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Frontiers in Public Health 2024Antimicrobial resistance (AMR) is a major public health threat. With the growing emphasis on patient-centred care/ shared decision making, it is important for healthcare...
INTRODUCTION
Antimicrobial resistance (AMR) is a major public health threat. With the growing emphasis on patient-centred care/ shared decision making, it is important for healthcare professionals' (HCPs) who prescribe, dispense, administer and/or monitor antimicrobials to be adequately equipped to facilitate appropriate antimicrobial use. We systematically identified existing interventions which aim to improve HCPs interaction with patients and examined barriers and facilitators of appropriate the use of such interventions and appropriate antimicrobial use among both HCPs and patientsantimicrobial use while using these interventions.
METHODS
We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and internet (via Google search engine). We included primary studies, published in English from 2010 to 2023 [PROSPERO (CRD42023395642)]. The protocol was preregistered with PROSPERO (CRD42023395642). We performed quality assessment using mixed methods appraisal tool. We applied narrative synthesis and used the COM-B (Capability, Opportunity, Motivation -Behaviour) as a theoretical framework for barriers and facilitators at HCP and patient levels.
RESULTS
Of 9,172 citations retrieved from database searches, From 4,979 citations remained after removal of duplicates. We included 59 studies spanning over 13 countries. Interventions often involved multiple components beyond HCPs' interaction with patients. From 24 studies reporting barriers and facilitators, we identified issues relating to capability (such as, knowledge/understanding about AMR, diagnostic uncertainties, awareness of interventions and forgetfulness); opportunity (such as, time constraint and intervention accessibility) and motivation (such as, patient's desire for antibiotics and fear of litigation).
CONCLUSION
The findings of this review should be considered by intervention designers/adopters and policy makers to improve utilisation and effectiveness.
Topics: Humans; Health Personnel; Professional-Patient Relations; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 38841670
DOI: 10.3389/fpubh.2024.1359790 -
Expert Opinion on Therapeutic Patents May 2024This review offers an updated perspective on the biomedical applications of prokaryotic carbonic anhydrases (CAs), emphasizing their potential as targets for drug... (Review)
Review
INTRODUCTION
This review offers an updated perspective on the biomedical applications of prokaryotic carbonic anhydrases (CAs), emphasizing their potential as targets for drug development against antibiotic-resistant bacterial infections. A systematic review of literature from PubMed, Web of Science, and Google Scholar has been conducted to provide a comprehensive analysis.
AREA COVERED
It delves into the pivotal roles of prokaryotic CAs in bacterial metabolism and their distinctions from mammalian CAs. The review explores the diversity of CA classes in bacteria, discusses selective inhibitors targeting bacterial CAs, and explores their potential applications in biomedical research. Furthermore, it analyzes clinical trials investigating the efficacy of carbonic anhydrase inhibitors (CAIs) and patented approaches for developing antibacterial CAIs, highlighting their translational potential in creating innovative antibacterial agents.
EXPERT OPINION
Recent years have witnessed increased recognition of CA inhibition as a promising strategy against bacterial infections. Challenges persist in achieving selectivity over human isoforms and optimizing therapeutic efficacy. Structural biology techniques provide insights into unique active site architectures, guiding selective inhibitor design. The review underscores the importance of interdisciplinary collaborations, innovative drug delivery systems, and advanced drug discovery approaches in unlocking the full therapeutic potential of prokaryotic CA inhibitors. It emphasizes the significance of these efforts in addressing antibiotic resistance and improving patient outcomes.
Topics: Animals; Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Drug Delivery Systems; Drug Design; Drug Development; Drug Discovery; Drug Resistance, Bacterial; Patents as Topic
PubMed: 38840307
DOI: 10.1080/13543776.2024.2365407 -
Journal of Applied Microbiology Jun 2024Antimicrobial-resistance genes (ARGs) are spread among bacteria by horizontal gene transfer, however, the effect of environmental factors on the dynamics of the ARG in...
