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The Journal of Hospital Infection May 2022Antimicrobial resistance in Staphylococcus aureus imposes a high disease burden. Both phenotypic and genotypic monitoring are key to understanding and containing...
BACKGROUND
Antimicrobial resistance in Staphylococcus aureus imposes a high disease burden. Both phenotypic and genotypic monitoring are key to understanding and containing emerging resistant strains.
AIM
Phenotypic monitoring of emerging resistance in S. aureus and correlation of priority strain phenotypes with whole-genome sequencing (WGS) findings.
METHODS
Antimicrobial susceptibility test results of >40,000 isolates from 213 participating hospitals from 2011 to 2019 were exported from the national Japan Nosocomial Infections Surveillance (JANIS) database. Longitudinal and geographic distribution and prevalence of distinct multi-drug resistance phenotypes ('resistance profiles') of S. aureus were examined among hospitals and prefectures. We further conducted a genome sequence analysis of strains with specific resistance profiles of concern.
FINDINGS
The overall prevalence of meticillin-resistant S. aureus (MRSA) decreased from 40.3% to 35.1% from 2011 to 2019. However, among dozens of S. aureus resistance profiles, only one profile of a type of MRSA, exhibited a statistically significant increase in inpatient frequency, exceeding 10% during the nine years. This MRSA profile showed resistance to oxacillin, erythromycin and levofloxacin. Analysis of WGS results of S. aureus isolates with this phenotype revealed that most belonged to clonal complex 8, and all carried SCCmec IV, typical of community-acquired MRSA.
CONCLUSION
Tracking distinct resistance profiles deepened our understanding of the overall decrease in MRSA and led to recognition of the emergence of a new resistance phenotype. This study provides a model for future epidemiological research on antimicrobial resistance correlating multi-drug resistance phenotypes with selective genome sequencing, which can be applied to other bacterial species.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Humans; Japan; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Phenotype; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35202748
DOI: 10.1016/j.jhin.2022.02.011 -
Animal Health Research Reviews Jun 2020Bacteriophages are the most abundant form of life on earth and are present everywhere. The total number of bacteriophages has been estimated to be 1032 virions. The main... (Review)
Review
Bacteriophages are the most abundant form of life on earth and are present everywhere. The total number of bacteriophages has been estimated to be 1032 virions. The main division of bacteriophages is based on the type of nucleic acid (DNA or RNA) and on the structure of the capsid. Due to the significant increase in the number of multi-drug-resistant bacteria, bacteriophages could be a useful tool as an alternative to antibiotics in experimental therapies to prevent and to control bacterial infections in people and animals. The aim of this review was to discuss the history of phage therapy as a replacement for antibiotics, in response to EU regulations prohibiting the use of antibiotics in livestock, and to present current examples and results of experimental phage treatments in comparison to antibiotics. The use of bacteriophages to control human infections has had a high success rate, especially in mixed infections caused mainly by Staphylococcus, Pseudomonas, Enterobacter, and Enterococcus. Bacteriophages have also proven to be an effective tool in experimental treatments for combating diseases in livestock.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Livestock; Phage Therapy; Therapies, Investigational
PubMed: 32618543
DOI: 10.1017/S1466252319000161 -
Revista Espanola de Quimioterapia :... Sep 2022The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health... (Review)
Review
The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health problem that entails high morbidity and mortality: the antibiotic multi-drug resistance. In 2017 and 2019, the World Health Organization published a list of urgent threats and priorities in the context of drug resistance, which only included Gram-negative bacteria and specially focused on carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem and third generation cephalosporin-resistant Enterobacteriaceae. This scenario emphasizes the need of developing and testing new antibiotics from different families, such as new beta-lactams, highlighting cefiderocol and its original mechanism of action; new beta-lactamase inhibitors, with vaborbactam or relebactam among others; new quinolones such as delafloxacin, and also omadacycline or eravacycline, as members of the tetracycline family. The present work reviews the importance and impact of Gram-negative bacterial infections and their resistance mechanisms, and analyzes the current therapeutic paradigm as well as the role of new antibiotics with a promising future in the era of multi and pan-drug resistance.
