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81300.9743Fighting against evolution of antibiotic resistance by utilizing evolvable antimicrobial drugs. Antibiotic resistance is a worldwide public health problem (Bush et al. in Nat Rev Microbiol 9:894-896, 2011). The lack of effective therapies against resistant bacteria globally leads to prolonged treatments, increased mortality, and inflating health care costs (Oz et al. in Mol Biol Evol 31:2387-2401, 2014; Martinez in Science 321:365-367, 2008; Lipsitch et al. in Proc Natl Acad Sci USA 97:1938-1943, 2000; Taubes in Science 321:356-361, 2008; Laxminarayan et al. in Lancet, 2016; Laxminarayan et al. in Lancet Infect Dis 13:1057-1098, 2013). Current efforts towards a solution of this problem can be boiled down to two main strategies: (1) developing of new antimicrobial agents and (2) searching for smart strategies that can restore or preserve the efficacy of existing antimicrobial agents. In this short review article, we discuss the need for evolvable antimicrobial agents, focusing on a new antimicrobial technology that utilizes peptide-conjugated phosphorodiamidate morpholino oligomers to inhibit the growth of pathogenic bacteria by targeting bacterial genes.201728497241
23110.9731Lincosamides, Streptogramins, Phenicols, and Pleuromutilins: Mode of Action and Mechanisms of Resistance. Lincosamides, streptogramins, phenicols, and pleuromutilins (LSPPs) represent four structurally different classes of antimicrobial agents that inhibit bacterial protein synthesis by binding to particular sites on the 50S ribosomal subunit of the ribosomes. Members of all four classes are used for different purposes in human and veterinary medicine in various countries worldwide. Bacteria have developed ways and means to escape the inhibitory effects of LSPP antimicrobial agents by enzymatic inactivation, active export, or modification of the target sites of the agents. This review provides a comprehensive overview of the mode of action of LSPP antimicrobial agents as well as of the mutations and resistance genes known to confer resistance to these agents in various bacteria of human and animal origin.201627549310
480320.9731Antimicrobial resistance and resistance transfer in anaerobic. A review. A changing antimicrobial susceptibility pattern of anaerobic bacteria has been noted over the past decade. This paper reviews the mechanisms by which these organisms have become resistant to the selected antibiotics and reviews recent data demonstrating that anaerobic bacteria possess systems for transferring resistance determinants. Within Bacteroides there is widespread resistance to penicillins, cephalosporins and tetracycline compounds while there have been sporadic reports of resistance to clindamycin, cefoxitin, chloramphenicol and metronidazole. Transfer of resistance to penicillin, tetracycline and clindamycin has been demonstrated.19846377471
480430.9729Mechanism of antimicrobial resistance and resistance transfer in anaerobic bacteria. The antimicrobial susceptibility pattern of anaerobic bacteria has been changing over the past decade. This paper reviews the mechanisms by which these organisms have become resistant to selected antibiotics and reviews data demonstrating that Bacteroides fragilis and Clostridium perfringens possess systems for transferring resistance determinants. Within bacteroides there is widespread resistance to penicillins, cephalosporins and tetracycline compounds while there have been reports of resistance to clindamycin and cefoxitin, and there is rare resistance reported for chloramphenicol and metronidazole. Transfer of resistance to penicillin, tetracycline and clindamycin has been demonstrated in bacteroides, while transfer of tetracycline resistance has been documented in clostridia.19826300995
447540.9728Clindamycin resistance in anaerobic bacteria. Knowledge of the mechanisms of antimicrobial resistance and resistance transfer in anaerobic bacteria has been gained over the past several years. There is widespread resistance to the beta-lactam antibiotics in the B. fragilis group of organisms and there is emerging penicillin resistance in other Bacteroides species. These resistances are usually mediated by chromosomal beta-lactamases. There have been two new beta-lactamases described in Bacteroides; a penicillinase which inactivates ureidopenicillins and another that inactivates cefoxitin. The transfer of the common beta-lactamase, penicillinase, and cefoxitin resistance has been documented in B. fragilis. The mechanism of tetracycline resistance in B. fragilis is the lack of accumulation of intracellular drug; the resistance is widespread in anaerobic bacteria and is seen in two-thirds of the B. fragilis strains. The transfer of tetracycline resistance is common, however, no transfer factor has yet been isolated. Clindamycin-erythromycin resistance in Bacteroides was first recognized in the mid-1970s and transferable resistance was described in 1979. The mechanism of resistance is probably similar to macrolide-lincosamide-streptinogramin-resistance