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One Health Outlook Sep 2023Although antimicrobial resistance (AMR) bacteria present a significant and ongoing public health challenge, its magnitude remains poorly understood, especially in many... (Review)
Review
Drug resistance and extended-spectrum β-lactamase (ESBLs) - producing Enterobacteriaceae, Acinetobacter and Pseudomonas species from the views of one-health approach in Ethiopia: a systematic review and meta-analysis.
BACKGROUND
Although antimicrobial resistance (AMR) bacteria present a significant and ongoing public health challenge, its magnitude remains poorly understood, especially in many parts of the developing countries. Hence, this review was conducted to describe the current pooled prevalence of drug resistance, multidrug- resistance (MDR), and Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, Acinetobacter, and Pseudomonas species in humans, the environment, and animals or food of animal origin in Ethiopia.
METHODS
PubMed, Google Scholar, and other sources were searched for relevant articles as per the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. A critical appraisal for screening, eligibility, and inclusion in the meta-analysis was made based on the Joanna Briggs Institute's (JBI) essential appraisal tools. The meta-analysis was done on Statistical Software Package (STATA) version 17.0.
RESULTS
A total of 33 research articles were included in this systematic review and meta-analysis. Escherichia coli, Klebsiella species, Acinetobacter, and Pseudomonas species were the most frequently reported bacteria from two or more sources. More than 50% of Klebsiella species and 25% to 89% of Escherichia coli from two or more sources were resistant to all analysed antibiotics, except carbapenems. Fifty-five percent (55%) to 84% of Acinetobacter species and 33% to 79% of Pseudomonas species from human and environmental sources were resistant to all analyzed antibiotics. Carbapenem resistance was common in Acinetobacter and Pseudomonas species (38% to 64%) but uncommon in Enterobacteriaceae (19% to 44%). Acinetobacter species (92%), Klebsiella species (86%), and Pseudomonas species (79%) from human sources, and Proteus species (92%), and Acinetobacter species (83%), from environmental sources, were the common multidrug-resistant isolates. About 45% to 67% of E. coli, Klebsiella, Acinetobacter, and Pseudomonas species from human and environmental sources were ESBL producers.
CONCLUSION
Our review report concluded that there was a significant pooled prevalence of drug resistance, MDR, and ESBL-producing Enterobacteriaceae, Acinetobacter, and Pseudomonas species from two or more sources. Hence, our finding underlines the need for the implementation of integrated intervention approaches to address the gaps in reducing the emergence and spread of antibiotic- resistant bacteria.
PubMed: 37697359
DOI: 10.1186/s42522-023-00088-z -
Antibiotics (Basel, Switzerland) Jun 2023: The antimicrobial resistance (AMR) of bacteria is increasing rapidly against all classes of antibiotics, with the increasing detection of carbapenem-resistant...
: The antimicrobial resistance (AMR) of bacteria is increasing rapidly against all classes of antibiotics, with the increasing detection of carbapenem-resistant isolates. However, while growing prevalence has been reported around the world, data on the prevalence of carbapenem resistance in developing countries are fairly limited. In this study, we investigated and determined the resistance rate to carbapenems among multidrug-resistant Gram-negative bacteria (MDR-GNB) isolated in Djibouti and characterized their resistance mechanisms. : Of the 256 isolates, 235 (91.8%) were identified as Gram-negative bacteria (GNB). Of these GNBs, 225 (95.7%) isolates exhibited a multidrug resistance phenotype, and 20 (8.5%) isolates were resistant to carbapenems, including 13 coli, 4 , 2 and 1 . The most predominant GNB in this hospital setting were and species. Carbapenemase genes such as and were identified, respectively, in six and four isolates, whereas the carbapenemase was identified in three , two , one and one . Moreover, three isolates co-hosted and . : A total of 256 clinical strains collected between 2019 and 2020 were identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Antibiotic susceptibility testing was performed using disk diffusion and E-test methods. Real-time polymerase chain reaction (RT-PCR), standard PCR and sequencing were used to investigate genes encoding for extended-spectrum-β-lactamases, carbapenemases and colistin resistance genes. : We report, for the first time, the presence of MDR-GNB clinical isolates and the emergence of carbapenem-resistant isolates in Djibouti. In addition to performing antimicrobial susceptibility testing, we recommend phenotypic and molecular screening to track the spread of carbapenemase genes among clinical GNB isolates.
