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What is antibiotic resistance and how can we measure it?
Abstract
Antibiotic resistance is being found with increasing frequency in both pathogenic and commensal bacteria of humans and animals. Quantifying resistance within and between bacterial and host populations presents scientists with complex challenges in terms of laboratory methodologies and sampling design. Here, we discuss, from an epidemiological perspective, how antibiotic resistance can be defined and measured and the limitations of current approaches.
... Despite its significance, there is currently no universally agreed-upon definition for drug resistance, and comprehending its emergence, mechanisms, and detection remains a complex and challenging area of scientific research. The emergence of drug resistance has rendered infections more challenging and expensive to treat, as well as more difficult to control (Davison et al., 2000). The misuse and overuse of antibiotics in medical practice have significantly contributed to the development of drug resistance. ...
... Consequently, an antimicrobial resistance crisis has unfolded, and it is projected to result in 10 million deaths annually by 2050, with a significant contribution from ESBL-producing bacteria (Bush & Bradford, 2020;Kirchhelle et al., 2020). The excessive use of antibiotics in humans, animals, and plants has greatly contributed to the rapid emergence and spread of drug-resistant infections (Courvalin, 2016;WHO, 2012) and pathogenic and com-mensal bacteria in humans (Davison et al., 2000). This has led to the emergence of new forms of resistance genes that can quickly travel globally through various means, including human travelers, animal and insect vectors, agricultural products, and surface water (W. ...
... Wang et al., 2018). In bacteria, drug resistance is typically described based on phenotypic and genotypic characteristics and can be categorized according to its origin (intrinsic versus acquired) and type (single, multiple, co-resistance, or cross-resistance) (Courvalin, 2016; Davison et al., 2000). Intrinsic drug resistance can be either innate (passive) or mediated (active) (Citation, 2003). ...
Antibiotics are designed to effectively treat bacterial infections while minimizing harm to the human body. They work by targeting specific components of bacteria or by disrupting essential processes such as cell wall synthesis, membrane function, protein production, and metabolic pathways. However, the misuse and overuse of antibiotics have led to the emergence of drug resistance in humans, animals, and agriculture, contributing to the global spread of this problem. Drug resistance can be either innate or acquired, with acquired resistance involving changes in the bacterial chromosomes or transferable elements. Bacterial species employ various mechanisms of drug resistance, including modifying the antibiotic targets, inactivating the drug, reducing uptake or increasing efflux, overexpressing the target, utilizing alternative pathways, and forming biofilms. One significant concern in the realm of drug resistance revolves around the emergence and proliferation of extended-spectrum beta-lactamases (ESBLs), a gene that is found in most gram-negative bacteria, primarily carried by Escherichia coli and Klebsiella pneumoniae in healthcare settings. ESBL-mediated resistance poses challenges for diagnosis, treatment, infection control, and antibiotic stewardship. Accurate detection of ESBL genes is crucial, and phenotypic methods are commonly used for initial screening. However, these methods have limitations, and confirmatory molecular techniques such as PCR and DNA sequencing are employed to accurately identify ESBL genes. Despite the significant global concerns surrounding ESBLs, they have spread worldwide, mainly facilitated by healthcare settings, inappropriate antimicrobial use, and host susceptibility. Addressing this issue requires implementing comprehensive measures, including enhanced surveillance, strict infection control practices, antibiotic stewardship programs, rapid diagnostic methods, alternative therapies, public education initiatives, and research focused on developing new drugs. Furthermore, collaboration among the healthcare, public health, and research sectors is pivotal in effectively combating the escalating threat posed by ESBL-mediated resistance. Antibiotics have revolutionized medical care by effectively treating bacterial infections. However, the emergence of ESBL gene resistance poses a global challenge that requires an integrated approach to prevent a threatening future.
... Although different definitions of the term 'resistance' can be found in the antibiotic research literature depending on the field of research (e.g. epidemiology or clinical perspective [20]) all definitions have in common that resistance is based on genetic alterations caused by mutations or horizontal gene transfer, and thus a heritable trait [21]. In contrast to resistance, the term 'tolerance' refers to the transient state of a subpopulation of genetically identical bacteria that allows this subpopulation to survive antibiotic treatment better than their growing peers. ...
... Tolerance is thus not based on a genetic difference, but the result of a different cellular state. One example is the dormancy of cells that refers to a state of reduced metabolism that makes the dormant subpopulation less vulnerable to antibiotics than the fast-growing part of the population [20,21]. In the present study, we address the phenomenon of plasma resistance, since E. coli strains with different genetics were analysed (deletion mutants or strains over-expressing certain genes). ...
... The first screening of the KEIO collection of approximately 4000 E. coli single-gene knockout mutants [20] for sensitivity to treatment with the mAPPJ identified 87 genes that mediate protection against plasma. Among these are genes indicative of DNA damage such as ada encoding a transcriptional regulator with protective function against DNA-alkylating agents [39], or recA [40] with a number of functions related to DNA repair and recombination, most prominently the SOS response allowing error-prone DNA repair when high fidelity repair systems are overwhelmed. ...
Non-thermal atmospheric pressure plasmas are investigated as augmenting therapy to combat bacterial infections. The strong antibacterial effects of plasmas are attributed to the complex mixture of reactive species, (V)UV radiation and electric fields. The experience with antibiotics is that upon their introduction as medicines, resistance occurs in pathogens and spreads. To assess the possibility of bacterial resistance developing against plasma, we investigated intrinsic protective mechanisms that allow Escherichia coli to survive plasma stress. We performed a genome-wide screening of single-gene knockout mutants of E. coli and identified 87 mutants that are hypersensitive to the effluent of a microscale atmospheric pressure plasma jet. For selected genes (cysB, mntH, rep and iscS) we showed in complementation studies that plasma resistance can be restored and increased above wild-type levels upon over-expression. To identify plasma-derived components that the 87 genes confer resistance against, mutants were tested for hypersensitivity against individual stressors (hydrogen peroxide, superoxide, hydroxyl radicals, ozone, HOCl, peroxynitrite, NO†, nitrite, nitrate, HNO 3 , acid stress, diamide, heat stress and detergents). k-meansþþ clustering revealed that most genes protect from hydrogen peroxide, superoxide and/or nitric oxide. In conclusion, individual bacterial genes confer resistance against plasma providing insights into the antibacterial mechanisms of plasma. © 2019 The Author(s) Published by the Royal Society. All rights reserved.
... These assays can help us determine the bacterium's susceptibility to different antibiotic concentrations in broth, agar culture medium, or on paper discs. The term "minimum inhibitory concentration" (MIC) refers to the lowest concentration of antibiotic that stops bacterial growth [89]. These MIC values with the bacterial OD are necessary to obtain the antibiotic susceptibility interpretation because it provides information whether the test organism is susceptible, resistant, or intermediate to the antibiotic [90]. ...
... We now know a lot more about the connection between antibiotic usage and AMR of gut microbes thanks to culture-based investigations. It has been demonstrated that the prevalence of resistant fecal E. coli and other gramnegative bacteria is strongly associated with antibiotic use [88,89]. An association between the AMR of fecal E. coli and that of E. coli involved in diseases, including urinary tract infections (UTIs), has been shown by culture-based analysis of AMS of indicator bacteria [92]. ...
... In this case, mutations considered were only single-site mutations. For the quantitative comparison to the computational prediction, the antibiotic's minimum inhibitory concentration (MIC) was used [69]. ...
... Comparison between the statistical scores (∆φ = ∆E) and the experimental fitness, the minimum inhibitory concentration (MIC) of the antibiotic[69]. The five highest-scoring mutations shown in the figure (M182T, H153R, I247V, T265L/Q, and N276D) are reported as stabilizing mutants (red crosses). (Source[70]) ...
Over the last few decades, protein sequencing techniques have been developed and continuous experiments have been done. Thanks to all of these efforts, nowadays, we have obtained more than two hundred million protein sequence data. In order to deal with such a huge amount of biological data, now, we need theories and technologies to extract information that we can understand and interpret.The key idea to resolve this problem is statistical physics and the state of the art of machine learning (ML). Statistical physics is a field of physics that can successfully describe many complex systems by extracting or reducing variables to be interpretable variables based on simple principles. ML, on the other hand, can represent data (such as reconstruction and classification) without assuming how the data was generated, i.e. physical phenomenon behind of data. In this dissertation, we report studies of protein sequence generative modeling and protein-residue contact predictions using statistical physics-inspired modeling and ML-oriented methods. In the first part, we review the general background of biology and genomics. Then we discuss statistical modelings for protein sequence. In particular, we review Direct Coupling Analysis (DCA), which is the core technology of our research. We also discuss the effects of higher-order statistics contained in protein sequences and introduces deep learning-based generative models as a model that can go beyond pairwise interaction.
... However, the term "drug resistance" is used to mean different things in the research literature. For example, in Davison et al. 2000 (Davison, Woolhouse, andLow 2000), drug resistance is defined in terms of the drug concentration needed to inhibit growth or kill the pathogen. Brauner et al. 2016(Brauner et al. 2016) quantify cell populations overcoming drug effects in terms of MIC and the minimum time needed to kill the pathogens (MDK). ...
... However, the term "drug resistance" is used to mean different things in the research literature. For example, in Davison et al. 2000 (Davison, Woolhouse, andLow 2000), drug resistance is defined in terms of the drug concentration needed to inhibit growth or kill the pathogen. Brauner et al. 2016(Brauner et al. 2016) quantify cell populations overcoming drug effects in terms of MIC and the minimum time needed to kill the pathogens (MDK). ...
Density dependence is important in the ecology and evolution of microbial and cancer cells. Typically, we can only measure net growth rates, but the underlying density-dependent mechanisms that give rise to the observed dynamics can manifest in birth processes, death processes, or both. Therefore, we utilize the mean and variance of cell number fluctuations to separately identify birth and death rates from time series that follow stochastic birth-death processes with logistic growth. Our method provides a novel perspective on stochastic parameter identifiability, which we validate by analyzing the accuracy in terms of the discretization bin size. We apply our method to the scenario where a homogeneous cell population goes through three stages: (1) grows naturally to its carrying capacity, (2) is treated with a drug that reduces its carrying capacity, and (3) overcomes the drug effect to restore its original carrying capacity. In each stage, we disambiguate whether it happens through the birth process, death process, or some combination of the two, which contributes to understanding drug resistance mechanisms. In the case of limited data sets, we provide an alternative method based on maximum likelihood and solve a constrained nonlinear optimization problem to identify the most likely density dependence parameter for a given cell number time series. Our methods can be applied to other biological systems at different scales to disambiguate density-dependent mechanisms underlying the same net growth rate.
Mathematics Subject Classifications
60J27 · 92D25 · 62M10 · 60J25
... Pathogens such as bacteria, viruses and parasites are continually evolving. When a drug 2 resistant mutation occurs by chance, it is given a survival advantage if selection pressure 3 (from antimicrobials, such as antibiotics, antivirals and antimalarials) kills drug sensitive 4 pathogens, leaving the drug resistant pathogens within a host. These pathogens can 5 spread throughout a population, thereby leading to additional deaths and treatment 6 costs. ...
... The methods presented here are not limited to a particular drug resistant pathogen. 92 The model is general to any drug resistant pathogen where there is spatiotemporal data 93 about its occurrence, whether the data is from molecular markers studies in the case of 94 malaria, or by genome sequencing in the case of resistance to antivirals [13], or by 95 analysing multiplication bacteria rates from samples [4]. ...
When drug resistance is suspected to be in a region, patients in the region are sampled and the suspicion is confirmed. This biased sampling limits our ability to capture underlying dynamics, meaning strategies to lengthen the lifespan of drugs are reactionary, not proactive.
Testing for drug resistant infections is becoming easier and cheaper, therefore we should revisit sampling decisions. We present a hierarchical mechanistic Bayesian model, and apply it to a simulated dataset, where we sample between 5% and 30% of the population in a biased and unbiased manner. We show that unbiased spatiotemporal data on the presence of drug resistant infections, combined with our model, highlights underlying dynamics.
Our mechanistic model is more accurate than a generalised additive model with space and time components. Moreover, highlighting underlying dynamics creates novel strategies that lengthen the lifespan of drugs. In low to middle income countries, generally, drug resistance emerges into a population from hotspots such as treatment centres (perhaps the use of sub-standard drugs), or major transport hubs, and then resistance spreads throughout the population. Using our model, we rank resistance hotspots, enabling resources to be targeted - such as verifying the quality of drugs at a particular health care centre.
... The cell growth and the tellurite-resistance properties of different strains in this work were determined using the agar and broth dilution methods as described before [28][29][30]. The cell growth curve and the MIC value of tellurite to cells were assessed after a defined period of incubation [30]. ...
... To determine the cell growth and tellurite resistance properties of the recombinant strains, the minimal inhibitory concentration (MIC) of tellurite to cells was determined using the agar and broth dilution methods, and the cell growth was assessed after incubation for a defined period of time [28,29]. The growth curves were monitored with an Automated Microbiology Growth Curve Analyzer (Bioscreen, Oy Growth Curves Ab Ltd., Helsinki, Finland) at 37 • C for 24 h. ...
