Selection of Resistant Bacteria at Very Low Antibiotic Concentrations

Gullberg, Erik; Cao, Sha; Berg, Otto G.; Ilbäck, Carolina; Sandegren, Linus; Hughes, Diarmaid; Andersson, Dan I.

doi:10.1371/journal.ppat.1002158

Cited by 1,323 publications

(1,290 citation statements)

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“…It has been shown that even when bacteria was exposed to 200 times its minimum inhibitory concentration (MIC), it can develop resistance within 10 hours [57]. This suggests that our previous understanding that bacterial resistance is directly related to being exposed to below-MIC concentrations of antibiotics [58] may be incomplete. Nevertheless, by matching the vancomycin elution of VPE to clinically used vancomycin eluting bone cement (Figure 3d), we expect VPE to pose no extra risk in bacterial resistance development to antibiotic eluting bone cement.…”

Section: Discussionmentioning

confidence: 99%

A fully functional drug-eluting joint implant

et al. 2017

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Despite advances in orthopedic materials, the development of drug-eluting bone and joint implants that can sustain the delivery of the drug and maintain the necessary mechanical strength in order to withstand loading has remained elusive. Here, we demonstrate that modifying the eccentricity of drug clusters and the percolation threshold in ultrahigh molecular weight polyethylene (UHMWPE) results in maximized drug elution and in the retention of mechanical strength. The optimized UHMWPE eluted antibiotic at a higher concentration for longer than the clinical gold standard antibiotic-eluting bone cement while retaining the mechanical and wear properties of clinically used UHMWPE joint prostheses. Treatment of lapine knees infected with Staphylococcus aureus with the antibiotic-eluting UHMWPE led to complete bacterial eradication and to the absence of detectable systemic effects. We argue that the antibiotic-eluting UHMWPE joint implant is a promising candidate for clinical trials.

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Section: Discussionmentioning

confidence: 99%

A fully functional drug-eluting joint implant

et al. 2017

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“…The effects of veterinary antibiotics range from acute toxicity to Daphnia magna (Halling-Sørensen, 2000), development of resistant genes (Chee-Sanford et al, 2009;Gullberg et al, 2011), inhibition of soil bacteria growth, and changes in the composition of the soil microbial population. Veterinary antibiotics can thus also reduce the soil degradation properties for other organic substances (Thiele-Bruhn, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Veterinary antibiotics can thus also reduce the soil degradation properties for other organic substances (Thiele-Bruhn, 2003). Gullberg et al (2011) showed that resistant bacteria develop even in conditions with concentrations below the minimum inhibitory concentrations for tetracyclines and other antibiotics. Heuer and Smalla (2007) investigated the persistent effects of SDZ on soil bacterial communities, and showed that the numbers of culturable resistant bacteria and sulfonamide resistance genes increased.…”

Section: Introductionmentioning

confidence: 99%

Fate of the antibiotic sulfadiazine in natural soils: Experimental and numerical investigations

Engelhardt

Sittig

Šimůnek

et al. 2015

Journal of Contaminant Hydrology

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Based on small-scale laboratory and field-scale lysimeter experiments, the sorption and biodegradation of sulfonamide sulfadiazine (SDZ) were investigated in unsaturated sandy and silty-clay soils. Sorption and biodegradation were low in the laboratory, while the highest leaching rates were observed when SDZ was mixed with manure. The leaching rate decreased when SDZ was mixed with pure water, and was smallest with the highest SDZ concentrations. In the laboratory, three transformation products (TPs) developed after an initial lag phase. However, the amount of TPs was different for different mixing-scenarios. The TP 2-aminopyrimidine was not observed in the laboratory, but was the most prevalent TP at the field scale. Sorption was within the same range at the laboratory and field scales. However, distinctive differences occurred with respect to biodegradation, which was higher in the field lysimeters than at the laboratory scale. While the silty-clay soil favored sorption of SDZ, the sandy, and thus highly permeable, soil was characterized by short half-lives and thus a quick biodegradation of SDZ. For 2-aminopyrimidine, half-lives of only a few days were observed. Increased field-scale biodegradation in the sandy soil resulted from a higher water and air permeability that enhanced oxygen transport and limited oxygen depletion. Furthermore, low pH was more important than the organic matter and clay content for increasing the biodegradation of SDZ. A numerical analysis of breakthrough curves of bromide, SDZ, and its TPs showed that preferential flow pathways strongly affected the solute transport within shallow parts of the soil profile at the field scale. However, this effect was reduced in deeper parts of the soil profile. Due to high field-scale biodegradation in several layers of both soils, neither SDZ nor 2-aminopyrimidine was detected in the discharge of the lysimeter at a depth of 1 m. Synthetic 50 year long simulations, which considered the application of manure with SDZ for general agricultural practices in Germany and humid climate conditions, showed that the concentration of SDZ decreased below 0.1 μg/L in both soils below the depth of 50 cm.

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“…[18] The use of antibiotics, even in very low (sub-therapeutic) doses, may select for antibiotic-resistant bacteria. [29,30] These resistant strains can spread in the environment or survive in the food chain, where they pose a possible threat for human health. Resistant bacteria can pass resistance genes to commensals and pathogens via horizontal gene transfer.…”

Section: Introductionmentioning

confidence: 99%

Antibiotic use and resistance in animals: Belgian initiatives

Daeseleire¹,

Graef

Rasschaert³

et al. 2016

Drug Testing and Analysis

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The widespread use of antibiotics in animals is causing concerns about the growing risk for development and the spread of antibiotic-resistant bacteria. Antibiotic consumption is higher in animals than in humans as reported in a joint publication of EFSA (European Food Safety Agency), ECDC (European Centre for Disease Prevention and Control), and EMA (European Medicines Agency) using data from 2011 and 2012. Both in humans and animals, positive associations between the consumption of antibiotics and resistant bacteria are observed. Responsible use of antibiotics in humans and animals should therefore be promoted. In this paper some general aspects of antibiotic resistance such as microbiological versus clinical resistance, intrinsic versus acquired resistance, resistance mechanisms, and transfer of resistance are briefly introduced. In 2012, the Belgian Center of Expertise on Antimicrobial Consumption and Resistance in Animals (AMCRA) was founded. Its mission is to collect and analyze all data related to antibiotic use and resistance in animals in Belgium and to communicate these findings in a neutral and objective manner. One of AMCRA's 10 objectives is a 50% reduction in antibiotic consumption in veterinary medicine in Belgium by 2020. The aim of this paper is to report on the achievements of this national project. The Institute for Agricultural and Fisheries Research (ILVO, Merelbeke-Melle), in collaboration with Ghent University, is currently working on three nationally funded projects on antibiotic resistance in animal husbandry. In the first project, an in vitro model is used to study the influence of low antibiotic concentrations due to carry-over after production and usage of medicated feed on the development of resistance in the pig gut. Part of that project is to develop a quantitative risk assessment model. A second project focuses on tracking excreted antibiotics used in pig rearing and their influence on the development of antibiotic resistance in pig manure and the environment. In the last project, the relation between the use of biocides in animal husbandry and antibiotic resistance development are being studied. Copyright

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Selection of Resistant Bacteria at Very Low Antibiotic Concentrations

Cited by 1,323 publications

References 30 publications

A fully functional drug-eluting joint implant

A fully functional drug-eluting joint implant

Fate of the antibiotic sulfadiazine in natural soils: Experimental and numerical investigations

Antibiotic use and resistance in animals: Belgian initiatives

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