PubMed: 37508230
DOI: 10.3390/antibiotics12071132 -
Sensors (Basel, Switzerland) Sep 2023Bacterial resistance to antibiotics is a primary global healthcare concern as it hampers the effectiveness of commonly used antibiotics used to treat infectious...
Bacterial resistance to antibiotics is a primary global healthcare concern as it hampers the effectiveness of commonly used antibiotics used to treat infectious diseases. The development of bacterial resistance continues to escalate over time. Rapid identification of the infecting bacterium and determination of its antibiotic susceptibility are crucial for optimal treatment and can save lives in many cases. Classical methods for determining bacterial susceptibility take at least 48 h, leading physicians to resort to empirical antibiotic treatment based on their experience. This random and excessive use of antibiotics is one of the most significant drivers of the development of multidrug-resistant (MDR) bacteria, posing a severe threat to global healthcare. To address these challenges, considerable efforts are underway to reduce the testing time of taxonomic classification of the infecting bacterium at the species level and its antibiotic susceptibility determination. Infrared spectroscopy is considered a rapid and reliable method for detecting minor molecular changes in cells. Thus, the main goal of this study was the use of infrared spectroscopy to shorten the identification and the susceptibility testing time of and from 48 h to approximately 40 min, directly from patients' urine samples. It was possible to identify the and species with 99% accuracy and, simultaneously, to determine their susceptibility to different antibiotics with an accuracy exceeding 80%.
Topics: Humans; Pseudomonas; Microbial Sensitivity Tests; Proteus; Bacteria; Bacterial Infections; Anti-Bacterial Agents; Spectrophotometry, Infrared; Machine Learning; Urinary Tract Infections
PubMed: 37836961
DOI: 10.3390/s23198132 -
Ecotoxicology and Environmental Safety Jun 2024Cadmium (Cd) pollution is a serious global environmental problem, which requires a global concern and practical solutions. Microbial remediation has received widespread...
Cadmium (Cd) pollution is a serious global environmental problem, which requires a global concern and practical solutions. Microbial remediation has received widespread attention owing to advantages, such as environmental friendliness and soil amelioration. However, Cd toxicity also severely deteriorates the remediation performance of functional microorganisms. Analyzing the mechanism of bacterial resistance to Cd stress will be beneficial for the application of Cd remediation. In this study, the bacteria strain, up to 1400 mg/L Cd resistance, was employed and identified as Proteus mirabilis Ch8 (Ch8) through whole genome sequence analyses. The results indicated that the multiple pathways of immobilizing and detoxifying Cd maintained the growth of Ch8 under Cd stress, which also possessed high Cd extracellular adsorption. Firstly, the changes in surface morphology and functional groups of Ch8 cells were observed under different Cd conditions through SEM-EDS and FTIR analyses. Under 100 mg/L Cd, Ch8 cells exhibited aggregation and less flagella; the Cd biosorption of Ch8 was predominately by secreting exopolysaccharides (EPS) and no significant change of functional groups. Under 500 mg/L Cd, Ch8 were present irregular polymers on the cell surface, some cells with wrapping around; the Cd biosorption capacity exhibited outstanding effects (38.80 mg/g), which was mainly immobilizing Cd by secreting and interacting with EPS. Then, Ch8 also significantly enhanced the antioxidant enzyme activity and the antioxidant substance content under different Cd conditions. The activities of SOD and CAT, GSH content of Ch8 under 500 mg/L Cd were significantly increased by 245.47%, 179.52%, and 241.81%, compared to normal condition. Additionally, Ch8 significantly induced the expression of Acr A and Tol C (the resistance-nodulation-division (RND) efflux pump), and some antioxidant genes (SodB, SodC, and Tpx) to reduce Cd damage. In particular, the markedly higher expression levels of SodB under Cd stress. The mechanism of Ch8 lays a foundation for its application in solving soil remediation.