Topics: Animals; Anti-Bacterial Agents; Carbapenems; Cattle; Cephalosporins; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Quinolones; Tetracyclines; beta-Lactamase Inhibitors; beta-Lactams
PubMed: 36193979
DOI: 10.37201/req/s02.01.2022 -
Cancer Reports (Hoboken, N.J.) Dec 2022The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies,... (Review)
Review
BACKGROUND
The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for the treatment of cancer. However, cancer cells reprogram themselves in multiple ways to evade the effect of these therapies, and over a period of time, the drug becomes inactive due to the development of multi-drug resistance (MDR). MDR is a complex phenomenon where malignant cells become insensitive to anticancer drugs and attain the ability to survive even after several exposures of anticancer drugs. In this review, we have discussed the molecular and cellular paradigms of multidrug resistance in cancer.
RECENT FINDINGS
An Extensive research in cancer biology revealed that drug resistance in cancer is the result of perpetuated intracellular and extracellular mechanisms such as drug efflux, drug inactivation, drug target alteration, oncogenic mutations, altered DNA damage repair mechanism, inhibition of programmed cell death signaling, metabolic reprogramming, epithelial mesenchymal transition (EMT), inherent cell heterogeneity, epigenetic changes, redox imbalance, or any combination of these mechanisms. An inevitable cross-link between inflammation and drug resistance has been discussed. This review provided insight molecular mechanism to understand the vulnerabilities of cancer cells to develop drug resistance.
CONCLUSION
MDR is an outcome of interplays between multiple intricate pathways responsible for the inactivation of drug and development of resistance. MDR is a major obstacle in regimens of successful application of anti-cancer therapy. An improved understanding of the molecular mechanism of multi drug resistance and cellular reprogramming can provide a promising opportunity to combat drug resistance in cancer and intensify anti-cancer therapy for the upcoming future.
Topics: Humans; Drug Resistance, Neoplasm; Drug Resistance, Multiple; Neoplasms; Antineoplastic Agents; Drug Delivery Systems
PubMed: 33052041
DOI: 10.1002/cnr2.1291 -
Nanomedicine : Nanotechnology, Biology,... Feb 2022Multidrug resistance (MDR) in cancer chemotherapy is a growing concern for medical practitioners. P-glycoprotein (P-gp) overexpression is one of the major reasons for... (Review)
Review
Multidrug resistance (MDR) in cancer chemotherapy is a growing concern for medical practitioners. P-glycoprotein (P-gp) overexpression is one of the major reasons for multidrug resistance in cancer chemotherapy. The P-gp overexpression in cancer cells depends on several factors like adenosine triphosphate (ATP) hydrolysis, hypoxia-inducible factor 1 alpha (HIF-1α), and drug physicochemical properties such as lipophilicity, molecular weight, and molecular size. Further multiple exposures of anticancer drugs to the P-gp efflux protein cause acquired P-gp overexpression. Unique structural and functional characteristics of nanotechnology-based drug delivery systems provide opportunities to circumvent P-gp mediated MDR. The primary mechanism behind the nanocarrier systems in P-gp inhibition includes: bypassing or inhibiting the P-gp efflux pump to combat MDR. In this review, we discuss the role of P-gp in MDR and highlight the recent progress in different nanocarriers to overcome P-gp mediated MDR in terms of their limitations and potentials.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms
PubMed: 34775061
DOI: 10.1016/j.nano.2021.102494 -
Journal of Nepal Health Research Council Mar 2022Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen frequently causing healthcare-associated infections. The apocalyptic rise of antimicrobial resistance...
