Finding alternatives to antibiotics Allen, Heather K; Trachsel, Julian; Looft, Torey ...
Annals of the New York Academy of Sciences,
September 2014, Letnik:
1323, Številka:
1
Journal Article
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The spread of antibiotic-resistant pathogens requires new treatments. As the rate of development of new antibiotics has severely declined, alternatives to antibioticsmust be considered in both animal ...agriculture and humanmedicine. Products for disease prevention are different from those for disease treatment, and examples of both are discussed here. For example, modulating the gut microbial community, either through feed additives or fecal transplantation, could be a promising way to prevent certain diseases; for disease treatment, non-antibiotic approaches include phage therapy, phage lysins, bacteriocins, and predatory bacteria. Interestingly, several of these methods augment antibiotic efficacy by improving bacterial killing and decreasing antibiotic resistance selection. Because bacteria can ultimately evolve resistance to almost any therapeutic agent, it is important to continue to use both antibiotics and their alternatives judiciously.
As emerging contaminants, antibiotics are frequently present in various environments, particularly rivers, albeit often at sublethal concentrations (ng/L∼μg/L). Assessing the risk associated with ...these low levels, which are far below the lethal threshold for most organisms, remains challenging. In this study, using microcosms containing planktonic bacteria and biofilm, we examined how antibiotic resistance genes (ARGs) in different physical states, including intracellular ARGs (iARGs) and extracellular ARGs (eARGs) responded to these low-level antibiotics. Our findings reveal a positive correlation between sub-lethal antibiotic exposure (ranging from 0.1 to 10 μg/L) and increased prevalence (measured as ARG copies/16s rDNA) of both iARGs and eARGs in planktonic bacteria. Notably, eARGs demonstrated greater sensitivity to antibiotic exposure compared to iARGs, with a lower threshold (0.1 μg/L for eARGs versus 1 μg/L for iARGs) for abundance increase. Moreover, ARGs in biofilms demonstrates higher sensitivity to antibiotic exposure compared to planktonic bacteria. To elucidate the underlying mechanisms, we established an integrated population dynamics-pharmacokinetics-pharmacodynamics (PD-PP) model. This model indicates that the enhanced sensitivity of eARGs is primarily driven by an increased potential for plasmid release from cells under low antibiotic concentrations. Furthermore, the accumulation of antibiotic in biofilms induces a greater sensitivity of ARG compared to the planktonic bacteria. This study provides a fresh perspective on the development of antibiotic resistance and offers an innovative approach for assessing the risk of sublethal antibiotic in the environment.
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•Extracellular and intracellular ARGs increase with low level antibiotic exposure.•iARGs in water and biofilm respond dose-dependently to antibiotics.•eARGs exhibit heightened sensitivity to antibiotic exposure.•eARGs' sensitivity is driven by increased plasmid release potential.
This review identifies evidence on supply-side interventions to change the practices of antibiotic prescribers and gatekeepers in low- and middle-income countries (LMICs). A total of 102 studies met ...the inclusion criteria, of which 70 studies evaluated interventions and 32 provided insight into prescribing contexts. All intervention studies were from human healthcare settings, none were from animal health. Only one context study examined antibiotic use in animal health. The evidence base is uneven, with the strongest evidence on knowledge and stewardship interventions. The review found that multiplex interventions that combine different strategies to influence behaviour tend to have a higher success rate than interventions based on single strategies. Evidence on prescribing contexts highlights interacting influences including health system quality, education, perceptions of patient demand, bureaucratic processes, profit, competition, and cultures of care. Most interventions took place within one health setting. Very few studies targeted interventions across different kinds of providers and settings. Interventions in hospitals were the most commonly evaluated. There is much less evidence on private and informal private providers who play a major role in drug distribution in LMICs. There were no interventions involving drug detailers or the pharmaceutical companies despite their prominent role in the contextual studies.
