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European Journal of Clinical... Dec 2023In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health... (Review)
Review
In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health Organization as a priority one for the need of new therapeutic agents. A. baumannii has the capacity to develop robust biofilms on biotic and abiotic surfaces. Biofilm development allows these bacteria to resist various environmental stressors, including antibiotics and lack of nutrients or water, which in turn allows the persistence of A. baumannii in the hospital environment and further outbreaks. Investigation into therapeutic alternatives that will act on both biofilm formation and antimicrobial resistance (AMR) is sorely needed. The aim of the present review is to critically discuss the various mechanisms by which AMR and biofilm formation may be co-regulated in A. baumannii in an attempt to shed light on paths towards novel therapeutic opportunities. After discussing the clinical importance of A. baumannii, this critical review highlights biofilm-formation genes that may be associated with the co-regulation of AMR. Particularly worthy of consideration are genes regulating the quorum sensing system AbaI/AbaR, AbOmpA (OmpA protein), Bap (biofilm-associated protein), the two-component regulatory system BfmRS, the PER-1 β-lactamase, EpsA, and PTK. Finally, this review discusses ongoing experimental therapeutic strategies to fight A. baumannii infections, namely vaccine development, quorum sensing interference, nanoparticles, metal ions, natural products, antimicrobial peptides, and phage therapy. A better understanding of the mechanisms that co-regulate biofilm formation and AMR will help identify new therapeutic targets, as combined approaches may confer synergistic benefits for effective and safer treatments.
Topics: Humans; Anti-Bacterial Agents; Acinetobacter baumannii; Drug Resistance, Bacterial; Biofilms; Quorum Sensing; Drug Resistance, Multiple, Bacterial
PubMed: 37897520
DOI: 10.1007/s10096-023-04677-8 -
Frontiers in Public Health 2024
Topics: Humans; Antimicrobial Stewardship; COVID-19; SARS-CoV-2; Anti-Bacterial Agents; Drug Resistance, Microbial; COVID-19 Drug Treatment
PubMed: 38751594
DOI: 10.3389/fpubh.2024.1398981 -
Current Opinion in Infectious Diseases Dec 2023The aim of this narrative review is to compare the prognostic utility of the new definition of difficult-to-treat resistance (DTR) vs. established definitions in... (Review)
Review
PURPOSE OF REVIEW
The aim of this narrative review is to compare the prognostic utility of the new definition of difficult-to-treat resistance (DTR) vs. established definitions in patients with Pseudomonas aeruginosa infection to understand the therapeutic implications of resistance classification and its impact on clinical outcome.
RECENT FINDINGS
Among Gram-negative bacteria (GNB), P. aeruginosa (PA) is associated with high rates of morbidity and mortality, mostly related to its intrinsic capacity of developing antibiotic resistance. Several classifications of antibiotic resistance have been proposed in the last 15 years. The most common used is that from Magiorakos et al. including multidrug resistance (MDR), extensively drug-resistant (XDR) and pan drug resistance (PDR) according to the number of antibiotic classes showing in vitro activity. A further classification based on the resistance to specific antibiotic classes (i.e. fluoroquinolones, cephalosporins, carbapenem resistance) was also proposed. However, both of them have been criticized because of limited usefulness in clinical practice and for poor correlation with patient outcome, mainly in infections due to PA. More recently the new definition of difficult-to-treat resistance (DTR) has been proposed referring to nonsusceptibility to all first-line agents showing high-efficacy and low-toxicity (i.e. carbapenems, β-lactam-β-lactamase inhibitor combinations, and fluoroquinolones). Studies including large cohorts of patients with GNB bloodstream infections have confirmed the prognostic value of DTR classification and its clinical usefulness mainly in infections due to PA. Indeed, in the recent documents from the Infectious Diseases Society of America (IDSA) on the management of antibiotic resistant GNB infections, the DTR classification was applied to PA.