seen in aerobic bacteria. Two clindamycin resistance transfer factors, pBFTM10 and pIP410 (pBF4) have been described. A common resistance determinant found both on plasmids and chromosomes is widely distributed in nature and it probably resides on a transposon. DNA homology studies indicate that there is more than one type of clindamycin resistance in Bacteroides; a newly recognized clindamycin resistance determinant is transferable. Local outbreaks of clindamycin resistance have been noted in the United States and in Europe. The susceptibility of Bacteroides in the United States in 1983 from a multi-center study reveals a 5% incidence of resistance in B. fragilis and 1% in Bacteroides species. The rate of clindamycin resistance has remained steady over the past three years in the Bacteroides fragilis group.19846598519
994550.9728The Ellis Island Effect: A novel mobile element in a multi-drug resistant Bacteroides fragilis clinical isolate includes a mosaic of resistance genes from Gram-positive bacteria. Objectives: Bacteroides fragilis, a Gram-negative anaerobic bacterium, is alternately a gut commensal or virulent pathogen and is an important reservoir for horizontal gene transfer (HGT) of bacterial resistance and virulence genes in the human gastrointestinal tract. We identified a unique conjugative transposon (CTn) in a multidrug resistant clinical isolate of B. fragilis (BF-HMW615); we named this element CTnHyb because it included a hybrid mosaic of foreign elements. This study reports the characterization of CTnHyb and discusses the potential impact on horizontal spread of resistance genes. Results: CTnHyb contains several efflux pump genes and several genes that confer or may confer antibiotic resistance to tetracycline, kanamycin, metronidazole and spectinomycin (truncated gene). CTnHyb also contains a mosaic of mobile elements from Gram-positive organisms. CTnHyb is easily transferred from BF-HMW615 (the original isolate) to BF638R (lab strain) and integrated into the BF638R chromosome. The "foreign" (from Gram-positive bacteria) nucleotide sequences within CTnHyb were > 99% preserved indicating that the gene acquisition from the Gram-positive bacteria was very recent. Conclusion: CTnHyb is a novel CTn residing in a multidrug resistant strain of B. fragilis. The global nature and wide phylogenetic reach of HGT means that any gene in any bacterium can potentially be mobilized. Understanding the mechanisms that drive the formation and transfer of these elements and, potentially, ways to limit the transfer are necessary to prevent a devastating spread of resistance elements.201425165618
514260.9728Comparative genomics of Clostridium bolteae and Clostridium clostridioforme reveals species-specific genomic properties and numerous putative antibiotic resistance determinants. BACKGROUND: Clostridium bolteae and Clostridium clostridioforme, previously included in the complex C. clostridioforme in the group Clostridium XIVa, remain difficult to distinguish by phenotypic methods. These bacteria, prevailing in the human intestinal microbiota, are opportunistic pathogens with various drug susceptibility patterns. In order to better characterize the two species and to obtain information on their antibiotic resistance genes, we analyzed the genomes of six strains of C. bolteae and six strains of C. clostridioforme, isolated from human infection. RESULTS: The genome length of C. bolteae varied from 6159 to 6398 kb, and 5719 to 6059 CDSs were detected. The genomes of C. clostridioforme were smaller, between 5467 and 5927 kb, and contained 5231 to 5916 CDSs. The two species display different metabolic pathways. The genomes of C. bolteae contained lactose operons involving PTS system and complex regulation, which contribute to phenotypic differentiation from C. clostridioforme. The Acetyl-CoA pathway, similar to that of Faecalibacterium prausnitzii, a major butyrate producer in the human gut, was only found in C. clostridioforme. The two species have also developed diverse flagella mobility systems contributing to gut colonization. Their genomes harboured many CDSs involved in resistance to beta-lactams, glycopeptides, macrolides, chloramphenicol, lincosamides, rifampin, linezolid, bacitracin, aminoglycosides and tetracyclines. Overall antimicrobial resistance genes were similar within a species, but strain-specific resistance genes were found. We discovered a new group of genes coding for rifampin resistance in C. bolteae. C. bolteae 90B3 was resistant to phenicols and linezolide in producing a 23S rRNA methyltransferase. C. clostridioforme 90A8 contained the VanB-type Tn1549 operon conferring vancomycin resistance. We also detected numerous genes encoding proteins related to efflux pump systems. CONCLUSION: Genomic comparison of C. bolteae and C. clostridiofrome revealed functional differences in butyrate pathways and in flagellar systems, which play a critical role within human microbiota. Most of the resistance genes detected in both species were previously characterized in other bacterial species. A few of them were related to antibiotics inactive against Clostridium spp. Some were part of mobile genetic elements suggesting that these commensals of the human microbiota act as reservoir of antimicrobial resistances.201627769168
