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PLoS Pathogens Apr 2024Drug-resistant tuberculosis (DR-TB) threatens progress in the control of TB. Mathematical models are increasingly being used to guide public health decisions on managing...
Drug-resistant tuberculosis (DR-TB) threatens progress in the control of TB. Mathematical models are increasingly being used to guide public health decisions on managing both antimicrobial resistance (AMR) and TB. It is important to consider bacterial heterogeneity in models as it can have consequences for predictions of resistance prevalence, which may affect decision-making. We conducted a systematic review of published mathematical models to determine the modelling landscape and to explore methods for including bacterial heterogeneity. Our first objective was to identify and analyse the general characteristics of mathematical models of DR-mycobacteria, including M. tuberculosis. The second objective was to analyse methods of including bacterial heterogeneity in these models. We had different definitions of heterogeneity depending on the model level. For between-host models of mycobacterium, heterogeneity was defined as any model where bacteria of the same resistance level were further differentiated. For bacterial population models, heterogeneity was defined as having multiple distinct resistant populations. The search was conducted following PRISMA guidelines in five databases, with studies included if they were mechanistic or simulation models of DR-mycobacteria. We identified 195 studies modelling DR-mycobacteria, with most being dynamic transmission models of non-treatment intervention impact in M. tuberculosis (n = 58). Studies were set in a limited number of specific countries, and 44% of models (n = 85) included only a single level of "multidrug-resistance (MDR)". Only 23 models (8 between-host) included any bacterial heterogeneity. Most of these also captured multiple antibiotic-resistant classes (n = 17), but six models included heterogeneity in bacterial populations resistant to a single antibiotic. Heterogeneity was usually represented by different fitness values for bacteria resistant to the same antibiotic (61%, n = 14). A large and growing body of mathematical models of DR-mycobacterium is being used to explore intervention impact to support policy as well as theoretical explorations of resistance dynamics. However, the majority lack bacterial heterogeneity, suggesting that important evolutionary effects may be missed.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Models, Theoretical; Antitubercular Agents
PubMed: 38598556
DOI: 10.1371/journal.ppat.1011574 -
Journal of Digestive Diseases Mar 2024To update evidence-based data comparing the efficacy and safety of high-dose dual therapy (HDDT) and bismuth-containing quadruple therapy (BQT) in eradicating... (Meta-Analysis)
Meta-Analysis Comparative Study Review
OBJECTIVE
To update evidence-based data comparing the efficacy and safety of high-dose dual therapy (HDDT) and bismuth-containing quadruple therapy (BQT) in eradicating Helicobacter pylori infection through meta-analysis.
METHODS
Multiple databases were systematically searched for randomized controlled trials (RCTs) published up to May 18, 2023. Dichotomous data were evaluated using risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis, sensitivity analysis, risk of bias assessment, and quality of evidence evaluation were performed.
RESULTS
Twenty RCTs containing 7891 subjects were included in the analysis. There was no statistically significant difference in H. pylori eradication rate between HDDT and BQT in the intention-to-treat (ITT) analysis (86.31% vs 84.88%; RR 1.02, 95% CI 1.00-1.04, P = 0.12). In the per-protocol (PP) analysis, the eradication rates for HDDT and BQT were 90.27% and 89.94%, respectively (RR 1.01, 95% CI 0.99-1.03, P = 0.44). Adverse events were significantly lower with HDDT than with BQT (RR 0.44, 95% CI 0.38-0.51, P < 0.00001). Patient adherence was significantly different between the two groups (RR 1.01, 95% CI 1.00-1.03, P = 0.02). Subgroup analysis based on antibiotic combinations within the BQT group showed a significantly higher eradication rate for HDDT than for BQT only when BQT used amoxicillin combined with clarithromycin (P = 0.0009).
CONCLUSIONS
HDDT showed comparable efficacy with BQT for H. pylori eradication, with fewer adverse effects and higher compliance. Due to regional differences, antibiotic resistance rates, and combined BQT antibiotics, more studies are needed for further validation and optimization of HDDT.
