitive chemical architecture that would reduce accumulation in the environment.

The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal

PubMed Central

Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

2014-01-01

Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level. PMID:24637798

The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal.

PubMed

Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

2014-01-01

Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level.

Clinical, economic and societal impact of antibiotic resistance.

PubMed

Barriere, Steven L

2015-02-01

The concern over antibiotic resistance has been voiced since the discovery of modern antibiotics > 75 years ago. The concerns have only increased with time, with efforts to control resistance caused by widespread overuse of antibiotics in human medicine and far more than appreciated use in the feeding of animals for human consumption to promote growth. The problem is worldwide, but certain regions and selected health care institutions report far more resistance, including strains of Gram-negative bacteria that are susceptible only to the once discarded drugs polymyxin B or colistin, and pan-resistant strains are on the rise. One of the central efforts to control resistance, apart from antimicrobial stewardship, is the development of new antimicrobial agents. This has lagged significantly over the past 10 - 15 years, for a variety of reasons; but promising new agents are being developed, unfortunately none thus far addressing all potentially resistant strains. There is the unlikely, but not unreal, possibility that we could return to a pre-antibiotic era, where morbidity and mortality rates have risen dramatically and routine surgical procedures are not performed for fear of post-operative infections. The onus of control of resistance is a moral imperative that falls on the shoulders of all.

Risk of antibiotic resistance from metal contaminated soils

NASA Astrophysics Data System (ADS)

Knapp, Charles

2013-04-01

It is known that contaminated soils can lead to increased incidence of illness and disease, but it may also prevent our ability to fight disease. Many antibiotic resistant genes (ARG) acquired by bacteria originate from the environment. It is important to understand factors that influence levels of ARG in the environment, which could affect us clinically and agriculturally. The presence of elevated metal content in soils often promotes antibiotic resistance in exposed microorganisms. Using qPCR, the abundances of ARG to compare levels with geochemical conditions in randomly selected soils from several countries. Many ARG positively correlated with soil metal content, especially copper, chromium, nickel, lead, and iron. Results suggest that geochemical metal conditions influence the potential for antibiotic resistance in soil, which might be used to estimate baseline gene presence on various landscape scales and may translate to epidemiological risk of antibiotic-resistance transmission from the environment. This suggests that we may have to reconsider tolerances of metal pollution in the environment.

Horizontal gene transfer and antibiotic resistance plasmids in multi-drug resistant Salmonella enterica serovars

USDA-ARS?s Scientific Manuscript database

Antibiotic resistant foodborne pathogens pose serious public health concerns and increase the burden of disease treatment. Antibiotic resistance genes can reside on the bacterial chromosome or on other self-replicating DNA molecules such as plasmids. The resistance genes/DNA can be transferred int...

Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

PubMed

Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy; Wang, Hua H

2013-08-01

This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

Overexpression of antibiotic resistance genes in hospital effluents over time

PubMed Central

Baker-Austin, Craig; Verner-Jeffreys, David W.; Ryan, Jim J.; Micallef, Christianne; Maskell, Duncan J.; Pearce, Gareth P.

2017-01-01

Objectives: Effluents contain a diverse abundance of antibiotic resistance genes that augment the resistome of receiving aquatic environments. However, uncertainty remains regarding their temporal persistence, transcription and response to anthropogenic factors, such as antibiotic usage. We present a spatiotemporal study within a river catchment (River Cam, UK) that aims to determine the contribution of antibiotic resistance gene-containing effluents originating from sites of varying antibiotic usage to the receiving environment. Methods: Gene abundance in effluents (municipal hospital and dairy farm) was compared against background samples of the receiving aquatic environment (i.e. the catchment source) to determine the resistome contribution of effluents. We used metagenomics and metatranscriptomics to correlate DNA and RNA abundance and identified differentially regulated gene transcripts. Results: We found that mean antibiotic resistance gene and transcript abundances were correlated for both hospital (ρ = 0.9, two-tailed P <0.0001) and farm (ρ = 0.5, two-tailed P  <0.0001) effluents and that two β-lactam resistance genes (blaGES and blaOXA) were overexpressed in all hospital effluent samples. High β-lactam resistance gene transcript abundance was related to hospital antibiotic usage over time and hospital effluents contained antibiotic residues. Conclusions: We conclude that effluents contribute high levels of antibiotic resistance genes to the aquatic environment; these genes are expressed at significant levels and are possibly related to the level of antibiotic usage at the effluent source. PMID:28175320

Selection and Transmission of Antibiotic-Resistant Bacteria.

PubMed

Andersson, Dan I; Hughes, Diarmaid

2017-07-01

Ever since antibiotics were introduced into human and veterinary medicine to treat and prevent bacterial infections there has been a steady selection and increase in the frequency of antibiotic resistant bacteria. To be able to reduce the rate of resistance evolution, we need to understand how various biotic and abiotic factors interact to drive the complex processes of resistance emergence and transmission. We describe several of the fundamental factors that underlay resistance evolution, including rates and niches of emergence and persistence of resistant bacteria, time- and space-gradients of various selective agents, and rates and routes of transmission of resistant bacteria between humans, animals and other environments. Furthermore, we discuss the options available to reduce the rate of resistance evolution and/ or transmission and their advantages and disadvantages.

ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection.

PubMed

Sharkey, Liam K R; Edwards, Thomas A; O'Neill, Alex J

2016-03-22

Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram-positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to anin vitrotranslation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosomein vitro To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection.IMPORTANCEAntimicrobial resistance ranks among the greatest threats currently facing human health. Elucidation of the mechanisms by which microorganisms resist the effect of antibiotics is central to understanding the biology of this phenomenon and has the potential to inform the development of new drugs capable of blocking or circumventing resistance. Members of the ABC-F family, which includelsa(A),msr(A),optr(A), andvga(A), collectively yield resistance to a broader range of clinically significant antibiotic classes than any other family of resistance determinants, although their mechanism of action has been controversial since their discovery 25 years ago. Here we present the first direct evidence that proteins of the ABC-F family act to protect the bacterial ribosome from antibiotic-mediated inhibition. Copyright © 2016 Sharkey et al.

Antibiotic-resistant Escherichia coli in migratory birds inhabiting remote Alaska

USGS Publications Warehouse

Ramey, Andy M.; Hernandez, Jorge; Tyrlöv, Veronica; Uher-Koch, Brian D.; Schmutz, Joel A.; Atterby, Clara; Järhult, Josef D.; Bonnedahl, Jonas

2018-01-01

We explored the abundance of antibiotic-resistant Escherichia coli among migratory birds at remote sites in Alaska and used a comparative approach to speculate on plausible explanations for differences in detection among species. At a remote island site, we detected antibiotic-resistant E. coli phenotypes in samples collected from glaucous-winged gulls (Larus glaucescens), a species often associated with foraging at landfills, but not in samples collected from black-legged kittiwakes (Rissa tridactyla), a more pelagic gull that typically inhabits remote areas year-round. We did not find evidence for antibiotic-resistant E. coli among 347 samples collected primarily from waterfowl at a second remote site in western Alaska. Our results provide evidence that glaucous-winged gulls may be more likely to be infected with antibiotic-resistant E. coli at remote breeding sites as compared to sympatric black-legged kittiwakes. This could be a function of the tendency of glaucous-winged gulls to forage at landfills where antibiotic-resistant bacterial infections may be acquired and subsequently dispersed. The low overall detection of antibiotic-resistant E. coli in migratory birds sampled at remote sites in Alaska is consistent with the premise that anthropogenic inputs into the local environment or the relative lack thereof influences the prevalence of antibiotic-resistant bacteria among birds inhabiting the area.

Molecular study on some antibiotic resistant genes in Salmonella spp. isolates

NASA Astrophysics Data System (ADS)

Nabi, Ari Q.

2017-09-01

Studying the genes related with antimicrobial resistance in Salmonella spp. is a crucial step toward a correct and faster treatment of infections caused by the pathogen. In this work Integron mediated antibiotic resistant gene IntI1 (Class I Integrase IntI1) and some plasmid mediated antibiotic resistance genes (Qnr) were scanned among the isolated non-Typhoid Salmonellae strains with known resistance to some important antimicrobial drugs using Sybr Green real time PCR. The aim of the study was to correlate the multiple antibiotics and antimicrobial resistance of Salmonella spp. with the presence of integrase (IntI1) gene and plasmid mediated quinolone resistant genes. Results revealed the presence of Class I Integrase gene in 76% of the isolates with confirmed multiple antibiotic resistances. Moreover, about 32% of the multiple antibiotic resistant serotypes showed a positive R-PCR for plasmid mediated qnrA gene encoding for nalidixic acid and ciprofloxacin resistance. No positive results could be revealed form R-PCRs targeting qnrB or qnrS. In light of these results we can conclude that the presence of at least one of the qnr genes and/or the presence of Integrase Class I gene were responsible for the multiple antibiotic resistance to for nalidixic acid and ciprofloxacin from the studied Salmonella spp. and further studies required to identify the genes related with multiple antibiotic resistance of the pathogen.

Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action

PubMed Central

2012-01-01

Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs. PMID:22958833

An evolutionary model to predict the frequency of antibiotic resistance under seasonal antibiotic use, and an application to Streptococcus pneumoniae

PubMed Central

Lehtinen, Sonja; Fraser, Christophe

2017-01-01

The frequency of resistance to antibiotics in Streptococcus pneumoniae has been stable over recent decades. For example, penicillin non-susceptibility in Europe has fluctuated between 12% and 16% without any major time trend. In spite of long-term stability, resistance fluctuates over short time scales, presumably in part due to seasonal fluctuations in antibiotic prescriptions. Here, we develop a model that describes the evolution of antibiotic resistance under selection by multiple antibiotics prescribed at seasonally changing rates. This model was inspired by, and fitted to, published data on monthly antibiotics prescriptions and frequency of resistance in two communities in Israel over 5 years. Seasonal fluctuations in antibiotic usage translate into small fluctuations of the frequency of resistance around the average value. We describe these dynamics using a perturbation approach that encapsulates all ecological and evolutionary forces into a generic model, whose parameters quantify a force stabilizing the frequency of resistance around the equilibrium and the sensitivity of the population to antibiotic selection. Fitting the model to the data revealed a strong stabilizing force, typically two to five times stronger than direct selection due to antibiotics. The strong stabilizing force explains that resistance fluctuates in phase with usage, as antibiotic selection alone would result in resistance fluctuating behind usage with a lag of three months when antibiotic use is seasonal. While most antibiotics selected for increased resistance, intriguingly, cephalosporins selected for decreased resistance to penicillins and macrolides, an effect consistent in the two communities. One extra monthly prescription of cephalosporins per 1000 children decreased the frequency of penicillin-resistant strains by 1.7%. This model emerges under minimal assumptions, quantifies the forces acting on resistance and explains up to 43% of the temporal variation in resistance. PMID

A potent synthetic inorganic antibiotic with activity against drug-resistant pathogens

PubMed Central

Hubick, Shelby; Jayaraman, Arumugam; McKeen, Alexander; Reid, Shelby; Alcorn, Jane; Stavrinides, John; Sterenberg, Brian T.

2017-01-01

The acronymously named “ESKAPE” pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to “eskape” antibiotic treatment12. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). We show that this potent antibiotic is bactericidal, and exhibits low toxicity in an acute dose assay in mice. As a synthetic compound that does not occur naturally, phosphopyricin would be evolutionarily foreign to microbes, thereby slowing the evolution of resistance. In addition, it loses antibiotic activity upon exposure to light, meaning that the active antibiotic will not accumulate in the general environment where strong selective pressures imposed by antibiotic residuals are known to accelerate resistance. Phosphopyricin represents an innovation in antimicrobials, having a synthetic core, and a photosensitive chemical architecture that would reduce accumulation in the environment. PMID:28165020

Effective Antibiotic Resistance Mitigation during Cheese Fermentation ▿

PubMed Central

Li, Xinhui; Li, Yingli; Alvarez, Valente; Harper, Willis James; Wang, Hua H.

2011-01-01

Controlling antibiotic-resistant (ART) bacteria in cheese fermentation is important for food safety and public health. A plant-maintained culture was found to be a potential source for ART bacterial contamination in cheese fermentation. Antibiotics had a detectable effect on the ART population from contamination in the finished product. The decrease in the prevalence of antibiotic resistance (AR) in retail cheese samples from 2010 compared to data from 2006 suggested the effectiveness of targeted AR mitigation in related products. PMID:21784910

Treatment of acute otitis media - challenges in the era of antibiotic resistance.

PubMed

Dagan, R

2000-12-08

The last decade is characterized by the increase in antibiotic resistance among respiratory bacterial pathogens in the presence of only modest progress in the development of new antibacterial agents to overcome this resistance. A series of recent studies show clearly that the increased resistance among the main AOM pathogens (namely Streptococcus pneumoniae and Haemophilus influenzae) is associated with a dramatic decrease in bacteriologic response to antibiotic treatment, which in turn has an impact on clinical response. Thus, the individual patient is affected by the increasing antibiotic resistance. Moreover, the society as a whole is now also affected because the carriage and spread of antibiotic resistant AOM pathogens is remarkably impacted by antibiotic treatment. New studies show the remarkable ability of antibiotics to rapidly promote nasopharyngeal carriage and spread of antibiotic-resistant AOM pathogens. In these studies, the increase in carriage of antibiotic resistant S. pneumoniae is shown already after 3-4 days from initiation of antibiotic treatment and may last for weeks to months after treatment. Children carrying antibiotic-resistant organisms transmit those organisms to their family and to their day care centers and thus a vicious cycle is created in which increased antibiotic resistance with decreased response leads to increased antibiotic use, which in turn leads to further increase in resistance. New antibiotics are not likely to improve this situation. It is clear that the challenge in the next decade is to prevent AOM rather than to treat it. Efforts to prevent AOM include improved environmental factors, immunization with bacterial and viral vaccines and some creative measures such as prevention of colonization and attachment to epithelium of AOM pathogens. Whether these efforts will prove successful or, even if successful, will only modify the clinical and bacteriologic picture presenting new challenges, only time will tell.

Overexpression of antibiotic resistance genes in hospital effluents over time.

PubMed

Rowe, Will P M; Baker-Austin, Craig; Verner-Jeffreys, David W; Ryan, Jim J; Micallef, Christianne; Maskell, Duncan J; Pearce, Gareth P

2017-06-01

Effluents contain a diverse abundance of antibiotic resistance genes that augment the resistome of receiving aquatic environments. However, uncertainty remains regarding their temporal persistence, transcription and response to anthropogenic factors, such as antibiotic usage. We present a spatiotemporal study within a river catchment (River Cam, UK) that aims to determine the contribution of antibiotic resistance gene-containing effluents originating from sites of varying antibiotic usage to the receiving environment. Gene abundance in effluents (municipal hospital and dairy farm) was compared against background samples of the receiving aquatic environment (i.e. the catchment source) to determine the resistome contribution of effluents. We used metagenomics and metatranscriptomics to correlate DNA and RNA abundance and identified differentially regulated gene transcripts. We found that mean antibiotic resistance gene and transcript abundances were correlated for both hospital ( ρ  = 0.9, two-tailed P  <0.0001) and farm ( ρ  = 0.5, two-tailed P   <0.0001) effluents and that two β-lactam resistance genes ( bla GES and bla OXA ) were overexpressed in all hospital effluent samples. High β-lactam resistance gene transcript abundance was related to hospital antibiotic usage over time and hospital effluents contained antibiotic residues. We conclude that effluents contribute high levels of antibiotic resistance genes to the aquatic environment; these genes are expressed at significant levels and are possibly related to the level of antibiotic usage at the effluent source. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Functional Repertoire of Antibiotic Resistance Genes in Antibiotic Manufacturing Effluents and Receiving Freshwater Sediments

PubMed Central

González-Plaza, Juan J.; Šimatović, Ana; Milaković, Milena; Bielen, Ana; Wichmann, Fabienne; Udiković-Kolić, Nikolina

2018-01-01

Environments polluted by direct discharges of effluents from antibiotic manufacturing are important reservoirs for antibiotic resistance genes (ARGs), which could potentially be transferred to human pathogens. However, our knowledge about the identity and diversity of ARGs in such polluted environments remains limited. We applied functional metagenomics to explore the resistome of two Croatian antibiotic manufacturing effluents and sediments collected upstream of and at the effluent discharge sites. Metagenomic libraries built from an azithromycin-production site were screened for resistance to macrolide antibiotics, whereas the libraries from a site producing veterinary antibiotics were screened for resistance to sulfonamides, tetracyclines, trimethoprim, and beta-lactams. Functional analysis of eight libraries identified a total of 82 unique, often clinically relevant ARGs, which were frequently found in clusters and flanked by mobile genetic elements. The majority of macrolide resistance genes identified from matrices exposed to high levels of macrolides were similar to known genes encoding ribosomal protection proteins, macrolide phosphotransferases, and transporters. Potentially novel macrolide resistance genes included one most similar to a 23S rRNA methyltransferase from Clostridium and another, derived from upstream unpolluted sediment, to a GTPase HflX from Emergencia. In libraries deriving from sediments exposed to lower levels of veterinary antibiotics, we found 8 potentially novel ARGs, including dihydrofolate reductases and beta-lactamases from classes A, B, and D. In addition, we detected 7 potentially novel ARGs in upstream sediment, including thymidylate synthases, dihydrofolate reductases, and class D beta-lactamase. Taken together, in addition to finding known gene types, we report the discovery of novel and diverse ARGs in antibiotic-polluted industrial effluents and sediments, providing a qualitative basis for monitoring the dispersal of ARGs

The Complex Relationship between Virulence and Antibiotic Resistance

PubMed Central

Schroeder, Meredith; Brooks, Benjamin D.; Brooks, Amanda E.

2017-01-01

Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e.g., quorum sensing or two-component systems), leading to global changes in gene expression, enhancing virulence, and expediting the acquisition of antibiotic resistance. Thus, one must examine a genetic change in virulence and resistance not only in the context of the biofilm but also as inextricably linked pathologies. Observationally, it is clear that increased virulence and the advent of antibiotic resistance often arise almost simultaneously; however, their genetic connection has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship, uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection. PMID:28106797

Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

DOE PAGES

Johnson, Timothy A.; Stedtfeld, Robert D.; Wang, Qiong; ...

2016-04-12

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundancemore » of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance

Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Timothy A.; Stedtfeld, Robert D.; Wang, Qiong

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundancemore » of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance

Clusters of Antibiotic Resistance Genes Enriched Together Stay Together in Swine Agriculture.

PubMed

Johnson, Timothy A; Stedtfeld, Robert D; Wang, Qiong; Cole, James R; Hashsham, Syed A; Looft, Torey; Zhu, Yong-Guan; Tiedje, James M

2016-04-12

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk. Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if

Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota

PubMed Central

Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy

2013-01-01

This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection. PMID:23689712

Addressing the Natural Antibiotic Resistome in Studies of Soil Resistance

USDA-ARS?s Scientific Manuscript database

The environment is recognized as a source and a reservoir of antibiotic resistance (AR). Many antibiotic compounds are derived from bacteria and fungi that are naturally present in the environment. These microbes carry genes encoding resistance to the antibiotic that they produce and their resistanc...

Genotypic Detection of Antibiotic Resistance in "Escherichia Coli.": A Classroom Exercise

ERIC Educational Resources Information Center

Longtin, Sarah; Guilfoile, Patrick; Asper, Andrea

2004-01-01

Bacterial antibiotic resistance remains a problem of clinical importance. Current microbiological methods for determining antibiotic resistance are based on culturing bacteria, and may require up to 48 hours to complete. Molecular methods are increasingly being developed to speed the identification of antibiotic resistance and to determine its…

Assessing Antibiotic Resistance of Staphyloccocus: Students Use Their Own Microbial Flora To Explore Antibiotic Resistance.