Antimicrobial-resistance genes (ARGs) are spread among bacteria by horizontal gene transfer, however, the effect of environmental factors on the dynamics of the ARG in water environments has not been very well understood. In this systematic review, we employed the regression tree algorithm to identify the environmental factors that facilitate/inhibit the transfer of ARGs via conjugation in planktonic/biofilm-formed bacterial cells based on the results of past relevant research. Escherichia coli strains were the most studied genus for conjugation experiments as donor/recipient in the intra-genera category. Conversely, Pseudomonas spp., Acinetobacter spp., and Salmonella spp. were studied primarily as recipients across inter-genera bacteria. The conjugation efficiency (ce) was found to be highly dependent on the incubation period. Some antibiotics, such as nitrofurantoin (at ≥0.2 µg ml-1) and kanamycin (at ≥9.5 mg l-1) as well as metallic compounds like mercury (II) chloride (HgCl2, ≥3 µmol l-1), and vanadium (III) chloride (VCl3, ≥50 µmol l-1) had enhancing effect on conjugation. The highest ce value (-0.90 log10) was achieved at 15°C-19°C, with linoleic acid concentrations <8 mg l-1, a recognized conjugation inhibitor. Identifying critical environmental factors affecting ARG dissemination in aquatic environments will accelerate strategies to control their proliferation and combat antibiotic resistance.
Topics: Gene Transfer, Horizontal; Anti-Bacterial Agents; Conjugation, Genetic; Bacteria; Drug Resistance, Bacterial; Water Microbiology; Escherichia coli; Genes, Bacterial; Acinetobacter; Biofilms
PubMed: 38830804
DOI: 10.1093/jambio/lxae129 -
The Journal of Hospital Infection Jun 2024With increasing awareness of water sinks as potential sources of outbreaks and transmission of multi-drug resistant (MDR) bacteria in intensive care units (ICUs), there... (Review)
Review
With increasing awareness of water sinks as potential sources of outbreaks and transmission of multi-drug resistant (MDR) bacteria in intensive care units (ICUs), there is growing interest in water-free patient care systems. This systematic review reviewed and synthesized available evidence on the effectiveness of sink removal with or without water-free activities in the ICU environment to reduce water-borne healthcare-associated infections. We searched five databases (PubMed, MEDLINE, Scopus, Web of Science and Embase) for studies published from 1 January 1980 to 2 April 2024 that examined water-less or water-free activities in the ICU to reduce healthcare-associated infections and patient colonization. Of 2075 articles, seven quasi-experimental studies (total: 332 patient beds) met the study selection criteria. Six of these seven studies (85.7%) were based in adult ICUs; one (14%) was in a neonatal ICU. Five of seven sites (71.4%) implemented water-less interventions after an outbreak. Water-free alternatives used included water-less bath products (six of seven; 85.7%), bottled water for consumption (three of seven; 42.9%), oral care (three of seven; 42.9%) and dissolving of oral medication (four of seven; 57.1%), designated 'contaminated' sink outside of patient and medication preparation areas for disposal of wastewater (four of seven; 57.1%). Implicated pathogens studied included MDR Gram-negative bacteria (four of seven; 57.1%), MDR Pseudomonas aeruginosa only (two of seven; 28.6%), and pulmonary non-tuberculous mycobacterium (NTB) (one of seven; 14.3%). Five of seven (71.4%) studies reported outbreak cessation. Preliminary evidence, from a limited number of studies of which the majority were conducted in an outbreak setting, suggest that sink removal and other water-free interventions in the ICU helped terminate outbreaks involving taps and decrease hospital-onset respiratory isolation of pulmonary NTB.
PubMed: 38830541
DOI: 10.1016/j.jhin.2024.05.012 -
Environmental Health Insights 2024Nosocomial pathogens are known to exacerbate morbidity and mortality in contemporary critical healthcare. Hospital fomites, which include inanimate surfaces, have been... (Review)
Review
BACKGROUND
Nosocomial pathogens are known to exacerbate morbidity and mortality in contemporary critical healthcare. Hospital fomites, which include inanimate surfaces, have been identified as "breeding grounds" for pathogens that cause nosocomial infections. This systematic review aimed to deliver incisive insights on nosocomial pathogens in intensive care units (ICUs) and the role of fomites as potential reservoirs for their transmission.
METHOD
An extensive exploration of electronic databases, including PubMed and Scopus, from 1990 to 2023, was carried out between 25 and 29 May 2023, per standard PRISMA guidelines. Information were extracted from articles that reported on fomites in the ICU. Studies that did not quantitatively report the fomite contamination, and those that exclusively took samples from patients in the ICU were excluded from the analysis.