Tellurite is highly toxic to bacteria and commonly used in the clinical screening for pathogens; it is speculated that there is a potential relationship between tellurite resistance and bacterial pathogenicity. Until now, the core function genes of tellurite resistance and their characteristics are still obscure. Pseudomonas citronellolis SJTE-3 was found able to resist high concentrations of tellurite (250 μg/mL) and formed vacuole-like tellurium nanostructures. The terZABCDE gene cluster located in the large plasmid pRBL16 endowed strain SJTE-3 with the tellurite resistance of high levels. Although the terC and terD genes were identified as the core function genes for tellurite reduction and resistance, the inhibition of cell growth was observed when they were used solely. Interestingly, co-expression of the terA gene or terZ gene could relieve the burden caused by the expression of the terCD genes and recover normal cell growth. TerC and TerD proteins commonly shared the conserved sequences and are widely distributed in many pathogenic bacteria, highly associated with the pathogenicity factors.
... Antibiotic has been applied for almost 100 years as a predominant strategy in controlling infectious diseases and improving the growth performance of animals (1). Along with the inappropriate and excessive use of antibiotics, antibiotic resistance issues have been gradually exposed (2). There is an increasing number of bacteria which have developed drug resistance, such as Salmonella with multidrug resistance (3). ...
... In addition, next-generation probiotics (Akkermansia muciniphila, Faecalibacterium prausnitzii, and Eubacterium hallii) and genetically modified probiotics (GM probiotics: mutation and overexpression) were vigorously researched (8,9). The basic mechanism by which probiotics exert beneficial effects is explained as follows: (1) colonization and restoration of disordered intestinal microbiota in the host, (2) competitive exclusion of harmful microbes and antimicrobial molecule production, (3) cell antagonism, cell adhesion, and mucin expression, and (4) regulation of innate and acquired immunity of the host (10). Studies demonstrated that B. subtilis supplementation could ameliorate heat-induced behavioral and inflammatory reactions (11). ...
Antibiotic resistance is an increasingly prevalent problem worldwide. Probiotics are live microorganisms that provide health benefits to human beings and animals and also antimicrobial activity against pathogens and might be an antibiotic alternative. The gastrointestinal tract of animals can be a suitable source of finding novel antimicrobial agents, where the vast majority of gut microbes inhabit and a plurality of antimicrobial producers exhibit either a wide or narrow spectrum. Animals that live in Northwest China might possess a special commensal community in the gut. Therefore, the purpose of this study was to assess the effects of three probiotic strains (including Lactobacillus salivarius ZLP-4b from swine, Lactobacillus plantarum FBL-3a from beef cattle, and Bacillus velezensis JT3-1 from yak), which were isolated from livestock in this area, on the overall growth performance, immune function, and gut microbiota of mice. The results showed that the L. salivarius ZLP-4b group not only improved the growth performance but also amended the intestinal mucosa morphology of mice. Furthermore, the supplementation of L. plantarum FBL-3a and L. salivarius ZLP-4b strains significantly increased the content of anti-inflammatory cytokines IL-4 and IL-10 but decreased the pro-inflammatory factor IL-17A. The levels of pro-inflammatory factors IL-6, IL-17A, and TNF-α were also decreased by the B. velezensis JT3-1 group pretreatment. The 16S rDNA sequence results showed that the probiotic administration could increase the proportion of Firmicutes/Bacteroidetes intestinal microbes in mice. Furthermore, the relative abundance of Lactobacillus was boosted in the JT3-1- and ZLP-4b-treated groups, and that of opportunistic pathogens (including Proteobacteria and Spirochaetes) was diminished in all treated groups compared with the control group. In conclusion, B. velezensis JT3-1 and L. salivarius ZLP-4b supplementation enhanced the overall performance, intestinal epithelial mucosal integrity, and immune-related cytokines and regulated the intestinal microbiota in mice.
... Resistance can be measured with phenotypic methods, e.g. cultivation and Minimum Inhibitory Concentration (MIC) [2]. These methods detect the AMR occurrence to specific antimicrobials using indicator bacteria, e.g. ...
... The sampling scheme reproducibility of sampler T1 versus T2 within farms and the metagenomic process reproducibility of sample A versus B within farms was estimated as the coefficient of variation (CV) using the formula [2]; ...
Objectives
With the continued spread of antimicrobial resistance in animals, it is important to assess its occurrence throughout a microbiome quantitatively in order to evaluate significantly affecting factors e.g. antimicrobial usage. Metagenomics methods makes it possible to measure the abundance of antimicrobial resistance genes in complex samples such as pooled faeces samples from batches of slaughter pigs. This study was performed to determine; the random error in antimicrobial resistance in pooled samples from batches pigs at slaughter, and the measurement error from the metagenomics processes.
Methods
In four farms, two pooled samples were obtained from a batch of slaughter pigs by two individual samplers, each pooled sample was hereafter processed twice. Hierarchically clustered heatmaps were applied to evaluate dissimilarities between samples. The coefficient of variation was used to calculate the percentage difference between samples from the same farm.
Results
The results of the analysis revealed that it was not possible to quantitatively separate the variation arising from sampling and metagenomics processes. They both contributed to the overall measurement error of antimicrobial resistance in batches of slaughter pigs.
Conclusions
Sampling of single pigs in 30 randomly selected pig pens within the farms provides a composition representative for frequently occurring antimicrobial resistance genes present within the farms, while rare genes were not dispersed in a similar manner. Aggregating the resistance abundance at gene family or antimicrobial class level will reduce the apparent variation originating from errors in sampling and metagenomics processing.
... Cette dernière permet de définir si une souche bactérienne est résistante ou non à l'antibiotique testé. La notion de résistance peut être définie selon différents critères en fonction des domaines de spécialité (microbiologie, épidémiologie, pharmacologie, clinique) (Davison, Low et al. 2000 (Turnidge and Paterson 2007). Bien que la détermination de la valeur de la CMI soit la méthode de référence, la détermination du niveau de résistance d'une souche bactérienne est possible par l'utilisation d'un antibiogramme. ...
... La quantification de la résistance au sein de la flore commensale des animaux de rente permet de documenter l'impact de l'administration d'antibiotiques sur la sélection et l'amplification des résistances dans la flore digestive. A l'heure actuelle, il n'existe aucune méthode de référence validée permettant de déterminer le niveau de résistance des flores digestives (Davison, Low et al. 2000). Il existe cependant plusieurs méthodes de quantification. ...
Au cours des dernières années, le microbiote intestinal de l'Homme et des animaux a été identifié comme étant le principal réservoir potentiel de gènes de résistance aux antibiotiques pouvant potentiellement être transmis aux pathogènes humains. Dans ce contexte, nous avons voulu déterminer, par des approches PK/PD, des outils et de nouvelles modalités d'utilisation des antibiotiques en médecine vétérinaire dans le but de réduire leur consommation mais également leur impact sur la flore digestive des animaux afin de réduire le phénomène d'antibiorésistance. Pour ce faire, nous avons développé, par des approches in vitro un indice pharmacodynamique permettant d'évaluer la sélectivité des antibiotiques, c'est-à-dire leur impact à la fois sur la flore pathogène et sur le microbiote intestinal. Nous avons également développé des modèles d'infection rongeurs qui nous ont permis de tester l'impact de traitements antibiotiques à l'amoxicilline et à la cefquinome, utilisant de faibles doses, initiés durant les phases précoces de l'infection et ciblant de faibles inocula pathogènes sur la guérison des animaux et sur l'émergence de bactéries résistantes au sein du microbiote intestinal. Enfin, nous avons testé l'impact de ce type de traitement sur l'émergence de bactéries résistantes au sein de la flore digestive de porcs, espèce cible potentielle. Nos résultats combinés nous ont permis de voir que cette modalité d'utilisation des antibiotiques pourrait se révéler très intéressante en médecine vétérinaire, notamment dans le cadre de la métaphylaxie.
... Antimicrobial Resistance (AMR) is a signi cant global health threat that leads to increased morbidity, mortality, and economic burden due to treatment failure and prolonged hospitalization [8]. AMR arises from extensive antibacterial use in humans and animals [9][10][11]. For optimal VO treatment, physicians should prescribe appropriate empiric antibiotics and adjust based on culture and sensitivity results to minimize unnecessary antibacterial exposure and enhance treatment e cacy [12][13][14]. ...
Background: Vertebral osteomyelitis (VO) is associated with high morbidity rates[A1] . We conducted a retrospective observational cohort study to evaluate the effects of appropriate antibacterial therapies on the clinical outcomes of patients with VO. This study compared the outcomes of proper and empirical therapies to determine whether empirical antibiotic treatment versus targeted treatment based on microbial culture results leads to different long-term prognoses regarding complications and sequelae in [E2] patients with VO. Methods: Patients diagnosed with VObetween January 2011 and February 2022 were selected from the Changhua Christian Hospital Clinical Research Database. The diagnosis of VO primarily relied on magnetic resonance imaging reports. We defined the microbiological relevance in patients with VO and identified the types of VO-related sequelae and complications in this cohort. This[A3] cohort was categorized into appropriate antibiotics(AA) and empirical therapy (ET). Results: This cross-sectional cohort study collected data over ten years. In total, 230 patients with VO were included in our study. The mean age was 64.7 years, and 110 participants were men (30.8 %). [A4] Most of the participants had underlying diseases. Overall, 33.9 % of patients experienced complications[A5] , with a mortality rate of 4 %. The AA group had a significantly lower incidence of chronic low back pain than the ET group (6.9 % vs. 20.7 %, p=0.031). Conclusions: Inappropriate antibiotic use in patients with VO has been associated with reduced symptomatic relief, highlighting the importance of antimicrobial stewardship. The symptoms improved with appropriate antibiotic therapy. Severe illness, rapid diagnosis, and early appropriate treatment are crucial for treating VO. This study emphasizes optimizing VO management within antimicrobial stewardship to enhance outcomes and reduce healthcare burden. Patients requiring surgery often experience spinal instability, severe nerve compression, or related complications. Severe lower back pain is joint, and appropriate antibiotics significantly alleviate this symptom compared with[E6] empirical therapy. Identifying the causative pathogens of targeted therapy is essential for better long-term outcomes.
... Different definitions of antibiotic resistance have been proposed, depending on the origin and type of microorganisms. All antibioticresistant bacteria (ARB) harbor cellular mechanisms that are responsible for tolerance to antimicrobials (Davison et al. 2000). Microbial competition for substrates is the key factor that has been driving the evolution of bacterial resistance mechanisms since ancient times (Frieri et al. 2017). ...
The increase in the prevalence of carbapenem-resistant Gram-negative bacteria, in particular Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA), poses a serious threat for public health worldwide. This article reviews the alarming data on the prevalence of infections caused by CRAB and CRPA pathogens and their presence in hospital and municipal wastewater, and it highlights the environmental impact of antibiotic resistance. The article describes the key role of antibiotic resistance genes (ARGs) in the acquisition of carbapenem resistance and sheds light on bacterial resistance mechanisms. The main emphasis was placed on the transfer of ARGs not only in the clinical setting, but also in the environment, including water, soil, and food. The aim of this review was to expand our understanding of the global health risks associated with CRAB and CRPA in hospital and municipal wastewater and to analyze the spread of these micropollutants in the environment. A review of the literature published in the last decade will direct research on carbapenem-resistant pathogens, support the implementation of effective preventive measures and interventions, and contribute to the development of improved strategies for managing this problem.
Graphical Abstract
... Antibiotic resistance (AR) is the capability of bacteria to resist and overcome exposure to antibiotics. This ability is facilitated by the acquisition of antibiotic resistance genes (ARGs) (Davison et al., 2000). ...
Purpose
Antibiotic resistance is a growing global concern with far-reaching implications for public health. This study investigates the link between human and environmental health monitoring data in Lower Saxony, adopting the One Health approach.
Methods
Health and environmental monitoring data are analyzed to examine the prevalence of antibiotic-resistant bacteria (ARB). To achieve this goal, existing reports publicly available in internet were reviewed and spatial and statistical tools such as ArcGIS Pro and R programming language were utilized. Health monitoring data is collected annually as part of the sentinel system ARMIN (Antimicrobial Resistance Monitoring), launched in 2006 by the Public Health Agency of Lower Saxony (Germany). Environmental monitoring data were extracted from one study conducted in 2018.
Results
Key findings suggest that the role of wastewater treatment plants (WWTPs) as sources of ARB in the environment, highlighting their limited efficiency in removing ARB. Spatial analysis reveals regional variations in ARB rates, with vancomycin-resistant enterococci (VRE) more prevalent in the East and multi-drug resistant Gram-negative bacteria (3MRGN) evenly distributed across the Western and Eastern regions in Lower Saxony.
Conclusion
Overall, this study underscores the need for comprehensive One Health surveillance programs encompassing human health and the environment to address the complex challenge of antibiotic resistance effectively.
... Furthermore, the definition of AMR is widespread, resulting in different interpretations and outcomes from clinicians and public health perspectives [25]. AMR is investigated in symptomatic populations (e.g., the emergence of infection, colonization) for pathogenic bacteria, in asymptomatic people (e.g., carriage, acquisition and transmission) for commensal bacteria and by molecular investigations (e.g., resistant genes) in humans, animals, and the environment [26,27]. Therefore, when reviewing the literature on variables of AMR, a broad perspective should be considered. ...
