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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 -
Infection and Immunity Jun 2023Acinetobacter infections have high rates of mortality due to an increasing incidence of infections by multidrug-resistant (MDR) and extensively-drug-resistant (XDR)... (Review)
Review
Acinetobacter infections have high rates of mortality due to an increasing incidence of infections by multidrug-resistant (MDR) and extensively-drug-resistant (XDR) strains. Therefore, new therapeutic strategies for the treatment of Acinetobacter infections are urgently needed. Acinetobacter spp. are Gram-negative coccobacilli that are obligate aerobes and can utilize a wide variety of carbon sources. Acinetobacter baumannii is the main cause of Acinetobacter infections, and recent work has identified multiple strategies A. baumannii uses to acquire nutrients and replicate in the face of host nutrient restriction. Some host nutrient sources also serve antimicrobial and immunomodulatory functions. Hence, understanding Acinetobacter metabolism during infection may provide new insights into novel infection control measures. In this review, we focus on the role of metabolism during infection and in resistance to antibiotics and other antimicrobial agents and discuss the possibility that metabolism may be exploited to identify novel targets to treat Acinetobacter infections.
Topics: Humans; Anti-Bacterial Agents; Acinetobacter Infections; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Cross Infection; Acinetobacter baumannii
PubMed: 37191522
DOI: 10.1128/iai.00433-22 -
Trends in Microbiology Dec 2023Acinetobacter baumannii is a Gram-negative opportunistic bacterium responsible for nosocomial and community-acquired infections. This pathogen is globally disseminated... (Review)
Review
Acinetobacter baumannii is a Gram-negative opportunistic bacterium responsible for nosocomial and community-acquired infections. This pathogen is globally disseminated and associated with high levels of antibiotic resistance, which makes it an important threat to human health. Recently, new evidence showed that several A. baumannii isolates can survive and proliferate within eukaryotic professional and/or nonprofessional phagocytic cells, with in vivo consequences. This review provides updated information and describes the tools that A. baumannii possesses to adhere, colonize, and replicate in host cells. Additionally, we emphasize the high genetic and phenotypic heterogeneity detected amongst A. baumannii isolates and its impact on the bacterial intracellular features. We also discuss the need for standardized methods to characterize this pathogen robustly and consequently consider some strains as facultative intracellular bacteria.
Topics: Humans; Drug Resistance, Multiple, Bacterial; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 37487768
DOI: 10.1016/j.tim.2023.06.007 -
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 -
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 -
Revista Argentina de Microbiologia 2023
Topics: Nanotechnology; Anti-Infective Agents; Drug Resistance, Multiple, Bacterial
PubMed: 37775252
DOI: 10.1016/j.ram.2023.08.001 -
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 -
Revista Espanola de Quimioterapia :... Nov 2023In recent years, new antimicrobials have been introduced in therapeutics, including new beta-lactam-beta-lactamase inhibitor combinations and cefiderocol in response to... (Review)
Review
In recent years, new antimicrobials have been introduced in therapeutics, including new beta-lactam-beta-lactamase inhibitor combinations and cefiderocol in response to therapeutic needs in the face of increasing resistance. There are also different treatment guidelines for infections caused by these microorganisms that have been approved by different professional societies, including those of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Disease Society of America (IDSA) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). All of them are based on scientific evidence, but with differences in the weight of expert opinion in their recommendations. Both ESCMID and IDSA include recommendations for the treatment of extended-spectrum beta-lactamase-producing microorganisms. The IDSA is the only one including AmpC producers, all address the treatment of infections caused by carbapenem-resistant Enterobacterales and Acinetobacter baumannii and multidrug-resistant or difficult-to-treat Pseudomonas aeruginosa, and the IDSA and SEIMC include recommendations on the treatment of Stenotrophomonas maltophilia. Future guidelines should integrate new antimicrobials and new innovative management options not covered by current guidelines.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Cephalosporins; Carbapenems; beta-Lactamase Inhibitors; Communicable Diseases; Gram-Negative Bacteria; Microbial Sensitivity Tests
PubMed: 37997871
DOI: 10.37201/req/s01.11.2023 -
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 -
Drug Resistance Updates : Reviews and... Mar 2024Antimicrobial resistance is a global threat to human health, and Acinetobacter baumannii is a paradigmatic example of how rapidly bacteria become resistant to clinically...
AIMS
Antimicrobial resistance is a global threat to human health, and Acinetobacter baumannii is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant A. baumannii strains has forced the revival of colistin as a last-resort drug, suddenly leading to the emergence of colistin resistance. We investigated the genetic and molecular basis of colistin resistance in A. baumannii, and the mechanisms implicated in its regulation and dissemination.
METHODS
Comparative genomic analysis was combined with genetic, biochemical, and phenotypic assays to characterize Φ19606, an A. baumannii temperate bacteriophage that carries a colistin resistance gene.
RESULTS
Ф19606 was detected in 41% of 523 A. baumannii complete genomes and demonstrated to act as a mobile vehicle of the colistin resistance gene eptA1, encoding a functional lipid A phosphoethanolamine transferase. The eptA1 gene is coregulated with its chromosomal homolog pmrC via the PmrAB two-component system and confers colistin resistance when induced by low calcium and magnesium levels. Resistance selection assays showed that the eptA1-harbouring phage Ф19606 promotes the emergence of spontaneous colistin-resistant mutants.
CONCLUSIONS
Φ19606 is an unprecedented example of a self-transmissible phage vector implicated in the dissemination of colistin resistance.
Topics: Humans; Colistin; Anti-Bacterial Agents; Acinetobacter baumannii; Bacterial Proteins; Drug Resistance, Bacterial; Acinetobacter Infections; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial
PubMed: 38301486
DOI: 10.1016/j.drup.2024.101061