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Heatmap visualization of genes related to particular antibiotic classes found in each case through using ARG qPCR arrays. Resistance genes to fluoroquinolones, multidrug efflux pumps, aminoglycosides, glycopeptides, tetracyclines, beta-lactams, and macrolides were discovered. Color and numbers represent the range of abundance of genes found to inhibit antibiotic classes. Blue represents no detection and red the highest detection.
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Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously...
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Context 1
... genes were found to be associated with resistance to 6 antibiotic drug classes (fluoroquinolones, aminoglycosides, glycopeptides, tetracyclines, beta-lactams, and macrolides), or part of multidrug efflux pumps. In total, genes expressing resistance to macrolides were detected 65 times, beta-lactams 56 times, tetracycline 10 times, glycopeptide 4 times, aminoglycoside 3 times, multidrug efflux pumps twice, and fluoroquinolones once (Fig 4). Genes detected in the highest abundance were ermB and mefA. ...
Citations
... We used shotgun metagenomics to analyze our HWW samples, which has the advantage of quantifying thousands of genes from culturable as well as nonculturable taxa simultaneously. PCR-based approaches may have greater sensitivity to low-abundance ARGs due to targeted amplification (49), but they are limited in the ARGs able to be detected. For example, a study comparing culture-based approaches and metagenomic methods showed that the culture-based technique isolated bacteria from 104 out of 539 clinical samples and therefore, captured resistance against 8 antibiotic types in only 16.17% of the clinical samples. ...
India is one of the largest consumers and producers of antibiotics and a hot spot for the emergence and proliferation of antimicrobial resistance genes (ARGs). Indian hospital wastewater (HWW) accumulates ARGs from source hospitals and often merges with urban wastewater, with the potential for environmental and human contamination. Despite its putative clinical importance, there is a lack of high-resolution resistome profiling of Indian hospital wastewater, with most studies either relying on conventional PCR-biased techniques or being limited to one city. In this study, we comprehensively analyzed antibiotic resistomes of wastewater from six Indian hospitals distributed in rural and urban areas of northern India through shotgun metagenomics. Our study revealed the predominance of ARGs against aminoglycoside, macrolide, carbapenem, trimethoprim, and sulfonamide antibiotics in all the samples through both read-based analysis and assembly-based analysis. We detected the mobile colistin resistance gene mcr-5.1 for the first time in Indian hospital sewage. blaNDM-1 was present in 4 out of 6 samples and was carried by Pseudomonas aeruginosa in HWW-2, Klebsiella pneumoniae in HWW-4 and HWW-6, and Acinetobacter baumanii in HWW-5. Most ARGs were plasmid-mediated and hosted by Proteobacteria. We identified virulence factors and transposable elements flanking the ARGs, highlighting the role of horizontal gene transmission of ARGs. IMPORTANCE There is a paucity of research on detailed antibiotic resistome and microbiome diversity of Indian hospital wastewater. This study reports the predominance of clinically concerning ARGs such as the beta-lactamases blaNDM and blaOXA and the colistin resistance gene mcr and their association with the microbiome in six different Indian hospital wastewaters of both urban and rural origin. The abundance of plasmid-mediated ARGs and virulence factors calls for urgent AMR crisis management. The lack of proper wastewater management strategies meeting international standards and open drainage systems further complicates the problem of containing the ARGs at these hospitals. This metagenomic study presents the current AMR profile propagating in hospital settings in India and can be used as a reference for future surveillance and risk management of ARGs in Indian hospitals.
... Sequence libraries were barcoded using the Nextera kit, and run on the Illumina HiSeq2000 platform as previously described. 58 The resulting paired-end reads were cleaned by Trim Galore version 0.6.4 (https://www.bioinformatics.babraham.ac.uk/projects/trim_galore/). ...
As opposed to de novo mutation, β-lactam resistance in S. pneumoniae is often conferred via homologous recombination during horizontal gene transfer. We hypothesize that β-lactam resistance in pathogenic streptococci is restricted to naturally competent species via intra-/interspecies recombination due to in vivo fitness trade-offs of de novo penicillin-binding protein (PBP) mutations. We show that de novo mutant populations have abrogated invasive disease capacity and are difficult to evolve in vivo. Conversely, serially transformed recombinant strains efficiently integrate resistant oral streptococcal DNA, gain penicillin resistance and tolerance, and retain virulence in mice. Large-scale changes in pbp2X, pbp2B, and non-PBP-related genes occur in recombinant isolates. Our results indicate that horizontal transfer of β-lactam resistance engenders initially favorable or minimal cost changes in vivo compared with de novo mutation(s), underscoring the importance of recombination in the emergence of β-lactam resistance and suggesting why some pathogenic streptococci lacking innate competence remain universally susceptible.