ERIC Educational Resources Information Center

Omoto, Charlotte K.; Malm, Kirstin

2003-01-01

Describes a microbiology laboratory experiment in which students test their own microbial flora of Staphylococcus for antibiotic resistance. Provides directions on how to conduct the experiment. (YDS)

Antibiotic resistance rates and physician antibiotic prescription patterns of uncomplicated urinary tract infections in southern Chinese primary care

PubMed Central

Kung, Kenny; Au-Doung, Philip Lung Wai; Ip, Margaret; Lee, Nelson; Fung, Alice; Wong, Samuel Yeung Shan

2017-01-01

Uncomplicated urinary tract infections (UTI) are common in primary care. Whilst primary care physicians are called to be antimicrobial stewards, there is limited primary care antibiotic resistance surveillance and physician antibiotic prescription data available in southern Chinese primary care. The study aimed to investigate the antibiotic resistance rate and antibiotic prescription patterns in female patients with uncomplicated UTI. Factors associated with antibiotic resistance and prescription was explored. A prospective cohort study was conducted in 12 primary care group clinics in Hong Kong of patients presenting with symptoms of uncomplicated UTI from January 2012 to December 2013. Patients’ characteristics such as age, comorbidity, presenting symptoms and prior antibiotic use were recorded by physicians, as well as any empirical antibiotic prescription given at presentation. Urine samples were collected to test for antibiotic resistance of uropathogens. Univariate analysis was conducted to identify factors associated with antibiotic resistance and prescription. A total of 298 patients were included in the study. E. coli was detected in 107 (76%) out of the 141 positive urine samples. Antibiotic resistance rates of E. coli isolates for ampicillin, co-trimoxazole, ciprofloxacin, amoxicillin and nitrofurantoin were 59.8%, 31.8%, 23.4%, 1.9% and 0.9% respectively. E. coli isolates were sensitive to nitrofurantoin (98.1%) followed by amoxicillin (78.5%). The overall physician antibiotic prescription rate was 82.2%. Amoxicillin (39.6%) and nitrofurantoin (28.6%) were the most common prescribed antibiotics. Meanwhile, whilst physicians in public primary care prescribed more amoxicillin (OR: 2.84, 95% CI: 1.67 to 4.85, P<0.001) and nitrofurantoin (OR: 2.01, 95% CI: 1.14 to 3.55, P = 0.015), physicians in private clinics prescribed more cefuroxime and ciprofloxacin (P<0.05). Matching of antibiotic prescription and antibiotic sensitivity of E. coli isolates occurred

Monitoring roadside ditches for antibiotic resistant E. coli in forest and agricultural landscapes

NASA Astrophysics Data System (ADS)

Storrer, S.; Archibald, J. A.

2009-12-01

There is growing concern over the threat of antibiotic resistant bacteria and how they travel through natural environments. This study was developed to: (1) measure the quantities of antibiotic resistant Escherichia coli present in stormwater collected from roadside ditches, (2) examine the spatial and temporal distribution of antibiotic resistance and (3) explore the difference in antibiotic resistance between different land uses. Autosamplers were used to collect composite samples of stormwater flowing in roadside ditches located near manure fertilized fields or forested areas. Samples were filtered using standard membrane filtration methods and grown with and without antibiotics on EC medium containing MUG. Three antibiotics commonly used to treat infection in humans and dairy cows were used to measure antibiotic resistance: penicillin, ampicillin and tetracycline. Though antibiotic resistance was found at forested and farm sites, preliminary data suggest higher counts of antibiotic resistant E. coli near agricultural areas.

Inactivation of an integrated antibiotic resistance gene in mammalian cells to re-enable antibiotic selection.

PubMed

Ni, Peiling; Zhang, Qian; Chen, Haixia; Chen, Lingyi

2014-01-01

Removing an antibiotic resistance gene allows the same antibiotic to be re-used in the next round of genetic manipulation. Here we applied the CRISPR/Cas system to disrupt the puromycin resistance gene in an engineered mouse embryonic stem cell line and then re-used puromycin selection in the resulting cells to establish stable reporter cell lines. With the CRISPR/Cas system, pre-engineered sequences, such as loxP or FRT, are not required. Thus, this technique can be used to disrupt antibiotic resistance genes that cannot be removed by the Cre-loxP and Flp-FRT systems.

Emergence of antibiotic-resistant bacteria in patients with Fournier gangrene.

PubMed

Lin, Wei-Ting; Chao, Chien-Ming; Lin, Hsin-Lan; Hung, Ming-Chran; Lai, Chih-Cheng

2015-04-01

This study was conducted to investigate the bacteriology and associated patterns of antibiotic resistance Fournier gangrene. Patients with Fournier's gangrene from 2008 to 2012 were identified from the computerized database in a medical center in southern Taiwan. The medical records of all patients with Fournier's gangrene were reviewed retrospectively. There were 61 microorganisms, including 60 bacteria and one Candida spp, isolated from clinical wound specimens from 32 patients. The most common isolates obtained were Streptococcus spp. (n=12), Peptoniphilus spp. (n=8), Staphylococcus aureus (n=7), Escherichia coli (n=7), and Klebsiella pneumoniae (n=7). Among 21 strains of gram-negative bacilli, five (23.8%) were resistant to fluoroquinolones, and three isolates were resistant to ceftriaxone. Two E. coli strains produced extended-spectrum beta-lactamase. Four of the seven S. aureus isolates were methicillin-resistant. Among 15 anaerobic isolates, nine (60%) were resistant to penicillin, and eight (53.3%) were resistant to clindamycin. Four (26.7%) isolates were resistant to metronidazole. The only independent risk factor associated with mortality was inappropriate initial antibiotic treatment (p=0.021). Antibiotic-resistant bacteria are emerging in the clinical setting of Fournier gangrene. Clinicians should use broad-spectrum antibiotics initially to cover possible antibiotic-resistant bacteria.

Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae

PubMed Central

Band, Victor I.; Crispell, Emily K.; Napier, Brooke A.; Herrera, Carmen M.; Tharp, Greg K.; Vavikolanu, Kranthi; Pohl, Jan; Read, Timothy D.; Bosinger, Steven E.; Trent, M. Stephen; Burd, Eileen M.; Weiss, David S.

2016-01-01

Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics. PMID:27572838

Impact of anthropogenic activities on the dissemination of antibiotic resistance across ecological boundaries.

PubMed

Tripathi, Vijay; Cytryn, Eddie

2017-02-28

Antibiotics are considered to be one of the major medical breakthroughs in history. Nonetheless, over the past four decades, antibiotic resistance has reached alarming levels worldwide and this trend is expected to continue to increase, leading some experts to forecast the coming of a 'post-antibiotic' era. Although antibiotic resistance in pathogens is traditionally linked to clinical environments, there is a rising concern that the global propagation of antibiotic resistance is also associated with environmental reservoirs that are linked to anthropogenic activities such as animal husbandry, agronomic practices and wastewater treatment. It is hypothesized that the emergence and dissemination of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) within and between environmental microbial communities can ultimately contribute to the acquisition of antibiotic resistance in human pathogens. Nonetheless, the scope of this phenomenon is not clear due to the complexity of microbial communities in the environment and methodological constraints that limit comprehensive in situ evaluation of microbial genomes. This review summarizes the current state of knowledge regarding antibiotic resistance in non-clinical environments, specifically focusing on the dissemination of antibiotic resistance across ecological boundaries and the contribution of this phenomenon to global antibiotic resistance. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Antibiotic Resistance and the Biology of History.

PubMed

Landecker, Hannah

2016-12-01

Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as 'the biology of history': the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today.

Antibiotic Resistance and the Biology of History

PubMed Central

2015-01-01

Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as ‘the biology of history’: the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today. PMID:28458609

Antibiotics, Bacteria, and Antibiotic Resistance Genes: Aerial Transport from Cattle Feed Yards via Particulate Matter

PubMed Central

McEachran, Andrew D.; Blackwell, Brett R.; Hanson, J. Delton; Wooten, Kimberly J.; Mayer, Gregory D.; Cox, Stephen B.

2015-01-01

Background: Emergence and spread of antibiotic resistance has become a global health threat and is often linked with overuse and misuse of clinical and veterinary chemotherapeutic agents. Modern industrial-scale animal feeding operations rely extensively on veterinary pharmaceuticals, including antibiotics, to augment animal growth. Following excretion, antibiotics are transported through the environment via runoff, leaching, and land application of manure; however, airborne transport from feed yards has not been characterized. Objectives: The goal of this study was to determine the extent to which antibiotics, antibiotic resistance genes (ARG), and ruminant-associated microbes are aerially dispersed via particulate matter (PM) derived from large-scale beef cattle feed yards. Methods: PM was collected downwind and upwind of 10 beef cattle feed yards. After extraction from PM, five veterinary antibiotics were quantified via high-performance liquid chromatography with tandem mass spectrometry, ARG were quantified via targeted quantitative polymerase chain reaction, and microbial community diversity was analyzed via 16S rRNA amplification and sequencing. Results: Airborne PM derived from feed yards facilitated dispersal of several veterinary antibiotics, as well as microbial communities containing ARG. Concentrations of several antibiotics in airborne PM immediately downwind of feed yards ranged from 0.5 to 4.6 μg/g of PM. Microbial communities of PM collected downwind of feed yards were enriched with ruminant-associated taxa and were distinct when compared to upwind PM assemblages. Furthermore, genes encoding resistance to tetracycline antibiotics were significantly more abundant in PM collected downwind of feed yards as compared to upwind. Conclusions: Wind-dispersed PM from feed yards harbors antibiotics, bacteria, and ARGs. Citation: McEachran AD, Blackwell BR, Hanson JD, Wooten KJ, Mayer GD, Cox SB, Smith PN. 2015. Antibiotics, bacteria, and antibiotic

Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics.

PubMed

Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

2016-06-27

Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σ(R) (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σ(R) called σ(R'). In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σ(R), eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σ(R). The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses.

Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics

PubMed Central

Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

2016-01-01

Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σR (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σR called σR′. In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σR, eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σR. The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses. PMID:27346454

Co-occurrence of antibiotic drugs, resistant bacteria and resistance genes in runoff from cattle feedlots

USDA-ARS?s Scientific Manuscript database

Agricultural uses of antibiotics raises concerns about the development of antibiotic resistance in food animals, and the potential to transmit resistance to human clinical settings via fecal contamination of surface and ground water. Although there is broad agreement that agricultural resistance can...

Cooperative Bacterial Growth Dynamics Predict the Evolution of Antibiotic Resistance

NASA Astrophysics Data System (ADS)

Artemova, Tatiana; Gerardin, Ylaine; Hsin-Jung Li, Sophia; Gore, Jeff

2011-03-01

Since the discovery of penicillin, antibiotics have been our primary weapon against bacterial infections. Unfortunately, bacteria can gain resistance to penicillin by acquiring the gene that encodes beta-lactamase, which inactivates the antibiotic. However, mutations in this gene are necessary to degrade the modern antibiotic cefotaxime. Understanding the conditions that favor the spread of these mutations is a challenge. Here we show that bacterial growth in beta-lactam antibiotics is cooperative and that the nature of this growth determines the conditions in which resistance evolves. Quantitative analysis of the growth dynamics predicts a peak in selection at very low antibiotic concentrations; competition between strains confirms this prediction. We also find significant selection at higher antibiotic concentrations, close to the minimum inhibitory concentrations of the strains. Our results argue that an understanding of the evolutionary forces that lead to antibiotic resistance requires a quantitative understanding of the evolution of cooperation in bacteria.

Multidrug evolutionary strategies to reverse antibiotic resistance

PubMed Central

Baym, Michael; Stone, Laura K.; Kishony, Roy

2017-01-01

Antibiotic treatment has two conflicting effects: the desired, immediate effect of inhibiting bacterial growth and the undesired, long-term effect of promoting the evolution of resistance. Although these contrasting outcomes seem inextricably linked, recent work has revealed several ways by which antibiotics can be combined to inhibit bacterial growth while, counterintuitively, selecting against resistant mutants. Decoupling treatment efficacy from the risk of resistance can be achieved by exploiting specific interactions between drugs, and the ways in which resistance mutations to a given drug can modulate these interactions or increase the sensitivity of the bacteria to other compounds. Although their practical application requires much further development and validation, and relies on advances in genomic diagnostics, these discoveries suggest novel paradigms that may restrict or even reverse the evolution of resistance. PMID:26722002

Calcined Eggshell Waste for Mitigating Soil Antibiotic-Resistant Bacteria/Antibiotic Resistance Gene Dissemination and Accumulation in Bell Pepper.

PubMed

Ye, Mao; Sun, Mingming; Feng, Yanfang; Li, Xu; Schwab, Arthur P; Wan, Jinzhong; Liu, Manqiang; Tian, Da; Liu, Kuan; Wu, Jun; Jiang, Xin

2016-07-13

The combined accumulation of antibiotics, heavy metals, antibiotic-resistant bacteria (ARB)/antibiotic resistance genes (ARGs) in vegetables has become a new threat to human health. This is the first study to investigate the feasibility of calcined eggshells modified by aluminum sulfate as novel agricultural wastes to impede mixed contaminants from transferring to bell pepper (Capsicum annuum L.). In this work, calcined eggshell amendment mitigated mixed pollutant accumulation in bell pepper significantly, enhanced the dissipation of soil tetracycline, sulfadiazine, roxithromycin, and chloramphenicol, decreased the water-soluble fractions of antibiotics, and declined the diversity of ARB/ARGs inside the vegetable. Moreover, quantitative polymerase chain reaction analysis detected that ARG levels in the bell pepper fruits significantly decreased to 10(-10) copies/16S copies, indicating limited risk of ARGs transferring along the food chain. Furthermore, the restoration of soil microbial biological function suggests that calcined eggshell is an environmentally friendly amendment to control the dissemination of soil ARB/ARGs in the soil-vegetable system.

Antibiotic resistance of microorganisms in agricultural soils in Russia

NASA Astrophysics Data System (ADS)

Danilova, Natasha; Galitskaya, Polina; Selivanovskaya, Svetlana

2017-04-01

Antibiotics are medicines widely used to treat and prevent bacterial infections not only in human medicine but also in veterinary. Besides, in animal husbandry antibiotics are often used in for stimulation of animal's growth. Many antibiotics used for veterinary purposes are weakly absorbed in the animal's gut. So up to 90% of the administered antibiotics are excreted with manure and urine. Therefore use of manure as an organic fertilizer leads to formation and spreading of antibiotic resistance among soil microbes. Another reason of such spreading is the horizontal transfer of genes encoding antibiotic resistance from manure to soil microflora. The level of antibiotic resistance genes pollution of soils has not been properly studied yet. The aim of this study was to estimate the contamination of agricultural soils by antibiotic resistant genes. 30 samples of agricultural soils were selected around of Kazan city (Tatarstan Republic) with 1.3 Mio citizens. Since tetracycline is reported to be the most wide spread veterinary antibiotic in Russia, we estimated the level of soil contamination by tet(X) gene encoding tetracycline decomposition in microbial cell. Real time PCR method with specific primers was used as a method of investigation. Particle size type distribution of 31% of soil samples was estimated to be sandy clay, and 69% of soil samples - to silty clay. Content of dissoluble organic carbon ranged from 0,02 mg g -1 (sample 20) to 0,46 mg g -1 (sample 16). Respiration activity and microbial biomass of soils were estimated to be 0,80-5,28 CO2 C mg g -1 h-1 and 263,51-935,77 µg kg - 1 respectively. The values presented are typical for soils of Tatarstan Republic. In terms of the antibiotic resistant gene content, 27 of 30 samples investigated contained tet(X) gene, while 52% of the samples were highly contaminated, 34% of samples were middle contaminated and 14% of samples - weakly contaminated.

Gamma irradiation reduces the survival and regrowth of inoculated antibiotic-resistant bacteria and antibiotic resistant genes on romaine lettuce

USDA-ARS?s Scientific Manuscript database

Introduction: Gamma irradiation effectively reduces foodborne pathogens and spoilage microorganisms on fresh produce. However, limited research is available regarding the effect of gamma irradiation on the survival and regrowth of antibiotic-resistant bacteria (ARB) or the persistence of antibiotic ...

Quantifying Attachment and Antibiotic Resistance of from Conventional and Organic Swine Manure.

PubMed

Zwonitzer, Martha R; Soupir, Michelle L; Jarboe, Laura R; Smith, Douglas R

2016-03-01

Broad-spectrum antibiotics are often administered to swine, contributing to the occurrence of antibiotic-resistant bacteria in their manure. During land application, the bacteria in swine manure preferentially attach to particles in the soil, affecting their transport in overland flow. However, a quantitative understanding of these attachment mechanisms is lacking, and their relationship to antibiotic resistance is unknown. The objective of this study is to examine the relationships between antibiotic resistance and attachment to very fine silica sand in collected from swine manure. A total of 556 isolates were collected from six farms, two organic and four conventional (antibiotics fed prophylactically). Antibiotic resistance was quantified using 13 antibiotics at three minimum inhibitory concentrations: resistant, intermediate, and susceptible. Of the 556 isolates used in the antibiotic resistance assays, 491 were subjected to an attachment assay. Results show that isolates from conventional systems were significantly more resistant to amoxicillin, ampicillin, chlortetracycline, erythromycin, kanamycin, neomycin, streptomycin, tetracycline, and tylosin ( < 0.001). Results also indicate that isolated from conventional systems attached to very fine silica sand at significantly higher levels than those from organic systems ( < 0.001). Statistical analysis showed that a significant relationship did not exist between antibiotic resistance levels and attachment in from conventional systems but did for organic systems ( < 0.001). Better quantification of these relationships is critical to understanding the behavior of in the environment and preventing exposure of human populations to antibiotic-resistant bacteria. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Antibiotic resistance genes in surface water of eutrophic urban lakes are related to heavy metals, antibiotics, lake morphology and anthropic impact.

PubMed

Yang, Yuyi; Xu, Chen; Cao, Xinhua; Lin, Hui; Wang, Jun

2017-08-01

Urban lakes are impacted by heavy human activities and represent potential reservoirs for antibiotic resistance genes. In this study, six urban lakes in Wuhan, central China were selected to analyze the distribution of sulfonamide resistance (sul) genes, tetracycline resistance (tet) genes and quinolone resistance (qnr) genes and their relationship with heavy metals, antibiotics, lake morphology and anthropic impact. sul1 and sul2 were detected in all six lakes and dominated the types of antibiotic resistance genes, which accounted for 86.28-97.79% of the total antibiotic resistance gene abundance. For eight tested tet genes, antibiotic efflux pumps (tetA, tetB, tetC, and tetG) genes were all observed in six lakes and had higher relative abundance than ribosomal protection protein genes (tetM and tetQ). For 4 plasmid mediated quinolone resistance genes, only qnrD is found in all six lakes. The class I integron (intI1) is also found to be a very important media for antibiotic resistance gene propagation in urban lakes. The results of redundancy analysis and variation partitioning analysis showed that antibiotic and co-selection with heavy metals were the major factors driving the propagation of antibiotic resistance genes in six urban lakes. The heavily eutrophic Nanhu Lake and Shahu Lake which located in a high density building area with heavy human activities had the higher relative abundance of total antibiotic resistance genes. Our study could provide a useful reference for antibiotic resistance gene abundance in urban lakes with high anthropic impact.

FARME DB: a functional antibiotic resistance element database

PubMed Central

Wallace, James C.; Port, Jesse A.; Smith, Marissa N.; Faustman, Elaine M.