Topics: Helicobacter Infections; Humans; Helicobacter pylori; Drug Therapy, Combination; Anti-Bacterial Agents; Bismuth; Proton Pump Inhibitors; Treatment Outcome; Randomized Controlled Trials as Topic; Amoxicillin
PubMed: 38577962
DOI: 10.1111/1751-2980.13263 -
The American Journal of Tropical... May 2024Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of...
Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of resources. We conducted a systematic search and review of publications in seven databases to compile resistance marker data from studies in India. The sample collection from the studies identified from this search was conducted between 1994 and 2020, and these studies were published between 1994 and 2022. In all, Plasmodium falciparum Kelch13 (PfK13), P. falciparum dihydropteroate synthase, and P. falciparum dihydrofolate reductase (PfDHPS) genotype data from 2,953, 4,148, and 4,222 blood samples from patients with laboratory-confirmed malaria, respectively, were extracted from these publications and uploaded onto the WorldWide Antimalarial Resistance Network molecular surveyors. These data were fed into hierarchical geostatistical models to produce maps with a predicted prevalence of the PfK13 and PfDHPS markers, and of the associated uncertainty. Zones with a predicted PfDHPS 540E prevalence of >15% were identified in central, eastern, and northeastern India. The predicted prevalence of PfK13 mutants was nonzero at only a few locations, but were within or adjacent to the zones with >15% prevalence of PfDHPS 540E. There may be a greater probability of artesunate-sulfadoxine-pyrimethamine failures in these regions, but these predictions need confirmation. This work can be applied in India and elsewhere to help identify the treatments most likely to be effective for malaria elimination.
Topics: Plasmodium falciparum; Pyrimethamine; Sulfadoxine; India; Drug Resistance; Antimalarials; Drug Combinations; Humans; Malaria, Falciparum; Artemisinins; Tetrahydrofolate Dehydrogenase; Genetic Markers; Dihydropteroate Synthase; Protozoan Proteins
PubMed: 38574550
DOI: 10.4269/ajtmh.23-0631 -
PLOS Global Public Health 2024Antimicrobial resistance is a global public health crisis. Effective antimicrobial stewardship requires an understanding of the factors and context that contribute to...
Antimicrobial resistance is a global public health crisis. Effective antimicrobial stewardship requires an understanding of the factors and context that contribute to inappropriate use of antimicrobials. The goal of this qualitative systematic review was to synthesize themes across levels of the social ecological framework that drive inappropriate use of antimicrobials in South Asia. In September 2023, we conducted a systematic search using the electronic databases PubMed and Embase. Search terms, identified a priori, were related to research methods, topic, and geographic location. We identified 165 articles from the initial search and 8 upon reference review (n = 173); after removing duplicates and preprints (n = 12) and excluding those that did not meet eligibility criteria (n = 115), 46 articles were included in the review. We assessed methodological quality using the qualitative Critical Appraisal Skills Program checklist. The studies represented 6 countries in South Asia, and included data from patients, health care providers, community members, and policy makers. For each manuscript, we wrote a summary memo to extract the factors that impede antimicrobial stewardship. We coded memos using NVivo software; codes were organized by levels of the social ecological framework. Barriers were identified at multiple levels including the patient (self-treatment with antimicrobials; perceived value of antimicrobials), the provider (antimicrobials as a universal therapy; gaps in knowledge and skills; financial or reputational incentives), the clinical setting (lack of resources; poor regulation of the facility), the community (access to formal health care; informal drug vendors; social norms), and policy (absence of a regulatory framework; poor implementation of existing policies). This study is the first to succinctly identify a range of norms, behaviors, and policy contexts driving inappropriate use of antimicrobials in South Asia, emphasizing the importance of working across multiple sectors to design and implement approaches specific to the region.
PubMed: 38573955
DOI: 10.1371/journal.pgph.0002507 -
Journal of Infection and Public Health May 2024Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and... (Meta-Analysis)
Meta-Analysis
Clinical outcomes of colistin methanesulfonate sodium in correlation with pharmacokinetic parameters in critically ill patients with multi-drug resistant bacteria-mediated infection: A systematic review and meta-analysis.