... 6 Under usual conditions, normal flora do not pose a danger to the host, but recent studies have reported that these bacteria possessed or can extrinsically acquire some genes responsible for resistance to some antibiotics, which has sounded the alarm bell for this emergency and drew attention to the necessity of conducting susceptibility testing for them. [7][8][9] After tracing and extrapolating the study that focused on bacterial flora, it became clear to us that information on susceptibility patterns of these microorganisms is very limited, especially those that settle in the urinary tract. Therefore, this study was conducted to investigate the urinary flora in young, healthy females and to assess the antibiotic susceptibility of recovered bacteria. ...
It has been established that the urinary tract is not sterile; however, research related to the study of urinary bacteria is limited. This study aimed to investigate the frequency and patterns of resistance of normal urinary aerobic bacterial flora and clean catch midstream urine specimens collected from 120 young healthy females and cultured. Bacterial identification and antimicrobial susceptibility were performed using the Biomérieux VITEK® 2 automated system. Participants who had undergone antimicrobial treatment within one month were not included. The incidence of positive bacterial cultures was 54.2%, of which 21.5% were polymicrobial. Approximately 107 bacterial isolates that encompass 12 genera and 27 species that were predominated by gram-positive bacteria (72%) were cultivated. Staphylococcaceae (46.1%) and Enterobacteriaceae (17.8%) were the most frequent isolates among gram-positive and gram-negative bacteria, respectively, of which 36 species have been identified as β-lactamase producers. The top four frequently isolated bacteria were Micrococcus spp. (16%), Staphylococcus haemolyticus (13.2%), Staphylococcus aureus (10%), and Klebsiella pneumoniae (10%). Twenty-two bacterial species were subjected to antimicrobial susceptibility testing using broad- and narrow-spectrum antibiotics and antimicrobials, which showed the lowest susceptibility rate against gram-positive bacteria, followed by erythromycin and azithromycin. A lower antimicrobial susceptibility potential among gram-negative bacteria was observed against ampicillin, followed by piperacillin and cefotaxime. Our findings emphasize the importance of highlighting urine bacterial flora in studies, especially those related to susceptibility patterns, by employing more advanced culture methods as multiple drug-resistant bacteria were isolated.
... For instance, the human skin and airways contain an antibiotic resistome harboring genes such as tetracyclines, amphenicol, aminoglycoside, and macrolides (DeVries and Pritchard, 1955;Zammit et al., 2011). Also, in the same study, oral and urogenital antibiotic resistome was found to harbor tetracycline-and macrolide-resistant genes (Abia et al., 2018;Finley et al., 2013;Burcham et al., 2019). ...
The chapter describes about various sources of antibiotics, and antibiotic resistant bacteria in the environment.
... Antibiotic resistance is a well-recognized major threat to global public health. Many studies have surveyed antibiotic resistant bacterial strains or their corresponding genes in hotspots or reservoirs of antimicrobial resistance such as hospitals, waste-water treatment plants (WWTP), sewage systems, and animal feeding operations, where antibiotics are commonly found at high concentrations (Bengtsson-Palme et al., 2018;Burcham et al., 2019;Kraemer et al., 2019;Maestre-Carballa et al., 2019;Xiang et al., 2020). In particular, attempts have been made to correlate the concentration of antibiotics with the occurrence of antibiotic resistant bacterial strains or genes in these hotspots (Rodriguez-Mozaz et al., 2015;Pärnänen et al., 2019). ...
Characterizing the response of microbial communities to a range of antibiotic concentrations is one of the strategies used to understand the impact of antibiotic resistance. Many studies have described the occurrence and prevalence of antibiotic resistance in microbial communities from reservoirs such as hospitals, sewage, and farm feedlots, where bacteria are often exposed to high and/or constant concentrations of antibiotics. Outside of these sources, antibiotics generally occur at lower, sub-minimum inhibitory concentrations (sub-MICs). The constant exposure to low concentrations of antibiotics may serve as a chemical “cue” that drives development of antibiotic resistance. Low concentrations of antibiotics have not yet been broadly described in reservoirs outside of the aforementioned environments, nor is the transfer and dissemination of antibiotic resistant bacteria and genes within natural microbial communities fully understood. This review will thus focus on low antibiotic-concentration environmental reservoirs and mechanisms that are important in the dissemination of antibiotic resistance to help identify key knowledge gaps concerning the environmental resistome.