SUMMARY
DTR definition seems to identify better than MDR/XDR/PDR and single class resistant categories the cases of PA with limited treatment options. It requires periodic revision in order to remain up-to-date with the introduction of new antibiotics and the evolving pattern of resistance.
Topics: Humans; Pseudomonas aeruginosa; Anti-Bacterial Agents; Cephalosporins; Gram-Negative Bacterial Infections; Drug Resistance, Multiple; beta-Lactamase Inhibitors; Fluoroquinolones; Gram-Negative Bacteria; Pseudomonas Infections; Seizures; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests
PubMed: 37930070
DOI: 10.1097/QCO.0000000000000966 -
PLoS Computational Biology May 2024Multi-drug combinations to treat bacterial populations are at the forefront of approaches for infection control and prevention of antibiotic resistance. Although the...
Multi-drug combinations to treat bacterial populations are at the forefront of approaches for infection control and prevention of antibiotic resistance. Although the evolution of antibiotic resistance has been theoretically studied with mathematical population dynamics models, extensions to spatial dynamics remain rare in the literature, including in particular spatial evolution of multi-drug resistance. In this study, we propose a reaction-diffusion system that describes the multi-drug evolution of bacteria based on a drug-concentration rescaling approach. We show how the resistance to drugs in space, and the consequent adaptation of growth rate, is governed by a Price equation with diffusion, integrating features of drug interactions and collateral resistances or sensitivities to the drugs. We study spatial versions of the model where the distribution of drugs is homogeneous across space, and where the drugs vary environmentally in a piecewise-constant, linear and nonlinear manner. Although in many evolution models, per capita growth rate is a natural surrogate for fitness, in spatially-extended, potentially heterogeneous habitats, fitness is an emergent property that potentially reflects additional complexities, from boundary conditions to the specific spatial variation of growth rates. Applying concepts from perturbation theory and reaction-diffusion equations, we propose an analytical metric for characterization of average mutant fitness in the spatial system based on the principal eigenvalue of our linear problem, λ1. This enables an accurate translation from drug spatial gradients and mutant antibiotic susceptibility traits to the relative advantage of each mutant across the environment. Our approach allows one to predict the precise outcomes of selection among mutants over space, ultimately from comparing their λ1 values, which encode a critical interplay between growth functions, movement traits, habitat size and boundary conditions. Such mathematical understanding opens new avenues for multi-drug therapeutic optimization.
Topics: Anti-Bacterial Agents; Models, Biological; Drug Resistance, Multiple, Bacterial; Computational Biology; Bacteria; Computer Simulation; Drug Resistance, Multiple; Evolution, Molecular; Humans
PubMed: 38820350
DOI: 10.1371/journal.pcbi.1012098 -
Parasitology Jan 2024Leishmaniasis is a vector-borne parasitic disease caused by parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral... (Review)
Review
Leishmaniasis is a vector-borne parasitic disease caused by parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral complications. Treatment of this infection has been extremely challenging with the concurrent emergence of drug resistance. The differential gene expression and the discrepancies in protein functions contribute to the appearance of 2 distinct phenotypes: resistant and sensitive, but the current diagnostic tools fail to differentiate between them. The identification of gene expression patterns and molecular mechanisms coupled with antimony (Sb) resistance can be leveraged to prompt diagnosis and select the most effective treatment methods. The present study attempts to use comparative expression of Sb resistance-associated genes in resistant and sensitive , to disclose their relative abundance in clinical or selected isolates to gain an understanding of the molecular mechanisms of Sb response/resistance. Data suggest that the analysis of resistance gene expression would verify the Sb resistance or susceptibility only to a certain extent; however, none of the individual expression patterns of the studied genes was diagnostic as a biomarker of Sb response of . The findings highlighted will be useful in bridging the knowledge gap and discovering innovative diagnostic tools and novel therapeutic targets.