To date, the scientific literature on health variables for Escherichia coli antimicrobial resistance (AMR) has been investigated throughout several systematic reviews, often with a focus on only one aspect of the One Health variables: human, animal, or environment. The aim of this umbrella review is to conduct a systematic synthesis of existing evidence on Escherichia coli AMR in humans in the community from a One Health perspective. PubMed, EMBASE, and CINAHL were searched on “antibiotic resistance” and “systematic review” from inception until 25 March 2022 (PROSPERO: CRD42022316431). The methodological quality was assessed, and the importance of identified variables was tabulated across all included reviews. Twenty-three reviews were included in this study, covering 860 primary studies. All reviews were of (critically) low quality. Most reviews focused on humans (20), 3 on animals, and 1 on both human and environmental variables. Antibiotic use, urinary tract infections, diabetes, and international travel were identified as the most important human variables. Poultry farms and swimming in freshwater were identified as potential sources for AMR transmission from the animal and environmental perspectives. This umbrella review highlights a gap in high-quality literature investigating the time between variable exposure, AMR testing, and animal and environmental AMR variables.
... The virulence genes vhh, chiA, vhpA, toxRVh, luxR, and serine protease, typical for the Harveyi clade, were detected in all their studied strains. Furthermore, bacteria can possess innate antimicrobial resistance genes in chromosomes or acquire resistance genes via plasmids (Davison et al., 2000;Loo et al., 2020). Genetic elements such as plasmids are transferred to other bacteria by horizontal or vertical gene transfer. ...
... The breakpoints for tetracyclines were ≤4 susceptible and ≥16 resistant. After determining the MIC values for each of the antibiotics and for all isolated strains, population analyses were carried out to determine the MIC 50 and MIC 90 values [35]. The multiple antibiotic resistance (MAR) index was calculated as the quotient between the number of antimicrobials to which isolates were resistant to the number of tested antimicrobials [36]. ...
The aim of this study was to determine the antibiotic resistance of E. rhusiopathiae when isolated from clinical outbreaks of erysipelas in geese to antimicrobials commonly used in poultry production. All isolates were susceptible to amoxicillin alone or with clavulanic acid, with MIC values ranging from 0.016 to 0.125 μg/mL. Ninety-six percent of isolates were fully sensitive to penicillin G (MIC 0.125–0.5 μg/mL). All isolates were fully or moderately sensitive to erythromycin (MIC 0.125–0.5 μg/mL). Most E. rhusiopathiae isolates proved resistant to fluoroquinolones (76.6% of isolates were resistant to enrofloxacin, with MIC values ranging from 0.064 to 32 μg/mL, and 68% were resistant to norfloxacin, with MIC values ranging from 0.094 to 96 μg/mL), and tetracyclines (61.7% of isolates were resistant to doxycycline, with MIC values ranging from 0.25 to 64 μg/mL, and 63.8% were resistant to tetracycline, with MIC values ranging from 0.38 to 256 μg/mL). Point mutations in the gyrA gene (responsible for fluoroquinolone resistance) and the presence of the tetM gene (responsible for tetracycline resistance) were noted in most of the resistant isolates. Multidrug resistance, defined as resistance to at least one substance in three or more antimicrobial classes, was not observed.
... However, the term "drug resistance" is used to mean different things in the research literature. For example, in (Davison et al. 2000), drug resistance is defined in terms of the drug concentration needed to inhibit growth or kill the pathogen. Brauner et al. (2016) quantify cell populations overcoming drug effects in terms of MIC and the minimum time needed to kill the pathogens (MDK). ...
Density dependence is important in the ecology and evolution of microbial and cancer cells. Typically, we can only measure net growth rates, but the underlying density-dependent mechanisms that give rise to the observed dynamics can manifest in birth processes, death processes, or both. Therefore, we utilize the mean and variance of cell number fluctuations to separately identify birth and death rates from time series that follow stochastic birth-death processes with logistic growth. Our nonparametric method provides a novel perspective on stochastic parameter identifiability, which we validate by analyzing the accuracy in terms of the discretization bin size. We apply our method to the scenario where a homogeneous cell population goes through three stages: (1) grows naturally to its carrying capacity, (2) is treated with a drug that reduces its carrying capacity, and (3) overcomes the drug effect to restore its original carrying capacity. In each stage, we disambiguate whether the dynamics occur through the birth process, death process, or some combination of the two, which contributes to understanding drug resistance mechanisms. In the case of limited sample sizes, we provide an alternative method based on maximum likelihood and solve a constrained nonlinear optimization problem to identify the most likely density dependence parameter for a given cell number time series. Our methods can be applied to other biological systems at different scales to disambiguate density-dependent mechanisms underlying the same net growth rate.
... By contrast, methicillin susceptible infection can be treated with a variety of less toxic antibiotics including cephalosporins and thus avoid the risk of renal failure. However, determination of methicillin susceptibility vs MRSA can take up to 72 h using standard techniques, such as antibiotic disk diffusion and when the infection is not in the bloodstream, it sometimes cannot be determined at all (33,34). For example, cultures are often negative with pneumonia. ...
Introduction
Antibiotic resistance in bacterial species constitutes a growing problem in the clinical management of infections. Not only does it limit therapeutic options, but application of ineffective antibiotics allows resistant species to progress prior to prescribing more effective treatment to patients. Methicillin resistance in Staphylococcus aureus is a major problem in clinical infections as it is the most common hospital acquired infection.
Methods
We developed a photoacoustic flow cytometer using engineered bacteriophage as probes for rapid determination of methicillin resistance in Staphylococcus aureus with thirteen clinical samples obtained from keratitis patients. This method irradiates cells under flow with 532 nm laser light and selectively generates acoustic waves in labeled bacterial cells, thus enabling detection and enumeration of them. Staphylococcus aureus isolates were classified from culture isolation as either methicillin resistant or susceptible using cefoxitin disk diffusion testing. The photoacoustic method enumerates bacterial cells before and after treatment with antibiotics. Decreasing counts of bacteria after treatment indicate susceptible strains. We quantified the bacterial cells in the treated and untreated samples.
Results
Using k-means clustering on the data, we achieved 100% concordance with the classification of Staphylococcus aureus resistance using culture.
Discussion
Photoacoustics can be used to differentiate methicillin resistant and susceptible strains of bacteria from ocular infections. This method may be generalized to other bacterial species using appropriate bacteriophages and testing for resistance using other antibiotics.
... Antimicrobials are also utilized for treatment purposes in broiler chickens (Gadde et al. 2018). Globally, antimicrobial resistance is developed as a result of extended use of various types of antibiotics causing serious public health problems (Davison et al. 2000). Moreover, the acquisition of antibiotic resistance by pathogenic bacteria may lead to more severe infections (Heidary et al. 2014). ...
Salmonella enteritidis (S. enteritidis) is considered a major cause of human salmonellosis and the infection is acquired through the consumption of contaminated meat and meat products with this pathogen. The objective of this study was to investigate the presence of virulence and resistance-associated genes in S. enteritidis isolates from local and imported raw chicken meat and to study their genetic diversity using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) profile analysis. The results of the current study showed that the prevalence of virulence genes was high and the isolates harbored more than five class of virulence-associated genes and their frequency were different among the isolates. All the isolates showed 100% positivity for the invite and hilA genes. Genes including lpfA, avrA, sopE2, spvB, sifA and flaK were in 91%, 82%, 82%, 82%, 73% and 54.5% respectively. The sipA was only present in one isolate. The susceptibly test showed 100% sensitivity to chloramphenicol, norfloxacin, ceftriaxone, and cefotaxime and all the isolates were 100% resistant to ampicillin. However, two of the isolates showed resistance to gentamycin and trimethoprim with sulphamethoxazole. The isolates were found to harbor the dfrA1 for trimethoprim, blaTEM for ampicillin, and the resistance rate was 100%. However, none of the S. enteritidis isolates were found to contain the resistance genes specific to fluoroquinolone, erythromycin, chloramphenicol, cefotaxime, and carbapenems (NDM and OXA) resistance. ERIC-PCR allowed the grouping of the isolates into 5 different ERIC patterns including ET1-ET5. It can be concluded that the detection of the high frequency of virulence genes and MDR suggests the high virulence potential of S. enteritidis isolates which could be of major public health concern.
... To evaluate the approach, we take the Escherichia coli beta-lactamase TEM-1, a model enzyme in biochemistry which provides resistance to betalactam antibiotics. Its mutational landscape has been quantitatively characterized measuring the minimum inhibitory concentration (MIC) of the antibiotic [11,22,50]. This abundance of mutagenesis data, the rich homology information and its well defined 3D structure make it a well-suited system for testing any computational model of protein mutational landscapes. ...
The quantitative characterization of mutational landscapes is a task of outstanding importance in evolutionary and medical biology: It is, e.g., of central importance for our understanding of the phenotypic effect of mutations related to disease and antibiotic drug resistance. Here we develop a novel inference scheme for mutational landscapes, which is based on the statistical analysis of large alignments of homologs of the protein of interest. Our method is able to capture epistatic couplings between residues, and therefore to assess the dependence of mutational effects on the sequence context where they appear. Compared recent large-scale mutagenesis data of the beta-lactamase TEM-1, a protein providing resistance against to beta-lactam antibiotics, our method leads to an increase of about 40% in explicative power as compared to approaches neglecting epistasis. We find that the informative sequence context extends to residues at native distances of about 20 Angstrom from the mutated site, reaching thus far beyond residues in direct physical contact.
... Bacteria have a natural resistance against antibiotics obtained by mutation. Resistance genes are present on chromosomes, plasmids, or transposons (Davison et al., 2000). Antibiotic resistance genes survive in the atmosphere for the long term since antibiotics are known as clinical mediators (D'Costaet al., 2011). ...
Objective of the study: Escherichia coli bacteria with increased antibiotic resistance represent a serious threat to public health. The aim of this study was to assess Cb6 (E)-1-& effectiveness against microorganisms (4-fluorophenyl), determine the effectiveness of Cb6 (E)-1-(4-fluorophenyl)-3-phenyl prop-2-en-1-one against anti-fungal agents and -3 -phenylprop-2-en-1-one against E. coli (Curvularia). StudyDesign:Study was designed by sample collection, culturing, biochemical tests, sensitivity assay and qRT-PCR. Place and Duration: The prospective study was carried out at the University of Agriculture in Faisalabad, Pakistan from 1st February 2019 to 18th June 2019. Methodology: Through horizontal and vertical gene transfer, Escherichia coli acquired resistance genes and developed resistance against many antibiotic classes. The following genes were examined in the current study in E. coli: Van B, ermC, Iva-A, Qnr-A, Qnr-B, tet M, tet O, and tet W resistance genes. To assess the effectiveness of the antibacterial and antifungal agents, antibiotic sensitivity testing was carried out. Results: E.coli chalcone resistance genes, have displayed highly significant (P 0.0001) expression in the patient sample when compared to the control. Conclusion: It was concluded that the chalcones are highly resistant to E coli in prediction. Van B, erm C, Iva-A, Qnr-A, Qnr-B, tet M, tet O, and tet Ware resistant genes of the Escherichia coli against the Cb6 (E)-1-(4-fluorophenyl)-3 -phenyl prop-2-en-1-one and it was showed the high expression level. Keywords: Chalcones Resistant gene, Antibacterial action, Antibiotic sensitivity, Expression.
... Antibiotic resistance is the loss of susceptibility of bacteria to antibiotics (Davison et al., 2000). The widespread use of antibiotics and unsafe disposal of hospital and livestock waste have led to the development of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARG) causing serious health concerns. ...
Open dumping of hospital and livestock waste pollutes soils and water with antibiotics, thus allowing open landfill sites to be lavish breeding grounds for antibiotic-resistant bacteria (ARB). The study investigates the antibiotic sensitivity of soil bacteria isolated from a major municipal solid waste landfill site (Gohagoda) in the Central Province of Sri Lanka, which is located close to the river Mahaweli, the main water source for residents of Kandy, the main city of the Central Province, and its immediate suburbs. Dominant bacterial isolates from soils of the Gohagoda landfill site (polluted, PO) and a nearby wooded area (relatively unpolluted, UP) were tested for antibiotic sensitivity against amikacin, amoxicillin-clavulanate, ciprofloxacin, cefotaxime, imipenem, meropenem and ticarcillin-clavulanate. The results were analyzed using t-test and z-test in Minitab 18.1. Mean diameters of inhibition zones of soil bacterial isolates from UP were significantly higher than those of PO for all antibiotics except for meropenem. The percentage of isolates resistant to all antibiotics was higher in PO compared to UP, except for amikacin and cefotaxime. The findings show a higher prevalence of ARB in the Gohagoda landfill site, emphasizing the importance of identifying alternative measures to dispose municipal solid waste and to introduce proper sanitation practices among landfill workers. Testing soil leachates for ARB is imperative to confirm any threats to the nearby water source.
... Antimicrobial Resistance (AMR) is the ability of microorganisms, including bacterial pathogens, to survive and grow despite exposure to substances that are supposed to kill them [1]. AMR has become one of the fastest-growing threats in global health and it is associated with increased morbidity and mortality, in addition to disastrous economic impacts due to treatment failure and prolonged hospitalization [2,3]. Several factors have been reported to increase the risk of bacterial resistance, including the widespread use of antibacterial agents in humans as well as in animals [4]. ...