RESULTS
About 40% of the total samples collected on fomites from all the studies yielded microbial growth, with species of being the most predominant. Other prevalent microbes were , , , spp., sp., and sp. The neonatal intensive care unit (NICU) had the highest proportion of contaminated fomites. Among known fomites, the sphygmomanometer exhibited a 100% detection rate of nosocomial pathogens. This included , , coagulase-negative (CoNS), , and Multidrug-resistant (MDR) bacteria, such as methicillin-resistant (MRSA), vancomycin-resistant (VRE), extended-spectrum beta-lactamase (ESBL)-producing , and MDR were commonly isolated on fomites in the ICUs.
CONCLUSION
Many fomites that are readily used in patient care in the ICU harbour nosocomial pathogens. The most common fomite appeared to be mobile phones, sphygmomanometers, and stethoscopes, with being the most common contaminant. Consequently, the need for rigorous disinfection and sterilization protocols on fomites in the ICU cannot be overemphasized. Additionally, heightened awareness on the subject among health professionals is crucial to mitigating the risk and burden of nosocomial infections caused by drug-resistant bacteria.
PubMed: 38828046
DOI: 10.1177/11786302241243239 -
BMC Cancer Jun 2024Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy... (Meta-Analysis)
Meta-Analysis
Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.
Topics: Humans; Colorectal Neoplasms; Bevacizumab; Trifluridine; Thymine; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Drug Combinations; Neoplasm Metastasis; Progression-Free Survival; Uracil; Drug Resistance, Neoplasm
PubMed: 38825703
DOI: 10.1186/s12885-024-12447-8 -
Journal of Global Antimicrobial... May 2024Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB)... (Review)
Review
BACKGROUND
Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB) strains. Drug-resistant TB, including mono-drug resistant TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB), presents significant public health challenges.
METHODS
We conducted a systematic literature review from January 2010 to February 2024 using databases such as PubMed, Embase, Web of Science, and Google Scholar. Our focus was on empirical data related to drug resistance patterns in newly diagnosed TB cases. Non-empirical studies were excluded through meticulous filtering. For meta-analysis, we used Review Manager (RevMan) 5.2 and assessed evidence quality using the Newcastle-Ottawa Scale (NOS).
RESULTS
Our search strategy identified 40 studies that met the inclusion criteria, encompassing a total sample size of 87,667 participants. Among new TB cases, the estimated prevalence of MDR-TB in China was 6.9% (95% CI: 5.6-8.1%). Prevalence rates for mono-drug resistance to first-line anti-TB medications were as follows: isoniazid at 18.2% (95% CI: 16.4-20.6%), rifampicin at 10.5% (95% CI: 8.6-12.8%), and ethambutol at 5.7% (95% CI: 4.1-7.3%). The prevalence of streptomycin resistance, a former first-line anti-TB drug, was 17.1% (95% CI: 14.6-19.1%). The prevalence of other types of mono-drug resistance was 15.2% (95% CI: 13.9-17.3%), and for XDR-TB, it was 0.9% (95% CI: 0.6-1.4%).
CONCLUSIONS
The high prevalence of drug-resistant TB in China poses a significant public health challenge. There is an urgent need for targeted interventions and continued surveillance to combat the spread of drug-resistant TB.
PubMed: 38825149
DOI: 10.1016/j.jgar.2024.05.018 -
Clinical Immunology (Orlando, Fla.) May 2024Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation... (Review)
Review
Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation and proliferation of the synovium. Various immune cells are involved in the pathophysiology of RA. The complex interplay of factors such as chronic inflammation, genetic susceptibility, dysregulation of serum antibody levels, among others, contribute to the complexity of the disease mechanism, disease activity, and treatment of RA. Recently, the cytokine storm leading to increased disease activity in RA has gained significant attention. Interleukin-33 (IL-33), a member of the IL-1 family, plays a crucial role in inflammation and immune regulation. ST2 (suppression of tumorigenicity 2 receptor), the receptor for IL-33, is widely expressed on the surface of various immune cells. When IL-33 binds to its receptor ST2, it activates downstream signaling pathways to exert immunoregulatory effects. In RA, IL-33 regulates the progression of the disease by modulating immune cells such as circulating monocytes, tissue-resident macrophages, synovial fibroblasts, mast cells, dendritic cells, neutrophils, T cells, B cells, endothelial cells, and others. We have summarized and analyzed these findings to elucidate the pathways through which IL-33 regulates RA. Furthermore, IL-33 has been detected in the synovium, serum, and synovial fluid of RA patients. Due to inconsistent research results, we conducted a meta-analysis on the association between serum IL-33, synovial fluid IL-33, and the risk of developing RA in patients. The pooled SMD was 1.29 (95% CI: 1.15-1.44), indicating that IL-33 promotes the onset and pathophysiological progression of RA. Therefore, IL-33 may serve as a biomarker for predicting the risk of developing RA and treatment outcomes. As existing drugs for RA still cannot address drug resistance in some patients, new therapeutic approaches are needed to alleviate the significant burden on RA patients and healthcare systems. In light of this, we analyzed the potential of targeting the IL-33/ST2-related signaling pathway to modulate immune cells associated with RA and alleviate inflammation. We also reviewed IL-33 and RA susceptibility-related single nucleotide polymorphisms, suggesting potential involvement of IL-33 and macrophage-related drug-resistant genes in RA resistance therapy. Our review elucidates the role of IL-33 in the pathophysiology of RA, offering new insights for the treatment of RA.