Topics: Leishmania; Antimony; Proteomics; Antiprotozoal Agents; Drug Resistance; Gene Expression
PubMed: 38012864
DOI: 10.1017/S0031182023001129 -
Epidemiology and Infection May 2024
Topics: Humans; One Health; Drug Resistance, Bacterial; Anti-Bacterial Agents
PubMed: 38711386
DOI: 10.1017/S0950268824000529 -
The Lancet. Healthy Longevity Nov 2023
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Healthy Aging
PubMed: 37924836
DOI: 10.1016/S2666-7568(23)00218-0 -
Frontiers in Cellular and Infection... 2023Biofilms are a common survival strategy employed by bacteria in healthcare settings, which enhances their resistance to antimicrobial and biocidal agents making... (Review)
Review
Biofilms are a common survival strategy employed by bacteria in healthcare settings, which enhances their resistance to antimicrobial and biocidal agents making infections difficult to treat. Mechanisms of biofilm-induced antimicrobial resistance involve reduced penetration of antimicrobial agents, increased expression of efflux pumps, altered microbial physiology, and genetic changes in the bacterial population. Factors contributing to the formation of biofilms include nutrient availability, temperature, pH, surface properties, and microbial interactions. Biofilm-associated infections can have serious consequences for patient outcomes, and standard antimicrobial therapies are often ineffective against biofilm-associated bacteria, making diagnosis and treatment challenging. Novel strategies, including antibiotics combination therapies (such as daptomycin and vancomycin, colistin and azithromycin), biofilm-targeted agents (such as small molecules (LP3134, LP3145, LP4010, LP1062) target c-di-GMP), and immunomodulatory therapies (such as the anti-PcrV IgY antibodies which target Type IIIsecretion system), are being developed to combat biofilm-induced antimicrobial resistance. A multifaceted approach to diagnosis, treatment, and prevention is necessary to address this emerging problem in healthcare settings.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Azithromycin; Biofilms; Colistin
PubMed: 38188636
DOI: 10.3389/fcimb.2023.1327069 -
International Journal of Molecular... Sep 2023A chemotherapeutic approach is crucial in malignancy management, which is often challenging due to the development of chemoresistance. Over time, chemo-resistant cancer... (Review)
Review
A chemotherapeutic approach is crucial in malignancy management, which is often challenging due to the development of chemoresistance. Over time, chemo-resistant cancer cells rapidly repopulate and metastasize, increasing the recurrence rate in cancer patients. Targeting these destined cancer cells is more troublesome for clinicians, as they share biology and molecular cross-talks with normal cells. However, the recent insights into the metabolic profiles of chemo-resistant cancer cells surprisingly illustrated the activation of distinct pathways compared with chemo-sensitive or primary cancer cells. These distinct metabolic dynamics are vital and contribute to the shift from chemo-sensitivity to chemo-resistance in cancer. This review will discuss the important metabolic alterations in cancer cells that lead to drug resistance.
Topics: Humans; Drug Resistance, Neoplasm; Glucose; Neoplasms
PubMed: 37762231
DOI: 10.3390/ijms241813928 -
Clinical Infectious Diseases : An... Dec 2023Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) gained insight into the range of national antimicrobial resistance...
Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) gained insight into the range of national antimicrobial resistance (AMR) stakeholders' long-term visions for AMR surveillance networks. As national AMR networks mature, stakeholders often contemplate adding laboratories to the network to achieve greater representativeness, boost data quantity, or meet other goals. Therefore, stakeholders should carefully select laboratories for expansion based on their goals and several practical criteria. Based on CAPTURA experience, the key criteria a national network may consider when expanding its AMR surveillance network include location, laboratory ownership, access to linked clinical and prescription databases, logistical ease, a laboratory's collaborative spirit, laboratory practices and equipment, laboratory staffing and quality assessments, laboratory methods and specimen types, data cleanliness and completeness, and the quantity of AMR data.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Laboratories; Asia
PubMed: 38118012
DOI: 10.1093/cid/ciad548