This is a cross-sectional study that was conducted at Jordan University Hospital (JUH) to evaluate the appropriateness of Urinary Tract Infection (UTI) empiric treatment based on microbial culture data and susceptibility testing. All urine cultures requested for adult patients (≥18 years) admitted to JUH within the period from January 2019–July 2021 were reviewed and only those cultures with positive episodes of infection were considered. In this study, 6950 urine culture episodes were screened; among them, 34.5% (n = 2400) revealed positive results. Among those patients with positive culture episodes, 1600 patients (66.7%) were discharged before the availability of culture results and were excluded. Of the remaining eligible 800 patients, 701 (87.6%) received empiric treatment. In 26.8% of the eligible cases (n = 214), the prescribed empiric agents failed to have appropriate coverage of the identified pathogens, and in 14.6% of the cases (n = 117) the identified microorganisms were reported as resistant to the prescribed empiric agents. Furthermore, only 13.4% of the patients (n = 107) were appropriately treated for their UTI with empiric antibacterial agents. We were not able to judge the appropriateness of UTI treatment for one third (n = 263, 32.9%) of the patients, because they did not have susceptibility reports performed. This study revealed an alarmingly high rate of inappropriate treatment of UTIs, which encourages the emergence of bacterial resistance and affects health-related outcomes negatively. Therefore, antimicrobial stewardship programs must be applied to optimize antibiotic consumption in hospital settings.
... In addition to being used for the treatment of infections in human patients and farm animals, antibiotics are also routinely given to healthy farm animals to promote growth and proactively prevent disease outbreaks. Antibiotic resistance (AR) is the ability of bacteria to overcome and resist exposure to antibiotic substances, this is made possible by the acquisition of antibiotic resistance genes (ARGs) (Davison et al., 2000;Wright, 2010). Extensive use of antibiotics since the successful purification and mass production of penicillin in the middle of the twentieth century until today has led to an increase in antibiotic resistance, compromising the effectiveness of antibiotics (Davies and Davies, 2010). ...
... Also, cross contamination can occur through water sources as street vendors frequently use municipal water for preparing fruit juices and for washing purposes [40]. Escherichia coli isolated from tap water collected from Dhaka, Jamalpur, Tangail, Netrokona, Kishoreganj showed resistance against tetracycline, erythromycin, amoxicillin, streptomycin and some other antibiotics [50,51]. The unhygienic condition of the vendors and the food preparing places are also accountable for cross contamination. ...
Background: Street vended foods contaminated with antibiotic resistant bacteria poses a great public health concern in developing countries like Bangladesh as foodborne diseases caused by such bacteria are difficult and sometimes impossible to treat. The aim of this review is to investigate the present scenario of the antibiotic resistance status of five selected Gram negative bacteria isolated from a variety of street vended foods of Bangladesh. Methodology: A methodical literature search was performed to identify relevant studies on Google Scholar, Science Direct and Research Gate using suitable keywords arranged in different manners to produce a meaningful search string. Weighted mean resistance was calculated to evaluate the resistance status from 20 studies selected through the PRISMA procedure. Results: Escherichia coli, Klebsiella spp., Salmonella spp., Pseudomonas spp. and Vibrio spp. showed relatively low resistance towards imipenem and gentamicin, whereas the antibiotics of penicillins and macrolides classes listed in this review were mostly ineffective. Relatively high resistance was found against tetracycline, vancomycin, and rifampicin. Conclusion: A considerable number of bacterial isolates present in the SVF are resistant to most of the commonly used antibiotics. Therefore, there is an urgent need for public awareness along with a robust national action plan to combat antibiotic resistance, before the situation worsens. Review Article Alim et al.; JAMB, 22(3): 8-15, 2022; Article no.JAMB.83631 9
... Today, different antibiotics are known as one of the most important and powerful substances to control bacterial infections (Davison et al. 2000;Livermore 2012;Uluseker et al. 2021). Unfortunately, excessive consumption of antibiotics has led to an emerging global challenge which is called antibiotic resistance. ...
Avian Pathogenic Escherichia coli is a serious infectious disease in the poultry industry. Owing to antibiotic resistance, prevention of this pathogen has been challenging. Consequently, an alternative strategy should be considered to control this infection. Antimicrobial peptides are a new and promising method which has recently been presented to the world. The current study was designed to identify a specific anti-Avian Pathogenic Escherichia coli peptide. To do so, 30 antimicrobial peptides were collected from the database, then the most important features of the peptide including antimicrobial probability, physicochemical parameters, solubility and hydrophobicity were accurately evaluated. After these analyses, the best antimicrobial peptides were identified and applied for investigation of molecular docking between these peptides and fimH protein of Avian Pathogenic Escherichia coli. The results of this study revealed that among 30 antimicrobial peptides, only 6 peptides including Cecropin-A, Latarcin-1, Stomoxyn, Manduca Sexta Morici, Moricin and Latarcin-2a could successfully pass all analyses. Finally, the molecular docking results showed that among remained peptides, Manduca Sexta Morici using 17 hydrogen bonds could strongly block the fimH protein. According to these results, it seems that Manduca Sexta Morici can be experimentally applied to prevent Avian Pathogenic Escherichia coli.
... A primary concern of antibiotic use in COPD, is the emergence and propagation of antimicrobial resistance (AMR). AMR can be defined according to microbiological or clinical resistance, but is considered here to denote any reduction in susceptibility in a bacterial strain compared to the susceptible wildtype [10,11]. AMR is recognised as a global threat and an NHS and UK government priority to reduce [12][13][14]. ...
A concern of antibiotic use in chronic obstructive pulmonary disease (COPD) is the emergence and propagation of antimicrobial resistance (AMR). A systematic review was conducted to determine prevalence, pattern, risk factors and consequences of AMR in COPD. Bibliographic databases were searched from inception to November 2020, with no language restrictions, including studies of any design that included patients with COPD and reported prevalence and pattern of AMR. 2748 unique titles and abstracts were identified, of which 63 articles, comprising 26,387 patients, met inclusion criteria. Forty-four (69.8%) studies were performed during acute exacerbation. The median prevalence of AMR ranged from 0–100% for Pseudomonas aeruginosa, Moraxella catarrhalis, Klebsiella pneumoniae and Acinetobacter baumannii. Median resistance rates of H influenzae and S pneumoniae were lower by comparison, with maximum rates ≤40% and ≤46%, respectively, and higher for Staphylococcus aureus. There was a trend towards higher rates of AMR in patients with poorer lung function and greater incidence of previous antibiotic exposure and hospitalisation. The impact of AMR on mortality was unclear. Data regarding antimicrobial susceptibility testing techniques and the impact of other risk factors or consequences of AMR were variable or not reported. This is the first review to systematically unify data regarding AMR in COPD. AMR is relatively common and strategies to optimise antibiotic use could be valuable to prevent the currently under-investigated potential adverse consequences of AMR.
Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.2000957 .
... These changes are due to bacterial evolution, horizontal gene transfer, and by mutations, and therefore threaten the single greatest therapeutic advance in the history of medicine (Bankevich et al., 2012). Antibiotic resistance is achieved by changes in the phenotypic and/or genotypic characteristics of bacteria, and can be classified according to its origin and mechanisms (Davison et al., 2000). Antibiotic resistance is an increasing threat for humankind since it increases mortality rates and the length of hospital stays for people infected with multi-drug-resistant (MDR) bacteria (Heffernan et al., 2018). ...
Anti-bacterial agents are divided into disinfectants and antibiotics. Disinfectants are mainly used for cleaning and disinfection, and antibiotics are used as drugs for animal and human consumption. Antibiotics can either stop bacterial growth or kill bacteria, being bacteriostatic or bactericidal. Anti-bacterial agents are highly specific and disrupt essential processes for dividing bacterial populations, including cell wall synthesis and their membranes, protein synthesis, nucleic acid synthesis, and metabolic processes. In this article, the main available antibiotics are grouped according to their mechanisms of action, and their antibacterial spectrum, the infections in which they are used, and known resistant mechanisms against them are discussed. In addition, the last section discusses the development and characteristics of the most promising novel anti-bacterial agents.
... In addition to being used for the treatment of infections in human patients and farm animals, antibiotics are also routinely given to healthy farm animals to promote growth and proactively prevent disease outbreaks. Antibiotic resistance (AR) is the ability of bacteria to overcome and resist exposure to antibiotic substances, this is made possible by the acquisition of antibiotic resistance genes (ARGs) (Davison et al., 2000;Wright, 2010). Extensive use of antibiotics since the successful purification and mass production of penicillin in the middle of the twentieth century until today has led to an increase in antibiotic resistance, compromising the effectiveness of antibiotics (Davies and Davies, 2010). ...
This paper reviews current knowledge on sources, spread and removal mechanisms of antibiotic resistance genes (ARGs) in microbial communities of wastewaters, treatment plants and downstream recipients. Antibiotic is the most important tool to cure bacterial infections in humans and animals. The over- and misuse of antibiotics have played a major role in the development, spread, and prevalence of antibiotic resistance (AR) in the microbiomes of humans and animals, and microbial ecosystems worldwide. AR can be transferred and spread amongst bacteria via intra- and interspecies horizontal gene transfer (HGT). Wastewater treatment plants (WWTPs) receive wastewater containing an enormous variety of pollutants, including antibiotics, and chemicals from different sources. They contain large and diverse communities of microorganisms and provide a favorable environment for the spread and reproduction of AR. Existing WWTPs are not designed to remove micropollutants, antibiotic resistant bacteria (ARB) and ARGs, which therefore remain present in the effluent. Studies have shown that raw and treated wastewaters carry a higher amount of ARB in comparison to surface water, and such reports have led to further studies on more advanced treatment processes. This review summarizes what is known about AR removal efficiencies of different wastewater treatment methods, and it shows the variations among different methods. Results vary, but the trend is that conventional activated sludge treatment, with aerobic and/or anaerobic reactors alone or in series, followed by advanced post treatment methods like UV, ozonation, and oxidation removes considerably more ARGs and ARB than activated sludge treatment alone. In addition to AR levels in treated wastewater, it examines AR levels in biosolids, settled by-product from wastewater treatment, and discusses AR removal efficiency of different biosolids treatment procedures. Finally, it puts forward key-points and suggestions for dealing with and preventing further increase of AR in WWTPs and other aquatic environments, together with a discussion on the use of mathematical models to quantify and simulate the spread of ARGs in WWTPs. Mathematical models already play a role in the analysis and development of WWTPs, but they do not consider AR and challenges remain before models can be used to reliably study the dynamics and reduction of AR in such systems.
... The processes by which these resistance mechanisms appear are different (single point mutations or acquisition of mobile genetic elements), and they strongly influence the frequency of emergence of resistant bacteria (Peterson & Kaur, 2018). For example, resistance to quinolones can be acquired via a low number of single mutations whose frequency of appearance depends on the antibiotic concentration (Harmand et al., 2017, 2018 Antibiotic resistance is often associated with reduced bacterial fitness in environments where antibiotics aren't in use (Davison et al., 2000). Depending on species, population structure, molecular mechanisms targeted, genetic background and environment, fitness costs range from several percent up to as much as 400%. ...
The increase in frequency of multidrug resistant bacteria worldwide is largely the result of the massive use of antibiotics in the second half of the 20th century. These relatively recent changes in human societies revealed the great evolutionary capacities of bacteria towards drug resistance. In this article, we hypothesize that the success of future antibacterial strategies lies in taking into account both these evolutionary processes and the way human activities influence them. Faced with the increasing prevalence of multidrug resistant bacteria and the scarcity of new antibacterial chemical molecules, the use of bacteriophages is considered as a complementary and/or alternative therapy. After presenting the evolutionary capacities of bacteriophages and bacteria, we show how the development model currently envisaged (based on the classification of bacteriophages as medicinal products similar to antibacterial chemical molecules) ignores the evolutionary processes inherent in bacteriophage therapy. This categorization imposes to bacteriophage therapy a specific conception of what a treatment and a therapeutic scheme should be as well as its mode of production and prescription. We argue that a new development model is needed that would allow the use of therapeutic bacteriophages fully adapted (after in vitro “bacteriophage training”) to the etiologic bacteria and/or aimed at rendering bacteria either avirulent or antibiotic‐susceptible (“bacteriophage steering”). To not repeat the mistakes made with antibiotics, we must now think about and learn from the ways in which the materialities of microbes (e.g. evolutionary capacities of both bacteriophages and bacteria) are intertwined with those of societies.
... En d'autres termes, c'est l'augmentation de la zone d'inhibition obtenue pour une céphalosporine en présence d'acide clavulanique, par rapport à la zone d'inhibition d'une céphalosporine seule, qui indique la présence d'une BLSE. Un test de synergie positif donne donc une image caractéristique, en «bouchon de Champagne» (effet potentialisateur de l'acide clavulanique) (Davison et al., 2000). La figure 2 présente la disposition des antibiotiques sur le milieu Muller Hinton. ...
La prise d’antibiotiques mal conservés et le non-respect de leur posologie et diverses contaminations peuvent être à l’origine de la résistance bactérienne. L’objectif de cette étude est d’évaluer le portage digestif des bêtalactamases à spectre élargi chez les patients de l’hôpital de la CNPS (Caisse Nationale de Prévoyance Sociale) de Maroua au Cameroun. Les bactéries du tube digestif ont été cultivées sur gélose Müller Hinton contenant des disques de céphalosporine de 3ème génération (céftriaxone) et incubés à 37°C pendant 18 à 24 heures. Les bactéries résistantes ont ensuite été retenues, caractérisées et identifiées par utilisation des galeries API 20E. Les souches productrices de bêta-lactamases à spectre élargi ont ensuite été détectées par la technique de double synergie. Les résultats ont révélé que parmi les patients reçus, la tranche d’âge de 20-30 ans était la plus représentée et 93% des patients avaient déjà pris des antibiotiques. Les bactéries telles que : Erwingella americana, Pantoea ssp, Serratia fumitica; Providenécia stuartii, Salmonella spp, Kluyvera spp, Cedecea spp, Klebsiella ozaenae, Vibrio cholerae et Pseudomonas spp ont été identifiées. Une forte résistance des souches identifiées a été observée vis-à-vis des antibiotiques suivants : l’amoxicilline (88,22%), le céftriaxone (88,22%), l’amoxicilline/acide clavulanique (82,35%), le céftaxidime (76,47%) et le céfotaxime (70,59%). Dans l’ensemble, la prévalence des Bêta-lactamases à spectre élargi est très élevée parmi les malades fréquentant l’hôpital de la CNPS de Maroua (Cameroun).