... S. aureus is an important anthropological bacterial pathogen of Gram-positive strain that leads to common infections in society. Regarding the resistance to antibiotics, and the report of the Centers for Disease Control and Prevention (CDC) about resistance to methicillin of S. aureus (MRSA) in 2013, S. aureus was distinguished as a critical and a persistent threat [17][18][19]. ...
Sortase A (SrtA) is an enzyme that catalyzes the attachment of proteins to the cell wall of Gram-positive bacterial membrane, preventing the spread of pathogenic bacterial strains. Here, one class of oxadiazole compounds was distinguished as an efficient inhibitor of SrtA via the “S. aureus Sortase A” substrate-based virtual screening. The current study on 3D-QSAR was done by utilizing preparation of the structure in the Schrödinger software suite and an assessment of 120 derivatives with the crystal structure of 1,2,4-oxadiazole which was extracted from the PDB data bank. The docking operation of the best compound in terms of pMIC (pMIC=2.77) was done to determine the drug likeliness and binding form of 1,2,4-oxadiazole derivatives as antibiotics in the active site. Using the kNN-MFA way, seven models of 3D-QSAR were created and amongst them, and one model was selected as the best. The chosen model based on q2 (pred_r2) and R2 values related to the sixth factor of PLS illustrates better and more acceptable external and internal predictions. Values of crossvalidation (pred_r2), validation (q2), and F were observed 0.5479, 0.6319, and 179.0, respectively, for a test group including 24 molecules and the training group including 96 molecules. The external reliability outcomes showed that the acceptable and the selective 3D-QSAR model had a high predictive potential (R2=0.9235) which was confirmed by the Y-randomization test. Besides, the model applicability domain was described successfully to validate the estimation of the model.
... recovered from uriniferous soils (44). Also, mexF has been identified in air, soil, marine, and humans (45)(46)(47)(48). In addition, mexF was detected exclusively across the 50-year succession age of the retreating glacier where microbes were the initial colonizers, and an increased trend of relative abundance in soil resistomes was reported (49). ...
This is the first study to examine how resistomes develop and evolve using GS. GS can be used to study the colonization and establishment of bacterial communities under antibiotic selection.
... The importance of metagenomics approaches on the description of general AR patterns, with the definition of critical geographical or activity-related areas or temporal AR trends (e.g. sewage, pharmaceutical industry) has been highlighted in different publications (Aarestrup and Woolhouse, 2020;Hendriksen et al., 2019a;Id et al., 2019;Sukhum et al., 2019). ...
Antibiotic resistance (AR) is a global problem requiring international cooperation and coordinated action. Global monitoring must rely on methods available and comparable across nations to quantify AR occurrence and identify sources and reservoirs, as well as paths of AR dissemination. Numerous analytical tools that are gaining relevance in microbiology, have the potential to be applied to AR research. This review summarizes the state of the art of AR monitoring methods, considering distinct needs, objectives and available resources. Based on the overview of distinct approaches that are used or can be adapted to monitor AR, it is discussed the potential to establish reliable and useful monitoring schemes that can be implemented in distinct contexts. This discussion places the environmental monitoring within the One-Health approach, where two types of risk, dissemination across distinct environmental compartments, and transmission to humans, must be considered. The plethora of methodological approaches to monitor AR and the variable features of the monitored sites challenge the capacity of the scientific community and policy makers to reach a common understanding. However, the dialogue between different methods and the production of action-oriented data is a priority. The review aims to warm up this discussion.
... Unlike other categories of medications, the irresponsible use of antibiotics not only has adverse consequences on the individual patients, but also to the larger community-as it increases the risk of antibiotic resistance (8,9). Infections caused by antibiotic-resistant bacteria can spread to the larger community when proper measurements are not taken (10)(11)(12). Hospitals, as the main providers of secondary and tertiary care, have seen medication as one of the most essential assets to ensure quality and continuity of health services. ...
