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Revue de L'infirmiere Oct 2023
Topics: Bacteria; Drug Resistance, Multiple, Bacterial
PubMed: 37838375
DOI: 10.1016/j.revinf.2023.08.015 -
La Tunisie Medicale Mar 2024In recent years, there has been a considerable increase in the prevalence of bacteria increasingly resistant to multiple families of antibiotics, which constitutes a...
INTRODUCTION
In recent years, there has been a considerable increase in the prevalence of bacteria increasingly resistant to multiple families of antibiotics, which constitutes a major problem for public health.
AIM
To determine the prevalence and different risk factors for the acquisition of multi-resistant bacteria.
METHODS
This is an analytical and prospective study including patients hospitalized in the Batna University Hospital during the period from January 2023 to March 2023 presenting a documented infection with isolation of sensitive or multi-resistant strains. An operating sheet based on the different risk factors for acquiring multi-resistant bacteria has been established.
RESULTS
We collected 250 patients. There are 160 men and 90 women with an average age of 44 years. Of all the strains that were identified, 100 isolates were multi-resistant bacteria. ESBL-producing Enterobacteriaceae are the most frequently isolated multi-resistant bacteria. Multivariate logistic regression analysis identified four risk factors that are significantly related to the risk of acquiring multi-resistant bacteria infection: prior antibiotic therapy [P = 0,029], use of invasive medical care [P = 0,024], the nosocomial origin of the infection [P = 0,036] and the use of public toilets [P = 0,015].
CONCLUSION
Our results clearly demonstrate that the inappropriate use of antibiotics, especially broad-spectrum antibiotics, and hand-held cross-transmission play a major role in the spread of multi-resistant bacteria in our hospital.
Topics: Male; Humans; Female; Adult; Prospective Studies; Cross Infection; Risk Factors; Anti-Bacterial Agents; Hospitals, University; Microbial Sensitivity Tests; beta-Lactamases; Enterobacteriaceae Infections; Drug Resistance, Multiple, Bacterial
PubMed: 38545709
DOI: 10.62438/tunismed.v102i3.4578 -
Drug Metabolism and Disposition: the... Aug 2023Over the past two decades, technological advances in membrane protein structural biology have provided insight into the molecular mechanisms that transporters use to... (Review)
Review
Over the past two decades, technological advances in membrane protein structural biology have provided insight into the molecular mechanisms that transporters use to move diverse substrates across the membrane. However, the plasticity of these proteins' ligand binding pockets, which allows them to bind a range of substrates, also poses a challenge for drug development. Here we highlight the structure, function, and transport mechanism of ATP-binding cassette/solute carrier transporters that are related to several diseases and multidrug resistance: ABCB1, ABCC1, ABCG2, SLC19A1, and SLC29A1. SIGNIFICANCE STATEMENT: ATP-binding cassette transporters and solute carriers play vital roles in clinical chemotherapeutic outcomes. This paper describes the current understanding of the structure of five pharmacologically relevant transporters and how they interact with their ligands.
Topics: Membrane Transport Proteins; Cryoelectron Microscopy; Multidrug Resistance-Associated Proteins; ATP-Binding Cassette Transporters; Drug Resistance, Multiple; Drug Resistance, Neoplasm
PubMed: 37438132
DOI: 10.1124/dmd.122.001004 -
Current Opinion in Microbiology Oct 2023Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of... (Review)
Review
Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of resistance using adjuvants are always in demand. Recently, inhibitors have been identified that counteract enzymatic modification of the drugs isoniazid and rifampin, which have implications in the study of multi-drug-resistant mycobacteria. A wealth of structural studies on efflux pumps from diverse bacteria has also fueled the design of new small-molecule and peptide-based agents to prevent the active transport of antibiotics. We envision that these findings will inspire microbiologists to apply existing adjuvants to clinically relevant resistant strains, or to use described platforms to discover novel antibiotic adjuvant scaffolds.