... Antimicrobial activities of the synthesized binary nicotine complexes are given in Table 3. Antimicrobial activity of the complexes follows the order: Zinc > nickel > copper > magnesium > molybdenum > aluminum > vanadium > mercury > bismuth. It is worthwhile to diagnose the efficacy of molybdenum nicotine complex by determining the MIC (minimum inhibitory concentration) which is the lowest concentration of an antimicrobial agent that is able to inhibit the visible growth of a microorganism after overnight incubation [44]. In this work, minimum compound concentrations that inhibited 50% (MIC 50 ) and 90% (MIC 90 ) of the bacteria were determined. ...
A number of some main group and transition metal nicotine complexes were synthesized and fully characterized using detailed structural and spectroscopic analysis techniques such as elemental analysis, molar conductivities, magnetic susceptibilities, IR, Raman and NMR techniques. Moreover, scanning electron micrographs and thermogravimetric analyses were also done. Cytotoxic activities of the binary nicotine metal complexes were tested and evaluated against HepG2 (human hepatocellular carcinoma), HPC3 (human prostate cancer), and HCT116 (human colorectal carcinoma) tumor cell lines. The antioxidant activities were examined by free radical scavenging assay. The antimicrobial activities of the synthesized complexes were evaluated against Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive) microbes. The relationship between the chemical structure of the synthesized complexes and their biological influence as antimicrobial drugs was studied and evaluated. KEY WORDS: Nicotine metal complexes, Cytotoxicity, Antioxidant, Antimicrobial Bull. Chem. Soc. Ethiop. 2020, 34(3), 501-521. DOI: https://dx.doi.org/10.4314/bcse.v34i3.7
... Antibiotic resistance occurs when bacteria evolve to protect themselves from antimicrobial agents; it occurs when bacteria changes in response to the utilization of antibiotics. Antibiotic resistance implies that the bacteria's causing certain infections no longer respond to that specific antibiotic [7][8][9], leading the infectious ailment to continue untreated while, prolonging the morbidity status of the patient. ...
Background
The global increase in the utilization of non - prescribed antibiotics (NPA), is concerning, with high persistence within the low and middle-income countries (LMICs). With a negative impact on the health of individuals and communities the use of NPA paves the way to the propagation of superbugs that potentially predisposes to changes in bacterial resistance patterns, antibiotic resistance (AR) and antimicrobial resistance (AMR). This study aimed at estimating through a systematic review and meta-analysis, the prevalence of NPA utilisation and describe its primary sources in LMICs.
Methods
The study is a systematic review and meta-analysis which study protocol was registered in PROSPERO (CRD42017072954). The review used The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The studies searched in databases were deemed eligible if reported evidence of practices of self-medication with antibiotics (SMA) and the prevalence of NPA utilisation within adult participants from LMICs, published between 2007 to 2017. The pooled analyses were carried out using Meta XL statistical software. The pooled prevalence was calculated with a 95% confidence interval (CI). The risk of bias of the included studies was assessed using the Quality in Prognosis Studies (QUIPS) tool.
Results
The review included a total of 11 cross-sectional studies, involving 5080 participants and conducted in LMICs from Asia (India, Laos, Nepal, Pakistan, Sri Lanka and Yemen), Latin America (Guatemala), Africa (Nigeria). All studies reported existing practices of SMA, with reported prevalence ranging from 50% to 93,8%. The pooled prevalence of SMA was 78% (95% CI: 65–89%). The main sources of NPA were; pharmacies, family and friends, old prescriptions, home cabinet and leftover antibiotics.
Conclusion
This study revealed a high prevalence of utilisation of NPA in the studied LMICs, these were found to be twice as high in women than men and those participants aged between 18 and 40 years old. The review suggests f considering broader qualitative and comprehensive contextuallized research to better understand the nuances of NPA use. These would be benefitial to uncover uncover gray areas, inform decisions, support the (re) design and implementation of multifaceted interventions towards antibiotic stewardship and conservancy in LMICs.
... L'antibiorésistance est définie comme la capacité d'une bactérie usuellement sensible à un antibiotique à acquérir une résistance partielle ou totale à cet anti-infectieux. La conséquence de cette résistance est de rendre partiellement ou complètement inefficace l'utilisation de l'antibiotique pour l'usage médical dans le cadre d'une infection bactérienne [1,2]. Par la suite, nous utiliserons indifféremment les termes « antibiorésistance » et « résistance » pour décrire ce phénomène. ...
La résistance aux antibiotiques est considérée comme une menace majeure pour la santé publique mondiale. Le traitement des infections à germe résistant est plus difficile et conduit à des modifications de l’organisation des soins avec une augmentation des durées de séjour, de la morbidité et de la mortalité. L’évaluation du poids économique de la résistance aux antibiotiques pourrait éclairer les décideurs sur les priorités d’action à mener en termes de prévention, de recherche et de prise en charge. L’objectif général de cette thèse est d’évaluer l’impact économique de la résistance aux antibiotiques à partir des données du Système National des Données de Santé (SNDS). L’utilisation du SNDS permet d’identifier de façon exhaustive les patients hospitalisés atteints d’une infection bactérienne, suivis ou non par les professionnels libéraux ou en structure adaptée. Le suivi des séjours hospitaliers avec les consultations en médecine de ville rend possible la reconstitution des parcours de soins et les coûts qui y sont associés. La population étudiée concerne l’ensemble des patients hospitalisés présentant une infection bactérienne aiguë (regroupé en 13 sites infectieux). Dans un premier travail, nous nous sommes intéressés au coût hospitalier, du point de vue du payeur. Une étude cas-témoins appariés a permis d’estimer un surcoût hospitalier attribuable à la résistance de 110 millions € en 2015 et une extrapolation conduit à un surcoût de 290 millions €. Dans un second temps, nous nous sommes concentrés sur les conséquences à 12 mois d’une hospitalisation à germe résistant aux travers de quatre études : (1) Pour les patients ayant eu une infection à germe résistant, une analyse de séquence a permis d’identifier cinq parcours hospitaliers types. Les parcours hospitaliers les plus longs étaient observés suite à une infection ostéo-articulaire et une mortalité élevée concernait principalement les infections du cœur et du médiastin ou des voies respiratoires basses ; (2) La dépense ambulatoire étudiée par une approche de double différence, a montré que la surconsommation attribuable à la résistance aux antibiotiques était faible et limitée au premier mois qui suit une hospitalisation ; (3) La consommation de ressources hospitalières mesurée par la durée d’hospitalisations (en jours) attribuable à l’antibiorésistance est augmentée pour deux secteurs : en séjours hospitaliers en soins de courte durée pour infection et en hospitalisation à domicile ; (4) le surcoût hospitalier attribuable à la résistance aux antibiotiques l’année qui suit l’hospitalisation initiale a été estimé à 618 € [IC95% 419 ; 817] par patient. À travers 5 indicateurs économiques, cette thèse a mise en évidence que l’antibiorésistance provoque un coût substantiel pour l’assurance maladie.
... Early monitoring studies assessed antimicrobial resistance (AMR) at the isolate level by determining the percentage of resistant strains within a given collection (Moreno et al., 2007). The isolate level approach overlooked the role of the host and was deemed inadequate to detect emerging or latent AMR types, shifting the focus of investigations at the sample (host) level (i.e. percentage of samples colonised with resistant bacteria) with the use of antibiotic supplemented (hereafter selective) media (Davison et al., 2000;Moreno et al., 2007). However, surveillance programs, such as EFSA's annual AMR monitoring (EFSA/ECDC, 2018), combine both https://doi.org/10.1016/j.vetmic.2019.108536 ...
Presence of extended-spectrum β-lactamase (ESBL)- and AmpC β-lactamase (pAmpC)-producing Escherichia coli (ESBL/pAmpC-EC) in humans and animals is alarming due to the associated risks of antibiotic therapy failure. ESBL/pAmpC-EC transmission between the human and animal compartments remains controversial. Using cefotaxime-supplemented (selective) media, we recently showed high sample prevalence of ESBL/pAmpC-EC in an integrated broiler chain [i.e. Parent Stock (PS), offspring broilers and their carcasses]. Here, we used a different approach. In parallel with the selective isolation, samples were processed on non-selective media. E. coli isolates were tested for ESBL/pAmpC-production and those found positive were genotyped. For carcasses, total E. coli were enumerated. This approach enabled us to estimate prevalence at the isolate level, which mirrors ESBL/pAmpC-EC colonisation levels. We showed that although present in many animals, ESBL/pAmpC-EC were overall subdominant to intestinal E. coli, indicating that high sample prevalence is not associated with high levels of resistance in individual hosts. This is a relevant aspect for risk assessments, especially regarding the immediate exposure of farm personnel. An exception was a particularly dominant B2/blaCMY-2 lineage in the gut of imported PS chicks. This predominance obscured presence of latent genotypes, however bias towards particular ESBL/pAmpC-EC genotypes from the selective method or underestimation by the non-selective approach did not occur. At the slaughterhouse, we showed a link between total E. coli and ESBL/pAmpC-EC on carcasses. Mitigation strategies for reducing consumers’ exposure should aim at suppressing ESBL/pAmpC-EC in the broiler gut as well as controlling critical points in the processing line.
... Antimicrobial resistance is defined as by Davison et al. (2000); a property of bacteria that confers the capacity to inactivate or exclude antibiotics, or a mechanism that blocks the inhibitory or killing effects of antibiotics. 1. ...
Background: Antimicrobials revolutionized human as well as animal medicine in the 20th century by providing effective treatment of diseases caused by pathogenic microorganisms. However, microorganisms have the ability to develop antimicrobial resistant strains. This occurs when microorganisms mutate or when resistance genes are exchanged between them. The use of antimicrobial drugs accelerates the emergence of drug-resistant strains. A priority is to safeguard the efficacy of antimicrobial drugs we depend on for treatment of infectious diseases in humans. Use of antimicrobials in food animals can create a source of antimicrobial resistant bacteria that can spread to humans both by direct contact and through the food supply. Coccidiosis is an intestinal disease in animals caused by unicellular parasites called coccidia. As most of the damage of this infection is done by the time signs of the disease are widespread, preventive measures are preferred. Coccidiostats are animal feed additives used to prevent coccidiosis by inhibiting or killing coccidia. There are two major groups of coccidiostats; ionophores and non-ionophores, the latter also referred to as “non-ionophore coccidiostats” (but also called chemicals). One main difference between these groups is that ionophores also inhibit or kill some bacterial species, whereas non-ionophore coccidiostats do not. Consequently, some bacterial infections may also be controlled by ionophore coccidiostats, e.g. the poultry disease necrotic enteritis caused by the bacterium Clostridium perfringens (C. perfringens). Eleven different coccidiostats have been authorised for use in the EU, both ionophores and non-ionophore coccidiostats. Norway has been exempted from the EEA Agreement in this field and has approved only five; all ionophores. The two ionophore coccidiostats currently used in Norway are narasin for broilers and monensin for turkeys. Resistance to coccidiostats in coccidia and bacteria: Development of resistance in coccidia to all eleven coccidiostats has been described in the scientific literature, but the prevalence of resistance is unknown. Cross-resistance between various ionophore coccidiostats has also been shown, i.e. development of resistance to one ionophore may also render the coccidia resistant to another ionophore. Various rotation and shuttle programmes with exchange between ionophores and non-ionophore coccidiostats are believed to prevent or delay development of resistance in coccidia. In Norway, such programmes will have little effect as long as only ionophores and not non-ionophore coccidiostats are approved for use. Development of resistance against ionophores has also been observed in bacteria. In the Norwegian surveillance programme NORM-VET during the years 2002 - 2013, between 50 - 80% of the tested flocks had narasin resistant faecal enterococci, which are bacteria that are part of the normal intestinal microbiota. However, the pathogenic bacterium C. perfringens has not been shown to be resistant against any ionophore. Cross-resistance in bacteria to more than one ionophore has been observed. In addition, a limited amount of data may indicate an association between narasin and resistance to the antibacterials bacitracin and vancomycin. As these are antibacterials used for treatment in humans, more research should be performed to validate these results. Non-ionophore coccidiostats, which do not have antibacterial effect, are not approved in Norway. If such coccidiostats were approved in Norway, coccidiostats with negligible probability of inducing resistance in bacteria would be available. Human exposure to resistant bacteria and coccidiostats: Humans may theoretically be exposed to coccidiostat resistant bacteria from poultry in a number of ways, e.g. by handling live animals and their manure, through slaughtering and processing, and by preparation and consumption of poultry meat. Furthermore, bacteria of the human normal microbiota, which cover all skin and mucosal surfaces, might develop resistance if they are exposed to coccidiostats. In this assessment, the probabilities of exposure are classified as: Negligible (extremely low), Low (possible, but not likely), Medium (likely), High (almost certain) and Not assessable. The Panel has estimated the following probabilities of human exposure: Handling manure from coccidiostat fed poultry without sufficient risk-reducing measures entails a high probability of exposure to both resistant bacteria and coccidiostats. Without proper protection, the probability of exposure to coccidiostats is also high when handling coccidiostat premixes and feeds containing coccidiostats without proper protection measures. Various treatments, e.g. composting, of the manure may reduce the probability. The probability of exposure to resistant bacteria is medium for workers handling carcasses and raw meat on a daily basis if risk-reducing measures are not applied, whereas the probability of exposure to coccidiostats is negligible. For consumers, the probability of exposure to coccidiostats is negligible. The probability for exposure to resistant bacteria is also negligible in heat treated food since heat treatment kills the bacteria. The probability of exposure to coccidiostat resistant bacteria is low to medium if handling raw meat without proper hygienic procedures, because raw meat may harbour resistant bacteria. Risk-reducing measures will lower the probabilities. However, little is known concerning the consequences of human exposure to coccidiostat resistant bacteria or to to coccidiostats. There is little information in scientific literature indicating whether such bacteria in fact will colonize the human body, either transitionally or permanently. Furthermore, there is no information on the probability of exchange of resistance genes from transferred bacteria to bacteria of the human natural microbiota or to pathogens. Likewise, the Panel has no information on the level of exposure, e.g. the amount of coccidiostats and their metabolites, or the time period, necessary for the various bacteria to give rise to resistant variants. As coccidiostats are not used to treat infectious diseases in humans, concern of resistance is related to possible cross- or co-resistance with antibacterials considered important in human medicine. Such resistance has so far not been confirmed. Use of therapeutic antibacterials for poultry: If the ionophore coccidiostats used in Norway are replaced by one or more non-ionophore coccidiostat with no antibacterial effect and no other changes are done, the coccidiostats used will no longer inhibit the bacterium Clostridium perfringens, which is the cause of necrotic enteritis. Over time this will likely to lead to a need for intermittent or continuous use of higher levels of therapeutic antibacterials due to increased incidence of this desease in poultry production. The magnitude of the increase is difficult to predict. Alternatives to in-feed antimicrobials: Eradication from the birds’ environment of coccidia causing coccidiosis is difficult to achieve because the coccidia form oocysts that survive outside the host and resist commonly used disinfectants. Vaccination with non-pathogenic vaccines is now used increasingly in commercial Norwegian broiler farms, instead of in-feed coccidiostats. So far coccidiosis has not been reported as a problem in this transition process to broiler rearing without in-feed coccidiostats in Norway. Non-antimicrobial feed additives with purported health-promoting benefits, i.e. acid-based products, probiotics, prebiotics, synbiotics, yeast-based products, plant-derived products, combinations of these, and other products have been developed and used in feed. These products have been tested for efficacy against coccidia with conflicting, non-consistent or non-convincing results. The majority of these products appear to target the bacterial microbiota rather than coccidia. The Panel has not assessed possible effects of other types of management changes.
