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ACS Infectious Diseases Nov 2023Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One... (Review)
Review
Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One such WHO-critical group pathogen is . The extensive and inappropriate treatments for infections have led from multi-drug resistance (MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated systems and outer membrane proteins (OMPs) may favor MDR in . Differential expression of the efflux system and OMPs (influx) and positional mutations are the factors that can be correlated to the development of drug resistance. Insights into the mechanism of influx and efflux of antibiotics can aid in developing a structurally stable molecule that can be proficient at escaping from the resistance loops in . Understanding the strategic responsibilities and developing policies to address the surge of drug resistance at the national, regional, and global levels are the needs of the hour. In this Review, we attempt to aggregate all the available research findings and delineate the resistance mechanisms by dissecting the involvement of OMPs and efflux systems. Integrating major OMPs and the efflux system's differential expression and positional mutation in may provide insight into developing strategic therapies for one health application.
Topics: Membrane Proteins; Membrane Transport Proteins; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Salmonella
PubMed: 37910638
DOI: 10.1021/acsinfecdis.3c00408 -
Small (Weinheim An Der Bergstrasse,... Mar 2024Bacteria-induced epidemics and infectious diseases are seriously threatening the health of people around the world. In addition, antibiotic therapy has been inducing... (Review)
Review
Bacteria-induced epidemics and infectious diseases are seriously threatening the health of people around the world. In addition, antibiotic therapy has been inducing increasingly more serious bacterial resistance, which makes it urgent to develop new treatment strategies to combat bacteria, including multidrug-resistant bacteria. Natural extracts displaying antibacterial activity and good biocompatibility have attracted much attention due to greater concerns about the safety of synthetic chemicals and emerging drug resistance. These antibacterial components can be isolated and utilized as antimicrobials, as well as transformed, combined, or wrapped with other substances by using modern assistive technologies to fight bacteria synergistically. This review summarizes recent advances in natural extracts from three kinds of sources-plants, animals, and microorganisms-for antibacterial applications. This work discusses the corresponding antibacterial mechanisms and the future development of natural extracts in antibacterial fields.
Topics: Animals; Humans; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Drug Resistance, Multiple, Bacterial
PubMed: 37847896
DOI: 10.1002/smll.202306553 -
Surgical Infections Oct 2023Currently, the escalation of microbial resistance poses a significant global challenge. Children are more susceptible to develop infections and therefore are prescribed... (Review)
Review
Currently, the escalation of microbial resistance poses a significant global challenge. Children are more susceptible to develop infections and therefore are prescribed antibiotics more frequently. The overuse and misuse of antibiotics in pediatric patients can play a considerable role in developing microbial resistance. Accordingly, many policies, including research into new antibiotic agents have been recommended to combat microbial resistance. Recent developments in novel antibiotics have shown promising results against multi-drug resistant (MDR) and extensive drug resistance (XDR) pathogens. However, as pediatric patients are typically excluded from the clinical trials of new medications, labeling and information about approved antibiotics should be improved. This study aimed to evaluate antibiotics having been introduced to the market in the last decade focusing on pediatric population. This study reviewed the published literatures on novel FDA-approved antibiotics released between 2010 and 2022. Finally, seven newly approved antibiotics including ceftaroline fosamil, ceftazidime-avibactam, ceftolozane-tazobactam, ceftobiprole, imipenem-cilastatin-relebactam, meropenem-vaborbactam, and tedizolid were considered in the present review-article. All relevant data extracted from literatures, were discussed in different subtitles of "Pharmacology", "Mechanism of action", "Indication", "Dosage regimen and pharmacokinetic and pharmacodynamic properties", "Dosage adjustment in renal/liver failure", "Resistance pattern", and "Adverse drug events". This study reviewed available data on seven new antibiotic agents and their pharmacodynamic and pharmacokinetic properties, with a particular focus on their use in pediatric patients. The information presented in this review will be useful for healthcare professionals in selecting appropriate antibiotics for pediatric patients and for researchers in achieving the ideal therapeutic regimens.