447470.9727Mechanisms of resistance and resistance transfer in anaerobic bacteria: factors influencing antimicrobial therapy. The resistance of anaerobic bacteria to a number of antimicrobial agents has an impact on the selection of appropriate therapy for infections caused by these pathogens. Resistance to penicillin in Bacteroides fragilis has long been recognized. Most resistance is due to chromosomal beta-lactamases that are cephalosporinases. Two new enzymes that inactivate the ureidopenicillins and cefoxitin have been described in B. fragilis. The most common mechanisms of cefoxitin resistance is by the blocking of penetration of the drug into the periplasmic space. The transfer of beta-lactamase and penicillinase and of cefoxitin resistance has been demonstrated. Penicillin resistance in other Bacteroides is mediated by a penicillinase. Chloramphenicol resistance is mediated by a chloramphenicol acetyltransferase and by nitroreduction in anaerobic bacteria. Anaerobic bacteria are resistant to aminoglycosides because these organisms lack the oxidative transport system for intracellular drug accumulation. Metronidazole resistance, which is rarely encountered, is mediated by a decrease in nitroreduction of the compound to the active agent. Clindamycin-erythromycin resistance in B. fragilis is probably similar to macrolide-lincosamide-streptogramin resistance in aerobic bacteria. Two transfer factors, pBFTM10 and pBF4, which confer resistance to clindamycin have been described; the resistance determinant on them is widely distributed in nature. Tetracyline resistance in B. fragilis is mediated by a block in uptake of the drug. Transfer of tetracycline resistance is common; however, no transfer factor has been isolated. Transfer has been proposed to occur via a conjugal transposon. The special characteristics of the infected site influence the outcome of antimicrobial therapy, particularly in abscesses.(ABSTRACT TRUNCATED AT 250 WORDS)19846326243
444580.9727Genomic Analysis and Resistance Mechanisms in Shigella flexneri 2a Strain 301. Shigella flexneri is one of the most prominent pathogenic bacteria in developing countries. In the battle against shigellosis and other bacterial diseases, antibiotic resistance has become an increasing global public health threat. Although the serious phenomenon of multidrug resistance (MDR) has been identified as one of the top three burdens on human health, resistance mechanisms are still poorly understood at the molecular level. In this study, we analyzed genomic data and the evolution of resistance in Shigella flexneri under sequential selection stress from three separate antibiotics: ciprofloxacin (CIP), ceftriaxone (CRO), and tetracycline. Through whole-genome sequencing, 82 chromosomal antibiotic resistance genes were identified. Re-sequencing of the evolved populations identified single nucleotide polymorphisms (SNPs) that contributed to MDR and SNPs that were specific to a single drug. A total of 40 SNPs in 8 genes and 3 intergenic regions, including mutations in metG (L582R) and 1538924, 1538924, and 1538924, appeared under each antibiotic. Several nonsynonymous mutations in gyrB (S464Y), ydgA (E378A), rob (R156H), and narX (K75E) were observed under selective pressure from CIP or CRO. Based on a bioinformatic analysis and previous reports, we discuss the contribution of these mutated genes to resistance. Therefore, more circumspect selection and use of antimicrobial drugs for treating shigellosis is necessary.201828853989
249290.9727Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention. Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.202235979498
4479100.9727Metronidazole resistance and nim genes in anaerobes: A review. Acquired resistance to metronidazole, a 5-nitroimidazole drug largely used worldwide in the empirical treatment of infections caused by anaerobes, is worrisome, especially since such resistance has been described in multidrug-resistant anaerobic bacteria. In anaerobes, acquired resistance to metronidazole may be due to a combination of various and complex mechanisms. Among them, nim genes, possibly located on mobile genetic elements, encode nitro-imidazole-reductases responsible for drug inactivation. Since the first description of Nim proteins about 25 years ago, more nim genes have been identified; currently 11 nim genes are known (nimA to nimK). Mostly reported in Bacteroides fragilis group isolates, nim genes are now described in a variety of anaerobic genera encompassing the 4 main groups of Gram-negative and Gram-positive bacilli and cocci, with variable expression ranging from phenotypically silent to low-level or high-level resistance to metronidazole. This review describes the trends of metronidazole resistance rates among anaerobes over the past 20 years and summarizes current knowledge on mechanisms involved in this resistance. It also provides an update on the phylogenetic and geographical distribution of nim genes, the mechanisms involved in their expression and regulation, and their role in metronidazole resistance.201930316817