... This research examines how AMR data are based on and are shaped by established and emerging work practices in the context of surveillance in Country A. The study positions Data associated with AMR as a key object within surveillance activity. These Data include, phenotypic data (growth patterns) or genotypic (presence and expression of genes) characteristics of bacteria categorized according to origin (intrinsic vs. acquired resistance) or type (single, multiple, or cross-resistance) (Davison et al., 2000). Data serve as a focal point for lab activity and for interactions across distributed teams of health professionals working within the public health system. ...
Changing work practice is critical when addressing global challenges. The expansion of work is mediated by a range of tensions inherent in the complex systems within which global challenges exist. This study examines tensions that inhibit the expansion of work practices contextualized within the global health challenge of Antimicrobial Resistance (AMR). The study traces how an AMR surveillance system is being set up in a low-to-middle-income country in Asia (Country A). The research identifies a range of tensions that need to be considered when designing technology-enhanced learning interventions for professionals. This study is significant in moving technology-enhanced learning toward a wholistic approach that takes into account the work environment. This research takes an original standpoint by placing attention on specific work practices, then examining how technology-supported activities can build capacity. This places professionals at the center of a critical approach examining the ways technologies can add value to their professional lives. This work highlights the importance of professionals' “voice” as a lens through which researchers document their reality. The study calls for a fundamental shift in the orientation of technology-enhanced learning interventions, moving attention toward work practice and mapping supporting technologies around this, rather than focusing primarily on the technology and planning learning activity with technology tools.
... Antimicrobial resistance is defined as (Davison et al., 2000): ...
... Antimicrobial resistance is defined as (Davison et al., 2000): ...
... Contamination due to bacteria in hospitals are related directly or indirectly to the use of antibiotics in improper way by number of patients, and when the use of disinfectants ate at low concentrations comparing to the recommended one for purpose of cleaning in different hospitals in both developing and developed countries [5] . This improper use of disinfectants creates opportunities of new stains bacteria appearance that resist to current used antibiotics [6] . ...
Antimicrobial resistance (AMR) is one of the Global Health challenges of the 21st century. The inclusion of AMR on the global map parallels the scientific, technological, and organizational progress of the healthcare system and the socioeconomic changes of the last 100 years. Available knowledge about AMR has mostly come from large healthcare institutions in high-income countries and is scattered in studies across various fields, focused on patient safety (infectious diseases), transmission pathways and pathogen reservoirs (molecular epidemiology), the extent of the problem at a population level (public health), their management and cost (health economics), cultural issues (community psychology), and events associated with historical periods (history of science). However, there is little dialogue between the aspects that facilitate the development, spread, and evolution of AMR and various stakeholders (patients, clinicians, public health professionals, scientists, economic sectors, and funding agencies). This study consists of four complementary sections. The first reviews the socioeconomic factors that have contributed to building the current Global Healthcare system, the scientific framework in which AMR has traditionally been approached in such a system, and the novel scientific and organizational challenges of approaching AMR in the fourth globalization scenario. The second discusses the need to reframe AMR in the current public health and global health contexts. Given that the implementation of policies and guidelines are greatly influenced by AMR information from surveillance systems, in the third section, we review the unit of analysis (“the what” and “the who”) and the indicators (the “operational units of surveillance”) used in AMR and discuss the factors that affect the validity, reliability, and comparability of the information to be applied in various healthcare (primary, secondary, and tertiary), demographic, and economic contexts (local, regional, global, and inter-sectorial levels). Finally, we discuss the disparities and similarities between distinct stakeholders’ objectives and the gaps and challenges of combatting AMR at various levels. In summary, this is a comprehensive but not exhaustive revision of the known unknowns about how to analyze the heterogeneities of hosts, microbes, and hospital patches, the role of surrounding ecosystems, and the challenges they represent for surveillance, antimicrobial stewardship, and infection control programs, which are the traditional cornerstones for controlling AMR in human health.
Findings of conducted study showed that the predominant bacteria in Jimma University Veterinary Clinic. Among predominant bacteria identified includes; Escherichia coli 46 (34.3%), Klebsiella 23(17.2%), followed by Staphylococcus aureus 40(29.9%) and Streptococcus spp 25(18.7%). Among 4 species of bacteria isolated, 2 were gram negative and 2 of them was gram positive bacteria. Among the antibiotic susceptibility test, Staphylococcus aureus showed the total resistant on penicillin while tetracycline showed to have the highest sensitivity. Escherichia coli showed the total resistant on gentamicin (100%). Veterinary Clinic is at risk of acquiring bacterial infections due to the presence of mentioned bacteria during this study. The big issue is that these infections resist to antibiotics used in treatment according to results of the study. Health care workers in Veterinary Clinic should improve hygiene to control clinic acquired infections and much attention should be done during diagnosis to improve treatment of patients.
Resultado de anos de pesquisa e extensão na área de piscicultura, Protocolos para diagnóstico de doenças em peixes apresenta ferramentas para estudantes e pesquisadores da aquicultura que tenham interesse em explorar cientificamente patógenos como bactérias e parasitos que causam grandes perdas em ambientes de criação comercial de peixes.
Given the availability of technological solutions and guidelines for safe drinking water, direct potable reuse of reclaimed water has become a promising option to overcome severe lack of potable water in arid regions. However, the growing awareness of the presence of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARG) in corresponding raw wastes has led to new safety concerns. This study investigated the fate of ARB and intracellular and extracellular ARG after each treatment step of an advanced water treatment facility in Windhoek, Namibia. The New Goreangab Water Reclamation Plant (NGWRP) produces drinking water from domestic secondary wastewater treatment plant effluent and directly provides for roughly a quarter of Windhoek's potable water demand. Procedures to study resistance determinants were based on both molecular biology and culture-based microbiological methods. TaqMan real-time PCR was employed to detect and quantify intracellular resistance genes sul1, ermB, vanA, nptII and nptIII as well as extracellular resistance gene sul1. The NGWRP reduced the amount of both culturable bacterial indicators as well as the resistance genes to levels below the limit of detection in the final product. The main ozonation and the ultrafiltration had the highest removal efficiencies on both resistance determinants. HIGHLIGHTS
The final product contained none of the antibiotic resistance genes investigated.;
A subsequent series of water treatment steps can decrease antibiotic resistance genes to below LOD.;
All steps in the treatment train decreased the abundance of the sul1 resistance gene except for the pre-ozonation and the biological activated carbon.;
In the final product, extracellular and intracellular sul1 resistance genes were below LOD.;
With the wide utilization of antibiotics, antibiotic‐resistant bacteria have been often developed more frequently to cause potential global catastrophic consequences. Emerging photothermal ablation has been attracting extensive research interest for quick/effective eradication of pathogenic bacteria from contaminated surroundings and infected body. In this field, anisotropic gold nanostructures with tunable size/morphologies have been demonstrated to exhibit their outstanding photothermal performance through strong plasmonic absorption of near‐infrared (NIR) light, efficient light to heat conversion, and easy surface modification for targeting bacteria. To this end, this review first introduces thermal treatment of infectious diseases followed by photothermal therapy via heat generation on NIR‐absorbing gold nanostructures. Then, the usual synthesis and spectral features of diversified gold nanostructures and composites are systematically overviewed with the emphasis on the importance of size, shape, and composition to achieve strong plasmonic absorption in NIR region. Further, the innovated photothermal applications of gold nanostructures are comprehensively demonstrated to combat against bacterial infections, and some constructive suggestions are also discussed to improve photothermal technologies for practical applications.
Multidrug resistant (MDR) Salmonella are a leading cause of foodborne diseases and serious human health concerns worldwide. In this study we detected MDR Salmonella in broiler chicken along with the resistance genes and class 1 integron gene intl1. A total of 100 samples were collected from broiler farms comprising 50 cloacal swabs, 35 litter and 15 feed samples. Overall prevalence of Salmonella was 35% with the highest detected in cloacal swabs. Among the Salmonella, 30 isolates were confirmed as S. enterica serovar Typhimurium using molecular methods of PCR. Disk diffusion susceptibility test revealed that all the Salmonella were classified as MDR with the highest resistance to tetracycline (97.14%), chloramphenicol (94.28%), ampicillin (82.85%) and streptomycin (77.14%). The most prevalent resistance genotypes were tetA (97.14%), floR (94.28%), blaTEM-1 (82.85%) and aadA1 (77.14%). In addition, among the MDR Salmonella, 20% were positive for class 1 integron gene (intl1). As far as we know, this is the first study describing the molecular basis of antibiotic resistance in MDR Salmonella from broiler farms in Bangladesh. In addition to tetA, floR, blaTEM-1, aadA1 and intl1 were also detected in the isolated MDR Salmonella. The detection of MDR Salmonella in broiler chicken carrying intl1 is of serious public health concern because of their zoonotic nature and possibilities to enter into the food chain.
The genetic and biochemical basis of ampicillin resistance amongst the aerobic Gram-negative commensal faecal flora of healthy volunteers in South Africa has been determined. Amongst 608 ampicillin resistant strains isolated from 320 of the participants, 158 were able to transfer their ampicillin resistant determinants into Escheriehia coli K-12 J62–2. Iso-electric focusing of the β-lactamases, extracted from the transconjugants, demonstrated that ampicillin resistance resulted from the presence of the TEM-1, TEM-2 and SHV-1 β-lactamases in 94·3%, 2·5% and 3·2% of isolates respectively. Endonuclease restriction digests of the plasmids isolated from the transconjugants showed that the β-lactamase genes were present on a wide variety of plasmid types; 101 distinct plasmid endonuclease restriction patterns were identified. Transferable ampicillin resistance was associated with resistance to other antibiotics at the following frequencies: trimethoprim (48·7 %), streptomycin (35·4 %), tetracycline (27·2%), spectinomycin (9·5%), chloramphenicol (3·2%) and gentamicin (1·3%). One antibiotic resistance pattern, ampicillin and trimethoprim. predominated (28%). In total. 77·9% of the plasmids conferred resistance to other antibiotics raising the possibility that use of any of these agents, not simply ampicillin, may contribute to the maintenance of resistance genes.
Tetracycline resistance of fecal coliforms isolated from swine decreased from 82 to 42%, a decrease of less than 50%, after the use of all forms of antimicrobial agents were discontinued in the herd for 126 months.