2017-01-01

Antibiotic resistance (AR) is a major global public health threat but few resources exist that catalog AR genes outside of a clinical context. Current AR sequence databases are assembled almost exclusively from genomic sequences derived from clinical bacterial isolates and thus do not include many microbial sequences derived from environmental samples that confer resistance in functional metagenomic studies. These environmental metagenomic sequences often show little or no similarity to AR sequences from clinical isolates using standard classification criteria. In addition, existing AR databases provide no information about flanking sequences containing regulatory or mobile genetic elements. To help address this issue, we created an annotated database of DNA and protein sequences derived exclusively from environmental metagenomic sequences showing AR in laboratory experiments. Our Functional Antibiotic Resistant Metagenomic Element (FARME) database is a compilation of publically available DNA sequences and predicted protein sequences conferring AR as well as regulatory elements, mobile genetic elements and predicted proteins flanking antibiotic resistant genes. FARME is the first database to focus on functional metagenomic AR gene elements and provides a resource to better understand AR in the 99% of bacteria which cannot be cultured and the relationship between environmental AR sequences and antibiotic resistant genes derived from cultured isolates. Database URL: http://staff.washington.edu/jwallace/farme PMID:28077567

Effect of temperature on sulfonamide antibiotics degradation, and on antibiotic resistance determinants and hosts in animal manures.

PubMed

Lin, Hui; Zhang, Jin; Chen, Hongjin; Wang, Jianmei; Sun, Wanchun; Zhang, Xin; Yang, Yuyi; Wang, Qiang; Ma, Junwei

2017-12-31

Animal manure is a main reservoir of antibiotic residues and antibiotic resistance. Here, the effect of temperature on sulfonamide antibiotics (SAs), sulfonamide-resistant (SR) genes/bacteria was investigated by aerobically incubating swine and chicken manures at different temperatures. In swine manure, the SAs concentration declined with increasing temperature, with a minimum at 60°C. In chicken manure, the greatest degradation of SAs was noted at 30°C. The reduction of relative abundance of antibiotic resistance genes (ARGs) and sul-positive hosts in swine manure was more pronounced during thermophilic than mesospheric incubation; neither temperature conditions effectively reduced these parameters in chicken manure. The relationship between the residual levels/distribution profiles of SAs, ARGs (sul1, sul2 and intI1), cultivable SR bacteria and sul-positive hosts was further established. The antibiotic residual profile, rather than antibiotic concentration, acted as an important factor in the prevalence of ARGs and sul-positive hosts in manure. Corynebacterium and Leucobacter from the phylum Actinobacteria tend to be main carriers of sul1 and intI1; the relative abundance of sul2 was significantly correlated with the relative abundance of cultivable SR bacteria. Overall, differences in resistant bacterial communities also constitute a dominant factor affecting ARG variation. This study contributes to management options for reducing the pollution of antibiotics and antibiotic resistance within manure. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibiotic resistance--consequences for animal health, welfare, and food production.

PubMed

Bengtsson, Björn; Greko, Christina

2014-05-01

Most of the literature on the consequences of emergence and spread of bacteria resistant to antibiotics among animals relate to the potential impact on public health. But antibiotics are used to treat sick animals, and resistance in animal pathogens may lead to therapy failure. This has received little scientific attention, and therefore, in this article, we discuss examples that illustrate the possible impact of resistance on animal health and consequences thereof. For all animals, there may be a negative effect on health and welfare when diseases cannot be treated. Other consequences will vary depending on why and how different animal species are kept. Animals kept as companions or for sports often receive advanced care, and antibiotic resistance can lead to negative social and economic consequences for the owners. Further, spread of hospital-acquired infections can have an economic impact on the affected premises. As to animals kept for food production, antibiotics are not needed to promote growth, but, if infectious diseases cannot be treated when they occur, this can have a negative effect on the productivity and economy of affected businesses. Antibiotic resistance in animal bacteria can also have positive consequences by creating incentives for adoption of alternative regimes for treatment and prevention. It is probable that new antibiotic classes placed on the market in the future will not reach veterinary medicine, which further emphasizes the need to preserve the efficacy of currently available antibiotics through antibiotic stewardship. A cornerstone in this work is prevention, as healthy animals do not need antibiotics.

Broad-spectrum in vitro antibacterial activities of clay minerals against antibiotic-susceptible and antibiotic-resistant bacterial pathogens

PubMed Central

HAYDEL, SHELLEY E.; REMENIH, CHRISTINE M.; WILLIAMS, LYNDA B.

2008-01-01

SYNOPSIS Objectives The capacity to properly address the worldwide incidence of infectious diseases lies in the ability to detect, prevent, and effectively treat these infections. Therefore, identifying and analyzing inhibitory agents are worthwhile endeavors in an era when few new classes of effective antimicrobials have been developed. The use of geological nanomaterials to heal skin infections has been evident since the earliest recorded history, and specific clay minerals may prove valuable in the treatment of bacterial diseases, including infections for which there are no effective antibiotics, such as Buruli ulcer and multi-drug resistant infections. Methods We have subjected two iron-rich clay minerals, which have previously been used to treat Buruli ulcer patients, to broth culture testing of antibiotic-susceptible and -resistant pathogenic bacteria to assess the feasibility of using clay minerals as therapeutic agents. Results One specific mineral, CsAg02, demonstrated bactericidal activity against pathogenic Escherichia coli, extended-spectrum β-lactamase (ESBL) E. coli, S. enterica serovar Typhimurium, Pseudomonas aeruginosa, and Mycobacterium marinum and a combined bacteriostatic/bactericidal effect against Staphylococcus aureus, penicillin-resistant S. aureus (PRSA), methicillin-resistant S. aureus (MRSA), and Mycobacterium smegmatis, while another mineral with similar structure and bulk crystal chemistry, CsAr02, had no effect on or enhanced bacterial growth. The <0.2 μm fraction of CsAg02 and CsAg02 heated to 200°C or 550°C retained bactericidal activity, while cation-exchanged CsAg02 and CsAg02 heated to 900°C no longer killed E. coli. Conclusions Our results indicate that specific mineral products have intrinsic, heat-stable antibacterial properties, which could provide an inexpensive treatment against numerous human bacterial infections. PMID:18070832

Antibiotic resistance genes and residual antimicrobials in cattle feedlot surface soil

USDA-ARS?s Scientific Manuscript database

Cattle feedlot soils receive manure containing both antibiotic residues and antibiotic resistant bacteria. The fates of these constituents are largely unknown with potentially serious consequences for increased antibiotic resistance in the environment. Determine if common antimicrobials (tetracycl...

Computational gene network study on antibiotic resistance genes of Acinetobacter baumannii.

PubMed

Anitha, P; Anbarasu, Anand; Ramaiah, Sudha

2014-05-01

Multi Drug Resistance (MDR) in Acinetobacter baumannii is one of the major threats for emerging nosocomial infections in hospital environment. Multidrug-resistance in A. baumannii may be due to the implementation of multi-combination resistance mechanisms such as β-lactamase synthesis, Penicillin-Binding Proteins (PBPs) changes, alteration in porin proteins and in efflux pumps against various existing classes of antibiotics. Multiple antibiotic resistance genes are involved in MDR. These resistance genes are transferred through plasmids, which are responsible for the dissemination of antibiotic resistance among Acinetobacter spp. In addition, these resistance genes may also have a tendency to interact with each other or with their gene products. Therefore, it becomes necessary to understand the impact of these interactions in antibiotic resistance mechanism. Hence, our study focuses on protein and gene network analysis on various resistance genes, to elucidate the role of the interacting proteins and to study their functional contribution towards antibiotic resistance. From the search tool for the retrieval of interacting gene/protein (STRING), a total of 168 functional partners for 15 resistance genes were extracted based on the confidence scoring system. The network study was then followed up with functional clustering of associated partners using molecular complex detection (MCODE). Later, we selected eight efficient clusters based on score. Interestingly, the associated protein we identified from the network possessed greater functional similarity with known resistance genes. This network-based approach on resistance genes of A. baumannii could help in identifying new genes/proteins and provide clues on their association in antibiotic resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular characterization of antibiotic resistance in cultivable multidrug-resistant bacteria from livestock manure.

PubMed

Yang, Qingxiang; Tian, Tiantian; Niu, Tianqi; Wang, Panliang

2017-10-01

Diverse antibiotic-resistance genes (ARGs) are frequently reported to have high prevalence in veterinary manure samples due to extensive use of antibiotics in farm animals. However, the characteristics of the distribution and transmission of ARGs among bacteria, especially among different species of multiple antibiotic-resistant bacteria (MARB), have not been well explored. By applying high-throughput sequencing methods, our study uncovered a vast MARB reservoir in livestock manure. The genera Escherichia, Myroides, Acinetobacter, Proteus, Ignatzschineria, Alcaligenes, Providencia and Enterococcus were the predominant cultivable MARB, with compositions of 40.6%-85.7%. From chicken manure isolates, 33 MARB were selected for investigation of the molecular characteristics of antibiotic resistance. A total of 61 ARGs and 18 mobile genetic elements (MGEs) were investigated. We found that 47 ARGs were widely distributed among the 33 MARB isolates. Each isolate carried 27-36 genes responsible for resistance to eight classes of antibiotics frequently used in clinic or veterinary settings. ARGs to the six classes of antibiotics other than streptogramins and vancomycin were present in all 33 MARB isolates with a prevalence of 80%-100%. A total of 12 MGEs were widely distributed among the 33 MARB, with intI1, IS26, ISaba1, and ISEcp1 simultaneously present in 100% of isolates. In addition, 9 gene cassettes within integrons and ISCR1 were detected among MARB isolates encoding resistance to different antibiotic classes. This is the first report revealing the general co-presence of multiple ARGs, various MGEs and ARG cassettes in different species of individual MARB isolates in chicken manure. The results highlight a much higher risk of ARGs spreading through livestock manure to humans than we expected. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibiotic-resistant fecal bacteria, antibiotics, and mercury in surface waters of Oakland County, Michigan, 2005-2006

USGS Publications Warehouse

Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

2007-01-01

Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/ or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic-resistance

Genomic and metagenomic analysis of antibiotic resistance in dairy animals

USDA-ARS?s Scientific Manuscript database

The extent to which carriage of antibiotic resistant bacteria in food animals is responsible for the burden of antibiotic resistance in human infections is currently not well known. Thus, there is a need to further evaluate the genomic diversity of multidrug resistant (MDR) bacteria and the microbi...

Potential impact of environmental bacteriophages in spreading antibiotic resistance genes.

PubMed

Muniesa, Maite; Colomer-Lluch, Marta; Jofre, Juan

2013-06-01

The idea that bacteriophage transduction plays a role in the horizontal transfer of antibiotic resistance genes is gaining momentum. Such transduction might be vital in horizontal transfer from environmental to human body-associated biomes and here we review many lines of evidence supporting this notion. It is well accepted that bacteriophages are the most abundant entities in most environments, where they have been shown to be quite persistent. This fact, together with the ability of many phages to infect bacteria belonging to different taxa, makes them suitable vehicles for gene transfer. Metagenomic studies confirm that substantial percentages of the bacteriophage particles present in most environments contain bacterial genes, including mobile genetic elements and antibiotic resistance genes. When specific genes of resistance to antibiotics are detected by real-time PCR in the bacteriophage populations of different environments, only tenfold lower numbers of these genes are observed, compared with those found in the corresponding bacterial populations. In addition, the antibiotic resistance genes from these bacteriophages are functional and generate resistance to the bacteria when these genes are transfected. Finally, reports about the transduction of antibiotic resistance genes are on the increase.

Prevalence of Antibiotic-Resistant Escherichia coli in Drinking Water Sources in Hangzhou City.

PubMed

Chen, Zhaojun; Yu, Daojun; He, Songzhe; Ye, Hui; Zhang, Lei; Wen, Yanping; Zhang, Wenhui; Shu, Liping; Chen, Shuchang

2017-01-01

This study investigated the distribution of antibiotic resistant Escherichia coli ( E. coli ) and examined the possible relationship between water quality parameters and antibiotic resistance from two different drinking water sources (the Qiantang River and the Dongtiao Stream) in Hangzhou city of China. E. coli isolates were tested for their susceptibility to 18 antibiotics. Most of the isolates were resistant to tetracycline (TE), followed by ampicillin (AM), piperacillin (PIP), trimethoprim/sulfamethoxazole (SXT), and chloramphenicol (C). The antibiotic resistance rate of E. coli isolates from two water sources was similar; For E. coli isolates from the Qiantang River, their antibiotic resistance rates decreased from up- to downstream. Seasonally, the dry and wet season had little impact on antibiotic resistance. Spearman's rank correlation revealed significant correlation between resistance to TE and phenicols or ciprofloxacin (CIP), as well as quinolones (ciprofloxacin and levofloxacin) and cephalosporins or gentamicin (GM). Pearson's chi-square tests found certain water parameters such as nutrient concentration were strongly associated with resistance to some of the antibiotics. In addition, tet genes were detected from all 82 TE-resistant E. coli isolates, and most of the isolates (81.87%) contained multiple tet genes, which displayed 14 different combinations. Collectively, this study provided baseline data on antibiotic resistance of drinking water sources in Hangzhou city, which indicates drinking water sources could be the reservoir of antibiotic resistance, potentially presenting a public health risk.

Evolution of antibiotic resistance in biofilm and planktonic P. aeruginosa populations exposed to sub-inhibitory levels of ciprofloxacin.

PubMed

Ahmed, Marwa N; Porse, Andreas; Sommer, Morten Otto Alexander; Høiby, Niels; Ciofu, Oana

2018-05-14

The opportunistic Gram-negative pathogen Pseudomonas aeruginosa , known for its intrinsic and acquired antibiotic resistance, has a notorious ability to form biofilms, which often facilitate chronic infections. The evolutionary paths to antibiotic resistance have mainly been investigated in planktonic cultures and are less studied in biofilms. We experimentally evolved P. aeruginosa PAO1 colony-biofilms and stationary-phase planktonic cultures for seven passages in the presence of sub-inhibitory levels (0.1 mg/L) of ciprofloxacin (CIP) and performed a genotypic (whole bacterial population sequencing) and phenotypic assessment of the populations. We observed a higher proportion of CIP resistance in the CIP-evolved biofilm populations compared to planktonic populations exposed to the same drug concentrations. However, the minimal inhibitory concentrations (MICs) of ciprofloxacin were lower in CIP-resistant isolates selected from biofilm population compared to the MICs of CIP-resistant isolates from the planktonic cultures. We found common evolutionary trajectories between the different lineages, with mutations in known CIP resistance determinants as well as growth condition-dependent adaptations. A general trend towards a reduction in type IV-pili dependent motility (twitching) in CIP-evolved populations, and towards loss of virulence associated traits in the populations evolved in the absence of antibiotic, was observed. In conclusion, our data indicate that biofilms facilitate the development of low-level mutational resistance, probably due to the lower effective drug exposure compared to planktonic cultures. These results provide a framework for the selection process of resistant variants and the evolutionary mechanisms in the two different growth conditions. Copyright © 2018 American Society for Microbiology.

Occurrence and Antibiotic Resistance of Vibrio parahaemolyticus from Shellfish in Selangor, Malaysia

PubMed Central

Letchumanan, Vengadesh; Pusparajah, Priyia; Tan, Loh Teng-Hern; Yin, Wai-Fong; Lee, Learn-Han; Chan, Kok-Gan

2015-01-01

High consumer demand for shellfish has led to the need for large-scale, reliable shellfish supply through aquaculture or shellfish farming. However, bacterial infections which can spread rapidly among shellfish poses a major threat to this industry. Shellfish farmers therefore often resort to extensive use of antibiotics, both prophylactically and therapeutically, in order to protect their stocks. The extensive use of antibiotics in aquaculture has been postulated to represent a major contributing factor in the rising incidence of antimicrobial resistant pathogenic bacteria in shellfish. This study aimed to investigate the incidence of pathogenic Vibrio parahaemolyticus and determine the antibiotic resistance profile as well as to perform plasmid curing in order to determine the antibiotic resistance mediation. Based on colony morphology, all 450 samples tested were positive for Vibrio sp; however, tox-R assay showed that only 44.4% (200/450) of these were V. parahaemolyticus. Out of these 200 samples, 6.5% (13/200) were trh-positive while none were tdh-positive. Antibiotic resistance was determined for all V. parahaemolyticus identified against 14 commonly used antibiotics and the multiple antibiotic resistance index (MAR) was calculated. The isolates demonstrated high resistance to several antibiotics tested- including second and third-line antibiotics- with 88% resistant to ampicillin, 81% to amikacin,70.5% to kanamycin, 73% to cefotaxime, and 51.5% to ceftazidime. The MAR index ranged from 0.00 to 0.79 with the majority of samples having an index of 0.36 (resistant to five antibiotics). Among the 13 trh-positive strains, almost 70% (9/13) demonstrated resistance to 4 or more antibiotics. Plasmid profiling for all V. parahaemolyticus isolates revealed that 86.5% (173/200) contained plasmids - ranging from 1 to 7 plasmids with DNA band sizes ranging from 1.2 kb to greater than 10 kb. 6/13 of the pathogenic V. pathogenic strains contained plasmid. After plasmid

Metagenomic analysis of antibiotic resistance genes (ARGs) during refuse decomposition.

PubMed

Liu, Xi; Yang, Shu; Wang, Yangqing; Zhao, He-Ping; Song, Liyan

2018-04-12

Landfill is important reservoirs of residual antibiotics and antibiotic resistance genes (ARGs), but the mechanism of landfill application influence on antibiotic resistance remains unclear. Although refuse decomposition plays a crucial role in landfill stabilization, its impact on the antibiotic resistance has not been well characterized. To better understand the impact, we studied the dynamics of ARGs and the bacterial community composition during refuse decomposition in a bench-scale bioreactor after long term operation (265d) based on metagenomics analysis. The total abundances of ARGs increased from 431.0ppm in the initial aerobic phase (AP) to 643.9ppm in the later methanogenic phase (MP) during refuse decomposition, suggesting that application of landfill for municipal solid waste (MSW) treatment may elevate the level of ARGs. A shift from drug-specific (bacitracin, tetracycline and sulfonamide) resistance to multidrug resistance was observed during the refuse decomposition and was driven by a shift of potential bacteria hosts. The elevated abundance of Pseudomonas mainly contributed to the increasing abundance of multidrug ARGs (mexF and mexW). Accordingly, the percentage of ARGs encoding an efflux pump increased during refuse decomposition, suggesting that potential bacteria hosts developed this mechanism to adapt to the carbon and energy shortage when biodegradable substances were depleted. Overall, our findings indicate that the use of landfill for MSW treatment increased antibiotic resistance, and demonstrate the need for a comprehensive investigation of antibiotic resistance in landfill. Copyright © 2018. Published by Elsevier B.V.

Relationship between antibiotic- and disinfectant-resistance profiles in bacteria harvested from tap water.

PubMed

Khan, Sadia; Beattie, Tara K; Knapp, Charles W

2016-06-01

Chlorination is commonly used to control levels of bacteria in drinking water; however, viable bacteria may remain due to chlorine resistance. What is concerning is that surviving bacteria, due to co-selection factors, may also have increased resistance to common antibiotics. This would pose a public health risk as it could link resistant bacteria in the natural environment to human population. Here, we investigated the relationship between chlorine- and antibiotic-resistances by harvesting 148 surviving bacteria from chlorinated drinking-water systems and compared their susceptibilities against chlorine disinfectants and antibiotics. Twenty-two genera were isolated, including members of Paenibacillus, Burkholderia, Escherichia, Sphingomonas and Dermacoccus species. Weak (but significant) correlations were found between chlorine-tolerance and minimum inhibitory concentrations against the antibiotics tetracycline, sulfamethoxazole and amoxicillin, but not against ciprofloxacin; this suggest that chlorine-tolerant bacteria are more likely to also be antibiotic resistant. Further, antibiotic-resistant bacteria survived longer than antibiotic-sensitive organisms when exposed to free chlorine in a contact-time assay; however, there were little differences in susceptibility when exposed to monochloramine. Irrespective of antibiotic-resistance, spore-forming bacteria had higher tolerance against disinfection compounds. The presence of chlorine-resistant bacteria surviving in drinking-water systems may carry additional risk of antibiotic resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anthropogenic antibiotic resistance genes mobilization to the polar regions.