6629110.9727The rise of antibiotic resistance in Campylobacter. PURPOSE OF REVIEW: Campylobacter is a major foodborne pathogen that infects the human intestinal tract. This review discusses the current status of antibiotic resistance, transmission of antibiotic resistance genes, and strategies to combat the global Campylobacter epidemic. RECENT FINDINGS: Over the past 18 months, articles on Campylobacter antibiotic resistance have been published in ∼39 countries. Antibiotic-resistant Campylobacter have been detected in humans, livestock, poultry, wild animals, the environment, and food. Campylobacter spp. are resistant to a wide spectrum of antimicrobial agents, including the antibiotics quinolones, macrolides, tetracyclines, aminoglycosides, and chloramphenicols. Multidrug resistance is a globally emerging problem. Continuous antibiotic pressure promotes the spread of drug-resistant Campylobacter spp. Additionally, Campylobacter is well adapted to acquiring foreign drug resistance genes, including ermB, optrA, fexA, and cfrC, which are usually acquired from gram-positive bacteria. SUMMARY: The widespread use of antibiotics has caused a global epidemic of drug-resistant Campylobacter infections. Many countries are actively reducing the use of antibiotics and adopting alternatives in the livestock and poultry industries to control the spread of drug-resistant Campylobacter spp.202336504031
4141120.9727Aspects of bacterial resistance to antimicrobials used in veterinary dermatological practice. Aspects of bacterial resistance to the major classes of antimicrobials used in veterinary dermatology are presented in this review. Resistance of gram-positive and gram-negative bacteria to tetracyclines, macrolide-lincosamide-streptogramin antibiotics, chloramphenicol, mupirocin, sulphonamides, trimethoprim, aminoglycosides, fluoroquinolones and β-lactam antibiotics are depicted with respect to the different mechanisms of acquired and intrinsic resistance. Examples are given for the three major resistance mechanisms, enzymatic inactivation, decreased intracellular drug accumulation and target modification. In addition, basic information about mobile genetic elements which carry resistance genes, such as plasmids, transposons and gene cassettes, and their modes of spreading via transduction, conjugation, mobilization and transformation is provided.199934644923
4481130.9727New findings in beta-lactam and metronidazole resistant Bacteroides fragilis group. Beta-lactam antibiotics and 5-nitroimidazoles have been extensively used against anaerobic bacteria. However, antibiotic resistance is increasingly common among anaerobic Gram-negative bacilli. The classical mechanisms of resistance to beta-lactams are, (1) production of beta-lactamases; (2) alteration of penicillin-binding proteins (PBPs); and (3) changes in outer membrane permeability to beta-lactams. The 5-nitroimidazole molecule is a prodrug whose activation depends upon reduction of the nitro group in the absence of oxygen. Decreased uptake and altered reduction are believed to be responsible for metronidazole resistance. Five nim genes (A, B, C, D and E) have been identified in Bacteroides fragilis group spp. that confer resistance to 5-nitroimidazole antibiotics. Knowledge of the status and the mechanisms of resistance is critical for both the selection of antimicrobial therapy and the design of new antimicrobial agents. The purpose of this article is to review the mechanisms for and the prevalence of beta-lactam and metronidazole resistance in strains belonging to the B. fragilis group.200212007843
2602140.9726Human-wildlife ecological interactions shape Escherichia coli population and resistome in two sloth species from Costa Rica. Antimicrobial resistance (AMR) is a global health concern, with natural ecosystems acting as reservoirs for resistant bacteria. We assessed AMR in Escherichia coli isolated from two wild sloth species in Costa Rica. E. coli from two-toed sloths (Choloepus hoffmanni), a species with greater mobility and a broader diet, showed resistance to sulfamethoxazole (25%), tetracycline (9.4%), chloramphenicol (6.3%), ampicillin (6.3%), trimethoprim (3.1%), and ciprofloxacin (3.1%), which correlated with the presence of resistance genes (tet(A), tet(B), bla(TEM-1B), aph(3")-Id, aph(6)-Id, sul2, qnrS1, floR and dfrA8). E. coli from three-toed sloths (Bradypus variegatus) showed 40% resistance to sulfamethoxazole despite no detected resistance genes, suggesting a regional effect. A significant negative correlation was found between AMR and distance to human-populated areas, highlighting anthropogenic impact on AMR spread. Notably, E. coli isolates from remote areas with no human impact indicate that some ecosystems remain unaffected. Preserving these areas is essential to protect environmental and public health.202540610649