Topics: Proteus mirabilis; Cadmium; Soil Pollutants; Biodegradation, Environmental
PubMed: 38728947
DOI: 10.1016/j.ecoenv.2024.116432 -
Pathogens (Basel, Switzerland) Jul 2023Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1)...
Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1) Methods: Between January 2019 and July 2022, 240 isolates of enterobacteria resistant to third-generation cephalosporins and imipenem from biological samples from Fann Hospital (Dakar) and Hôpital Paix (Ziguinchor) were selected. The isolates were identified by MALDI-TOF mass spectrometry, and susceptibility tests were performed by the disk diffusion method. Antibiotic-resistance genes for class A beta-lactamases, carbapenemases, and plasmid resistance to colistin resistance () were screened by RT-PCR. (2) Results: The 240 enterobacteria were composed of: (60.83%), (21.67%), (13.75%), (2.08%), (0.83%), (0.42%), and (0.42%). Class A beta-lactamase genes were found in 229 isolates (70.41% , 37.5% , 83.75% , and 0.42% ). The carbapenemase genes and were found in 25 isolates, including 14 isolates with , 13 isolates with , and 2 isolates with both genes simultaneously. The gene was found in one isolate of . (3) Conclusions: The epidemiology of antibiotic-resistance genes in enterobacteria in Senegal shows the emergence of CPEs. This phenomenon is worrying, and rigorous surveillance is necessary to avoid further spread.
PubMed: 37623934
DOI: 10.3390/pathogens12080974 -
PloS One 2023Proteus mirabilis is an opportunistic pathogen associated with a variety of human infections, including urinary tract infections. The prevalence of P. mirabilis in foods...
Proteus mirabilis is an opportunistic pathogen associated with a variety of human infections, including urinary tract infections. The prevalence of P. mirabilis in foods of animal origin and in the manure by-products created in animal production is not well documented. Further, the prevalence and persistence of extended-spectrum cephalosporin (ESC) resistant P. mirabilis is largely unknown. In this study, we characterized ESC-resistant P. mirabilis recovered from various stages of dairy manure anaerobic digestion. Isolates were screened by PCR for blaCTX-M, blaCMY and blaSHV, and antimicrobial susceptibility testing was performed. Fifty-six P. mirabilis carrying CTX-M were sequenced with short and long read sequencing technologies, and the assembled chromosomes and plasmids were compared. ESC-resistant Proteus was found in four of the six manure digesters, an indication that not all digesters were colonized with resistant strains. Both CTX-M-1 and CTX-M-15 plasmids were found in P. mirabilis isolates. Transfer of plasmid DNA by conjugation was also explored, with ESC-resistance plasmids able to transfer to Escherichia coli at high frequency. We concluded that P. mirabilis can harbour and transfer ESC-resistance genes and plasmids, and may be an overlooked reservoir of antimicrobial resistance.
Topics: Animals; Cattle; Humans; Proteus mirabilis; Manure; Anaerobiosis; Cephalosporins; Escherichia coli; Plasmids; beta-Lactamases; Anti-Infective Agents; Anti-Bacterial Agents
PubMed: 37561682
DOI: 10.1371/journal.pone.0289703 -
American Heart Journal Sep 2023Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome.
METHODS
PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis.
DISCUSSION
This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE.
TRIAL REGISTRATION
Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199.