Topics: Bacteria; Anti-Bacterial Agents; Drug Resistance, Microbial; Biological Transport; Drug Resistance, Multiple, Bacterial
PubMed: 37329679
DOI: 10.1016/j.mib.2023.102334 -
Infectious Disease Clinics of North... Sep 2023The overall burden of the main clinically relevant bacterial multidrug-resistant organisms (MDROs) (eg, methicillin-resistant Staphylococcus aureus, vancomycin-resistant... (Review)
Review
The overall burden of the main clinically relevant bacterial multidrug-resistant organisms (MDROs) (eg, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum β-lactamase producing or extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant or carbapenemase-producing Enterobacterales, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii) in solid organ transplant (SOT) populations is summarized showing prevalence/incidence, risk factors, and impact on graft/patient outcome according to the type of SOT. The role of such bacteria in donor-derived infections is also reviewed. As for the management, the main prevention strategies and treatment options are discussed. Finally, nonantibiotic-based strategies are considered as future directions for the management of MDRO in SOT setting.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Methicillin-Resistant Staphylococcus aureus; Organ Transplantation; Transplant Recipients; Vancomycin-Resistant Enterococci
PubMed: 37244806
DOI: 10.1016/j.idc.2023.04.001 -
International Journal of Molecular... Jul 2023Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective...
Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective pressure that triggers the emergence of multi-drug resistance. We performed a large-scale analysis of closed bacterial genomes to identify multi-drug resistance considering the ResFinder antimicrobial classes. We found that more than 95% of the genomes harbor genes associated with resistance to disinfectants, glycopeptides, macrolides, and tetracyclines. On average, each genome encodes resistance to more than nine different classes of antimicrobial drugs. We found higher-than-expected co-occurrences of resistance genes in both plasmids and chromosomes for several classes of antibiotic resistance, including classes categorized as critical according to the World Health Organization (WHO). As a result of antibiotic-resistant priority pathogens, higher-than-expected co-occurrences appear in plasmids, increasing the potential for resistance dissemination. For the first time, co-occurrences of antibiotic resistance have been investigated for priority pathogens as defined by the WHO. For critically important pathogens, co-occurrences appear in plasmids, not in chromosomes, suggesting that the resistances may be epidemic and probably recent. These results hint at the need for new approaches to treating infections caused by critically important bacteria.
Topics: Genome, Bacterial; Plasmids; Anti-Bacterial Agents; Computational Biology; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Drug Resistance, Bacterial
PubMed: 37511196
DOI: 10.3390/ijms241411438 -
Frontiers in Cellular and Infection... 2024The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to... (Review)
Review
The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to acquire mobile genetic elements such as plasmids, represent one of the most hazardous microorganisms. This phenomenon poses a serious threat to public health. Notably, the significance of tigecycline, a member of the antibiotic group glycylcyclines and derivative of tetracyclines has increased. Tigecycline is one of the last-resort antimicrobial drugs used to treat complicated infections caused by multidrug-resistant (MDR) bacteria, extensively drug-resistant (XDR) bacteria or even pan-drug-resistant (PDR) bacteria. The primary mechanisms of tigecycline resistance include efflux pumps' overexpression, genes and outer membrane porins. Efflux pumps are crucial in conferring multi-drug resistance by expelling antibiotics (such as tigecycline by direct expelling) and decreasing their concentration to sub-toxic levels. This review discusses the problem of tigecycline resistance, and provides important information for understanding the existing molecular mechanisms of tigecycline resistance in . The emergence and spread of pathogens resistant to last-resort therapeutic options stands as a major global healthcare concern, especially when microorganisms are already resistant to carbapenems and/or colistin.