5442150.9725Prevalence, Antimicrobial Susceptibility and Resistance Gene Detection in Bacteria Isolated from Goldfish and Tiger Barb from Ornamental Fish Farms of Tamil Nadu. This study aims to determine the antimicrobial resistance (AMR) pattern in freshwater ornamental cyprinids, such as Goldfish and Tiger barb. Molecular characterization of bacterial isolates confirmed the presence of 7 bacterial isolates in Goldfish and 6 in Tiger barb. Antimicrobial susceptibility test using 36 antibiotics revealed a higher resistance pattern for bacitracin, rifampicin, trimethoprim, cefalexin, ampicillin, amoxicillin, nalidixic acid and nitrofurantoin. Sulphafurazole, norfloxacin and ciprofloxacin were effective against all the bacterial isolates derived from Goldfish and Tiger barb. Most bacterial isolates exhibited > 0.2 multi-drug resistance index (MDR), indicating the severity of antibiotic use in the culture system. The finding of the present study suggests that ornamental fish may act as the reservoir of MDR bacteria and dissemination of resistance genes to clinical and human commensal bacteria through horizontal gene transfer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-022-01023-y.202235974915
4202160.9724Surveillance of antimicrobial resistance in humans, food stuffs and livestock in Denmark. A general increase in antimicrobial resistance among pathogenic bacteria is causing concern worldwide that the widespread use of antimicrobial agents in animal production may promote the development of resistant bacteria or resistance genes that can be tr199712631822
3658170.9724Antibiotics for gram-positive bacterial infections. Vancomycin, teicoplanin, quinupristin/dalfopristin, and linezolid. Vancomycin is a safe, effective antibiotic for a variety of serious gram-positive infections. Because of emerging resistance in enterococci and staphylococci and the emerging threat of spread of vancomycin-resistant genes to other gram-positive organisms, judicious use of vancomycin should be promoted. Quinupristin/dalfopristin, a streptogramin antibiotic, and linezolid, an oxazolidinone, show promise against some strains of gram-positive bacteria that are resistant to vancomycin.200010829266
1399180.9724Nationwide Stepwise Emergence and Evolution of Multidrug-Resistant Campylobacter jejuni Sequence Type 5136, United Kingdom. We examined whole-genome-sequenced Campylobacter jejuni and C. coli from 2012-2015 isolated from birds and human stool samples in North East Scotland for the presence of antimicrobial resistance genes. We found that sequence type (ST) 5136 (clonal complex 464) was the most prevalent multidrug-resistant strain of C. jejuni exclusively associated with poultry host reservoirs and recovered from human cases of campylobacteriosis. Tetracycline resistance in ST5136 isolates was due to a tet(O/32/O) mosaic gene, ampicillin resistance was conferred by G → T transversion in the -10 promoter region of bla(OXA-193), fluoroquinolone resistance was due to C257T change in gyrA, and aminoglycoside resistance was conferred by aac. Whole-genome analysis showed that the strain ST5136 evolved from ST464. The nationwide emergence of ST5136 was probably due to stepwise acquisition of antimicrobial resistance genes selected by high use of β-lactam, tetracycline, fluoroquinolone, and aminoglycoside classes of drugs in the poultry industry.201931211671
2443190.9723Antibiotic Resistance among Fusobacterium, Capnocytophaga, and Leptotrichia Species of the Oral Cavity. PURPOSE: Antibiotics play an important role in treating periodontal diseases. Due to the effectiveness of antibiotic therapies, their usage in dentistry has significantly increased. The aim of this study focused on the in-vitro susceptibility of different gram-negative oral bacteria species - which are associated with periodontal diseases (Fusobacterium spp., Capnocytophaga spp. and Leptotrichia buccalis) and have different geographical origins (Asia and Europe) - against antimicrobials that are clinically relevant in dental therapy. MATERIALS AND METHODS: A total of 45 strains were tested (29 Fusobacterium spp., 13 Capnocytophaga spp. and 3 L. buccalis) that were either isolated from Chinese patients or were obtained from different strain collections. Their antimicrobial susceptibility to the antimicrobial agents benzylpenicillin, amoxicillin, amoxicillin-clavulanic acid, ciprofloxacin, moxifloxacin, clindamycin, doxycycline, tetracycline and metronidazole was tested using the E-Test. Strains with particular resistance to penicillin, clindamycin and metronidazole were further analysed for resistance genes. RESULTS: All tested bacterial isolates were sensitive to amoxicillin, amoxicillin-clavulanic acid, doxycycline and tetracycline, but showed variable sensitivity towards other antibiotics such as benzylpenicillin, ciprofloxacin, moxifloxacin, clindamycin and metronidazole. CONCLUSION: The results of the present study suggest that certain periodontal disease-related bacterial strains can be resistant towards antimicrobial agents commonly used in adjuvant periodontal therapy.202337014213