PubMed

Hernández, Jorge; González-Acuña, Daniel

2016-01-01

Anthropogenic influences in the southern polar region have been rare, but lately microorganisms associated with humans have reached Antarctica, possibly from military bases, fishing boats, scientific expeditions, and/or ship-borne tourism. Studies of seawater in areas of human intervention and proximal to fresh penguin feces revealed the presence of Escherichia coli strains least resistant to antibiotics in penguins, whereas E. coli from seawater elsewhere showed resistance to one or more of the following antibiotics: ampicillin, tetracycline, streptomycin, and trim-sulfa. In seawater samples, bacteria were found carrying extended-spectrum β-lactamase (ESBL)-type CTX-M genes in which multilocus sequencing typing (MLST) showed different sequence types (STs), previously reported in humans. In the Arctic, on the contrary, people have been present for a long time, and the presence of antibiotic resistance genes (ARGs) appears to be much more wide-spread than was previously reported. Studies of E coli from Arctic birds (Bering Strait) revealed reduced susceptibility to antibiotics, but one globally spreading clone of E. coli genotype O25b-ST131, carrying genes of ESBL-type CTX-M, was identified. In the few years between sample collections in the same area, differences in resistance pattern were observed, with E. coli from birds showing resistance to a maximum of five different antibiotics. Presence of resistance-type ESBLs (TEM, SHV, and CTX-M) in E. coli and Klebsiella pneumoniae was also confirmed by specified PCR methods. MLST revealed that those bacteria carried STs that connect them to previously described strains in humans. In conclusion, bacteria previously related to humans could be found in relatively pristine environments, and presently human-associated, antibiotic-resistant bacteria have reached a high global level of distribution that they are now found even in the polar regions.

Occurrence and prevalence of antibiotic resistance in landfill leachate.

PubMed

Wang, Yangqing; Tang, Wei; Qiao, Jing; Song, Liyan

2015-08-01

Antibiotic resistance (AR) is extensively present in various environments, posing emerging threat to public and environmental health. Landfill receives unused and unwanted antibiotics through household waste and AR within waste (e.g., activated sludge and illegal clinical waste) and is supposed to serve as an important AR reservoir. In this study, we used culture-dependent methods and quantitative molecular techniques to detect and quantify antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in 12 landfill leachate samples from six geographic different landfills, China. Five tested ARGs (tetO, tetW, bla(TEM), sulI, and sulII) and seven kinds of antibiotic-resistant heterotrophic ARB were extensively detected in all samples, demonstrating their occurrence in landfill. The detected high ratio (10(-2) to 10(-5)) of ARGs to 16S ribosomal RNA (rRNA) gene copies implied that ARGs are prevalent in landfill. Correlation analysis showed that ARGs (tetO, tetW, sulI, and sulII) significantly correlated to ambient bacterial 16S rRNA gene copies, suggesting that the abundance of bacteria in landfill leachate may play an important role in the horizontal spread of ARGs.

Evidence of Increased Antibiotic Resistance in Phylogenetically-Diverse Aeromonas Isolates from Semi-Intensive Fish Ponds Treated with Antibiotics.

PubMed

Patil, Hemant J; Benet-Perelberg, Ayana; Naor, Alon; Smirnov, Margarita; Ofek, Tamir; Nasser, Ahmed; Minz, Dror; Cytryn, Eddie

2016-01-01

The genus Aeromonas is ubiquitous in aquatic environments encompassing a broad range of fish and human pathogens. Aeromonas strains are known for their enhanced capacity to acquire and exchange antibiotic resistance genes and therefore, are frequently targeted as indicator bacteria for monitoring antimicrobial resistance in aquatic environments. This study evaluated temporal trends in Aeromonas diversity and antibiotic resistance in two adjacent semi-intensive aquaculture facilities to ascertain the effects of antibiotic treatment on antimicrobial resistance. In the first facility, sulfadiazine-trimethoprim was added prophylactically to fingerling stocks and water column-associated Aeromonas were monitored periodically over an 11-month fish fattening cycle to assess temporal dynamics in taxonomy and antibiotic resistance. In the second facility, Aeromonas were isolated from fish skin ulcers sampled over a 3-year period and from pond water samples to assess associations between pathogenic strains to those in the water column. A total of 1200 Aeromonas isolates were initially screened for sulfadiazine resistance and further screened against five additional antimicrobials. In both facilities, strong correlations were observed between sulfadiazine resistance and trimethoprim and tetracycline resistances, whereas correlations between sulfadiazine resistance and ceftriaxone, gentamicin, and chloramphenicol resistances were low. Multidrug resistant strains as well as sul1, tetA , and intI1 gene-harboring strains were significantly higher in profiles sampled during the fish cycle than those isolated prior to stocking and these genes were extremely abundant in the pathogenic strains. Five phylogenetically distinct Aeromonas clusters were identified using partial rpoD gene sequence analysis. Interestingly, prior to fingerling stocking the diversity of water column strains was high, and representatives from all five clusters were identified, including an A. salmonicida

Evidence of Increased Antibiotic Resistance in Phylogenetically-Diverse Aeromonas Isolates from Semi-Intensive Fish Ponds Treated with Antibiotics

PubMed Central

Patil, Hemant J.; Benet-Perelberg, Ayana; Naor, Alon; Smirnov, Margarita; Ofek, Tamir; Nasser, Ahmed; Minz, Dror; Cytryn, Eddie

2016-01-01

The genus Aeromonas is ubiquitous in aquatic environments encompassing a broad range of fish and human pathogens. Aeromonas strains are known for their enhanced capacity to acquire and exchange antibiotic resistance genes and therefore, are frequently targeted as indicator bacteria for monitoring antimicrobial resistance in aquatic environments. This study evaluated temporal trends in Aeromonas diversity and antibiotic resistance in two adjacent semi-intensive aquaculture facilities to ascertain the effects of antibiotic treatment on antimicrobial resistance. In the first facility, sulfadiazine-trimethoprim was added prophylactically to fingerling stocks and water column-associated Aeromonas were monitored periodically over an 11-month fish fattening cycle to assess temporal dynamics in taxonomy and antibiotic resistance. In the second facility, Aeromonas were isolated from fish skin ulcers sampled over a 3-year period and from pond water samples to assess associations between pathogenic strains to those in the water column. A total of 1200 Aeromonas isolates were initially screened for sulfadiazine resistance and further screened against five additional antimicrobials. In both facilities, strong correlations were observed between sulfadiazine resistance and trimethoprim and tetracycline resistances, whereas correlations between sulfadiazine resistance and ceftriaxone, gentamicin, and chloramphenicol resistances were low. Multidrug resistant strains as well as sul1, tetA, and intI1 gene-harboring strains were significantly higher in profiles sampled during the fish cycle than those isolated prior to stocking and these genes were extremely abundant in the pathogenic strains. Five phylogenetically distinct Aeromonas clusters were identified using partial rpoD gene sequence analysis. Interestingly, prior to fingerling stocking the diversity of water column strains was high, and representatives from all five clusters were identified, including an A. salmonicida cluster

[Antimicrobial resistance forever? Judicious and appropriate use of antibiotics].

PubMed

Cagliano, Stefano

2015-06-01

This article takes its cue from the original work of sir Alexander Fleming on penicillin, published in the first issue of Recenti Progressi in Medicina in 1946 and reproduced here on the occasion of the approaching 70-year anniversary of the journal. In 1928, at the time when penicillin was discovered, it could not be imagined that bacterial resistance to antibiotics would develop so rapidly: the introduction of every new class of antibiotics has been shortly followed by the emergence of new strains of bacteria resistant to that class. Bacterial resistance to antibiotic treatment is a huge concern. In this respect, an action plan against antimicrobial resistance has been devised in the United States that is targeted for a 50% reduction over the next five years.

Impact of Rapid Susceptibility Testing and Antibiotic Selection Strategy on the Emergence and Spread of Antibiotic Resistance in Gonorrhea

PubMed Central

Tuite, Ashleigh R; Gift, Thomas L; Chesson, Harrell W; Hsu, Katherine; Salomon, Joshua A; Grad, Yonatan H

2017-01-01

Abstract Background Increasing antibiotic resistance limits treatment options for gonorrhea. We examined the impact of a hypothetical point-of-care (POC) test reporting antibiotic susceptibility profiles on slowing resistance spread. Methods A mathematical model describing gonorrhea transmission incorporated resistance emergence probabilities and fitness costs associated with resistance based on characteristics of ciprofloxacin (A), azithromycin (B), and ceftriaxone (C). We evaluated time to 1% and 5% prevalence of resistant strains among all isolates with the following: (1) empiric treatment (B and C), and treatment guided by POC tests determining susceptibility to (2) A only and (3) all 3 antibiotics. Results Continued empiric treatment without POC testing was projected to result in >5% of isolates being resistant to both B and C within 15 years. Use of either POC test in 10% of identified cases delayed this by 5 years. The 3 antibiotic POC test delayed the time to reach 1% prevalence of triply-resistant strains by 6 years, whereas the A-only test resulted in no delay. Results were less sensitive to assumptions about fitness costs and test characteristics with increasing test uptake. Conclusions Rapid diagnostics reporting antibiotic susceptibility may extend the usefulness of existing antibiotics for gonorrhea treatment, but ongoing monitoring of resistance patterns will be critical. PMID:28968710

Helicobacter pylori resistance to six antibiotics by two breakpoint systems and resistance evolution in Bulgaria.

PubMed

Boyanova, Lyudmila; Gergova, Galina; Evstatiev, Ivailo; Spassova, Zoya; Kandilarov, Naiden; Yaneva, Penka; Markovska, Rumyana; Mitov, Ivan

2016-01-01

Helicobacter pylori resistance to antibiotics is the main cause for eradication failures. Antibiotic resistance in 299 H. pylori strains from 233 untreated adults, 26 treated adults, and 40 untreated children was assessed by E tests and, for metronidazole, by breakpoint susceptibility testing and two breakpoint systems. Using EUCAST breakpoints (EBPs) and previous breakpoints (PBPs), overall resistance rates were: amoxicillin 4.0 and 0.6%, metronidazole 33.8 and 33.8%, clarithromycin 28.1 and 27.4%, levofloxacin 19.4 and 19.4%, tetracycline 3.7 and 1.5%, respectively, and rifampin 8.3% (EBP). Multidrug resistance was detected in treated and untreated adults and an untreated child and included 17 (EBPs) and 15 strains (PBPs). Differences between susceptibility categories were found for amoxicillin (3.5% of strains), clarithromycin (0.7%), and tetracycline (2.2%). Using PBPs, from 2005-2007 to 2010-2015, overall primary clarithromycin resistance continued to increase (17.9-25.6%) as noted in our previous study. However, in 2010-2015, overall primary metronidazole (24.0-31.5%) and fluoroquinolone (7.6-18.3%) resistance rates also increased. Primary resistance rates in children and adults were comparable. Briefly, differences in resistance rates by the two breakpoint systems affected the results for three antibiotics. National antibiotic consumption was linked to macrolide resistance in adults. Current primary H. pylori resistance to three antibiotics increased in all untreated patients and in the untreated adults, with the sharpest rise for the fluoroquinolones. The presence of fivefold H. pylori resistance to metronidazole, clarithromycin, tetracycline, levofloxacin, and amoxicillin according to EBPs is alarming.

Restructuring of Enterococcus faecalis biofilm architecture in response to antibiotic-induced stress

DOE PAGES

Dale, Jennifer L.; Nilson, Jennifer L.; Barnes, Aaron M. T.; ...

2017-06-30

Bacterial biofilms are intrinsically resistant to antimicrobial treatment, which contributes to microbial persistence in clinical infections. Enterococcus faecalis is an opportunistic pathogen that readily forms biofilms and is the most prevalent enterococcal species identified in healthcare-associated infections. Since intrinsic resistance to multiple antibiotics is common for enterococci, and antibiotic resistance is elevated in biofilm populations, it is imperative to understand the mechanisms involved. Previously, we identified two glycosyltransferase genes whose disruption resulted in impaired nascent biofilm formation in the presence of antibiotic concentrations subinhibitory for parent growth and biofilm formation. The glycosyltransferases are involved in synthesis of the cell-wall-associated rhamnopolysaccharidemore » Epa. Here we examined the effect of epa mutations on the temporal development of E. faecalis biofilms, and on the effects of antibiotics on pre-formed biofilms using scanning electron microscopy. We show that ΔepaOX mutant cells arrange into complex multidimensional biofilms independent of antibiotic exposure, while parent cells form biofilms that are monolayers in the absence of antibiotics. Remarkably, upon exposure to antibiotics parent biofilm cells restructure into complex three-dimensional biofilms resembling those of the ΔepaOX mutant without antibiotics. All biofilms exhibiting complex cellular architectures were less structurally stable than monolayer biofilms, with the biofilm cells exhibiting increased detachment. Our results indicate that E. faecalis biofilms restructure in response to cellular stress whether induced by antibiotics in the case of parent cells, or by deficiencies in Epa composition for the ΔepaOX strain. The data demonstrate a link between cellular architecture and antibiotic resistance of E. faecalis biofilms.« less

Restructuring of Enterococcus faecalis biofilm architecture in response to antibiotic-induced stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dale, Jennifer L.; Nilson, Jennifer L.; Barnes, Aaron M. T.

Bacterial biofilms are intrinsically resistant to antimicrobial treatment, which contributes to microbial persistence in clinical infections. Enterococcus faecalis is an opportunistic pathogen that readily forms biofilms and is the most prevalent enterococcal species identified in healthcare-associated infections. Since intrinsic resistance to multiple antibiotics is common for enterococci, and antibiotic resistance is elevated in biofilm populations, it is imperative to understand the mechanisms involved. Previously, we identified two glycosyltransferase genes whose disruption resulted in impaired nascent biofilm formation in the presence of antibiotic concentrations subinhibitory for parent growth and biofilm formation. The glycosyltransferases are involved in synthesis of the cell-wall-associated rhamnopolysaccharidemore » Epa. Here we examined the effect of epa mutations on the temporal development of E. faecalis biofilms, and on the effects of antibiotics on pre-formed biofilms using scanning electron microscopy. We show that ΔepaOX mutant cells arrange into complex multidimensional biofilms independent of antibiotic exposure, while parent cells form biofilms that are monolayers in the absence of antibiotics. Remarkably, upon exposure to antibiotics parent biofilm cells restructure into complex three-dimensional biofilms resembling those of the ΔepaOX mutant without antibiotics. All biofilms exhibiting complex cellular architectures were less structurally stable than monolayer biofilms, with the biofilm cells exhibiting increased detachment. Our results indicate that E. faecalis biofilms restructure in response to cellular stress whether induced by antibiotics in the case of parent cells, or by deficiencies in Epa composition for the ΔepaOX strain. The data demonstrate a link between cellular architecture and antibiotic resistance of E. faecalis biofilms.« less

Antibiotic Resistance in Aeromonas Upstream and Downstream of a Water Resource Recovery Facility

PubMed Central

Henderson, Samantha K.; Askew, Maegan L.; Risenhoover, Hollie G.; McAndrews, Chrystle R.; Kennedy, S. Dawn; Paine, C. Sue

2014-01-01

Aeromonas strains isolated from sediments upstream and downstream of a water resource recovery facility (WRRF) over a two-year time period were tested for susceptibility to thirteen antibiotics. Incidence of resistance to antibiotics, antibiotic resistance phenotypes, and diversity (based on resistance phenotypes) were compared in the two populations. At the beginning of the study, the upstream and downstream Aeromonas populations were different for incidence of antibiotic resistance (p < 0.01), resistance phenotypes (p < 0.005), and diversity. However, these differences declined over time and were not significant at the end of the study. These results (1) indicate that antibiotic resistance in Aeromonas in stream sediments fluctuates considerably over time and (2) suggest that WRRF effluent does not, when examined over the long term, affect antibiotic resistance in Aeromonas in downstream sediment. PMID:25327024

Resistant Traits in Digital Organisms Do Not Revert Preselection Status despite Extended Deselection: Implications to Microbial Antibiotics Resistance

PubMed Central

Castillo, Clarence F. G.; Ling, Maurice H. T.

2014-01-01

Antibiotics resistance is a serious biomedical issue as formally susceptible organisms gain resistance under its selective pressure. There have been contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics. Here, we use experimental evolution in “digital organisms” to examine the rate of gain and loss of resistance under the assumption that there is no fitness cost for maintaining resistance. Our results show that selective pressure is likely to result in maximum resistance with respect to the selective pressure. During deselection as a result of disuse of the specific antibiotics, a large initial loss and prolonged stabilization of resistance are observed, but resistance is not lost to the stage of preselection. This suggests that a pool of partial persists organisms persist long after withdrawal of selective pressure at a relatively constant proportion. Hence, contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics may be a statistical variation about constant proportion. Our results also show that subsequent reintroduction of the same selective pressure results in rapid regain of maximal resistance. Thus, our simulation results suggest that complete elimination of specific antibiotics resistance is unlikely after the disuse of antibiotics once a resistant pool of microorganisms has been established. PMID:24977157

A Survey and Analysis of the American Public's Perceptions and Knowledge About Antibiotic Resistance

PubMed Central

Carter, Rebecca R.; Sun, Jiayang; Jump, Robin L. P.

2016-01-01

Background. Little is known about the American public's perceptions or knowledge about antibiotic-resistant bacteria or antibiotic misuse. We hypothesized that although many people recognize antibiotic resistance as a problem, they may not understand the relationship between antibiotic consumption and selection of resistant bacteria. Methods. We developed and tested a survey asking respondents about their perceptions and knowledge regarding appropriate antibiotic use. Respondents were recruited with the Amazon Mechanical Turk crowdsourcing platform. The survey, carefully designed to assess a crowd-sourced population, asked respondents to explain “antibiotic resistance” in their own words. Subsequent questions were multiple choice. Results. Of 215 respondents, the vast majority agreed that inappropriate antibiotic use contributes to antibiotic resistance (92%), whereas a notable proportion (70%) responded neutrally or disagreed with the statement that antibiotic resistance is a problem. Over 40% of respondents indicated that antibiotics were the best choice to treat a fever or a runny nose and sore throat. Major themes from the free-text responses included that antibiotic resistance develops by bacteria, or by the infection, or the body (ie, an immune response). Minor themes included antibiotic overuse and antibiotic resistance caused by bacterial adaptation or an immune response. Conclusions. Our findings indicate that the public is aware that antibiotic misuse contributes to antibiotic resistance, but many do not consider it to be an important problem. The free-text responses suggest specific educational targets, including the difference between an immune response and bacterial adaptation, to increase awareness and understanding of antibiotic resistance. PMID:27382598

Increased antibiotic resistance exhibited by the biofilm of Vibrio cholerae O139.

PubMed

Gupta, Preeti; Mankere, Bharti; Chekkoora Keloth, Shami; Tuteja, Urmil; Pandey, Pratibha; Chelvam, Kulanthaivel Thava

2018-04-24

Vibrio cholerae, the aetiological agent of the deadly diarrhoeal disease cholera, is known to form biofilm. The antibiotic susceptibility status of biofilm of V. cholerae O139, an important epidemic strain in India and other countries, has not previously been studied in detail. Antibiotic susceptibility status of planktonic and biofilm cultures of V. cholerae O139 was evaluated by determining MIC, MBC and minimum biofilm eradication concentration (MBEC) values of five different classes of antibiotics using established methods. Effects of antibiotic treatment on planktonic and biofilm cultures were analysed by scanning electron microscopy. The virulence of the antibiotic-surviving population (ASP) was evaluated using an infant mouse model. The frequency of spontaneous mutants and inheritability of antibiotic resistance were determined with standard methods. The antibiotic resistance exhibited by biofilm of V. cholerae O139 was found to be significantly higher (P < 0.05) than its planktonic counterpart. The biofilm-associated antibiotic resistance was found to be transient and exclusive to the biofilm culture. The frequency of ASP clones among antibiotic-treated biofilm cultures occurred at a rate of 0.012%-0.95% and these clones were found to retain the virulence and antibiotic resistance of their parent strains. The biofilm of V. cholerae O139 was found to be resistant to different types of antibiotics tested. This unconventional biofilm resistance highlights the hidden danger of antimicrobial escape by V. cholerae, increased risk of cholera transmission and its continued persistence in the environment.