Though numerous studies have shown that gene transfer occurs between distantly related bacterial genera under laboratory conditions, the frequency and breadth of horizontal transfer events in nature remain unknown. Previous evidence for natural intergeneric transfers came from studies of genes in human pathogens, bacteria that colonize the same host. We present evidence that natural transfer of a tetracycline resistance gene, tetQ, has occurred between bacterial genera that normally colonize different hosts. A DNA sequence comparative approach was taken to examine the extent of horizontal tetQ dissemination between species of Bacteroides, the predominant genus of the human colonic microflora, and between species of Bacteroides and of the distantly related genus Prevotella, a predominant genus of the microflora of the rumens and intestinal tracts of farm animals. Virtually identical tetQ sequences were found in a number of isolate pairs differing in taxonomy and geographic origin, indicating that extensive natural gene transmission has occurred. Among the exchange events indicated by the evidence was the very recent transfer of an allele of tetQ usually found in Prevotella spp. to a Bacteroides fragilis strain.
Supplementing animal feed with antimicrobial agents to enhance growth has been common practice for more than 30 years and is estimated to constitute more than half the total antimicrobial use worldwide. The potential public health consequences of this use have been debated; however, until recently, clear evidence of a health risk was not available. Accumulating evidence now indicates that the use of the glycopeptide avoparcin as a growth promoter has created in food animals a major reservoir of Enterococcus faecium, which contains the high level glycopeptide resistance determinant vanA, located on the Tn1546 transposon. Furthermore, glycopeptide-resistant strains, as well as resistance determinants, can be transmitted from animals to humans. Two antimicrobial classes expected to provide the future therapeutic options for treatment of infections with vancomycin-resistant enterococci have analogues among the growth promoters, and a huge animal reservoir of resistant E. faecium has already been created, posing a new public health problem.
Restriction patterns obtained with EcoRI and Southern hybridization were used for the differentiation of tetracycline-resistant (Tet(r)) R plasmids in enterobaemorrhagic Escherichia coli (EHEC) O157:H7 isolates from a mass outbreak at a kindergarten in Obihiro-City, Hokkaido, Japan, 1996. Two kinds of Tet(r) R plasmids of 50 and 95 kb were detected. The 50-kb plasmids were identical to each other, while the 93-kb plasmids were of three types that were very similar to each other. The tet genes of both 50- and 95-kb R plasmids were 100% identical to the tet gene of pSC101 and all plasmids hybridized to a probe for tet. Because food-origin O157 strains were sensitive to tetracycline, we concluded that such Tet(r) R-plasmids might transfer to drug-sensitive O157 strains in the infected individuals.
Resistance to antibiotics is an increasingly common problem in both veterinary and human medicine, and its management is the subject of urgent debate. Efforts to reduce this resistance are based on the assumption that it is maintained in bacterial populations as a result of exposure to antibiotics, and that restricting the use of antibiotics should therefore restrain the spread of resistance. But we have found that antibiotic resistance is prevalent in populations of wild rodents that have not been exposed to antibiotics, indicating that approaches to control it based on this assumption may be overoptimistic.
A multilaboratory study was undertaken to determine the accuracy of the current National Committee for Clinical Laboratory Standards (NCCLS) oxacillin breakpoints for broth microdilution and disk diffusion testing of coagulase-negative staphylococci (CoNS) by using a PCR assay for mecA as the reference method. Fifty well-characterized strains of CoNS were tested for oxacillin susceptibility by the NCCLS broth microdilution and disk diffusion procedures in 11 laboratories. In addition, organisms were inoculated onto a pair of commercially prepared oxacillin agar screen plates containing 6 microg of oxacillin per ml and 4% NaCl. The results of this study and of several other published reports suggest that, in order to reliably detect the presence of resistance mediated by mecA, the oxacillin MIC breakpoint for defining resistance in CoNS should be lowered from >/=4 to >/=0.5 microg/ml and the breakpoint for susceptibility should be lowered from </=2 to </=0.25 microg/ml. In addition, a single disk diffusion breakpoint of </=17 mm for resistance and >/=18 mm for susceptibility is suggested. Due to the poor sensitivity of the oxacillin agar screen plate for predicting resistance in this study, this test can no longer be recommended for use with CoNS. The proposed interpretive criteria for testing CoNS have been adopted by the NCCLS.
A general problem for microbiologists is determining the number of phenotypically similar colonies growing on an agar plate that must be analyzed in order to be confident of identifying all of the different strains present in the sample. If a specified number of colonies is picked from a plate on which the number of unique strains of bacteria is unknown, assigning a probability of correctly identifying all of the strains present on the plate is not a simple task. With Escherichia coli of avian cellulitis origin as a case study, a statistical model was designed that would delineate sample sizes for efficient and consistent identification of all the strains of phenotypically similar bacteria in a clinical sample. This model enables the microbiologist to calculate the probability that all of the strains contained within the sample are correctly identified and to generate probability-based sample sizes for colony identification. The probability of cellulitis lesions containing a single strain of E. coli was 95.4%. If one E. coli strain is observed out of three colonies randomly selected from a future agar plate, the probability is 98.8% that only one strain is on the plate. These results are specific for this cellulitis E. coli scenario. For systems in which the number of bacterial strains per sample is variable, this model provides a quantitative means by which sample sizes can be determined.
This chapter elaborates the concept of antibiotic resistance in bacteria. The development of antibiotic resistance can be viewed as a global problem in microbial genetic ecology. It is a very complex problem to contemplate, let alone solve, because of the geographic scale, the variety of environmental factors, and the enormous number and diversity of microbial participants. The ideal target for a chemotherapeutic agent is a constituent that is present in the target cell and not present in the host cell. The first antibiotics to be employed generally, the penicillin, targeted the synthesis of peptidoglycan, a component unique to the bacterial cell wall. Antibiotics have been found that inhibit the synthesis or interfere with the function of essentially all cellular macromolecules. Aminoglycosides, which are broad-spectrum antibiotics, are composed of three or more aminocyclitol units. They bind to the 30 S subunit and prevent the transition from the initiated complex to the elongation complex and they also interfere with the decoding process. The efflux proteins exchange a proton for a tetracycline–cation complex against a concentration gradient. The other major mechanism for tetracycline resistance is target protection. Ribosome protection is conferred by a 72.5-kDa cytoplasmic protein. Sequence analysis has shown regions with a high degree of homology to elongation factors, Tu and G.
Unlabelled:
1. Barrier effect. Relevant models should include an anaerobic dominant flora that antagonizes minor bacterial populations such as drug resistant E. coli. 2. Anaerobes vs. aerobes. Aerobe counts are more precise and much less time consuming than anaerobe counts. Minor populations of drug resistant aerobes are sensitive markers of the ecosystem balance, and are directly relevant to the potential risk of antimicrobial residues. 3. MIC vs. plate counts. The determination of minimum inhibitory concentrations (MIC) of selected clones in time consuming, does not detect subdominant resistance (less than 1%), and the MIC shift is difficult to test statistically. In contrast, direct counts of bacteria on drug supplemented media allows a rapid measure of minor resistant populations. 4.
Statistics:
Most published designs do not include adequate statistical evaluation. This is critical for trials made in conventional humans and animals, where data are highly variable. 5. Human trials: The lowest concentration of antibiotic tested in human volunteers (2 mg oxytetracycline/d for 7d in 6 subjects) significantly increased the proportion of resistant fecal enterobacteria (P = 0.05). However, the huge day-to-day and interindividual variations of human floras make this evidence rather weak. 6. Gnotobiotic mice inoculated with human flora are living isolated models in which the effect of any antimicrobial on the human gut flora can be tested. This in vivo model does include the barrier effect of dominant anaerobes. Interindividual and day-to-day variations of bacterial populations are lower in those mice than in humans. 7. Most resistant enterobacteria in the human gut of untreated people come from bacterial contamination of raw foods. The relative contribution of residues in selecting antibiotic resistance seems to be low when compared to bacterial contamination.
More than 250 coliform and noncoliform bacteria, isolated by standard membrane filtration methods from rural, untreated groundwater supplies, were examined for resistance to 16 antibiotics. All of the noncoliforms and 87% of the coliforms were resistant to at least one antibiotic, with resistance most commonly directed toward novobiocin, cephalothin, and ampicillin. The frequency of multiple antibiotic resistance (MAR) within each species was also determined. Approximately 60% of the coliforms were MAR, including 14, 64, and 94% of Escherichia coli, Citrobacter freundii, and Enterobacter cloacae isolates, respectively. In comparison, MAR was demonstrated by more than 95% of the noncoliforms and included isolates of Acinetobacter calcoaceticus, Aeromonas hydrophila, and Serratia marcescens. Ampicillin-resistant environmental isolates were assayed for ability to transfer resistance to ampicillin-sensitive strains of E. coli and Salmonella typhimurium. Environmental E. coli isolates were capable of in vitro transfer to both recipients in a nutrient-rich environment (trypticase soy broth) at frequencies ranging from 1.1 × 10−5 to 1.0 × 10−4. Isolates of C. freundii and Klebsiella pneumoniae exhibited resistance transfer to the E. coli recipient under similar conditions at reduced rates. None of the environmental isolates demonstrated transfer of ampicillin resistance when placed in an environment containing filter-sterilized well water. The presence of antibiotic resistant bacteria, and particularly MAR bacteria, in rural groundwater supplies used as drinking water sources may have important public health implications.
Treatment of food-producing animals with antimicrobial agents that are important in human therapy may present a public health risk by the transfer of resistant zoonotic pathogens from animals to humans. Resistant bacteria can diminish the effectiveness of antibiotics and demand the use of more expensive or less safe alternatives. In 1996, the Centers for Disease Control (CDC), United States Department of Agriculture (USDA), and Food and Drug Administration (FDA) established the National Antimicrobial Monitoring System to prospectively monitor changes in antimicrobial susceptibilities of zoonotic pathogens from human and animal clinical specimens, healthy farm animals, and carcasses of food-producing animals at slaughter plants. This article describes the development, implementation, and objectives of the monitoring system and presents initial data generated by the system.
The present paper reports on the antibiotic resistance of E. coli isolated from Danish piglets and calves in 1987-1988, and compares the results with similar investigations performed during the periods 1971-1972 and 1977-1978. Rectal swabs from 52 piglets and from 78 calves were examined. All the animals studied harboured resistant E. coli. This is a significant increase compared to the previously conducted investigations. The number of strains having three or more resistance markers did not differ significantly from the previous findings. The spectrum of resistance markers among Danish piglets and calves had increased through all three investigations and resistance to chloramphenicol was still found to be considerable 10 years after the withdrawal of chloramphenicol as a therapeutic drug for farm animals in Denmark in 1978. Certain resistance patterns (sulfonamide + streptomycin, sulfonamide + streptomycin + tetracycline, sulfonamide + streptomycin + tetracycline + ampicillin) were found to be shared by numerous strains, suggesting a genetic linkage of the resistance markers.
This study in 12 cancer treatment centres across the United States was designed to evaluate the potential for increased resistance
to amikacin with unrestricted use. An initial 3-month baseline period during which the use of amikacin was restricted and
that of tobramycin and gentamicin unrestricted was followed by a period of at least 12 months when amikacin was the primary
aminoglycoside. Resistance of Gram-negative bacilli to these aminoglycosides from hospitalized patients was monitored and
compared for the two periods. Amikacin usage increased from a mean of 20·1 to a mean of 83·9% of aminoglycoside patient-days.
A reduction in the use of tobramycin and gentamicin were observed with means of 66·1 and 10%, and 13·9 and 6·1%, respectively
for the two periods. Resistance to amikacin was 0·85% at baseline and 1·3% at end-point which was not clinically significant
(P = 0·614). Baseline resistance was 6·5 and 7·6%, while final resistance was 2·6 and 4·8%, respectively for tobramycin (P = 0·001) and gentamicin (P = 0·052).
Since 1982, when olaquindox was introduced as a pig-feed additive in the UK, about 12 commercial farms in Suffolk have been monitored annually to check for the possible emergence of resistance to olaquindox and chloramphenicol among the coliform flora of the pigs and their environment. In spite of the sampling variability and the impossibility of controlling the use of feed additives and management on the farms, the overall results obtained were consistent and, it is suggested, the method is widely applicable. A steady, albeit low, increasing incidence and level of resistance to olaquindox was recorded (1982-1984) on farms using it and, to a lesser degree, on neighbouring farms that did not. No significant increase in the level of chloramphenicol resistance was observed. Genetical studies on a selection of olaquindox-resistant isolates suggested that the genes determining resistance were likely to be borne on the chromosome.
The phenomenon of drug resistance among bacteria, particularly Escherichia coli, has been a major research interest of the University of Bristol's departments of microbiology and veterinary medicine during the past 15 years. Tens of thousands of E coli isolates from man and farm animals have been examined in studies of both the ecology of the species and the epidemiology of their resistance to therapeutic antibacterial agents. The principal findings obtained in these investigations are described.
The paper outlines some of the problems encountered in assessing the occurrence of antibiotic resistance in the normal flora of animals, using Escherichia coli as an example. Additional information is provided on the occurrence and mechanisms of resistance in Clostridium perfringens, Pasteurella haemolytica and Staphylococcus aureus, and some of the factors which may affect this resistance. The paper concludes with general considerations about the choice of organism, the sample size and the desirability of designing standard protocols.
