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Clinical Microbiology and Infection :... Oct 2023Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due...
OBJECTIVES
Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option. Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole-genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCCs), the likelihood of patient-to-patient transmission and the presence of prophages.
METHODS
Antibiotic susceptibility testing was performed using CLSI breakpoints (n = 95), and plaque assays were used for phage susceptibility testing (subset of n = 88, 35 rough and 53 smooth morphology). WGS was completed using the Illumina platform and analysed using Snippy/snp-dists and Discovery and Extraction of Phages Tool (DEPhT).
RESULTS
Amikacin and Tigecycline were the most active drugs (with 2 strains resistant to amikacin, and one strain with Tigecycline MIC of 4 μg/mL). Most strains were resistant to all other drugs tested, with Linezolid and Imipenem showing the least resistance, at 38% (36/95) and 55% (52/95), respectively. Rough colony morphotype strains were more phage-susceptible than smooth strains (77%-27/35 versus 48%-25/53 in the plaque assays, but smooth strains are not killed efficiently by those phages in liquid infection assay). We have also identified 100 resident prophages, some of which were propagated lytically. DCC1 (20%-18/90) and DCC4 (22%-20/90) were observed to be the major clones and WGS identified 6 events of possible patient-to-patient transmission.
DISCUSSION
Many strains of M. abscessus complex are intrinsically resistant to available antibiotics and bacteriophages represent an alternative therapeutic option, but only for strains with rough morphology. Further studies are needed to elucidate the role of hospital-borne M. abscessus transmission.
Topics: Humans; Mycobacterium abscessus; Amikacin; Tigecycline; Bacteriophages; Phylogeny; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Drug Resistance, Multiple; Delivery of Health Care; Microbial Sensitivity Tests
PubMed: 37364635
DOI: 10.1016/j.cmi.2023.06.026 -
Frontiers in Cellular and Infection... 2023Drug-resistant tuberculosis (DR-TB) in children is a growing global health concern, This review provides an overview of the current epidemiology of childhood TB and... (Review)
Review
Drug-resistant tuberculosis (DR-TB) in children is a growing global health concern, This review provides an overview of the current epidemiology of childhood TB and DR-TB, including prevalence, incidence, and mortality. We discuss the challenges in diagnosing TB and DR-TB in children and the limitations of current diagnostic tools. We summarize the challenges associated with treating multi-drug resistance TB in childhood, including limitations of current treatment options, drug adverse effects, prolonged regimens, and managing and monitoring during treatment. We highlight the urgent need for improved diagnosis and treatment of DR-TB in children. The treatment of children with multidrug-resistant tuberculosis will be expanded to include the evaluation of new drugs or new combinations of drugs. Basic research is needed to support the technological development of biomarkers to assess the phase of therapy, as well as the urgent need for improved diagnostic and treatment options.
Topics: Child; Humans; Antitubercular Agents; Tuberculosis; Tuberculosis, Multidrug-Resistant; Prevalence; Drug Resistance, Multiple; Mycobacterium tuberculosis
PubMed: 37333849
DOI: 10.3389/fcimb.2023.1183590 -
Annals of the New York Academy of... Jan 2020Most clinical antibiotics do not have efficacy against Gram-negative pathogens, mainly because these cells are protected by the permeability barrier comprising the two... (Review)
Review
Most clinical antibiotics do not have efficacy against Gram-negative pathogens, mainly because these cells are protected by the permeability barrier comprising the two membranes with active efflux. The emergence of multidrug-resistant Gram-negative strains threatens the utility even of last resort therapeutic treatments. Significant efforts at different levels of resolution are currently focused on finding a solution to this nonpermeation problem and developing new approaches to the optimization of drug activities against multidrug-resistant pathogens. The exceptional efficiency of the Gram-negative permeability barrier is the result of a complex interplay between the two opposing fluxes of drugs across the two membranes. In this review, we describe the current state of understanding of the problem and the recent advances in theoretical and empirical approaches to characterization of drug permeation and active efflux in Gram-negative bacteria.
Topics: Animals; Anti-Bacterial Agents; Biological Transport; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Permeability
PubMed: 31165502
DOI: 10.1111/nyas.14134 -
Life Sciences Dec 2020Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and... (Review)
Review
Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and radiotherapy are the most common sarcoma treatments. However, sarcomas' response rates to chemotherapy are quite low and sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multi-drug resistance (MDR). Cancer cellular plasticity plays pivotal roles in cancer initiation, progression, therapy resistance and cancer relapse. Moreover, cancer cellular plasticity can be regulated by a multitude of factors, such as genetic and epigenetic alterations, tumor microenvironment (TME) or selective pressure imposed by treatment. Recent studies have demonstrated that cellular plasticity is involved in sarcoma progression and chemoresistance. It's essential to understand the molecular mechanisms of cellular plasticity as well as its roles in sarcoma progression and drug resistance. Therefore, this review focuses on the regulatory mechanisms and pathological roles of these diverse cellular plasticity programs in sarcoma. Additionally, we propose cellular plasticity as novel therapeutic targets to reduce sarcoma drug resistance.