Studying modification of aminoglycoside antibiotics by resistance-causing enzymes via microarray.

PubMed

Disney, Matthew D

2012-01-01

Widespread bacterial resistance to antibiotics is a significant public health concern. To remain a step ahead of evolving bacteria, new methods to study resistance to antibacterials and to uncover novel antibiotics that evade resistance are urgently needed. Herein, microarray-based methods that have been developed to study aminoglycoside modification by resistance-causing enzymes are reviewed. These arrays can also be used to study the binding of aminoglycoside antibiotics to a mimic of their therapeutic target, the rRNA aminoacyl site (A-site), and how modification by resistance-causing enzymes affects their abilities to bind RNA.

Efficient removal of antibiotics in surface-flow constructed wetlands, with no observed impact on antibiotic resistance genes.

PubMed

Berglund, Björn; Khan, Ghazanfar Ali; Weisner, Stefan E B; Ehde, Per Magnus; Fick, Jerker; Lindgren, Per-Eric

2014-04-01

Recently, there have been growing concerns about pharmaceuticals including antibiotics as environmental contaminants. Antibiotics of concentrations commonly encountered in wastewater have been suggested to affect bacterial population dynamics and to promote dissemination of antibiotic resistance. Conventional wastewater treatment processes do not always adequately remove pharmaceuticals causing environmental dissemination of low levels of these compounds. Using constructed wetlands as an additional treatment step after sewage treatment plants have been proposed as a cheap alternative to increase reduction of wastewater contaminants, however this means that the natural microbial community of the wetlands becomes exposed to elevated levels of antibiotics. In this study, experimental surface-flow wetlands in Sweden were continuously exposed to antibiotics of concentrations commonly encountered in wastewater. The aim was to assess the antibiotic removal efficiency of constructed wetlands and to evaluate the impact of low levels of antibiotics on bacterial diversity, resistance development and expression in the wetland bacterial community. Antibiotic concentrations were measured using liquid chromatography-mass spectrometry and the effect on the bacterial diversity was assessed with 16S rRNA-based denaturing gradient gel electrophoresis. Real-time PCR was used to detect and quantify antibiotic resistance genes and integrons in the wetlands, during and after the exposure period. The results indicated that the antibiotic removal efficiency of constructed wetlands was comparable to conventional wastewater treatment schemes. Furthermore, short-term treatment of the constructed wetlands with environmentally relevant concentrations (i.e. 100-2000 ng×l(-1)) of antibiotics did not significantly affect resistance gene concentrations, suggesting that surface-flow constructed wetlands are well-suited for wastewater treatment purposes. Copyright © 2014 Elsevier B.V. All rights

Patient perceptions of antibiotic use and resistance at a single university dermatology clinic.

PubMed

Goettsche, Lainee S; Weig, Emily A; Chung, Jina; Hoff, Brian M; Ince, Dilek; Wanat, Karolyn A

2018-05-21

Antibiotic resistance is an important problem that requires continued patient education and important prescribing stewardship. Dermatologists prescribe the most antibiotics per provider in comparison to other specialties and have an important role to play in the campaign of mindful prescribing. Data on the dermatology patients' knowledge and perception regarding antibiotic resistance is lacking and could play a role in providers' continuation of medications. We conducted a single institution survey of 512 dermatology clinic patients to understand patient's knowledge and potential gaps. Overall, our results demonstrated an overall higher level of knowledge than expected, there were still several knowledge gaps identified. Ninety-one percent of respondents were aware of the term 'antibiotic resistance'. However, 65% of participants believed that a short course of antibiotics could not cause resistance. While our patients have awareness of antibiotic resistance, it is imperative to continue to assess patients' knowledge about antibiotic resistance and provide education whenever possible in order to continue to practice antibiotic stewardship.

Antibiotic Resistance in the Food Chain: A Developing Country-Perspective

PubMed Central

Founou, Luria Leslie; Founou, Raspail Carrel; Essack, Sabiha Yusuf

2016-01-01

Antibiotics are now “endangered species” facing extinction due to the worldwide emergence of antibiotic resistance (ABR). Food animals are considered as key reservoirs of antibiotic-resistant bacteria with the use of antibiotics in the food production industry having contributed to the actual global challenge of ABR. There are no geographic boundaries to impede the worldwide spread of ABR. If preventive and containment measures are not applied locally, nationally and regionally, the limited interventions in one country, continent and for instance, in the developing world, could compromise the efficacy and endanger ABR containment policies implemented in other parts of the world, the best-managed high-resource countries included. Multifaceted, comprehensive, and integrated measures complying with the One Health approach are imperative to ensure food safety and security, effectively combat infectious diseases, curb the emergence and spread of ABR, and preserve the efficacy of antibiotics for future generations. Countries should follow the World Health Organization, World Organization for Animal Health, and the Food and Agriculture Organization of the United Nations recommendations to implement national action plans encompassing human, (food) animal, and environmental sectors to improve policies, interventions and activities that address the prevention and containment of ABR from farm-to-fork. This review covers (i) the origin of antibiotic resistance, (ii) pathways by which bacteria spread to humans from farm-to-fork, (iii) differences in levels of antibiotic resistance between developed and developing countries, and (iv) prevention and containment measures of antibiotic resistance in the food chain. PMID:27933044

Prevalence of Antibiotic-Resistant Escherichia coli in Drinking Water Sources in Hangzhou City

PubMed Central

Chen, Zhaojun; Yu, Daojun; He, Songzhe; Ye, Hui; Zhang, Lei; Wen, Yanping; Zhang, Wenhui; Shu, Liping; Chen, Shuchang

2017-01-01

This study investigated the distribution of antibiotic resistant Escherichia coli (E. coli) and examined the possible relationship between water quality parameters and antibiotic resistance from two different drinking water sources (the Qiantang River and the Dongtiao Stream) in Hangzhou city of China. E. coli isolates were tested for their susceptibility to 18 antibiotics. Most of the isolates were resistant to tetracycline (TE), followed by ampicillin (AM), piperacillin (PIP), trimethoprim/sulfamethoxazole (SXT), and chloramphenicol (C). The antibiotic resistance rate of E. coli isolates from two water sources was similar; For E. coli isolates from the Qiantang River, their antibiotic resistance rates decreased from up- to downstream. Seasonally, the dry and wet season had little impact on antibiotic resistance. Spearman's rank correlation revealed significant correlation between resistance to TE and phenicols or ciprofloxacin (CIP), as well as quinolones (ciprofloxacin and levofloxacin) and cephalosporins or gentamicin (GM). Pearson's chi-square tests found certain water parameters such as nutrient concentration were strongly associated with resistance to some of the antibiotics. In addition, tet genes were detected from all 82 TE-resistant E. coli isolates, and most of the isolates (81.87%) contained multiple tet genes, which displayed 14 different combinations. Collectively, this study provided baseline data on antibiotic resistance of drinking water sources in Hangzhou city, which indicates drinking water sources could be the reservoir of antibiotic resistance, potentially presenting a public health risk. PMID:28670309

Antibiotic prophylaxis in the era of multidrug-resistant bacteria.

PubMed

Wittekamp, Bastiaan H J; Bonten, Marc J M

2012-06-01

The prophylactic use of antibiotics can only be justified when clinical benefits on relevant patient outcomes, such as morbidity or mortality, cost-effectiveness, and absence of immediate emergence of antibiotic resistance have been unequivocally demonstrated. In some intensive care unit (ICU) patients, antibiotic prophylaxis is used as part of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD). Recent trials in ICUs with low levels of antibiotic resistance strongly suggest that both regimens reduce the incidence of ICU-acquired infections and improve patient survival. Naturally, the unique microbial ecology of such settings reduce generalizability of results. Therefore, the routine use of SOD and SDD remains highly controversial, especially in ICUs with higher levels of antibiotic resistance. Moreover, convincing evidence is still missing on several important aspects related to efficacy and safety. Despite numerous trials, effects of SDD and SOD on antibiotic resistance during and after decolonization treatment have still been insufficiently investigated, and existing results are contradicting. Furthermore, the effects of both regimens on the non-culturable part of the intestinal flora remain unknown. Finally, cost-effectiveness has not been thoroughly investigated, and prices of the antimicrobial agents that have been used have increased dramatically in recent years. In this review, important knowledge gaps that so far prevent the widespread use of SDD and SOD will be addressed.

[Does the emergence of antibiotic resistance announce the return of the dark ages?].

PubMed

Elhani, Dalèle

2011-01-01

Antibiotic revolution changed the course of modern medicine, by decreasing mortality due to bacterial infections. However, bacteria have developed several ways of resistance against all antibiotics used. In view of the rise of resistance and of its dissemination to different bacterial families, new effective antibiotics are scare and the return in the pre-antibiotic era seems to be a reality for some parts of the world. This review revises the worrying phenomenon of antibiotic resistance focusing on some examples of "superbugs", which represent a daily challenge for the medical profession, such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, extended spectrum ß-lactamae-producing Enterobacteriaceae as well as carbapenem-resistant Pseudomonas aeruginosa. Facing the emergence of the multiresistant strains, the priority is obviously to control the spread of these microorganisms. It is only through the prudent use of antimicrobial drugs and the introduction of new and effective antibiotics that the antibiotic resistance will be slowed down and that we continue to treat bacterial infections.

Exploring the links between antibiotic occurrence, antibiotic resistance, and bacterial communities in water supply reservoirs.

PubMed

Huerta, Belinda; Marti, Elisabet; Gros, Meritxell; López, Pilar; Pompêo, Marcelo; Armengol, Joan; Barceló, Damià; Balcázar, Jose Luis; Rodríguez-Mozaz, Sara; Marcé, Rafael

2013-07-01

Antibiotic resistance represents a growing global health concern due to the overuse and misuse of antibiotics. There is, however, little information about how the selective pressure of clinical antibiotic usage can affect environmental communities in aquatic ecosystems and which bacterial groups might be responsible for dissemination of antibiotic resistance genes (ARGs) into the environment. In this study, chemical and biological characterization of water and sediments from three water supply reservoirs subjected to a wide pollution gradient allowed to draw an accurate picture of the concentration of antibiotics and prevalence of ARGs, in order to evaluate the potential role of ARGs in shaping bacterial communities, and to identify the bacterial groups most probably carrying and disseminating ARGs. Results showed significant correlation between the presence of ARG conferring resistance to macrolides and the composition of bacterial communities, suggesting that antibiotic pollution and the spreading of ARG might play a role in the conformation of bacterial communities in reservoirs. Results also pointed out the bacterial groups Actinobacteria and Firmicutes as the ones probably carrying and disseminating ARGs. The potential effect of antibiotic pollution and the presence of ARGs on the composition of bacterial communities in lacustrine ecosystems prompt the fundamental question about potential effects on bacterial-related ecosystem services supplied by lakes and reservoirs. Copyright © 2013 Elsevier B.V. All rights reserved.

Seasonal Variations in Water-Quality, Antibiotic Residues, Resistant Bacteria and Antibiotic Resistance Genes of Escherichia coli Isolates from Water and Sediments of the Kshipra River in Central India.

PubMed

Diwan, Vishal; Hanna, Nada; Purohit, Manju; Chandran, Salesh; Riggi, Emilia; Parashar, Vivek; Tamhankar, Ashok J; Stålsby Lundborg, Cecilia

2018-06-17

To characterize the seasonal variation, over one year, in water-quality, antibiotic residue levels, antibiotic resistance genes and antibiotic resistance in Escherichia coli isolates from water and sediment of the Kshipra River in Central India. Water and sediment samples were collected from seven selected points from the Kshipra River in the Indian city of Ujjain in the summer, rainy season, autumn and winter seasons in 2014. Water quality parameters (physical, chemical and microbiological) were analyzed using standard methods. High-performance liquid chromatography⁻tandem mass spectrometry was used to determine the concentrations of antibiotic residues. In river water and sediment samples, antibiotic resistance and multidrug resistance patterns of isolated E. coli to 17 antibiotics were tested and genes coding for resistance and phylogenetic groups were detected using multiplex polymerase chain reaction. One-way analysis of variance (ANOVA) and Fisher tests were applied to determine seasonal variation. In river water, seasonal variation was significantly associated with various water quality parameters, presence of sulfamethoxazole residues, bacteria resistant to ampicillin, cefepime, meropenem, amikacin, gentamicin, tigecycline, multidrug resistance and CTX-M-1 gene. The majority of the Extended Spectrum Beta-Lactamase (ESBL)-producing E. coli isolates from river water and sediment in all different seasons belonged to phylogenetic group A or B1. Antibiotic pollution, resistance and resistance genes in the Kshipra River showed significant seasonal variation. Guidelines and regulatory standards are needed to control environmental dissemination of these “pollutants” in this holy river.

Presence of antibiotic resistance genes in a sewage treatment plant in Thibodaux, Louisiana, USA.

PubMed

Naquin, Anthony; Shrestha, Arsen; Sherpa, Mingma; Nathaniel, Rajkumar; Boopathy, Raj

2015-01-01

Increasing uses and disposals of antibiotics to the environment have increased emergence of various antibiotic resistance. One of the sources for the spread of antibiotic resistance is wastewater treatment plant, where bacteria and antibiotics can come in contact and can acquire antibiotics resistance. There are very few studies on this subject from a small town sewage treatment plant. Therefore, this study was conducted using raw sewage as well as treated sewage from a sewage treatment plant in Thibodaux in rural southeast Louisiana in USA. Samples were collected monthly from the Thibodaux sewage treatment plant and the presence of antibiotic resistance genes was monitored. The study showed the presence of antibiotic resistance genes in both raw and treated sewage in every month of the study period. The genetic transformation assay showed the successful transformation of methicillin resistant gene, mecA to an antibiotic sensitive Staphylococcus aureus, which became antibiotic resistant within 24h. Copyright © 2015 Elsevier Ltd. All rights reserved.

Graphene oxide in the water environment could affect tetracycline-antibiotic resistance.

PubMed

Guo, Mei-Ting; Zhang, Guo-Sheng

2017-09-01

In recent years, the influence of new materials like nanoparticles in the water environment on biological substances has been widely studied. Antibiotic resistance genes (ARGs) represent a new type of pollutant in the environment. Graphene oxide (GO), as a nano material, because of its unique structure, may have an impact on antibiotic resistance bacteria (ARB) and ARGs; however the research in this area is rarely reported. Therefore, this study mainly investigated the effects of GO on bacterial antibiotic resistance. The results showed that GO had a limited effect on ARB inactivation. A high concentration of GO (>10 mg/L) can damage resistant plasmids to reduce bacterial resistance to antibiotics, but low concentrations of GO (<1 mg/L) led to almost no damage to the plasmid. However, all tested concentrations of GO promoted the conjugative transfer from 1to over 3 folds, with low concentrations and high concentration (1-10 and 100 mg/L) of GO samples the least promoted. The overall effect of GO on antibiotic resistance needs further investigation. Copyright © 2017. Published by Elsevier Ltd.

Taxing Meat: Taking Responsibility for One’s Contribution to Antibiotic Resistance

PubMed Central

Giubilini, Alberto; Birkl, Patrick; Douglas, Thomas; Savulescu, Julian; Maslen, Hannah

2018-01-01

Antibiotic use in animal farming is one of the main drivers of antibiotic resistance both in animals and in humans. In this paper we propose that one feasible and fair way to address this problem is to tax animal products obtained with the use of antibiotics. We argue that such tax is supported both by (a) deontological arguments, which are based on the duty individuals have to compensate society for the antibiotic resistance to which they are contributing through consumption of animal products obtained with the use of antibiotics; and (b) a cost-benefit analysis of taxing such animal products and of using revenue from the tax to fund alternatives to use of antibiotics in animal farming. Finally, we argue that such a tax would be fair because individuals who consume animal products obtained with the use of antibiotics can be held morally responsible, i.e. blameworthy, for their contribution to antibiotic resistance, in spite of the fact that each individual contribution is imperceptible. PMID:29515330

Antibiotic resistance genes and residual antimicrobials in cattle feedlot surface soil

USDA-ARS?s Scientific Manuscript database

Antibiotic residues and resistant bacteria in cattle feedlot manure may impact antibiotic resistance in the environment. This study investigated common antimicrobials (tetracyclines and monensin) and associated resistance genes in cattle feedlot soils over time. Animal diets and other feedlot soil...

Occurrence of antibiotic resistance and characterization of resistant genes and integrons in Enterobacteriaceae isolated from integrated fish farms south China

USGS Publications Warehouse

Su, Hao-Chang; Ying, Guang-Guo; Tao, Ran; Zhang, Rui-Quan; Fogarty, Lisa R.; Kolpin, Dana W.

2011-01-01

Antibiotics are still widely applied in animal husbandry to prevent diseases and used as feed additives to promote animal growth. This could result in antibiotic resistance to bacteria and antibiotic residues in animals. In this paper, Enterobacteriaceae isolated from four integrated fish farms in Zhongshan, South China were tested for antibiotic resistance, tetracycline resistance genes, sulfonamide resistance genes, and class 1 integrons. The Kirby-Bauer disk diffusion method and polymerase chain reaction (PCR) assays were carried out to test antibiotic susceptibility and resistance genes, respectively. Relatively high antibiotic resistance frequencies were found, especially for ampicillin (80%), tetracycline (52%), and trimethoprim (50%). Out of 203 Enterobacteriaceae isolates, 98.5% were resistant to one or more antibiotics tested. Multiple antibiotic resistance (MAR) was found highest in animal manures with a MAR index of 0.56. Tetracycline resistance genes (tet(A), tet(C)) and sulfonamide resistance genes (sul2) were detected in more than 50% of the isolates. The intI1 gene was found in 170 isolates (83.7%). Both classic and non-classic class 1 integrons were found. Four genes, aadA5, aadA22, dfr2, and dfrA17, were detected. To our knowledge, this is the first report for molecular characterization of antibiotic resistance genes in Enterobacteriaceae isolated from integrated fish farms in China and the first time that gene cassette array dfrA17-aadA5 has been detected in such fish farms. Results of this study indicated that fish farms may be a reservoir of highly diverse and abundant antibiotic resistant genes and gene cassettes. Integrons may play a key role in multiple antibiotic resistances posing potential health risks to the general public and aquaculture.

A WWW-based information system on resistance of bacteria to antibiotics.

PubMed

Schindler, J; Schindler, Z; Schindler, J

1998-01-01

The information system on resistance of bacteria to antibiotics (WARN--World Antibiotic Resistance Network) is implemented as a WWW server at Charles University in Prague (http:/(/)www.warn.cas.cz). Its main goal is to give information about problems of antibiotic resistance of bacteria and to process data on isolated strains. The WARN web-site contains six main topics. Four of them form the core of the system: Topics of Interest bring information on selected timely topics in antibiotic resistance--pneumococci, staphylococci, beta-lactamases, glycopeptide--and aminoglycoside resistance. Global Monitor brings references and reports on resistance in the world as well as recommended method of surveillance. The topic Data contains raw data on strains in particular countries and hospitals. Data can be viewed in their original form as a list of records (strains) or processed to provide statistics about the resistance rates in the selected country or hospital respectively. The topic Search allows one to search for one or several terms in the whole document. Counts of accessed pages show, that there is a standing demand for information about the serious problems of antibiotic therapy of infectious diseases.