Manure from food-producing animals, rich in antibiotic-resistant bacteria and antibiotic resistance genes (ARGs), poses significant environmental and healthcare risks. Despite global efforts, most ...manure is not adequately processed before use on fields, escalating the spread of antimicrobial resistance. This study examined how different cattle manure treatments, including composting and storage, affect its microbiome and resistome. The changes occurring in the microbiome and resistome of the treated manure samples were compared with those of raw samples by high-throughput qPCR for ARGs tracking and sequencing of the V3–V4 variable region of the 16S rRNA gene to indicate bacterial community composition. We identified 203 ARGs and mobile genetic elements (MGEs) in raw manure. Post-treatment reduced these to 76 in composted and 51 in stored samples. Notably, beta-lactam, cross-resistance to macrolides, lincosamides and streptogramin B (MLSB), and vancomycin resistance genes decreased, while genes linked to MGEs, integrons, and sulfonamide resistance increased after composting. Overall, total resistance gene abundance significantly dropped with both treatments. During composting, the relative abundance of genes was lower midway than at the end. Moreover, higher biodiversity was observed in samples after composting than storage. Our current research shows that both composting and storage effectively reduce ARGs in cattle manure. However, it is challenging to determine which method is superior, as different groups of resistance genes react differently to each treatment, even though a notable overall reduction in ARGs is observed.
As one of the most diverse habitats of microorganisms, soil has been recognised as a reservoir of both antibiotics and the antibiotic resistance genes (ARGs). Bacteria naturally inhabiting soil or ...water often possess innate ARGs to counteract the chemical compounds produced by competitors living in the same environment. When such bacteria are able to cause infections in immunocompromised patients, their strong innate antibiotic resistance mechanisms make treatment difficult. We generated functional gene libraries using antibiotic-resistant
and
spp. bacteria isolated from agricultural soils in Lithuania to select for the genetic determinants responsible for their resistance. We were able to find novel variants of aminoglycoside and β-lactam resistance genes, with β-lactamases isolated from the
spp. functional gene library, one of which is a variant of IND-like metallo-β-lactamase (MBL) IND-17 and the other of which is a previously uncharacterised MBL we named CHM (
metallo β-lactamase). Our results indicate that soil microorganisms possess a diversity of ARG variants, which could potentially be transferred to the clinical setting.
Among the different pharmaceuticals present in soil and water ecosystems as micro-contaminants, considerable attention has been paid to antibiotics, since their increasing use and the consequent ...development of multi-resistant bacteria pose serious risks to human and veterinary health. Moreover, once they have entered the environment, antibiotics can affect natural microbial communities. The latter play a key role in fundamental ecological processes, most importantly the maintenance of soil and water quality. In fact, they are involved in biogeochemical cycling and organic contaminant degradation thanks to their large reservoir of genetic diversity and metabolic capability. When antibiotics occur in the environment, they can hamper microbial community structure and functioning in different ways and have both direct (short-term) and indirect (long-term) effects on microbial communities. The short-term ones are bactericide and bacteriostatic actions with a consequent disappearance of some microbial populations and their ecological functioning. The indirect impact includes the development of antibiotic resistant bacteria and in some cases bacterial strains able to degrade them by metabolic or co-metabolic processes. Biodegradation makes it possible to completely remove a toxic compound from the environment if it is mineralized.
Several factors can influence the significance of such direct and indirect effects, including the antibiotic's concentration, the exposure time, the receiving ecosystem (e.g. soil or water) and the co-occurrence of other antibiotics and/or other contaminants.
This review describes the current state of knowledge regarding the effects of antibiotics on natural microbial communities in soil and water ecosystems.
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•Antibiotics affect the diversity of natural bacterial communities.•Biodegradation is a homeostatic response by the natural microbial community.•Antibiotics and antibiotic resistance genes (ARGs) are emerging contaminants.•ARGs are naturally found in the chromosomes of some environmental bacteria.•Antibiotics are signals that trigger microbial community functioning.
Abstract
Biofilms are surface-attached groups of microbial cells encased in an extracellular matrix that are significantly less susceptible to antimicrobial agents than non-adherent, planktonic ...cells. Biofilm-based infections are, as a result, extremely difficult to cure. A wide range of molecular mechanisms contribute to the high degree of recalcitrance that is characteristic of biofilm communities. These mechanisms include, among others, interaction of antimicrobials with biofilm matrix components, reduced growth rates and the various actions of specific genetic determinants of antibiotic resistance and tolerance. Alone, each of these mechanisms only partially accounts for the increased antimicrobial recalcitrance observed in biofilms. Acting in concert, however, these defences help to ensure the survival of biofilm cells in the face of even the most aggressive antimicrobial treatment regimens. This review summarises both historical and recent scientific data in support of the known biofilm resistance and tolerance mechanisms. Additionally, suggestions for future work in the field are provided.