BACKGROUND
Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and nephrotoxicity risks hinder its clinical use. Thus, the aim of this study is to investigate clinical outcomes in correlation with pharmacokinetic differences and infection types in critically ill patients on intravenous colistin methanesulfornate sodium (CMS).
METHODS
A systematic literature search of Embase, Google Scholars, and PubMed was performed to identify clinical trials evaluating pharmacokinetic parameters along with clinical outcomes of CMS treatment from inception to July 2023. The pooled analyses of clinical impact of CMS on nephrotoxicity, mortality, clinical cure, and colistin concentration at steady state (C) were performed. This study was registered in the PROSPERO (CRD 42023456120).
RESULTS
Total of 695 critically ill patients from 17 studies were included. The mortality was substantially lower in clinically cured patients (OR 0.05; 95% CI 0.02 - 0.14), whereas the mortality rate was statistically insignificant between nephrotoxic and non-nephrotoxic patients. Inter-patient variability of pharmacokinetic parameters of CMS and colistin was observed in critically ill patients. The standard mean differences of C were statistically insignificant between clinically cure and clinically failure groups (standard mean difference (SMD) -0.25; 95% CI -0.69 - 0.19) and between nephrotoxic and non-nephrotoxic groups (SMD 0.67; 95% CI -0.27-1.61). The clinical cure rate is substantially lower in pneumonia patients (OR 0.09; 95% CI 0.01 - 0.56), and pharmacokinetic parameters pertaining to microbiological cure were different among strains.
CONCLUSION
The mortality rate was substantially lower in clinically cured patients with CMS. However, no significant differences in C of colistin were examined to determine the impact of pharmacokinetic differences on clinical outcomes including mortality rate and nephrotoxicity risk. Nevertheless, the clinical cure rate is substantially lower in patients with respiratory infection than patients with urinary tract infection.
Topics: Humans; Colistin; Critical Illness; Anti-Bacterial Agents; Bacterial Infections; Bacteria; Mesylates; Gram-Negative Bacterial Infections
PubMed: 38554590
DOI: 10.1016/j.jiph.2024.03.021 -
International Journal of Molecular... Mar 2024Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22...
Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.
Topics: Humans; Drug Resistance, Neoplasm; Fusion Proteins, bcr-abl; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Signal Transduction
PubMed: 38542279
DOI: 10.3390/ijms25063307 -
Cells Mar 2024Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer... (Review)
Review
Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer therapies, offering a possible solution to overcome chemoresistance. This systematic review aimed to explore the role of mushroom extracts in enhancing chemotherapy and reversing chemoresistance in cancer cells. We searched the PubMed, Web of Science and Scopus databases, following the PRISMA guidelines, and registered on PROSPERO. The extracts acted by inhibiting the proliferation of cancer cells, as well as enhancing the effect of chemotherapy. The mechanisms by which they acted included regulating anti-apoptotic proteins, inhibiting the JAK2/STAT3 pathway, inhibiting the ERK1/2 pathway, modulating microRNAs and regulating p-glycoprotein. These results highlight the potential of mushroom extracts to modulate multiple mechanisms in order to improve the efficacy of chemotherapy. This work sheds light on the use of mushroom extracts as an aid to chemotherapy to combat chemoresistance. Although studies are limited, the diversity of mushrooms and their bioactive compounds show promising results for innovative strategies to treat cancer more effectively. It is crucial to carry out further studies to better understand the therapeutic potential of mushroom extracts to improve the efficacy of chemotherapy in cancer cells.
Topics: Agaricales; Neoplasms; MicroRNAs; MAP Kinase Signaling System
PubMed: 38534354
DOI: 10.3390/cells13060510 -
Journal of Orthopaedic Translation Mar 2024Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in... (Review)
Review
OBJECTIVE
Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models.
METHODS
A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included.
RESULTS
A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag and Cu; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation.
CONCLUSION
Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing . Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy.
THE TRANSLATIONAL POTENTIAL OF THIS PAPER
The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.
PubMed: 38495742
DOI: 10.1016/j.jot.2023.12.006 -
BMC Nursing Mar 2024Antimicrobial resistance has become one of the world's most important public health problems. Accordingly, nursing strategies to manage antimicrobials in hospital...