Banyaknya jumlah obat-obatan di rumah sakit seringkali meningkatkan risiko ketidaktepatan dalam manajemen persediaan farmasi, oleh karena itu, perlu dilakukan studi pengelolaan dan penggunaannya. Penelitian ini dimaksudkan untuk mengkaji efektivitas pengelolaan dan penggunaan obat di Bima, Nusa Tenggara Barat. Adapun metode penelitian ini bersifat observasional retrospektif. Analisa data dilakukan secara deskriptif. Evaluasi pengelolaan dilakukan pada tahap perencanaan, pengadaan, penyimpanan dan pendistribusian, sedangkan evaluasi penggunaan dilakukan dengan menghitung DDD/100 patient-days untuk antibiotika yang paling banyak digunakan. Hasil penelitian pada evaluasi perencanaan, diperoleh tiga jenis obat pada matrik AV yaitu Ringer Lactat, Fentanil dan Tetagam; satu jenis obat vital pada Matrik BV, yaitu anti bisa ular; dan sembilan jenis obat pada matrik CV yaitu Aminophylline inj 24mg, Serum anti tetanus 1.500IU, Fenobarbital inj, Levosol inj, Magnesium sulfat inj 20%, Norepinefrin inj, Otsu D40, Otsu MgSO4 40, Pethidine 50mg/ml. Kesesuaian dana pengadaan obat 107,3% dan rerata ketepatan pengadaan 275%; terdapat 2 jenis obat rusak pada penyimpanan (0,476 %). Analisa DDD/100 patient-days untuk 12 injeksi antibiotika diperoleh total 45,44 DDD/100 patient-days. Kesimpulan: Hasil temuan pada penelitian ini memberikan gambaran informasi awal yang dapat digunakan untuk menyempurnakan praktek pengelolaan obat yang lebih efektif dan efisien di rumah sakit-rumah sakit khususnya di RSUD Bima di masa mendatang.The large number of medications circulating in hospitals may increase the risks of mismanagement of pharmaceutical inventory; hence studies on the management and use of medication are needed. This present study aims to analyse medication management and use in Bima Regional Public Hospital. This is a retrospective observational study, using descriptive data analysis. The analysis of medication management was conducted for the planning, procurement, storage and distribution stages; while the evaluation of medication use was done on antibiotic injections commonly prescribed using DDD/100 patient-days. The results showed that in the planning stage, three medications were in the AV category (i.e. Lactated Ringer’s Infusion, Fentanyl and Tetagam Inj.); one vital medication was in the BV category (i.e. anti-snake venom serum); and nine medications were in the CV category (i.e. Aminophylline Inj. 24mg, Anti-Tetanus Serum 1500 IU, Phenobarbital Inj., Levosol Inj., Magnesium Sulphate Inj. 20%, Norepinephrine Inj., OTSU D40 Infusion, OTSU MgSO4-40 Inj., Pethidine Inj. 50 mg/ml). The conformity of procurement funding was 107.3%, while the accuracy of procurement process (medication purchased/prescribed) was 275%; and there were two damaged products during storage (0.476 %). The evaluation of medication use for 12 antibiotic injections found a total 45.44 DDD/100 patient-days. The findings in this study provides a baseline data in optimising future practices of medication management and use in hospitals, especially in Bima Regional Public Hospital.
... The clinical utility of having an in depth understanding of how antibiotics alter the composition and function of gut microbiome is unquestionable. Detecting changes in the microbiome that occur due to antibiotics and chemotherapy can predict bloodstream infection with MDR pathogens [33]; in addition, detection of MDR pathogens and AMR genes in the gut microbiome hold potential in controlling hospital and community outbreaks [34]. Balancing confounders between 2 groups in a randomized controlled trial setting is essential to answer this question (Table 3). ...
Despite the accepted dogma that antibiotic use is the largest contributor to antimicrobial resistance (AMR) and human microbiome disruption, our knowledge of specific antibiotic-microbiome effects remains basic. Detection of associations between new or old antimicrobials and specific AMR burden is patchy and heterogeneous. Various microbiome analysis tools have become available that enable accurate descriptions of antibiotic effects on microbial communities in vivo over a period of time. Microbiome analysis of treatment groups in antibiotic clinical trials, powered to measure clinically meaningful endpoints would greatly assist the antibiotic development pipeline and clinician antibiotic decision making.