Antibiotic resistance of Clostridium perfringens isolates from broiler chickens in Egypt.

PubMed

Osman, K M; Elhariri, M

2013-12-01

The use of antibiotic feed additives in broiler chickens results in a high prevalence of resistance among their enteric bacteria, with a consequent emergence of antibiotic resistance in zoonotic enteropathogens. Despite growing concerns about the emergence of antibiotic-resistant strains, which show varying prevalences in different geographic regions, little work has been done to investigate this issue in the Middle East. This study provides insight into one of the world's most common and financially crippling poultry diseases, necrotic enteritis caused by Clostridium perfringens. The study was designed to determine the prevalence of antibiotic resistance in C. perfringens isolates from clinical cases of necrotic enteritis in broiler chickens in Egypt. A total of 125 isolates were obtained from broiler flocks in 35 chicken coops on 17 farms and were tested using the disc diffusion method. All 125 isolates were resistant to gentamicin, streptomycin, oxolinic acid, lincomycin, erythromycin and spiramycin. The prevalence of resistance to other antibiotics was also high: rifampicin (34%), chloramphenicol (46%), spectinomycin (50%), tylosin-fosfomycin (52%), ciprofloxacin (58%), norfloxacin (67%), oxytetracycline (71%), flumequine (78%), enrofloxacin (82%), neomycin (93%), colistin (94%), pefloxacin (94%), doxycycline (98%) and trimethoprim-sulfamethoxazole (98%). It is recommended that C. perfringens infections in Egypt should be treated with antibiotics for which resistant isolates are rare at present; namely, amoxicillin, ampicillin, cephradine, fosfomycin and florfenicol.

Distribution and quantification of antibiotic resistant genes and bacteria across agricultural and non-agricultural metagenomes.

PubMed

Durso, Lisa M; Miller, Daniel N; Wienhold, Brian J

2012-01-01

There is concern that antibiotic resistance can potentially be transferred from animals to humans through the food chain. The relationship between specific antibiotic resistant bacteria and the genes they carry remains to be described. Few details are known about the ecology of antibiotic resistant genes and bacteria in food production systems, or how antibiotic resistance genes in food animals compare to antibiotic resistance genes in other ecosystems. Here we report the distribution of antibiotic resistant genes in publicly available agricultural and non-agricultural metagenomic samples and identify which bacteria are likely to be carrying those genes. Antibiotic resistance, as coded for in the genes used in this study, is a process that was associated with all natural, agricultural, and human-impacted ecosystems examined, with between 0.7 to 4.4% of all classified genes in each habitat coding for resistance to antibiotic and toxic compounds (RATC). Agricultural, human, and coastal-marine metagenomes have characteristic distributions of antibiotic resistance genes, and different bacteria that carry the genes. There is a larger percentage of the total genome associated with antibiotic resistance in gastrointestinal-associated and agricultural metagenomes compared to marine and Antarctic samples. Since antibiotic resistance genes are a natural part of both human-impacted and pristine habitats, presence of these resistance genes in any specific habitat is therefore not sufficient to indicate or determine impact of anthropogenic antibiotic use. We recommend that baseline studies and control samples be taken in order to determine natural background levels of antibiotic resistant bacteria and/or antibiotic resistance genes when investigating the impacts of veterinary use of antibiotics on human health. We raise questions regarding whether the underlying biology of each type of bacteria contributes to the likelihood of transfer via the food chain.

Self-resistance in Streptomyces, with Special Reference to β-Lactam Antibiotics.

PubMed

Ogawara, Hiroshi

2016-05-10

Antibiotic resistance is one of the most serious public health problems. Among bacterial resistance, β-lactam antibiotic resistance is the most prevailing and threatening area. Antibiotic resistance is thought to originate in antibiotic-producing bacteria such as Streptomyces. In this review, β-lactamases and penicillin-binding proteins (PBPs) in Streptomyces are explored mainly by phylogenetic analyses from the viewpoint of self-resistance. Although PBPs are more important than β-lactamases in self-resistance, phylogenetically diverse β-lactamases exist in Streptomyces. While class A β-lactamases are mostly detected in their enzyme activity, over two to five times more classes B and C β-lactamase genes are identified at the whole genomic level. These genes can subsequently be transferred to pathogenic bacteria. As for PBPs, two pairs of low affinity PBPs protect Streptomyces from the attack of self-producing and other environmental β-lactam antibiotics. PBPs with PASTA domains are detectable only in class A PBPs in Actinobacteria with the exception of Streptomyces. None of the Streptomyces has PBPs with PASTA domains. However, one of class B PBPs without PASTA domain and a serine/threonine protein kinase with four PASTA domains are located in adjacent positions in most Streptomyces. These class B type PBPs are involved in the spore wall synthesizing complex and probably in self-resistance. Lastly, this paper emphasizes that the resistance mechanisms in Streptomyces are very hard to deal with, despite great efforts in finding new antibiotics.

Efforts to slacken antibiotic resistance: Labeling meat products from animals raised without antibiotics in the United States.

PubMed

Centner, Terence J

2016-09-01

As bacteria and diseases spread due to climatic change, greater amounts of antibiotics will be used thereby exacerbating the problem of antibiotic resistance. To help slacken the development of resistant bacteria, the medical community is attempting to reduce unnecessary and excessive usage of antibiotics. One of the targets is the use of antibiotics for enhancing animal growth and promoting feed efficiency in the production of food animals. While governments can adopt regulations prohibiting nontherapeutic uses of antibiotics in food animals and strategies to reduce antibiotic usage, another idea is to publicize when antibiotics are used in food animal production by allowing labeled meat products. This paper builds upon existing labeling and marketing efforts in the United States to show how a government can develop a verified antibiotic-free labeling program that would allow consumers to purchase meat products from animals that had never received antibiotics. Copyright © 2016 Elsevier B.V. All rights reserved.

Surveillance and Control of Antibiotic Resistance in the Mediterranean Region.

PubMed

Ricciardi, Walter; Giubbini, Gabriele; Laurenti, Patrizia

2016-01-01

Antibiotic resistance is one of the most relevant problems in the healthcare: the growth of resistant microorganisms in healthcare settings is a worrisome threat, raising length to stay (LOS), morbidity and mortality in those patients. The importance of the antibiotic resistance and its spread around the world, gave rise to the activation of several surveillance systems, based especially on the collection of laboratory data to local or national level. The objective of this work is to carry out a review of the scientific literature existing on the topic and scientific activities related to surveillance of antibiotic resistance in the countries bordering the Mediterranean Sea. Recent Data from European Centre for Disease Prevention and Control (November 2015) show, for different combinations bacterium-drug, an increase of resistance from North to South and from West to East of Europe. It is of particular concern the phenomenon of resistance carried out by some gram-negative, specifically Klebsiella pneumoniae and Escherichia coli to third-generation cephalosporin, often combined in opposition to fluoroquinolones and aminoglycosides. Is particularly high the incidence of resistance to carbapenems by strains of Enterobacteriaceae (Klebsiella included). The resistance exerted by MRSA (Methicillin-resistant Staphylococcus aureus) continues to be relevant, albeit showing some decline in recent years. The incidence of resistance carried on by Streptococcus pneumoniae is stable and is mainly relevant to macrolides. Finally, a significant increase in recording relatively exercised by Enterococcus faecium to Vancomycin. Detecting, preventing, and controlling antibiotic resistance requires strategic, coordinated, and sustained efforts. It also depends on the engagement of governments, academia, industry, healthcare providers, the general public, and the agricultural community, as well as international partners. Committing to combating antibiotic-resistant microbes does support

Photodynamic inactivation of antibiotic-resistant bacteria and biofilms by hematoporphyrin monomethyl ether.

PubMed

Liu, Chengcheng; Hu, Min; Ma, Dandan; Lei, Jin'e; Xu, Jiru

2016-02-01

The worldwide increase in bacterial antibiotic resistance has led to a search for alternative antibacterial therapies. A promising approach to killing antibiotic-resistant bacteria is photodynamic antimicrobial chemotherapy, which uses light in combination with a photosensitizer to induce a phototoxic reaction. We evaluated the photodynamic inactivation (PDI) efficiency of hematoporphyrin monomethyl ether (HMME) on antibiotic-resistant bacteria and biofilms. HMME exhibited no significant dark toxicity and provided dose-dependent inactivation of antibiotic-resistant bacteria and biofilms. After incubation with 100-μM HMME and irradiation with 72-J cm(-2) white light, 4.19-7.59 log10 reductions in survival were achieved in planktonic suspension. Antibiotic-resistant strains were as susceptible to PDI in biofilms as in planktonic suspensions, but the inactivation of bacterial cells in biofilms was attenuated. In addition, gram-positive bacterial strains and biofilms were more susceptible than gram-negative strains and biofilms to the PDI effect of HMME. Thus, HMME is a promising photosensitizer for the treatment of infectious diseases caused by antibiotic-resistant bacteria, especially gram-positive bacteria.

Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment.

PubMed

Gomez, James E; Kaufmann-Malaga, Benjamin B; Wivagg, Carl N; Kim, Peter B; Silvis, Melanie R; Renedo, Nikolai; Ioerger, Thomas R; Ahmad, Rushdy; Livny, Jonathan; Fishbein, Skye; Sacchettini, James C; Carr, Steven A; Hung, Deborah T

2017-02-21

Antibiotic resistance arising via chromosomal mutations is typically specific to a particular antibiotic or class of antibiotics. We have identified mutations in genes encoding ribosomal components in Mycobacterium smegmatis that confer resistance to several structurally and mechanistically unrelated classes of antibiotics and enhance survival following heat shock and membrane stress. These mutations affect ribosome assembly and cause large-scale transcriptomic and proteomic changes, including the downregulation of the catalase KatG, an activating enzyme required for isoniazid sensitivity, and upregulation of WhiB7, a transcription factor involved in innate antibiotic resistance. Importantly, while these ribosomal mutations have a fitness cost in antibiotic-free medium, in a multidrug environment they promote the evolution of high-level, target-based resistance. Further, suppressor mutations can then be easily acquired to restore wild-type growth. Thus, ribosomal mutations can serve as stepping-stones in an evolutionary path leading to the emergence of high-level, multidrug resistance.

NOVEL ANTIBIOTIC RESISTANCE DETERMINANTS FROM AGRICULTURAL SOIL EXPOSED TO ANTIBIOTICS WIDELY USED IN HUMAN MEDICINE AND ANIMAL FARMING.

PubMed

Lau, Calvin Ho-Fung; van Engelen, Kalene; Gordon, Stephen; Renaud, Justin; Topp, Edward

2017-06-16

Antibiotic resistance has emerged globally as one of the biggest threats to human and animal health. Although the excessive use of antibiotics is recognized for accelerating the selection for resistance, there is a growing body of evidence suggesting that natural environments are "hotspots" for the development of both ancient and contemporary resistance mechanisms. Given that pharmaceuticals can be entrained onto agricultural land through anthropogenic activities, this could be a potential driver for the emergence and dissemination of resistance in soil bacteria. Using functional metagenomics, we interrogated the "resistome" of bacterial communities found in a collection of Canadian agricultural soil, some of which had been receiving antibiotics widely used in human medicine (macrolides) or food animal production (sulfamethazine, chlortetracycline and tylosin) for up to 16 years. Of the 34 new antibiotic resistance genes (ARGs) recovered, the majority were predicted to encode for (multi)drug efflux systems, while a few share little to no homology with established resistance determinants. We characterized several novel gene products, including putative enzymes that can confer high-level resistance against aminoglycosides, sulfonamides, and broad range of beta-lactams, with respect to their resistance mechanisms and clinical significance. By coupling high-resolution proteomics analysis with functional metagenomics, we discovered an unusual peptide, PPP AZI 4 , encoded within an alternative open-reading frame not predicted by bioinformatics tools. Expression of the proline-rich PPP AZI 4 can promote resistance against different macrolides but not other ribosomal-targeting antibiotics, implicating a new macrolide-specific resistance mechanism that could be fundamentally linked to the evolutionary design of this peptide. IMPORTANCE Antibiotic resistance is a clinical phenomenon with an evolutionary link to the microbial pangenome. Genes and protogenes encoding for

Current trends of human infections and antibiotic resistance of the genus Shewanella.

PubMed

Yousfi, K; Bekal, S; Usongo, V; Touati, A

2017-08-01

Shewanella spp. are commonly known as environmental bacteria and are most frequently isolated from aquatic areas. Currently, diseases syndromes and multidrug resistance have increasingly been reported in the genus Shewanella. Some species are associated with various infections, such as skin and soft tissue infections, as well as bacteremia. Generally, these bacteria are opportunistic and mostly affect people with an impaired immune system. This genus is also a probable vehicle and progenitor of antibiotic resistance genes. In fact, several resistance genes and mobile genetic elements have been identified in some resistant species isolated from environmental or clinical settings. These genes confer resistance to different antibiotic classes, including those used in therapies such as β-lactams and quinolones, and are generally located on the chromosome. Recently, a multidrug-resistant (MDR) plasmid harboring several drug resistance genes associated with transposons and integrons has been identified in Shewanella xiamenensis. These antibiotic resistance genes can circulate in the environment and contribute to the emergence of antibiotic resistance. This review describes different aspects of Shewanella, focusing on the infections caused by this genus, as well as their role in the propagation of antibiotic resistance via mobile genetic elements.

Determinants of between-country differences in ambulatory antibiotic use and antibiotic resistance in Europe: a longitudinal observational study.

PubMed

Blommaert, A; Marais, C; Hens, N; Coenen, S; Muller, A; Goossens, H; Beutels, P

2014-02-01

To identify key determinants explaining country-year variations in antibiotic use and resistance. Ambulatory antibiotic use data [in defined daily doses per 1000 inhabitants per day (DIDs)] for 19 European countries from 1999 to 2007 were collected, along with 181 variables describing countries in terms of their agriculture, culture, demography, disease burden, education, healthcare organization and socioeconomics. After assessing data availability, overlap and relevance, multiple imputation generalized estimating equations were applied with a stepwise selection procedure to select significant determinants of global antibiotic use (expressed in DIDs), relative use of subgroups (amoxicillin and co-amoxiclav) and resistance of Escherichia coli and Streptococcus pneumoniae. Relative humidity, healthcare expenditure proportional to gross domestic product, feelings of distrust, proportion of population aged >65 years and availability of treatment guidelines were associated with higher total antibiotic use expressed in DIDs. Restrictions on marketing activities towards prescribers, population density, number of antibiotics, educational attainment and degree of atheism were associated with a lower number of total DIDs used. Relative prescribing of amoxicillin and co-amoxiclav was mainly determined by healthcare system choices [e.g. general practitioner (GP) registration and restricted marketing]. Specific antibiotic use was found to be a significant determinant of resistance for some but not all drug/organism combinations. Incentives to stimulate GP gatekeeping were associated with lower levels of resistance, and life expectancy at age 65+ and atheism were associated with more resistance. Myriad factors influence antibiotic use and resistance at the country level and an important part of these can be modified by policy choices.

The antibiotic resistance "mobilome": searching for the link between environment and clinic.

PubMed

Perry, Julie A; Wright, Gerard D

2013-01-01

Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental "resistome" is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity), while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-encoded β-lactamases). The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone resistance gene qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance.

Antibiotic Resistance Patterns of Pseudomonas spp. Isolated from the River Danube

PubMed Central

Kittinger, Clemens; Lipp, Michaela; Baumert, Rita; Folli, Bettina; Koraimann, Günther; Toplitsch, Daniela; Liebmann, Astrid; Grisold, Andrea J.; Farnleitner, Andreas H.; Kirschner, Alexander; Zarfel, Gernot

2016-01-01

Spread and persistence of antibiotic resistance pose a severe threat to human health, yet there is still lack of knowledge about reservoirs of antibiotic resistant bacteria in the environment. We took the opportunity of the Joint Danube Survey 3 (JDS3), the world's biggest river research expedition of its kind in 2013, to analyse samples originating from different sampling points along the whole length of the river. Due to its high clinical relevance, we concentrated on the characterization of Pseudomonas spp. and evaluated the resistance profiles of Pseudomonas spp. which were isolated from eight sampling points. In total, 520 Pseudomonas isolates were found, 344 (66.0%) isolates were identified as Pseudomonas putida, and 141 (27.1%) as Pseudomonas fluorescens, all other Pseudomonas species were represented by less than five isolates, among those two P. aeruginosa isolates. Thirty seven percent (37%) of all isolated Pseudomonas species showed resistance to at least one out of 10 tested antibiotics. The most common resistance was against meropenem (30.4%/158 isolates) piperacillin/tazobactam (10.6%/55 isolates) and ceftazidime (4.2%/22 isolates). 16 isolates (3.1%/16 isolates) were multi-resistant. For each tested antibiotic at least one resistant isolate could be detected. Sampling points from the upper stretch of the River Danube showed more resistant isolates than downriver. Our results suggest that antibiotic resistance can be acquired by and persists even in Pseudomonas species that are normally not in direct contact with humans. A possible scenario is that these bacteria provide a reservoir of antibiotic resistance genes that can spread to related human pathogens by horizontal gene transfer. PMID:27199920

Self-Medication with Antibiotics, Attitude and Knowledge of Antibiotic Resistance among Community Residents and Undergraduate Students in Northwest Nigeria.

PubMed

Ajibola, Olumide; Omisakin, Olusola Akintoye; Eze, Anthonius Anayochukwu; Omoleke, Semeeh Akinwale

2018-04-27

This study set out to evaluate self-medicated antibiotics and knowledge of antibiotic resistance among undergraduate students and community members in northern Nigeria. Antibiotic consumption pattern, source of prescription, illnesses commonly treated, attitude towards antibiotics, and knowledge of antibiotic resistance were explored using a structured questionnaire. Responses were analyzed and summarized using descriptive statistics. Of the 1230 respondents from undergraduate students and community members, prescription of antibiotics by a physician was 33% and 57%, respectively, amongst undergraduate students and community members. We tested the respondents’ knowledge of antibiotic resistance (ABR) and found that undergraduate students displayed less knowledge that self-medication could lead to ABR (32.6% and 42.2% respectively). Self-medication with antibiotics is highly prevalent in Northwest Nigeria, with most medicines being purchased from un-licensed stores without prescription from a physician. We also observed a significant gap in respondents’ knowledge of ABR. There is an urgent need for public health authorities in Nigeria to enforce existing laws on antibiotics sales and enlighten the people on the dangers of ABR.

How Nature Morphs Peptide Scaffolds into Antibiotics

PubMed Central

Nolan, Elizabeth M.; Walsh, Christopher T.

2010-01-01

The conventional notion that peptides are poor candidates for orally available drugs because of protease-sensitive peptide bonds, intrinsic hydrophilicity, and ionic charges contrasts with the diversity of antibiotic natural products with peptide-based frameworks that are synthesized and utilized by Nature. Several of these antibiotics, including penicillin and vancomycin, are employed to treat bacterial infections in humans and have been best-selling therapeutics for decades. Others might provide new platforms for the design of novel therapeutics to combat emerging antibiotic-resistant bacterial pathogens. PMID:19058272

Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection

PubMed Central

2016-01-01

Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and

Prevalence of veterinary antibiotics and antibiotic-resistant Escherichia coli in the surface water of a livestock production region in northern China.