Topics: Humans; Child; Anti-Bacterial Agents; Cephalosporins; Drug Combinations; Azabicyclo Compounds; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial
PubMed: 37831932
DOI: 10.1089/sur.2023.055 -
Microbial Drug Resistance (Larchmont,... Aug 2023The use of tigecycline (TG) for the treatment of is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of... (Meta-Analysis)
Meta-Analysis
The use of tigecycline (TG) for the treatment of is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR , published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR . However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.
Topics: Humans; Tigecycline; Anti-Bacterial Agents; Colistin; Acinetobacter baumannii; Microbial Sensitivity Tests; Acinetobacter Infections; Treatment Outcome; Mycobacterium tuberculosis; Drug Resistance, Multiple, Bacterial
PubMed: 37192494
DOI: 10.1089/mdr.2022.0248 -
Trends in Cancer Feb 2024Human ATP-binding cassette (ABC) transporters are ubiquitously expressed and transport a broad range of endogenous and xenobiotic substrates across extra- and... (Review)
Review
Human ATP-binding cassette (ABC) transporters are ubiquitously expressed and transport a broad range of endogenous and xenobiotic substrates across extra- and intracellular membranes. Mutations in ABC genes cause 21 monogenic diseases, and polymorphisms in these genes are associated with susceptibility to complex diseases. ABC transporters also play a major role in drug bioavailability, and they mediate multidrug resistance in cancer. At least 13 ABC transporters were shown to be involved in drug resistance in vitro. In the past decade, efforts have been made to elucidate their roles in tumor biology. Herein, we explore their involvement in tumorigenesis, focusing on the hallmarks of cells as they make their way from normalcy to neoplastic growth states.
Topics: Humans; ATP-Binding Cassette Transporters; Neoplasms; Drug Resistance, Multiple
PubMed: 37884430
DOI: 10.1016/j.trecan.2023.09.013 -
Medicina Clinica Apr 2024
Topics: Humans; Cross Infection; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents
PubMed: 38290873
DOI: 10.1016/j.medcli.2023.12.004 -
Frontiers in Immunology 2023Non-Hodgkin Lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy with B cell origin. Combinatorial treatment of rituximab, cyclophsphamide,...
INTRODUCTION
Non-Hodgkin Lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy with B cell origin. Combinatorial treatment of rituximab, cyclophsphamide, hydroxydaunorubicin, oncovin, prednisone (R-CHOP) is the standard treatment regimen for NHL, yielding a complete remission (CR) rate of 40-50%. Unfortunately, considerable patients undergo relapse after CR or initial treatment, resulting in poor clinical implications. Patient's response to chemotherapy varies widely from static disease to cancer recurrence and later is primarily associated with the development of multi-drug resistance (MDR). The immunosuppressive cells within the tumor microenvironment (TME) have become a crucial target for improving the therapy efficacy. However, a better understanding of their involvement is needed for distinctive response of NHL patients after receiving chemotherapy to design more effective front-line treatment algorithms based on reliable predictive biomarkers.
METHODS
Peripheral blood from 61 CD20 NHL patients before and after chemotherapy was utilized for immunophenotyping by flow-cytometry at different phases of treatment. and doxorubicin (Dox) resistance models were developed with murine Dalton's lymphoma and Jurkat/Raji cell-lines respectively and impact of responsible immune cells on generation of drug resistance was studied by RT-PCR, flow-cytometry and colorimetric assays. Gene silencing, ChIP and western blot were performed to explore the involved signaling pathways.
RESULTS
We observed a strong positive correlation between elevated level of CD33CD11bCD14CD15 monocytic MDSCs (M-MDSC) and MDR in NHL relapse cohorts. We executed the role of M-MDSCs in fostering drug resistance phenomenon in doxorubicin-resistant cancer cells in both models. Moreover, supplementation of MDSCs in murine and human lymphoma culture augments early expression of MDR phenotypes than culture without MDSCs, correlated well with drug efflux and tumor progression. We found that MDSC secreted cytokines IL-6, IL-10, IL-1β are the dominant factors elevating MDR expression in cancer cells, neutralization of MDSC secreted IL-6, IL-10, IL-1β reversed the MDR trait. Moreover, we identified MDSC secreted IL-6/IL-10/IL-1β induced STAT1/STAT3/NF-κβ signaling axis as a targeted cascade to promote early drug resistance in cancer cells.