BACKGROUND
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen frequently causing healthcare-associated infections. The apocalyptic rise of antimicrobial resistance has rekindled interest in age-old phage therapy that uses phages (viruses that infect bacteria) to kill the targeted pathogenic bacteria. Because of its specificity, phages are often considered as potential personalized therapeutic candidate for treating bacterial infections.
METHODS
In this study, we isolated and purified lytic phages against multi-drug resistant P. aeruginosa using soft agar overlay technique. Phage characteristics like thermal and pH stability, latent period and burst size were determined using one-step growth assay while multiple host range spectrum was determined by spot assay. The phages were further characterized using protein profiling.
RESULTS
Three Pseudomonas phages (øCDBT-PA31, øCDBT-PA56 and øCDBT-PA58) were isolated from the holy rivers of Kathmandu valley. Among 3 phages, øCDBT-PA31 demonstrated multiple host range and could lyse multi-drug resistant strain of P. aeruginosa. Further, øCDBT-PA31 showed latent period of 30 minutes with corresponding burst sizes of 423-525 PFU/cell. Interestingly, øCDBT-PA31 also tolerated a wide range of adverse conditions, such as high temperature (50°C) and pH 3-11. Further, protein profiling revealed that øCDBT-PA31 has 4 and øCDBT-PA11 had 3 distinct bands in the gradient gel ranging from approximately 3.5-29 kilodaltons (kDa) suggesting them to be morphologically distinct from each other.
CONCLUSIONS
As multi-drug resistant bacteria are emerging as a global problem, lytic phages can be an alternative treatment strategy when all available antibiotics fail.
Topics: Bacteriophages; Drug Resistance, Multiple, Bacterial; Humans; Nepal; Pseudomonas Phages; Pseudomonas aeruginosa
PubMed: 35615828
DOI: 10.33314/jnhrc.v19i04.3837 -
Biomaterials Mar 2021High intracellular glutathione (GSH) levels play an important role in multidrug resistance (MDR) in cancer cells. It remains challenging to develop a drug delivery...
High intracellular glutathione (GSH) levels play an important role in multidrug resistance (MDR) in cancer cells. It remains challenging to develop a drug delivery system that is simultaneously capable of GSH depletion and drug activation for multidrug resistance reversal. Herein, we designed a polyprodrug (denoted as PSSD) based on poly(disulfide) conjugated with doxorubicin (DOX) on the polymer side chains that exhibits GSH depletion and cascade DOX activation for drug resistance reversal. The poly(disulfide) backbone with a high disulfide density depletes intracellular antioxidant GSH via the disulfide-thiol exchange reaction to disrupt intracellular redox homeostasis in cells. Simultaneously, DOX can be activated through a cascade reaction, and degradation of the poly(disulfide) backbone further facilitates its drug release. Therefore, poly(disulfide) can be used as a GSH scavenger to reverse MDR as well as a prodrug backbone to target high intracellular GSH levels in cancer cells, providing a general strategy for drug resistance reversal.
Topics: Activation, Metabolic; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Glutathione
PubMed: 33588139
DOI: 10.1016/j.biomaterials.2020.120649 -
Current Medicinal Chemistry 2022Bacterial infections are among the leading causes of death worldwide. The emergence of antimicrobial resistance factors threatens the efficacy of all current... (Review)
Review
Bacterial infections are among the leading causes of death worldwide. The emergence of antimicrobial resistance factors threatens the efficacy of all current antimicrobial agents, with some already made ineffective, and, as a result, there is an urgent need for new treatment approaches. International organizations, such as the World Health Organization and the European Centre for Diseases Control, have recognized infections caused by multi-drug-resistant (MDR) bacteria as a priority for global health action. Classical antimicrobial drug discovery involves in vitro screening for antimicrobial candidates, Structure-Activity Relationship analysis, followed by in vivo testing for toxicity. Bringing drugs from the bench to the bedside involves huge expenditures in time and resources. This, along with the relatively short window of therapeutic application for antibiotics attributed to the rapid emergence of drug resistance, has, at least until recently, resulted in a waning interest in antibiotic discovery among pharmaceutical companies. In this environment, "repurposing" (defined as investigating new uses for existing approved drugs) has gained renewed interest, as reflected by several recent studies, and may help to speed up the drug development process and save years of expensive research invested in antimicrobial drug development. The goal of this review is to provide an overview of the scientific evidence on potential anthelmintic drugs targeting Gram-negative bacilli (GNB). In particular, we aim to: (i) highlight the potential of anthelmintic drugs for treatments of GNB infections, (ii) review their mechanisms of action against these bacteria, (iii) summarize the outcome of preclinical studies investigating approved anthelmintic drugs that target these bacteria, (iv) provide critical challenges for further anthelmintic repurposing drugs development, and (v) list the specific anthelmintic drugs that may be more likely to be repurposed.