PubMed

Zhang, Xuelian; Li, Yanxia; Liu, Bei; Wang, Jing; Feng, Chenghong; Gao, Min; Wang, Lina

2014-01-01

This study investigated the occurrence of 12 veterinary antibiotics (VAs) and the susceptibility of Escherichia coli (E. coli) in a rural water system that was affected by livestock production in northern China. Each of the surveyed sites was determined with at least eight antibiotics with maximum concentration of up to 450 ng L(-1). The use of VAs in livestock farming probably was a primary source of antibiotics in the rivers. Increasing total antibiotics were measured from up- to mid- and downstream in the two tributaries. Eighty-eight percent of the 218 E. coli isolates that were derived from the study area exhibited, in total, 48 resistance profiles against the eight examined drugs. Significant correlations were found among the resistance rates of sulfamethoxazole-trimethoprim, chloromycetin and ampicillin as well as between tetracycline and chlortetracycline, suggesting a possible cross-selection for resistance among these drugs. The E. coli resistance frequency also increased from up- to midstream in the three rivers. E. coli isolates from different water systems showed varying drug numbers of resistance. No clear relationship was observed in the antibiotic resistance frequency with corresponding antibiotic concentration, indicating that the antibiotic resistance for E. coli in the aquatic environment might be affected by factors besides antibiotics. High numbers of resistant E. coli were also isolated from the conserved reservoir. These results suggest that rural surface water may become a large pool of VAs and resistant bacteria. This study contributes to current information on VAs and resistant bacteria contamination in aquatic environments particularly in areas under intensive agriculture. Moreover, this study indicates an urgent need to monitor the use of VAs in animal production, and to control the release of animal-originated antibiotics into the environment.

Prevalence of Veterinary Antibiotics and Antibiotic-Resistant Escherichia coli in the Surface Water of a Livestock Production Region in Northern China

PubMed Central

Zhang, Xuelian; Li, Yanxia; Liu, Bei; Wang, Jing; Feng, Chenghong; Gao, Min; Wang, Lina

2014-01-01

This study investigated the occurrence of 12 veterinary antibiotics (VAs) and the susceptibility of Escherichia coli (E. coli) in a rural water system that was affected by livestock production in northern China. Each of the surveyed sites was determined with at least eight antibiotics with maximum concentration of up to 450 ng L−1. The use of VAs in livestock farming probably was a primary source of antibiotics in the rivers. Increasing total antibiotics were measured from up- to mid- and downstream in the two tributaries. Eighty-eight percent of the 218 E. coli isolates that were derived from the study area exhibited, in total, 48 resistance profiles against the eight examined drugs. Significant correlations were found among the resistance rates of sulfamethoxazole-trimethoprim, chloromycetin and ampicillin as well as between tetracycline and chlortetracycline, suggesting a possible cross-selection for resistance among these drugs. The E. coli resistance frequency also increased from up- to midstream in the three rivers. E. coli isolates from different water systems showed varying drug numbers of resistance. No clear relationship was observed in the antibiotic resistance frequency with corresponding antibiotic concentration, indicating that the antibiotic resistance for E. coli in the aquatic environment might be affected by factors besides antibiotics. High numbers of resistant E. coli were also isolated from the conserved reservoir. These results suggest that rural surface water may become a large pool of VAs and resistant bacteria. This study contributes to current information on VAs and resistant bacteria contamination in aquatic environments particularly in areas under intensive agriculture. Moreover, this study indicates an urgent need to monitor the use of VAs in animal production, and to control the release of animal-originated antibiotics into the environment. PMID:25372873

Genetic Determinants of Intrinsic Colistin Tolerance in Acinetobacter baumannii

PubMed Central

Hood, M. Indriati; Becker, Kyle W.; Roux, Christelle M.; Dunman, Paul M.

2013-01-01

Acinetobacter baumannii is a leading cause of multidrug-resistant infections worldwide. This organism poses a particular challenge due to its ability to acquire resistance to new antibiotics through adaptation or mutation. This study was undertaken to determine the mechanisms governing the adaptability of A. baumannii to the antibiotic colistin. Screening of a transposon mutant library identified over 30 genes involved in inducible colistin resistance in A. baumannii. One of the genes identified was lpsB, which encodes a glycosyltransferase involved in lipopolysaccharide (LPS) synthesis. We demonstrate that loss of LpsB function results in increased sensitivity to both colistin and cationic antimicrobial peptides of the innate immune system. Moreover, LpsB is critical for pathogenesis in a pulmonary model of infection. Taken together, these data define bacterial processes required for intrinsic colistin tolerance in A. baumannii and underscore the importance of outer membrane structure in both antibiotic resistance and the pathogenesis of A. baumannii. PMID:23230287

Rapid determination of antibiotic resistance in E. coli using dielectrophoresis

NASA Astrophysics Data System (ADS)

Hoettges, Kai F.; Dale, Jeremy W.; Hughes, Michael P.

2007-09-01

In recent years, infections due to antibiotic-resistant strains of bacteria such as methillicin-resistant Staphylococcus aureus and ciprofloxacin-resistant Escherichia coli are on the rise, and with them the demand for rapid antibiotic testing is also rising. Conventional tests, such as disc diffusion testing, require a primary sample to be tested in the presence of a number of antibiotics to verify which antibiotics suppress growth, which take approximately 24 h to complete and potentially place the patient at severe risk. In this paper we describe the use of dielectrophoresis as a rapid marker of cell death, by detecting changes in the electrophysiology of the cell caused by the administration of an antibiotic. In contrast to other markers, the electrophysiology of the cell changes rapidly during cell death allowing live cells to be distinguished from dead (or dying) cells without the need for culturing. Using polymyxin B as an example antibiotic, our studies indicate that significant changes in cell characteristics can be observed as soon as 1 h passes after isolating a culture from nutrient broth.

[Influence of personal attitude of the manager on antibiotic use in pig production].

PubMed

Malik, J; Kaufmann, G; Hirsiger, P; Kümmerlen, D; Arnold, C; Spring, P; Sidler, X

2015-12-01

The attitude as well as the expertise of a person affect the behavior and actions in daily life. To investigate the influence of attitude and knowledge of pig producers on the use of antibiotics in farms, 220 Swiss pig producers were questioned on health awareness, attitude towards sustainable production, risk behavior, intrinsic motivation and knowledge about antibiotics and resistance development. In addition, the strategy of antibiotic use (therapeutic or prophylactic) and the business practice (single or group therapy) for the amount of antibiotics on one hand and for the risk of antibiotic resistance development on the other hand, were determined in a personal interview. Farmers using antibiotics only therapeutically had a better business practice. A direct link between the personal attitude and the antibiotic use or a higher risk of development of antibiotic resistance was not found in this investigation.

Antibiotic Resistance Determinants in a Pseudomonas putida Strain Isolated from a Hospital

PubMed Central

Duque, Estrella; Fernández, Matilde; Molina-Santiago, Carlos; Roca, Amalia; Porcel, Mario; de la Torre, Jesús; Segura, Ana; Plesiat, Patrick; Jeannot, Katy; Ramos, Juan-Luis

2014-01-01

Environmental microbes harbor an enormous pool of antibiotic and biocide resistance genes that can impact the resistance profiles of animal and human pathogens via horizontal gene transfer. Pseudomonas putida strains are ubiquitous in soil and water but have been seldom isolated from humans. We have established a collection of P. putida strains isolated from in-patients in different hospitals in France. One of the isolated strains (HB3267) kills insects and is resistant to the majority of the antibiotics used in laboratories and hospitals, including aminoglycosides, ß-lactams, cationic peptides, chromoprotein enediyne antibiotics, dihydrofolate reductase inhibitors, fluoroquinolones and quinolones, glycopeptide antibiotics, macrolides, polyketides and sulfonamides. Similar to other P. putida clinical isolates the strain was sensitive to amikacin. To shed light on the broad pattern of antibiotic resistance, which is rarely found in clinical isolates of this species, the genome of this strain was sequenced and analysed. The study revealed that the determinants of multiple resistance are both chromosomally-borne as well as located on the pPC9 plasmid. Further analysis indicated that pPC9 has recruited antibiotic and biocide resistance genes from environmental microorganisms as well as from opportunistic and true human pathogens. The pPC9 plasmid is not self-transmissible, but can be mobilized by other bacterial plasmids making it capable of spreading antibiotic resistant determinants to new hosts. PMID:24465371

Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure

PubMed Central

Kubicek-Sutherland, Jessica Z.; Heithoff, Douglas M.; Ersoy, Selvi C.; Shimp, William R.; House, John K.; Marth, Jamey D.; Smith, Jeffrey W.; Mahan, Michael J.

2015-01-01

Current antibiotic testing does not include the potential influence of host cell environment on microbial susceptibility and antibiotic resistance, hindering appropriate therapeutic intervention. We devised a strategy to identify the presence of host–pathogen interactions that alter antibiotic efficacy in vivo. Our findings revealed a bacterial mechanism that promotes antibiotic resistance in vivo at concentrations of drug that far exceed dosages determined by standardized antimicrobial testing. This mechanism has escaped prior detection because it is reversible and operates within a subset of host tissues and cells. Bacterial pathogens are thereby protected while their survival promotes the emergence of permanent drug resistance. This host-dependent mechanism of transient antibiotic resistance is applicable to multiple pathogens and has implications for the development of more effective antimicrobial therapies. PMID:26501114

Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure.

PubMed

Kubicek-Sutherland, Jessica Z; Heithoff, Douglas M; Ersoy, Selvi C; Shimp, William R; House, John K; Marth, Jamey D; Smith, Jeffrey W; Mahan, Michael J

2015-09-01

Current antibiotic testing does not include the potential influence of host cell environment on microbial susceptibility and antibiotic resistance, hindering appropriate therapeutic intervention. We devised a strategy to identify the presence of host-pathogen interactions that alter antibiotic efficacy in vivo. Our findings revealed a bacterial mechanism that promotes antibiotic resistance in vivo at concentrations of drug that far exceed dosages determined by standardized antimicrobial testing. This mechanism has escaped prior detection because it is reversible and operates within a subset of host tissues and cells. Bacterial pathogens are thereby protected while their survival promotes the emergence of permanent drug resistance. This host-dependent mechanism of transient antibiotic resistance is applicable to multiple pathogens and has implications for the development of more effective antimicrobial therapies.

Activation of Antibiotic Production in Bacillus spp. by Cumulative Drug Resistance Mutations

PubMed Central

Tojo, Shigeo; Tanaka, Yukinori

2015-01-01

Bacillus subtilis strains produce a wide range of antibiotics, including ribosomal and nonribosomal peptide antibiotics, as well as bacilysocin and neotrehalosadiamine. Mutations in B. subtilis strain 168 that conferred resistance to drugs such as streptomycin and rifampin resulted in overproduction of the dipeptide antibiotic bacilysin. Cumulative drug resistance mutations, such as mutations in the mthA and rpsL genes, which confer low- and high-level resistance, respectively, to streptomycin, and mutations in rpoB, which confer resistance to rifampin, resulted in cells that overproduced bacilysin. Transcriptional analysis demonstrated that the enhanced transcription of biosynthesis genes was responsible for the overproduction of bacilysin. This approach was effective also in activating the cryptic genes of Bacillus amyloliquefaciens, leading to actual production of antibiotic(s). PMID:26369962

Ribosome protection by antibiotic resistance ATP-binding cassette protein.

PubMed

Su, Weixin; Kumar, Veerendra; Ding, Yichen; Ero, Rya; Serra, Aida; Lee, Benjamin Sian Teck; Wong, Andrew See Weng; Shi, Jian; Sze, Siu Kwan; Yang, Liang; Gao, Yong-Gui

2018-05-15

The ribosome is one of the richest targets for antibiotics. Unfortunately, antibiotic resistance is an urgent issue in clinical practice. Several ATP-binding cassette family proteins confer resistance to ribosome-targeting antibiotics through a yet unknown mechanism. Among them, MsrE has been implicated in macrolide resistance. Here, we report the cryo-EM structure of ATP form MsrE bound to the ribosome. Unlike previously characterized ribosomal protection proteins, MsrE is shown to bind to ribosomal exit site. Our structure reveals that the domain linker forms a unique needle-like arrangement with two crossed helices connected by an extended loop projecting into the peptidyl-transferase center and the nascent peptide exit tunnel, where numerous antibiotics bind. In combination with biochemical assays, our structure provides insight into how MsrE binding leads to conformational changes, which results in the release of the drug. This mechanism appears to be universal for the ABC-F type ribosome protection proteins. Copyright © 2018 the Author(s). Published by PNAS.

Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistance.

PubMed

Ashbolt, Nicholas J; Amézquita, Alejandro; Backhaus, Thomas; Borriello, Peter; Brandt, Kristian K; Collignon, Peter; Coors, Anja; Finley, Rita; Gaze, William H; Heberer, Thomas; Lawrence, John R; Larsson, D G Joakim; McEwen, Scott A; Ryan, James J; Schönfeld, Jens; Silley, Peter; Snape, Jason R; Van den Eede, Christel; Topp, Edward

2013-09-01

Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental "hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways. We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.

New resources to address antibiotic resistance are just a click away

PubMed Central

Dowd-Schmidtke, C; Tremblay, G; Gale-Rowe, M; Dodds, J; Finley, R

2014-01-01

Antibiotic resistance is a complex issue with multiple causes, and there are many roles to play in addressing it. As part of its response, the Public Health Agency of Canada is launching a pilot antibiotic awareness campaign for Canadian families and health care professionals. Coinciding with Antibiotic Awareness Week, starting on November 17, 2014, the goal of this campaign is to improve knowledge and awareness of antibiotic resistance in Canada. To achieve this, the Agency has developed a suite of resources for both Canadian families and health care providers featuring a variety of key messages explaining antibiotic resistance, why it is important, and how to reduce the risks associated with it. Resources for Canadian families include an online informational video, an educational brochure, and infographics for both adults and children. Resources for health care professionals include two online Continuing Medical Education Modules, a letter that physicians can sign and provide to parents explaining why an antibiotic was not prescribed, and two webinars to present trends in antimicrobial resistance (AMR) and antimicrobial use. Health professionals will also receive an electronic postcard and a bilingual campaign poster. Promoting the campaign messages and using these campaign resources will support health professionals in discussions about antibiotic resistance with their patients or clients, and in their continuing efforts to be part of the solution in addressing this important global health challenge.

New resources to address antibiotic resistance are just a click away.

PubMed

Dowd-Schmidtke, C; Tremblay, G; Gale-Rowe, M; Dodds, J; Finley, R

2014-11-07

Antibiotic resistance is a complex issue with multiple causes, and there are many roles to play in addressing it. As part of its response, the Public Health Agency of Canada is launching a pilot antibiotic awareness campaign for Canadian families and health care professionals. Coinciding with Antibiotic Awareness Week, starting on November 17, 2014, the goal of this campaign is to improve knowledge and awareness of antibiotic resistance in Canada. To achieve this, the Agency has developed a suite of resources for both Canadian families and health care providers featuring a variety of key messages explaining antibiotic resistance, why it is important, and how to reduce the risks associated with it. Resources for Canadian families include an online informational video, an educational brochure, and infographics for both adults and children. Resources for health care professionals include two online Continuing Medical Education Modules, a letter that physicians can sign and provide to parents explaining why an antibiotic was not prescribed, and two webinars to present trends in antimicrobial resistance (AMR) and antimicrobial use. Health professionals will also receive an electronic postcard and a bilingual campaign poster. Promoting the campaign messages and using these campaign resources will support health professionals in discussions about antibiotic resistance with their patients or clients, and in their continuing efforts to be part of the solution in addressing this important global health challenge.

Antibiotic resistance of microorganisms in agricultural soils in Russia

NASA Astrophysics Data System (ADS)

Danilova, N. V.; Galitskaya, P. Yu; Selivanovskaya, S. Yu

2018-01-01

Antibiotics are medicines that are widely used in livestock production not only for the prevention and treatment of infectious diseases, but also for accelerating the growth of animals. The application of manure for fertilizing agricultural soils leads to the entry into the soil ecosystem not only of the antibiotics themselves, but also the resistance genes to them. In this study, 30 samples of arable soils were tested for the presence of the tet(X) gene, which encodes bacterial resistance to antibiotics of the tetracycline group. Using real-time PCR, it was found that 27 out of 30 soil samples contained tet(X). 52% of these samples were heavily contaminated, 34% had a medium level of contamination and 14% were slightly contaminated by the resistance gene tet(X).

Adaptive Landscapes of Resistance Genes Change as Antibiotic Concentrations Change.

PubMed

Mira, Portia M; Meza, Juan C; Nandipati, Anna; Barlow, Miriam

2015-10-01

Most studies on the evolution of antibiotic resistance are focused on selection for resistance at lethal antibiotic concentrations, which has allowed the detection of mutant strains that show strong phenotypic traits. However, solely focusing on lethal concentrations of antibiotics narrowly limits our perspective of antibiotic resistance evolution. New high-resolution competition assays have shown that resistant bacteria are selected at relatively low concentrations of antibiotics. This finding is important because sublethal concentrations of antibiotics are found widely in patients undergoing antibiotic therapies, and in nonmedical conditions such as wastewater treatment plants, and food and water used in agriculture and farming. To understand the impacts of sublethal concentrations on selection, we measured 30 adaptive landscapes for a set of TEM β-lactamases containing all combinations of the four amino acid substitutions that exist in TEM-50 for 15 β-lactam antibiotics at multiple concentrations. We found that there are many evolutionary pathways within this collection of landscapes that lead to nearly every TEM-genotype that we studied. While it is known that the pathways change depending on the type of β-lactam, this study demonstrates that the landscapes including fitness optima also change dramatically as the concentrations of antibiotics change. Based on these results we conclude that the presence of multiple concentrations of β-lactams in an environment result in many different adaptive landscapes through which pathways to nearly every genotype are available. Ultimately this may increase the diversity of genotypes in microbial populations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

In tepid defense of population health: physicians and antibiotic resistance.

PubMed

Saver, Richard S

2008-01-01

Antibiotic resistance menaces the population as a dire public health threat and costly social problem. Recent proposals to combat antibiotic resistance focus to a large degree on supply side approaches. Suggestions include tinkering with patent rights so that pharmaceutical companies have greater incentives to discover novel antibiotics as well as to resist overselling their newer drugs already on market. This Article argues that a primarily supply side emphasis unfortunately detracts attention from physicians' important demand side influences. Physicians have a vital and unavoidably necessary role to play in ensuring socially optimal access to antibiotics. Dismayingly, physicians' management of the antibiotic supply has been poor and their defense of population health tepid at best. Acting as a prudent steward of the antibiotic supply often seems to be at odds with a physician's commonly understood fiduciary duties, ethical obligations, and professional norms, all of which traditionally emphasize the individual health paradigm as opposed to population health responsibilities. Meanwhile, physicians face limited incentives for antibiotic conservation from other sources, such as malpractice liability, regulatory standards, and reimbursement systems. While multifaceted efforts are needed to combat antibiotic resistance effectively, physician gatekeeping behavior should become a priority area of focus. This Article considers how health law and policy tools could favorably change the incentives physicians face for antibiotic conservation. A clear lesson from the managed care reform battles of the recent past is that interventions, to have the best chance of success, need to respect physician interest in clinical autonomy and individualized medicine even if, somewhat paradoxically, vigorously promoting population health perspectives. Also, physicians' legal and ethical obligations need to be reconceptualized in the antibiotic context in order to better support

Impact of pre-application treatment on municipal sludge composition, soil dynamics of antibiotic resistance genes, and abundance of antibiotic-resistance genes on vegetables at harvest.