Topics: Tigecycline; Anti-Bacterial Agents; Enterobacteriaceae; Humans; Drug Resistance, Multiple, Bacterial; Drug Resistance, Bacterial; Minocycline; Microbial Sensitivity Tests; Plasmids; Enterobacteriaceae Infections
PubMed: 38655285
DOI: 10.3389/fcimb.2024.1289396 -
Frontiers in Cellular and Infection... 2023In the past few decades, drug-resistant (DR) strains of (), the causative agent of tuberculosis (TB), have become increasingly prevalent and pose a threat to worldwide... (Review)
Review
In the past few decades, drug-resistant (DR) strains of (), the causative agent of tuberculosis (TB), have become increasingly prevalent and pose a threat to worldwide public health. These strains range from multi (MDR) to extensively (XDR) drug-resistant, making them very difficult to treat. Further, the current and future impact of the Coronavirus Disease 2019 (COVID-19) pandemic on the development of DR-TB is still unknown. Although exhaustive studies have been conducted depicting the uniqueness of the cell envelope, little is known about how its composition changes in relation to drug resistance acquisition. This knowledge is critical to understanding the capacity of DR- strains to resist anti-TB drugs, and to inform us on the future design of anti-TB drugs to combat these difficult-to-treat strains. In this review, we discuss the complexities of the cell envelope along with recent studies investigating how structurally and biochemically changes in relation to drug resistance. Further, we will describe what is currently known about the influence of drug resistance on infection outcomes, focusing on its impact on fitness, persister-bacteria, and subclinical TB.
Topics: Humans; Mycobacterium tuberculosis; Antitubercular Agents; Tuberculosis; Tuberculosis, Multidrug-Resistant; Global Health; Drug Resistance, Multiple, Bacterial
PubMed: 38029252
DOI: 10.3389/fcimb.2023.1274175 -
Drug Resistance Updates : Reviews and... Nov 2023Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may...
AIMS
Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer.
METHODS
The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo.
RESULTS
CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX. Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells.
CONCLUSIONS
Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.
Topics: Animals; Mice; Antineoplastic Combined Chemotherapy Protocols; Pancreatic Neoplasms; Cardiotoxicity; Cell Membrane; Drug Resistance, Multiple
PubMed: 37647746
DOI: 10.1016/j.drup.2023.101005 -
The Journal of Antimicrobial... Jul 2023To analyse the dynamics and mechanisms of stepwise resistance development to cefiderocol in Pseudomonas aeruginosa.
OBJECTIVES
To analyse the dynamics and mechanisms of stepwise resistance development to cefiderocol in Pseudomonas aeruginosa.
METHODS
Cefiderocol resistance evolution was analysed in WT PAO1, PAOMS (mutS mutator derivate) and three XDR clinical isolates belonging to ST111, ST175 and ST235 clones. Strains were incubated in triplicate experiments for 24 h in iron-depleted CAMHB with 0.06-128 mg/L cefiderocol. Tubes from the highest antibiotic concentration showing growth were reinoculated into fresh medium containing concentrations up to 128 mg/L for 7 consecutive days. Two colonies per strain and experiment were characterized by determining the susceptibility profiles and WGS.
RESULTS
Evolution of resistance was significantly enhanced in PAOMS, but was variable for the XDR strains, including levels similar to PAOMS (ST235), similar to PAO1 (ST175) or even below PAO1 (ST111). WGS revealed 2-5 mutations for PAO1 lineages and 35-58 for PAOMS. The number of mutations in the XDR clinical strains ranged from 2 to 4 except for one of the ST235 experiments in which a mutL lineage was selected, thus increasing the number of mutations. The most frequently mutated genes were piuC, fptA and pirR, related to iron uptake. Additionally, an L320P AmpC mutation was selected in multiple lineages and cloning confirmed its major impact on cefiderocol (but not ceftolozane/tazobactam or ceftazidime/avibactam) resistance. Mutations in CpxS and PBP3 were also documented.
CONCLUSIONS
This work deciphers the potential resistance mechanisms that may emerge upon the introduction of cefiderocol into clinical practice, and highlights that the risk of resistance development might be strain-specific even for XDR high-risk clones.
Topics: Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Cephalosporins; Anti-Bacterial Agents; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; Cefiderocol
PubMed: 37253034
DOI: 10.1093/jac/dkad172