BACKGROUND
Antimicrobial resistance has become one of the world's most important public health problems. Accordingly, nursing strategies to manage antimicrobials in hospital environments are fundamental to promoting patient health. The aim of this study was to summarise the best evidence available on nursing strategies for the safe management of antimicrobials in hospital environments.
METHODS
This qualitative systematic review used meta-aggregation in accordance with the recommendations of the Joanna Briggs Institute. The protocol was registered in the data base of the Prospective Register of Systematic Reviews under No. CRD42021224804. The literature search was conducted, in April and May 2021, in the following data bases and journal repositories: Latin American and Caribbean Health Sciences Literature (LILACS) via the Virtual Health Library (VHL), Medical Literature Analysis and Retrieval System on-line (Medline) via PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scientific Electronic Library Online (SciELO) and Excerpta Medica Database (EMBASE). The findings of each study were summarized and the results were meta-aggregated in JBI SUMARI software.
RESULTS
The search resulted in a total of 447 studies and, after selection, the review included 26 studies, in which 42 nursing strategies were identified. The strategies were first categorised as care- or stewardship-related and then into the subcategories: Screening, Administration, Monitoring and Discharge, Nursing Team, Multi-professional Teams, Patients and Institutional Leadership. The 42 strategies were meta-aggregated and represented in flow diagrams. The best evidence was synthesized related to nursing strategies in the safe management of antimicrobials in the hospital environment.
CONCLUSIONS
Nurses play an indispensable function in antimicrobial stewardship in the hospital environment, because they work directly at the core of safe patient care. Significant contributions by nursing towards reducing antimicrobial resistance were found in care-related practice, education activities, research and policy.
PubMed: 38429699
DOI: 10.1186/s12912-024-01753-y -
Helicobacter 2024Helicobacter pylori antibiotic resistance has undergone vast changes in the last two decades. No systematic review has been done on the prevalence of antibiotic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Helicobacter pylori antibiotic resistance has undergone vast changes in the last two decades. No systematic review has been done on the prevalence of antibiotic resistant H. pylori in India in the last two decades. We evaluated the pattern of resistance rates across various regions of India.
MATERIALS AND METHODS
A systematic review of the geographical variations in antibiotic resistance pattern of H. pylori was conducted using PubMed, Google Scholar, Web of Science, Science Direct, etc. for articles published between January 1, 2000 and May 30, 2023. Random effects-model-based Cochran's Q test, I statistics, and chi-squared tests were used to measure heterogeneity.
RESULTS
The overall resistance was highest against metronidazole (77.65%) followed by amoxicillin (37.78%), levofloxacin (32.8%), clarithromycin (35.64%), furazolidone (12.03%), and tetracycline (11.63%). 14.7% of the H. pylori isolates were multi-drug resistant. Under meta-analysis of each antibiotic, high heterogeneity levels were observed having I ranges from 86.53% to 97.70% at p < 0.0001. In sub-group analysis, Metronidazole has a stable rate of resistance as compared to other antibiotics. Other antibiotics have had a downtrend in the last 5 years except for levofloxacin, which has had an uptrend in the resistance rate for the past 5 years. Hence, one should avoid using metronidazole for any kind of first-line treatment.
CONCLUSIONS
Metronidazole resistance is high in most regions of India except Assam and Mumbai while clarithromycin is found to be ineffective in South India, Gujarat, and Kashmir. As compared to other antibiotics, resistance to amoxicillin is generally low except in certain regions (Hyderabad, Chennai, and the Gangetic belt of North India). Tetracycline and Furazolidone have the least resistance rates and should be part of anti- H. pylori regimens. The resurgence of high single and multidrug resistance to the commonly used drugs suggests the need for newer antibiotics and regular resistance surveillance studies.
Topics: Humans; Metronidazole; Clarithromycin; Helicobacter pylori; Levofloxacin; Furazolidone; India; Helicobacter Infections; Anti-Bacterial Agents; Amoxicillin; Tetracycline; Antibodies; Drug Resistance, Microbial
PubMed: 38415810
DOI: 10.1111/hel.13057