Topics: Humans; Echocardiography, Stress; Artificial Intelligence; State Medicine; Coronary Artery Disease; Coronary Angiography
PubMed: 37192698
DOI: 10.1016/j.ahj.2023.05.003 -
Biomedicine & Pharmacotherapy =... Sep 2023The pleckstrin homology [PH] domain is a structural fold found in more than 250 proteins making it the 11th most common domain in the human proteome. 25% of family... (Review)
Review
The pleckstrin homology [PH] domain is a structural fold found in more than 250 proteins making it the 11th most common domain in the human proteome. 25% of family members have more than one PH domain and some PH domains are split by one, or several other, protein domains although still folding to give functioning PH domains. We review mechanisms of PH domain activity, the role PH domain mutation plays in human disease including cancer, hyperproliferation, neurodegeneration, inflammation, and infection, and discuss pharmacotherapeutic approaches to regulate PH domain activity for the treatment of human disease. Almost half PH domain family members bind phosphatidylinositols [PIs] that attach the host protein to cell membranes where they interact with other membrane proteins to give signaling complexes or cytoskeleton scaffold platforms. A PH domain in its native state may fold over other protein domains thereby preventing substrate access to a catalytic site or binding with other proteins. The resulting autoinhibition can be released by PI binding to the PH domain, or by protein phosphorylation thus providing fine tuning of the cellular control of PH domain protein activity. For many years the PH domain was thought to be undruggable until high-resolution structures of human PH domains allowed structure-based design of novel inhibitors that selectively bind the PH domain. Allosteric inhibitors of the Akt1 PH domain have already been tested in cancer patients and for proteus syndrome, with several other PH domain inhibitors in preclinical development for treatment of other human diseases.
Topics: Humans; Pleckstrin Homology Domains; Binding Sites; Blood Proteins; Phosphoproteins; Protein Binding
PubMed: 37399719
DOI: 10.1016/j.biopha.2023.115024 -
Infectious Diseases and Therapy Jul 2023Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate...
INTRODUCTION
Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria.
METHODS
The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic.
RESULTS
Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p < 0.05). The largest decreases were seen in carbapenem-resistant phenotypes of P. mirabilis, Klebsiella, and M. morganii (AAPCs: - 22.9%, - 20.7%, and - 20.6%, respectively). In 2020, percent susceptibility was over 80% for all organisms tested against aminoglycosides, cefepime, ertapenem, meropenem, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam.
CONCLUSION
We observed significant decreases in antibiotic resistance for P. aeruginosa and Enterobacterales over the past decade. According to the 2020 antibiogram, in vitro antimicrobial activity was observed for most treatment options. These results may be related to the robust infection control and antimicrobial stewardship programs instituted nationally among VAMCs.
PubMed: 37326931
DOI: 10.1007/s40121-023-00827-9 -
ACS Omega Aug 2023A series of 32 thiourea-based urease inhibitors were synthesized and evaluated against native bacterial enzyme and whole cells of and strains. The proposed inhibitors...
A series of 32 thiourea-based urease inhibitors were synthesized and evaluated against native bacterial enzyme and whole cells of and strains. The proposed inhibitors represented structurally diverse thiosemicarbazones and thiocarbohydrazones, benzyl-substituted thiazolyl thioureas, 1-pyrazole-1-carbothioamides, and dihydropirimidine-2(1)-thiones. Kinetic characteristics with purified enzyme determined low micromolar inhibitors within each structural group. ()-2-(1-Phenylethylidene)hydrazine-1-carbothioamide ( = 0.39 ± 0.01 μM), ()-2-(4-methylbenzylidene)hydrazine-1-carbothioamide ( = 0.99 ± 0.04 μM), and '-((1,2)-1,3-diphenylallylidene)hydrazinecarbothiohydrazide ( = 2.23 ± 0.19 μM) were used in modeling studies that revealed sulfur ion coordination of the active site nickel ion and hydrogen bonds between the amide group and the side chain of Asp363 and Ala366 carbonyl moiety. Whole-cell studies proved the activity of compounds in Gram-positive and Gram-negative microorganisms. Ureolysis control observed in PCM 543 (e.g., IC = 304 ± 14 μM for 1-benzyl-3-(4-(4-hydroxyphenyl)thiazol-2-yl)thiourea ) is a valuable achievement, as urease is recognized as a major virulence factor of this urinary tract pathogen.
PubMed: 37576686
DOI: 10.1021/acsomega.3c03702