PubMed

Lau, Calvin Ho-Fung; Li, Bing; Zhang, Tong; Tien, Yuan-Ching; Scott, Andrew; Murray, Roger; Sabourin, Lyne; Lapen, David R; Duenk, Peter; Topp, Edward

2017-06-01

In many jurisdictions sludge recovered from the sewage treatment process is a valued fertilizer for crop production. Pre-treatment of sewage sludge prior to land application offers the potential to abate enteric microorganisms that carry genes conferring resistance to antibiotics. Pre-treatment practices that accomplish this should have the desirable effect of reducing the risk of contamination of crops or adjacent water with antibiotic resistance genes carried in these materials. In the present study, we obtained municipal sludge that had been subjected to one of five treatments. There were, anaerobic-digestion or aerobic-digestion, in both instances with and without dewatering; and heat-treatment and pelletization. Each of the five types of biosolids was applied to an agricultural field at commercial rates, following which lettuce, carrots and radishes were planted. Based on qPCR, the estimated antibiotic gene loading rates were comparable with each of the five biosolids. However, the gene abundance in soil following application of the pelletized biosolids was anomalously lower than expected. Following application, the abundance of antibiotic resistance genes decreased in a generally coherent fashion, except sul1 which increased in abundance during the growing season in the soil fertilized with pelletized biosolids. Based on qPCR and high throughput sequencing evidence for transfer of antibiotic resistance genes from the biosolids to the vegetables at harvest was weak. Clostridia were more abundant in soils receiving any of the biosolids except the pelletized. Overall, the behavior of antibiotic resistance genes in soils receiving aerobically or anaerobically-digested biosolids was consistent and coherent with previous studies. However, dynamics of antibiotic resistance genes in soils receiving the heat treated pelletized biosolids were very different, and the underlying mechanisms merit investigation. Crown Copyright © 2017. Published by Elsevier B.V. All

Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus.

PubMed

Monaco, Monica; Pimentel de Araujo, Fernanda; Cruciani, Melania; Coccia, Eliana M; Pantosti, Annalisa

2017-01-01

Staphylococcus aureus is an important human pathogen, responsible for infections in the community and the healthcare setting. Although much of the attention is focused on the methicillin-resistant "variant" MRSA, the methicillin-susceptible counterpart (MSSA) remains a prime species in infections. The epidemiology of S. aureus, especially of MRSA, showed a rapid evolution in the last years. After representing a typical nosocomial multidrug-resistant pathogen, MRSA has recently emerged in the community and among farmed animals thanks to its ability to evolve and adapt to different settings. Global surveillance has shown that MRSA represents a problem in all continents and countries where studies have been carried out, determining an increase in mortality and the need to use last-resource expensive antibiotics. S. aureus can easily acquire resistance to antibiotics and MRSA is characteristically multidrug resistant. Resistance to vancomycin, the principal anti-MRSA antibiotic is rare, although isolates with decreased susceptibility are recovered in many areas. Resistance to the more recently introduced antibiotics, linezolid and daptomycin, has emerged; however, they remain substantially active against the large majority of MSSA and MRSA. Newer antistaphylococcal drugs have been developed, but since their clinical use has been very limited so far, little is known about the emergence of resistance. Molecular typing techniques have allowed to identify the major successful clones and lineages of MSSA and MRSA, including high-risk clones, and to trace their diffusion. In the face of a continuously evolving scenario, this review depicts the most common clones circulating in different geographical areas and in different settings at present. Since the evolution of S. aureus will continue, it is important to maintain the attention on the epidemiology of S. aureus in the future with a global view.

Diverse and abundant antibiotic resistance genes in Chinese swine farms

PubMed Central

Zhu, Yong-Guan; Johnson, Timothy A.; Su, Jian-Qiang; Qiao, Min; Guo, Guang-Xia; Stedtfeld, Robert D.; Hashsham, Syed A.; Tiedje, James M.

2013-01-01

Antibiotic resistance genes (ARGs) are emerging contaminants posing a potential worldwide human health risk. Intensive animal husbandry is believed to be a major contributor to the increased environmental burden of ARGs. Despite the volume of antibiotics used in China, little information is available regarding the corresponding ARGs associated with animal farms. We assessed type and concentrations of ARGs at three stages of manure processing to land disposal at three large-scale (10,000 animals per year) commercial swine farms in China. In-feed or therapeutic antibiotics used on these farms include all major classes of antibiotics except vancomycins. High-capacity quantitative PCR arrays detected 149 unique resistance genes among all of the farm samples, the top 63 ARGs being enriched 192-fold (median) up to 28,000-fold (maximum) compared with their respective antibiotic-free manure or soil controls. Antibiotics and heavy metals used as feed supplements were elevated in the manures, suggesting the potential for coselection of resistance traits. The potential for horizontal transfer of ARGs because of transposon-specific ARGs is implicated by the enrichment of transposases—the top six alleles being enriched 189-fold (median) up to 90,000-fold in manure—as well as the high correlation (r2 = 0.96) between ARG and transposase abundance. In addition, abundance of ARGs correlated directly with antibiotic and metal concentrations, indicating their importance in selection of resistance genes. Diverse, abundant, and potentially mobile ARGs in farm samples suggest that unmonitored use of antibiotics and metals is causing the emergence and release of ARGs to the environment. PMID:23401528

Awareness of antibiotic resistance and antibiotic prescribing in UTI treatment: a qualitative study among primary care physicians in Sweden.

PubMed

Björkman, Ingeborg; Berg, Johanna; Viberg, Nina; Stålsby Lundborg, Cecilia

2013-03-01

To improve education and information for general practitioners in relation to rational antibiotic prescribing for urinary tract infection (UTI), it is important to be aware of GPs' views of resistance and how it influences their choice of UTI treatment. The aim of this study was to explore variations in views of resistance and UTI treatment decisions among general practitioners (GPs) in a county in Sweden. Qualitative, semi-structured interviews were analysed with a phenomenographic approach and content analysis. Primary care in Kronoberg, a county in southern Sweden. Subjects. A purposeful sample of 20 GPs from 15 of 25 health centres in the county. The variation of perceptions of antibiotic resistance in UTI treatment. How UTIs were treated according to the GPs. Three different ways of viewing resistance in UTI treatment were identified. These were: (A) No problem, I have never seen resistance, (B) The problem is bigger somewhere else, and (C) The development of antibiotic resistance is serious and we must be careful. Moreover, GPs' perceptions of antibiotic resistance were mirrored in how they reported their treatment of UTIs in practice. There was a hierarchal scale of how GPs viewed resistance as an issue in UTI treatment. Only GPs who expressed concerns about resistance followed prescribing guidelines completely. This offers valuable insights into the planning and most likely the outcome of awareness or educational activities aimed at changed antibiotic prescribing behaviour.

Primary Antibiotic Resistance of Helicobacter pylori in China.

PubMed

Hu, Yi; Zhu, Yin; Lu, Nong-Hua

2017-05-01

Antibiotic resistance is the most important factor leading to the failure of eradication regimens; thus, it is important to obtain regional antibiotic resistance information. This review focuses on the prevalence of Helicobacter pylori primary resistance to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone in China. We searched the PubMed, EMBASE, the China National Knowledge Infrastructure, and Chinese Biomedical databases from the earliest date of each database to October 2016. The search terms included the following: H. pylori, antibiotic (including clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone) resistance with or without China or different regions of China. The data analysis was performed using MedCalc 15.2.2. Each article was weighted according to the number of isolated H. pylori strains. A pooled proportion analysis was performed. Twenty-three studies (14 studies in English and 9 in Chinese) were included in this review. A total of 6274, 6418, 3921, 5468, 2802, and 275 H. pylori strains were included in this review to evaluate the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone, respectively. Overall, the primary resistance rates of clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone were 28.9, 63.8, 28.0, 3.1, 3.9, and 1.7%, respectively. In China, the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, and levofloxacin was high and increased over time, whereas the resistance rates to amoxicillin, tetracycline, and furazolidone were low and stable over time.

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial.

PubMed

van Duijn, Pleun Joppe; Verbrugghe, Walter; Jorens, Philippe Germaine; Spöhr, Fabian; Schedler, Dirk; Deja, Maria; Rothbart, Andreas; Annane, Djillali; Lawrence, Christine; Nguyen Van, Jean-Claude; Misset, Benoit; Jereb, Matjaz; Seme, Katja; Šifrer, Franc; Tomiç, Viktorija; Estevez, Francisco; Carneiro, Jandira; Harbarth, Stephan; Eijkemans, Marinus Johannes Cornelis; Bonten, Marc

2018-04-01

Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum β-lactamase production or piperacillin-tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were

Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water

PubMed Central

Schwartz, Thomas; Armant, Olivier; Bretschneider, Nancy; Hahn, Alexander; Kirchen, Silke; Seifert, Martin; Dötsch, Andreas

2015-01-01

The fitness of sensitive and resistant Pseudomonas aeruginosa in different aquatic environments depends on genetic capacities and transcriptional regulation. Therefore, an antibiotic-sensitive isolate PA30 and a multi-resistant isolate PA49 originating from waste waters were compared via whole genome and transcriptome Illumina sequencing after exposure to municipal waste water and tap water. A number of different genomic islands (e.g. PAGIs, PAPIs) were identified in the two environmental isolates beside the highly conserved core genome. Exposure to tap water and waste water exhibited similar transcriptional impacts on several gene clusters (antibiotic and metal resistance, genetic mobile elements, efflux pumps) in both environmental P. aeruginosa isolates. The MexCD-OprJ efflux pump was overexpressed in PA49 in response to waste water. The expression of resistance genes, genetic mobile elements in PA49 was independent from the water matrix. Consistently, the antibiotic sensitive strain PA30 did not show any difference in expression of the intrinsic resistance determinants and genetic mobile elements. Thus, the exposure of both isolates to polluted waste water and oligotrophic tap water resulted in similar expression profiles of mentioned genes. However, changes in environmental milieus resulted in rather unspecific transcriptional responses than selected and stimuli-specific gene regulation. PMID:25186059

Irrigation waters and pipe-based biofilms as sources for antibiotic-resistant bacteria.

PubMed

Blaustein, Ryan A; Shelton, Daniel R; Van Kessel, Jo Ann S; Karns, Jeffrey S; Stocker, Matthew D; Pachepsky, Yakov A

2016-01-01

The presence of antibiotic-resistant bacteria in environmental surface waters has gained recent attention. Wastewater and drinking water distribution systems are known to disseminate antibiotic-resistant bacteria, with the biofilms that form on the inner-surfaces of the pipeline as a hot spot for proliferation and gene exchange. Pipe-based irrigation systems that utilize surface waters may contribute to the dissemination of antibiotic-resistant bacteria in a similar manner. We conducted irrigation events at a perennial stream on a weekly basis for 1 month, and the concentrations of total heterotrophic bacteria, total coliforms, and fecal coliforms, as well as the concentrations of these bacterial groups that were resistant to ampicillin and tetracycline, were monitored at the intake water. Prior to each of the latter three events, residual pipe water was sampled and 6-in. sections of pipeline (coupons) were detached from the system, and biofilm from the inner-wall was removed and analyzed for total protein content and the above bacteria. Isolates of biofilm-associated bacteria were screened for resistance to a panel of seven antibiotics, representing five antibiotic classes. All of the monitored bacteria grew substantially in the residual water between irrigation events, and the biomass of the biofilm steadily increased from week to week. The percentages of biofilm-associated isolates that were resistant to antibiotics on the panel sometimes increased between events. Multiple-drug resistance was observed for all bacterial groups, most often for fecal coliforms, and the distributions of the numbers of antibiotics that the total coliforms and fecal coliforms were resistant to were subject to change from week to week. Results from this study highlight irrigation waters as a potential source for antibiotic-resistant bacteria, which can subsequently become incorporated into and proliferate within irrigation pipe-based biofilms.

Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network

PubMed Central

Lázár, Viktória; Nagy, István; Spohn, Réka; Csörgő, Bálint; Györkei, Ádám; Nyerges, Ákos; Horváth, Balázs; Vörös, Andrea; Busa-Fekete, Róbert; Hrtyan, Mónika; Bogos, Balázs; Méhi, Orsolya; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs; Papp, Balázs; Pál, Csaba

2014-01-01

Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies. PMID:25000950

Spatial mapping of antibiotic resistance

USDA-ARS?s Scientific Manuscript database

A serious concern for modern animal production is the fear that feed antimicrobials, such as monensin, increase the potential for high levels of antibiotic resistant (AR) gene prevalence in the manure, which may subsequently be shared with soil communities and eventually be taken up by human pathoge...

Distribution of antibiotic-resistant bacteria in chicken manure and manure-fertilized vegetables.

PubMed

Yang, Qingxiang; Ren, Siwei; Niu, Tianqi; Guo, Yuhui; Qi, Shiyue; Han, Xinkuan; Liu, Dong; Pan, Feng

2014-01-01

Veterinary manure is an important pollution reservoir of antibiotics and antibiotic-resistant bacteria (ARB). However, little is known of the distribution of ARB in plant endophytic bacteria and the number/types of ARB in chicken manure. In this study, 454-pyrosequencing was used to investigate the distribution and composition of ARBs in chicken manure and fertilized vegetables. The prevalence of ARB in the samples of the chicken manure compost recovered from farms on which amoxicillin, kanamycin, gentamicin, and cephalexin were used was 20.91-65.9% for ARBs and 8.24-20.63% simultaneously resistant to two or more antibiotics (multiple antibiotic resistant bacteria (MARB)). Antibiotic-resistant endophytic bacteria were widely detected in celery, pakchoi, and cucumber with the highest rate of resistance to cephalexin. The pyrosequencing indicated that the chicken manure dominantly harbored Firmicutes, Bacteroidetes, Synergistetes, and Proteobacteria and that Bacteroidetes was significantly enhanced in farms utilizing antibiotics. In the total cultivable colonies, 62.58-89.43% ARBs and 95.29% MARB were clustered in Bacteroidetes with the dominant species (Myroides ordoratimimus and Spningobacterium spp., respectively) related to human clinical opportunistic pathogens.

[Identification of lactic acid bacteria in commercial yogurt and their antibiotic resistance].

PubMed

Qin, Yuxuan; Li, Jing; Wang, Qiuya; Gao, Kexin; Zhu, Baoli; Lv, Na

2013-08-04

To identify lactic acid bacteria (LAB) in commercial yogurts and investigate their antibiotic resistance. LABs were cultured from 5 yogurt brands and the isolates were identified at the species level by 16S rRNA sequence. Genotyping was performed by repetitive extragenic palindromic PCR (rep-PCR). The sensitivity to 7 antibiotics was tested for all LAB isolates by Kirby-Bauer paper diffusion (K-B method). Meanwhile, 9 antibiotic resistance genes (ARGs), including erythromycin resistance genes (ermA and ermB) and tetracycline resistance genes (tetM, tetK, tetS, tetQ, tetO, tetL and tetW), were detected by PCR amplification in the identified LAB isolates. The PCR products were confirmed by sequencing. Total 100 LABs were isolated, including 23 Lactobacillus delbrueckii ssp. bulgaricus, 26 Lactobacillus casei, 30 Streptococcus thermophilus, 5 Lactobacillus acidophilus, 6 Lactobacillus plantarum, and 10 Lactobacillus paracasei. The drug susceptibility test shows that all 100 isolates were resistant to gentamicin and streptomycin, 42 isolates were resistant to vancomycin, and on the contrary all were sensitive to cefalexin, erythromycin, tetracycline and oxytetracycline. Moreover, 5 ARGs were found in the 28 sequencing confirmed isolates, ermB gene was detected in 8 isolates, tet K in 4 isolates, tetL in 2 isolates, tetM in 4 isolates, tetO in 2 isolates. erm A, tet S, tet Q and tet W genes were not detected in the isolates. Antibiotic resistance genes were found in 53.57% (15/28) sequenced isolates, 2 -3 antibiotic resistance genes were detected in 4 isolates of L. delbrueckii ssp. bulgaricus. Some LABs were not labeled in commercial yogurt products. Antibiotic resistance genes tend to be found in the starter culture of L. delbrueckii ssp. Bulgaricus and S. thermophilus. All the LAB isolates were sensitive to erythromycin and tetracycline, even though some carried erythromycin and/or tetracycline resistance genes. We proved again that LAB could carry antibiotic

Fingerprinting microbiomes towards screening for microbial antibiotic resistance.

PubMed

Jin, Naifu; Zhang, Dayi; Martin, Francis L

2017-05-22

There is an increasing need to investigate microbiomes in their entirety in a variety of contexts ranging from environmental to human health scenarios. This requirement is becoming increasingly important with the emergence of antibiotic resistance. In general, more conventional approaches are too expensive and/or time-consuming and often predicated on prior knowledge of the microorganisms one wishes to study. Herein, we propose the use of biospectroscopy tools as relatively high-throughput, non-destructive approaches to profile microbiomes under study. Fourier-transform infrared (FTIR) or Raman spectroscopy both generate fingerprint spectra of biological material and such spectra can readily be subsequently classed according to biochemical changes in the microbiota, such as emergence of antibiotic resistance. FTIR spectroscopy techniques generally can only be applied to desiccated material whereas Raman approaches can be applied to more hydrated samples. The ability to readily fingerprint microbiomes could lend itself to new approaches in determining microbial behaviours and emergence of antibiotic resistance.

Antibiotic resistance ofKlebsiella pneumoniae through β-arrestin recruitment-induced β-lactamase signaling pathway.

PubMed

Wei, Jiang; Wenjie, Yang; Ping, Liu; Na, Wang; Haixia, Ren; Xuequn, Zhao

2018-03-01

Overuse and misuse of antibiotics leads to rapid evolution of antibiotic-resistant bacteria and antibiotic resistance genes. Klebsiella pneumoniae has become the most common pathogenic bacterium accountable for nosocomial infections due to its high virulence factor and general occurrence of resistance to most antibiotics. The β-lactamase signaling pathway has been suggested to be involved in antibiotic resistance against β-lactams in Klebsiella pneumoniae . In the present study, the molecular mechanism of the antibiotic resistance of Klebsiella pneumoniae was investigated and the results indicated involvement of the β-arrestin recruitment-induced β-lactamase signaling pathway. Antimicrobial susceptibility of Klebsiella pneumoniae was assessed using automated systems and extended-spectrum β-lactamase (ESBL) and β-arrestin expression levels in Klebsiella pneumoniae were analyzed by reverse-transcription quantitative PCR. β-lactam resistance in Klebsiella pneumoniae was determined using β-lactam agar screening plates. The results demonstrated that β-arrestin recruitment was increased in Klebsiella pneumoniae with antibiotic resistance (AR- K.P .) compared with that in the native Klebsiella pneumoniae strain (NB- K.P .). Increased production of ESBL was observed in AR- K.P . after treatment with the β-lactam penicillin. Of note, inhibition of β-arrestin recruitment significantly suppressed ESBL expression in AR- K.P . and in addition, genes encoding β-arrestin and ESBL were upregulated in Klebsiella pneumoniae . Restoration of endogenous β-arrestin markedly increased antibiotic resistance of Klebsiella pneumoniae to β-lactam. Knockdown of endogenous β-arrestin downregulated antibiotic resistance genes and promoted the inhibitory effects of β-lactam antibiotic treatment on Klebsiella pneumoniae growth. In conclusion, the present study identified that β-arrestin recruitment was associated with growth and resistance to β-lactams, which suggested that �

Activation of Antibiotic Production in Bacillus spp. by Cumulative Drug Resistance Mutations.

PubMed

Tojo, Shigeo; Tanaka, Yukinori; Ochi, Kozo

2015-12-01

Bacillus subtilis strains produce a wide range of antibiotics, including ribosomal and nonribosomal peptide antibiotics, as well as bacilysocin and neotrehalosadiamine. Mutations in B. subtilis strain 168 that conferred resistance to drugs such as streptomycin and rifampin resulted in overproduction of the dipeptide antibiotic bacilysin. Cumulative drug resistance mutations, such as mutations in the mthA and rpsL genes, which confer low- and high-level resistance, respectively, to streptomycin, and mutations in rpoB, which confer resistance to rifampin, resulted in cells that overproduced bacilysin. Transcriptional analysis demonstrated that the enhanced transcription of biosynthesis genes was responsible for the overproduction of bacilysin. This approach was effective also in activating the cryptic genes of Bacillus amyloliquefaciens, leading to actual production of antibiotic(s). Copyright © 2015, American Society for Microbiology. All Rights Reserved.