PubMed: 38825072
DOI: 10.1016/j.clim.2024.110264 -
Water Research Aug 2024Legionella is an opportunistic waterborne pathogen that causes Legionnaires' disease. It poses a significant public health risk, especially to vulnerable populations in...
Legionella is an opportunistic waterborne pathogen that causes Legionnaires' disease. It poses a significant public health risk, especially to vulnerable populations in health care facilities. It is ubiquitous in manufactured water systems and is transmitted via inhalation or aspiration of aerosols/water droplets generated from water fixtures (e.g., showers and hand basins). As such, the effective management of premise plumbing systems (building water systems) in health care facilities is essential for reducing the risk of Legionnaires' disease. Chemical disinfection is a commonly used control method and chlorine-based disinfectants, including chlorine, chloramine, and chlorine dioxide, have been used for over a century. However, the effectiveness of these disinfectants in premise plumbing systems is affected by various interconnected factors that can make it challenging to maintain effective disinfection. This systematic literature review identifies all studies that have examined the factors impacting the efficacy and decay of chlorine-based disinfectant within premise plumbing systems. A total of 117 field and laboratory-based studies were identified and included in this review. A total of 20 studies directly compared the effectiveness of the different chlorine-based disinfectants. The findings from these studies ranked the typical effectiveness as follows: chloramine > chlorine dioxide > chlorine. A total of 26 factors were identified across 117 studies as influencing the efficacy and decay of disinfectants in premise plumbing systems. These factors were sorted into categories of operational factors that are changed by the operation of water devices and fixtures (such as stagnation, temperature, water velocity), evolving factors which are changed in-directly (such as disinfectant concentration, Legionella disinfectant resistance, Legionella growth, season, biofilm and microbe, protozoa, nitrification, total organic carbon(TOC), pH, dissolved oxygen(DO), hardness, ammonia, and sediment and pipe deposit) and stable factors that are not often changed(such as disinfectant type, pipe material, pipe size, pipe age, water recirculating, softener, corrosion inhibitor, automatic sensor tap, building floor, and construction activity). A factor-effect map of each of these factors and whether they have a positive or negative association with disinfection efficacy against Legionella in premise plumbing systems is presented. It was also found that evaluating the effectiveness of chlorine disinfection as a water risk management strategy is further complicated by varying disinfection resistance of Legionella species and the form of Legionella (culturable/viable but non culturable, free living/biofilm associated, intracellular replication within amoeba hosts). Future research is needed that utilises sensors and other approaches to measure these key factors (such as pH, temperature, stagnation, water age and disinfection residual) in real time throughout premise plumbing systems. This information will support the development of improved models to predict disinfection within premise plumbing systems. The findings from this study will inform the use of chlorine-based disinfection within premise plumbing systems to reduce the risk of Legionnaires disease.
Topics: Disinfectants; Chlorine; Legionella; Disinfection; Chlorine Compounds; Water Microbiology; Chloramines; Water Supply; Oxides; Water Purification
PubMed: 38824796
DOI: 10.1016/j.watres.2024.121794 -
BMC Infectious Diseases May 2024Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients.
METHODS
Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model.
RESULTS
Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I > 50.00%, P < 0.01), except for caspofungin (I = 0.00%, P = 0.65).
CONCLUSIONS
Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin.
REGISTRATION
The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
Topics: Humans; Candidiasis, Oral; Antifungal Agents; HIV Infections; Drug Resistance, Fungal; Candida; Prevalence; Microbial Sensitivity Tests; AIDS-Related Opportunistic Infections; Fluconazole
PubMed: 38822256
DOI: 10.1186/s12879-024-09442-6