CONCLUSION
Our data suggests that screening patients for high titre of M-MDSCs might be considered as a new potential biomarker and treatment modality in overcoming chemo-resistance in NHL patients.
Topics: Humans; Animals; Mice; Myeloid-Derived Suppressor Cells; Rituximab; Vincristine; Interleukin-10; Prednisone; Interleukin-6; Neoplasm Recurrence, Local; Lymphoma, Non-Hodgkin; Cyclophosphamide; Doxorubicin; Lymphoma; Biomarkers; Drug Resistance, Multiple; Tumor Microenvironment
PubMed: 38304256
DOI: 10.3389/fimmu.2023.1303959 -
Pharmacological Research Apr 2024Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the... (Review)
Review
Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.
Topics: Humans; Antineoplastic Agents; Biological Products; Neoplasms; Drug Resistance, Multiple; Drug Resistance, Neoplasm
PubMed: 38342327
DOI: 10.1016/j.phrs.2024.107099 -
International Journal of Urology :... Mar 2024Antibiotic treatment is extremely stressful for bacteria and has profound effects on their viability. Such administration induces physiological changes in bacterial...
OBJECTIVES
Antibiotic treatment is extremely stressful for bacteria and has profound effects on their viability. Such administration induces physiological changes in bacterial cells, with considerable impact on their genome structure that induces mutations throughout the entire genome. This study investigated drug resistance profiles and structural changes in the entire genome of uropathogenic Escherichia coli (UPEC) strains isolated from six adapted clones that had evolved under laboratory conditions.
METHODS
Eight UPEC strains, including two parental strains and six adapted clones, with different fluoroquinolone resistance levels originally isolated from two patients were used. The minimum inhibitory concentration (MIC) of 28 different antibiotics including levofloxacin was determined for each of the eight strains. In addition, the effects of mutations acquired with increased drug resistance in the levofloxacin-resistant strains on expression of genes implicated to be involved in drug resistance were examined.
RESULTS
Of the eight UPEC strains used to test the MIC of 28 different antibiotics, two highly fluoroquinolone-resistant strains showed increased MIC in association with many of the antibiotics. As drug resistance increased, some genes acquired mutations, including the transcriptional regulator acrR and DNA-binding transcriptional repressor marR. Two strain groups with genetically different backgrounds (GUC9 and GFCS1) commonly acquired mutations in acrR and marR. Notably, acquired mutations related to efflux pump upregulation also contributed to increases in MIC for various antibiotics other than fluoroquinolone.
CONCLUSIONS
The present results obtained using strains with artificially acquired drug resistance clarify the underlying mechanism of resistance to fluoroquinolones and other types of antibiotics.
Topics: Humans; Levofloxacin; Uropathogenic Escherichia coli; Anti-Bacterial Agents; Fluoroquinolones; Drug Resistance, Multiple; Escherichia coli Infections; Urinary Tract Infections; Drug Resistance, Bacterial
PubMed: 38041251
DOI: 10.1111/iju.15348 -
Clinical Infectious Diseases : An... Nov 2023In the past decade, the prevalence of multidrug-resistant gram-negative (MDR-GN) bacterial infections has increased significantly, leading to higher rates of morbidity... (Review)
Review
In the past decade, the prevalence of multidrug-resistant gram-negative (MDR-GN) bacterial infections has increased significantly, leading to higher rates of morbidity and mortality. Treating these infections poses numerous challenges, particularly when selecting appropriate empiric therapy for critically ill patients for whom the margin for error is low. Fortunately, the availability of new therapies has improved the treatment landscape, offering safer and more effective options. However, there remains a need to establish and implement optimal clinical and therapeutic approaches for managing these infections. Here, we review strategies for identifying patients at risk for MDR-GN infections, propose a framework for the choice of empiric and definitive treatment, and explore effective multidisciplinary approaches to managing patients in the hospital while ensuring a safe transition to outpatient settings.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals
PubMed: 37738671
DOI: 10.1093/cid/ciad499