TRANSFER of drug resistance among Enterobacteriaceae is mediated by cytoplasmic particles called R factors which seem to consist of a transfer factor (RTF) coupled to genes which determine the drug resisting capacity of the bacterial host2. Although the origin of the intact R factor is obscure3, there is some evidence4 that the transfer factors are widely distributed in the Enterobacteriaceae, and that they may on some occasions have picked up bacterial chromosome genes which determined drug resistance. Another possibility1 is that R factors arose in otherwise unrecognized plasmids during the course of mutations to a resistant form, but whatever mechanism is responsible, there is no doubt that R factors are selected and maintained by drugs in the environment4. The finding5 of transmissible drug resistance in a strain of Escherichia coli lyophilized in 1946 may indicate that R factors were already present in pre-antibiotic cultures. The purpose of this investigation was to determine the incidence of R factors in intestinal Gram-negative bacteria of wild animals and humans living in surroundings free of drugs.
It has been difficult to document the postulated sequence of events that begins with the selection of drug-resistant organisms in animals fed subtherapeutic amounts of antimicrobials and ends with clinically important infections in human beings. In early 1983 we identified 18 persons in four Midwestern states who were infected with Salmonella newport that was resistant to ampicillin, carbenicillin, and tetracycline and characterized by a 38-kilobase R plasmid. Twelve of these patients had been taking penicillin derivatives for medical problems other than diarrhea in the 24 to 48 hours before the onset of salmonellosis. Eleven patients were hospitalized for salmonellosis for an average of eight days, and one had a fatal nosocomial infection. We compared plasmid profiles of all human (six-state area) and animal (United States) S. newport isolates over an 18-month period and examined selected records of meat distribution. The results indicated that the patients had been infected before they took antimicrobials, by eating hamburger originating from South Dakota beef cattle fed subtherapeutic chlortetracycline for growth promotion. This study demonstrates that antimicrobial-resistant organisms of animal origin cause serious human illness, and emphasizes the need for more prudent use of antimicrobials in both human beings and animals.
Survival in the mouse and human intestine of Escherichia coli host-vector systems used and proposed for recombinant DNA technology was assessed. There was no detectable survival of severely disabled E. coli K12 strain X1776 in mice or in human subjects 24 hours after ingestion. The same strain bearing the plasmid pBR322, however, was recovered from human subjects for 4 days in amounts of six organisms for every million ingested. Nondisabled E. coli K12 strain X1666, with or without pBR322, survived in 10(4)-fold greater numbers and for 2 days longer, with better recovery of the plasmid-containing derivative. Although the plasmid-bearing strains were recovered for longer periods, no intestinal colonization was noted. Despite the presence of pBR322 for a maximum of 6 days in the human intestine, there was no evidence that it was transferred from either bacterial host to endogenous aerobic fecal bacteria.
Faecal samples collected from three populations of healthy adult volunteers (290 pigfarmers, 316 abattoir workers, 160 (sub)urban residents) living in the south of The Netherlands were analysed for the prevalence and degree of antibiotic resistance of Escherichia coli .
Significant differences in prevalence of resistance to amoxicillin, neomycin, oxytetracycline, sulfamethoxazole and trimethoprim were observed. The pig-farmers showed the highest percentages of resistance and the (sub)urban residents the lowest. In contrast no significant differences in high degrees of resistance were observed, except for neomycin.
Although both pigfarmers and abattoir workers have regular contact with pigs differences in prevalences of resistance were observed. However, because abattoir workers with intensive and less intensive pig(carcass) contact did not show significant differences, this is probably not the only important source of resistant E. coli in pigfarmers.
The high antibiotic use by pigfarmers (5%) and abattoir workers (8%) than by (sub)urban residents (0%) did not result in significantly different resistance percentages.
The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly
for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example,
resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target
for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur
much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as
close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only
in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin,
are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic
would be produced by rational design, rather than by the modification of a natural product.
The emergence of multidrug-resistant bacteria is a phenomenon of concern to the clinician and the pharmaceutical industry,
as it is the major cause of failure in the treatment of infectious diseases. The most common mechanism of resistance in pathogenic
bacteria to antibiotics of the aminoglycoside, beta-lactam (penicillins and cephalosporins), and chloramphenicol types involves
the enzymic inactivation of the antibiotic by hydrolysis or by formation of inactive derivatives. Such resistance determinants
most probably were acquired by pathogenic bacteria from a pool of resistance genes in other microbial genera, including antibiotic-producing
organisms. The resistance gene sequences were subsequently integrated by site-specific recombination into several classes
of naturally occurring gene expression cassettes (typically "integrons") and disseminated within the microbial population
by a variety of gene transfer mechanisms. Although bacterial conjugation once was believed to be restricted in host range,
it now appears that this mechanism of transfer permits genetic exchange between many different bacterial genera in nature.
The development of antibacterial agents has provided a means of treating bacterial diseases which were, previously, often fatal in both man and animal and thus represents one of the major advances of the 20th century. However, the efficacy of these agents is increasingly being compromised by the development of bacterial resistance to the drugs currently available for therapeutic use. Bacterial resistance can be combated in two ways. New drugs to which bacteria are susceptible can be developed and policies to contain the development and spread of resistance can be implemented. Both strategies require an understanding of the mechanisms of drug resistance, its epidemiology and the role of environmental factors in promoting resistance. Over the past thirty years our knowledge of bacterial resistance has increased dramatically mainly due to new technology that has become available. Bacteria are able to resist antibacterials by a variety of mechanisms: for example, altering the target to decrease susceptibility to the antibacterial, inactivating or destroying the drug, reducing drug transport into the cell or metabolic bypass. These drug resistance determinants are mediated via one of two distinct genetic mechanisms, a mutation in the bacterial chromosome or by a transmissible element; either a plasmid or a transposon. Significant differences exist between these two types of drug resistance as transmissible resistance, which is mainly plasmid-mediated, permits intraspecies and even interspecies transfer to occur. In contrast, chromosomal resistance can only be passed on to progeny. Transmissible antibacterial resistance is the major cause of concern as it can lead to the rapid spread of antibacterial resistance and has proven difficult, if not impossible, to eradicate. Furthermore, plasmids and transposons can code for multiple antibiotic resistance as well as virulence genes. Antibacterials for which transferable resistance has been identified include most commonly used antibacterials such as beta-lactams, aminoglycosides, macrolides, sulphonamides, tetracyclines, chloramphenicol and trimethoprim. One notable exception is the 4-quinolones for which plasmid-mediated resistance has yet to be identified.
For Salmonella typhimurium from humans in England and Wales, the incidence of multiple resistance more than doubled over the 8-year period 1981–8 and, over the next 2 years, increased by a further 7%. From 1981 to 1988 both resistance and multiple resistance also increased significantly in S. virchow and although multiple resistance did not increase over the next 2 years, the overall incidence of resistance has continued to rise. In 1990 the majority of S. typhimurium from cattle were multiply-resistant and the occurrence of such resistance has quadrupled since 1981. Multiple resistance has also increased in S. typhimurium from pigs and, to a lesser extent, from poultry. In contrast, multiple resistance has remained uncommon in the poultry-associated serotype S. enteritidis . For S. virchow , multiple resistance was common in a phage type frequently associated with poultry meat imported from France.
The continuing use of a range of different antimicrobials in calf husbandry has been an important factor in promoting the emergence of multiply-resistant strains of S. typhimurium in cattle. In contrast, multiple resistance has remained rare in those serotypes associated with poultry, where the use of such antimicrobials has been less intensive.
It is hoped that recent recommendations discouraging, in veterinary medicine, the prophylactic use of antibiotics with cross resistances to those used in human medicine will result in a reduction in the occurrence of multiresistant strains in food animals and subsequently in humans.
Since 1982, a national veterinary network has been involved in the monitoring of resistance to antimicrobial agents in the main pathogenic bacteria isolated from diseased cattle in France. It is based on 40 regional veterinary diagnostic laboratories and managed by a central reference laboratory (CNEVA Lyon). Highly standardized methods are used in the diagnostic laboratories. This network collects up-to-date information on antimicrobial resistance in veterinary isolates and gathers strains for specific studies on fastidious bacteria and for the analysis of mechanisms of resistance to antibiotics. Such a permanent survey is essential to establish a rational veterinary antibiotic policy. It could be connected to other compatible systems developed in other fields such as human medicine, food, and environment, to evaluate the importance of resistance and R-factors spread for public health. The limits and perspectives of this surveillance system are discussed.
Two treatments with praziquantel (PZQ) 40 mg/kg, 40 d apart, were given to individuals in a recently established (< 6 years) Schistosoma mansoni focus in the Senegal River Basin (SRB). Efficacy of treatment was evaluated 4 weeks after each treatment. Among 130 individuals who provided stool samples on days 0, 118 and 153 and were treated on days 85 and 125, 113 (87%) were infected with S. mansoni before treatment. The overall geometric mean faecal egg count of the infected individuals was 478 eggs/g. Four weeks after the first treatment (day 118), the overall cure rate was only 42.5% and the overall reduction in intensity of infection was 70.7%. However, 4 weeks after the second treatment (day 153), the overall cure rate rose to 76.1% and the overall reduction in intensity was 88.1%. The greatest increase in cure rate between the 2 treatments was in those individuals who were initially the most heavily infected (> 1000 eggs/g). There was no apparent difference in cure rate between younger (< 20 years) and older individuals (> 20 years). No evidence for the existence of a PZQ tolerant strain of S. mansoni was found. Two treatments of PZQ 40 mg/kg, 40 d apart, were sufficient to give an adequate cure rate and high reductions in the intensity of infection. As there was insufficient time for reinfection between treatment and follow-up to result in egg production, the low cure rate observed after one treatment was probably the result of a combination of high infection intensity and the maturation of pre-existing prepatents S. mansoni infections.
Although the qualitative aspects of antibiotic resistance are increasingly well understood, our understanding of the quantitative aspects has always lagged. Deficiency of understanding or of investigation affects the methods used to characterize the phenotypes of organisms from clinical sources, delays acquisition of knowledge of the importance of quantitative diversity in patient management, and introduces error into epidemiological studies of the prevalence of resistance. This, in turn, gives rise to a devaluation of the work done in diagnostic laboratories in relation to the technology of sensitivity testing, to the interpretation of their results for clinicians, including those used in clinical trials, and to the statistical analyses of resistance trends used inter alia as a guide to empirical antibiotic therapy and to test the efficacy of methods of control. There is a need to bring about a shift of opinion of those who provide funds, in relation to the role of clinical microbiologists and infectious diseases clinicians in defining and solving these problems.
The frequency of infections with multiply antibiotic-resistant gram-positive bacteria is increasing, and in some cases these
organisms remain susceptible only to the glycopeptides vancomycin and teicoplanin. The appearance of transferable high-level
glycopeptide resistance in enterococci— producing some strains that are now resistant to all available antibiotics—is thus
a cause for concern. The enterococci readily colonize the bowel, spread rapidly among hospital patients, and transfer their
antibiotic resistances widely among themselves and other gram-positive species. Glycopeptide resistance has not yet transferred
in vivo to other significant pathogens, but experimental transfer to Staphylococcus aureus has been achieved in vitro. The emergence of glycopeptideresistant enterococci has been encouraged by the increasing use
of aminoglycosides, cephalosporins, and quinolones for the treatment of infections due to gram-negative bacteria and glycopeptides
for infections due to staphylococci and Clostridium difficile. In Europe this antibiotic pressure has been aggravated by the use of the glycopeptide avoparcin in animal feeds. The enterococci
may now be poised to disseminate glycopeptide resistance among other more pathogenic gram-positive bacteria.
The objective of this study was to determine the most efficient means of sampling faeces of finisher pigs for accurate and precise farm-level estimates of antimicrobial resistance among faecal Escherichia coli. Resistance to tetracycline and gentamicin of 8250 isolates of E. coli from 55 finisher pigs on one farm was measured with a hydrophobic grid membrane filter method. The between-pig, within-pen component of variance in resistance was large (97.5%), while between-pen, within-room and between-room components were small (2.5% and 0%, respectively). Using these resistance data, the abilities of two sampling strategies to estimate prevalence were modelled with a Monte Carlo 'bootstrap' procedure. Compositing faecal samples from several pigs before testing produced unbiased and precise estimates of prevalence and is simpler technically than individual animal testing.
Food-borne salmonella infections have become a major problem in industrialized countries. The strain of Salmonella enterica serotype typhimurium known as definitive phage type 104 (DT104) is usually resistant to five drugs: ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline. An increasing proportion of DT104 isolates also have reduced susceptibility to fluoroquinolones.
The Danish salmonella surveillance program determines the phage types of all typhimurium strains from the food chain, and in the case of suspected outbreaks, five-drug-resistant strains are characterized by molecular methods. All patients infected with five-drug-resistant typhimurium are interviewed to obtain clinical and epidemiologic data. In 1998, an outbreak of salmonella occurred, in which the strain of typhimurium DT104 was new to Denmark. We investigated this outbreak and report here our findings.
Until 1997, DT104 infections made up less than 1 percent of all human salmonella infections. The strain isolated from patients in the first community outbreak of DT104 in Denmark, in 1998 was resistant to nalidixic acid and had reduced susceptibility to fluoroquinolones. The outbreak included 25 culture-confirmed cases. Eleven patients were hospitalized, and two died. The molecular epidemiology and data from patients indicated that the primary source was a Danish swine herd. Furthermore, the investigation suggested reduced clinical effectiveness of treatment with fluoroquinolones.
Our investigation of an outbreak of DT104 documented the spread of quinolone-resistant bacteria from food animals to humans; this spread was associated with infections that were difficult to treat. Because of the increase in quinolone resistance in salmonella, the use of fluoroquinolones in food animals should be restricted.