This review article provides a discussion of the wide range of molecular mechanisms that contribute to the ability of pathogenic bacteria in biofilm communities to withstand antimicrobial therapy.
What is antimicrobial stewardship? Dyar, O.J.; Huttner, B.; Schouten, J. ...
Clinical microbiology and infection,
11/2017, Letnik:
23, Številka:
11
Journal Article
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The use of the term ‘antimicrobial stewardship’ has grown exponentially in recent years, typically referring to programmes and interventions that aim to optimize antimicrobial use. Although ...antimicrobial stewardship originated within human healthcare, it is increasingly applied in broader contexts including animal health and One Health. As the use of the term ‘antimicrobial stewardship’ becomes more common, it is important to consider what antimicrobial stewardship is, as well as what it is not.
To review the emergence and evolution of the term ‘antimicrobial stewardship’.
We searched and reviewed existing literature and official documents, which mostly focused on antibiotics. We contacted the authors of the first publications that mentioned antimicrobial stewardship.
We describe the historical background behind how antimicrobial stewardship came into use in clinical settings. We discuss challenges emerging from the varied descriptions of antimicrobial stewardship in the literature, including an over-emphasis on individual prescriptions, an under-emphasis on the societal implications of antimicrobial use, and language translation problems.
To help address these challenges, we suggest viewing antimicrobial stewardship as a strategy, a coherent set of actions which promote using antimicrobials responsibly. We stress the continuous need for ‘responsible use’ to be defined and translated into context-specific and time-specific actions. Furthermore, we present examples of actions that can be undertaken within antimicrobial stewardship across human and animal health.
To assess whether a two-phase intervention was associated with improvements in antibiotic prescribing among non-hospitalized children with community-acquired pneumonia.
In a large health care ...organization, a phase one intervention was implemented in September 2020 directed at antibiotic choice and duration for children 2 months through 17 years of age with pneumonia. Activities included clinician education and implementation of a pneumonia-specific order set in the electronic health record (EHR). In October 2021, a second phase comprised additional education and order set revisions. A narrow spectrum antibiotic (eg, amoxicillin) was recommended in most circumstances. EHR data were used to identify pneumonia cases and antibiotics ordered. Using interrupted time series analyses, antibiotic choice and duration after phase one (September 2020 to September 2021) and after phase two (October 2021 to October 2022) were compared with a pre-intervention pre-pandemic period (January 2016 to early March 2020).
Overall, 3570 cases of community-acquired pneumonia were identified: 3246 cases pre-intervention, 98 post-phase-one, and 226 post-phase-two. The proportion receiving narrow spectrum monotherapy increased from 40.6% pre-intervention to 68.4% post-phase-one to 69.0% post-phase-two (p<0.001). For children with an initial narrow spectrum antibiotic, duration decreased from pre-intervention (mean duration 9.9 days, standard deviation SD 0.5 days) to post-phase-one (mean 8.2, SD 1.9) to post-phase-two (mean 6.8, SD 2.3) periods (p<0.001).
A two-phase intervention with educational sessions combined with clinical decision support was associated with sustained improvements in antibiotic choice and duration among children with community-acquired pneumonia.
Controlled experimental evolution during antibiotic treatment can help to explain the processes leading to antibiotic resistance in bacteria. Recently, intermittent antibiotic exposures have been ...shown to lead rapidly to the evolution of tolerance—that is, the ability to survive under treatment without developing resistance. However, whether tolerance delays or promotes the eventual emergence of resistance is unclear. Here we used in vitro evolution experiments to explore this question. We found that in all cases, tolerance preceded resistance. A mathematical population-genetics model showed how tolerance boosts the chances for resistance mutations to spread in the population. Thus, tolerance mutations pave the way for the rapid subsequent evolution of resistance. Preventing the evolution of tolerance may offer a new strategy for delaying the emergence of resistance.
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