Topics: Humans; Anthelmintics; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria
PubMed: 35838224
DOI: 10.2174/0929867329666220714092916 -
Daru : Journal of Faculty of Pharmacy,... Jun 2020Infectious diseases associated with intracellular bacteria such as Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis are important public... (Review)
Review
INTRODUCTION
Infectious diseases associated with intracellular bacteria such as Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis are important public health concern. Emergence of multi and extensively drug-resistant bacterial strains have made it even more obstinate to offset such infections. Bacteria residing within intracellular compartments provide additional barriers to effective treatment.
METHOD
Information provided in this review has been collected by accessing various electronic databases including Google scholar, Web of science, Scopus, and Nature index. Search was performed using keywords nanoparticles, intracellular targeting, multidrug resistance, Staphylococcus aureus; Salmonella typhimurium; Mycobacterium tuberculosis. Information gathered was categorized into three major sections as 'Intracellular targeting of Staphylococcus aureus, Intracellular targeting of Salmonella typhimurium and Intracellular targeting of Mycobacterium tuberculosis' using variety of nanocarrier systems.
RESULTS
Conventional management for infectious diseases typically comprises of long-term treatment with a combination of antibiotics, which may lead to side effects and decreased patient compliance. A wide range of multi-functionalized nanocarrier systems have been studied for delivery of drugs within cellular compartments where bacteria including Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis reside. Such carrier systems along with targeted delivery have been utilized for sustained and controlled delivery of drugs. These strategies have been found useful in overcoming the drawbacks of conventional treatments including multi-drug resistance.
CONCLUSION
Development of multi-functional nanocargoes encapsulating antibiotics that are proficient in targeting and releasing drug into infected reservoirs seems to be a promising strategy to circumvent the challenge of multidrug resistance. Graphical abstract.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Carriers; Drug Resistance, Multiple, Bacterial; Humans; Nanoparticles
PubMed: 32193748
DOI: 10.1007/s40199-020-00337-w -
Experimental and Molecular Pathology Feb 2021Recent understanding of different molecular aspects of tumor initiation and progression has led to the discovery of a growing list of drugs. While these drugs have shown... (Review)
Review
Recent understanding of different molecular aspects of tumor initiation and progression has led to the discovery of a growing list of drugs. While these drugs have shown promising effects on tumor cells, their widespread usage has been hampered by the acquisition of drug resistance in a subpopulation of tumor cells. A differential pattern in the secretion of specialized vesicles named "exosomes" in drug-resistant cancer cells have recently received much attention. In addition, microRNAs (miRNAs) have been shown to be enriched in exosomes. Exosomal miRNAs (also known as exo-miRs) could be shuttled to recipient cells and play a role in the regulation of post-transcriptional gene expression, which may exert certain effects on cancer drug resistance. Here, we have reviewed the role of exo-miRs in chemotherapeutic resistance in different cancer types. Besides, studies which have focused on predictive role of circulating exo-miRs in cancer drug resistance are reviewed.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Exosomes; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms; Tumor Microenvironment
PubMed: 33296693
DOI: 10.1016/j.yexmp.2020.104592