Topics: Antineoplastic Agents; Cell Plasticity; Disease Progression; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Sarcoma; Tumor Microenvironment
PubMed: 33069737
DOI: 10.1016/j.lfs.2020.118589 -
Biomedicine & Pharmacotherapy =... Jun 2023Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically,... (Review)
Review
Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically, the reduced therapeutic performance of various drugs is predominantly due to the inherent over expression of ATP-binding cassette (ABC) transporter proteins on the cell membrane, resulting in the deprived uptake of drugs, augmenting drug detoxification, and DNA repair. In addition to various physiological abnormalities and extensive blood flow, MDR cancer phenotypes exhibit improved apoptotic threshold and drug efflux efficiency. These severe consequences have substantially directed researchers in the fabrication of various advanced therapeutic strategies, such as co-delivery of drugs along with various generations of MDR inhibitors, augmented dosage regimens and frequency of administration, as well as combinatorial treatment options, among others. In this review, we emphasize different reasons and mechanisms responsible for MDR in cancer, including but not limited to the known drug efflux mechanisms mediated by permeability glycoprotein (P-gp) and other pumps, reduced drug uptake, altered DNA repair, and drug targets, among others. Further, an emphasis on specific cancers that share pathogenesis in executing MDR and effluxed drugs in common is provided. Then, the aspects related to various nanomaterials-based supramolecular programmable designs (organic- and inorganic-based materials), as well as physical approaches (light- and ultrasound-based therapies), are discussed, highlighting the unsolved issues and future advancements. Finally, we summarize the review with interesting perspectives and future trends, exploring further opportunities to overcome MDR.
Topics: Humans; Antineoplastic Agents; Drug Resistance, Neoplasm; Drug Resistance, Multiple; ATP-Binding Cassette Transporters; Neoplasms; Pharmaceutical Preparations
PubMed: 37031496
DOI: 10.1016/j.biopha.2023.114643 -
European Journal of Medicinal Chemistry Aug 2021Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells... (Review)
Review
Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells readily emerge after long exposure to chemotherapeutics drugs, resulting in multi-drug resistance (MDR) and treatment failure. Recently, growing evidences indicate that the molecular action mechanisms of cancer MDR are closely associated with abnormalities in saccharides. In this review, saccharides affecting cancer MDR development are elaborated and analyzed in terms of aberrant aerobic glycolysis and its related enzymes, abnormal glycan structures and their associated enzymes, and glycoproteins. The reversal strategies including depletion of ATP, circumventing the original MDR pathway, activation by or inhibition of sugar-related enzymes, combination therapy with traditional cytotoxic agents, and direct modification on the sugar moiety, are ultimately proposed. It follows that abnormal saccharides have a significant effect on cancer MDR development, providing a new perspective for overcoming MDR and improving the outcome of chemotherapy.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Molecular Structure; Neoplasms; Polysaccharides
PubMed: 33933752
DOI: 10.1016/j.ejmech.2021.113487 -
Revista Argentina de Microbiologia 2023
Topics: Nanotechnology; Anti-Infective Agents; Drug Resistance, Multiple, Bacterial
PubMed: 37775252
DOI: 10.1016/j.ram.2023.08.001 -
Revue de L'infirmiere Oct 2023
Topics: Bacteria; Drug Resistance, Multiple, Bacterial
PubMed: 37838375
DOI: 10.1016/j.revinf.2023.08.015 -
Surgical Infections Feb 2021Infection is the most frequent complication after severe burns and remains the predominant cause of death. Burn patients may require multiple courses of antibiotics,...
Infection is the most frequent complication after severe burns and remains the predominant cause of death. Burn patients may require multiple courses of antibiotics, lengthy hospitalizations, and invasive procedures that place burn patients at especially high risk for infections with multi-drug-resistant organisms (MDROs). The published literature on MDROs in burn patients was reviewed to develop a strategy for managing these infections. Within a burn unit meticulous infection prevention and control measures and effective antimicrobial stewardship can limit MDRO propagation and decrease the antibiotic pressure driving the selection of MDROs from less resistant strains. Several new antimicrobial agents have been developed offering potential therapeutic options, but familiarity with their benefits and limitations is required for safe utilization. Successful management of MDRO burn infections is supported by a multifactorial approach. Novel non-antibiotic therapeutics may help combat MDRO infections and outbreaks. Multi-drug-resistant organisms are being identified with increasing frequency in burn patients. Effective sensitivity testing is essential to identify MDROs and to direct appropriate antibiotic choices for patient treatment.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Burn Units; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Pharmaceutical Preparations
PubMed: 32429798
DOI: 10.1089/sur.2020.129 -
The Journal of Hospital Infection Dec 2021Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant... (Review)
Review
Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Dysbiosis; Gastrointestinal Microbiome; Humans; Pharmaceutical Preparations
PubMed: 34492304
DOI: 10.1016/j.jhin.2021.09.001