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BMC Infectious Diseases Jul 2024Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can be directly transmitted or arise through resistance acquisition during first-line TB treatment. Limited evidence suggests that people living with HIV (PLHIV) might have an increased risk of acquired rifamycin-resistance (ARR).
METHODS
To assess HIV as a risk factor for ARR during first-line TB treatment, a systematic review and meta-analysis was conducted. ARR was defined as rifamycin-susceptibility at treatment start with rifamycin-resistance diagnosed during or at the end of treatment, or at recurrence. PubMed/MEDLINE, CINAHL, Cochrane Library, and Google Scholar databases were searched from inception to 23 May 2024 for articles in English; conference abstracts were also searched from 2004 to 2021. The Mantel-Haenszel random-effects model was used to estimate the pooled odds ratio of any association between HIV and ARR among individuals receiving first-line TB treatment.
RESULTS
Ten studies that included data collected between 1990 and 2014 were identified: five from the United States, two from South Africa and one each from Uganda, India and Moldova. A total of 97,564 individuals were included across all studies, with 13,359 (13.7%) PLHIV. Overall, 312 (0.32%) acquired rifamycin-resistance, among whom 115 (36.9%) were PLHIV. The weighted odds of ARR were 4.57 (95% CI, 2.01-10.42) times higher among PLHIV compared to HIV-negative individuals receiving first-line TB treatment.
CONCLUSION
The available data, suggest that PLHIV have an increased ARR risk during first-line TB treatment. Further research is needed to clarify specific risk factors, including advanced HIV disease and TB disease severity. Given the introduction of shorter, 4-month rifamycin-based regimens, there is an urgent need for additional data on ARR, particularly for PLHIV.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022327337.
Topics: Humans; HIV Infections; Rifamycins; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Risk Factors; Mycobacterium tuberculosis; South Africa
PubMed: 38956461
DOI: 10.1186/s12879-024-09514-7 -
Scientific Reports Jul 2024The intestinal epithelium dynamically controls cell cycle, yet no experimental platform exists for directly analyzing cell cycle phases in non-immortalized human...
The intestinal epithelium dynamically controls cell cycle, yet no experimental platform exists for directly analyzing cell cycle phases in non-immortalized human intestinal epithelial cells (IECs). Here, we present two reporters and a complete platform for analyzing cell cycle phases in live primary human IECs. We interrogate the transcriptional identity of IECs grown on soft collagen, develop two fluorescent cell cycle reporter IEC lines, design and 3D print a collagen press to make chamber slides for optimal imaging while supporting primary human IEC growth, live image cell cycle dynamics, then assemble a computational pipeline building upon free-to-use programs for semi-automated analysis of cell cycle phases. The PIP-FUCCI construct allows for assigning cell cycle phase from a single image of living cells, and our PIP-H2A construct allows for semi-automated direct quantification of cell cycle phase lengths using our publicly available computational pipeline. Treating PIP-FUCCI IECs with oligomycin demonstrates that inhibiting mitochondrial respiration lengthens G1 phase, and PIP-H2A cells allow us to measure that oligomycin differentially lengthens S and G2/M phases across heterogeneous IECs. These platforms provide opportunities for future studies on pharmaceutical effects on the intestinal epithelium, cell cycle regulation, and more.
Topics: Humans; Epithelial Cells; Intestinal Mucosa; Cell Cycle; Oligomycins; Cells, Cultured
PubMed: 38956443
DOI: 10.1038/s41598-024-66042-9 -
Scientific Reports Jul 2024Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve...
Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve drug efficiency without increasing dose, kidney-specific drug delivery may be used. Mesoscale nanoparticles (MNP) selectively target the proximal tubules in rodents. We explored whether MNPs can target cystic kidney tubules and whether rapamycin-encapsulated-MNPs (RapaMNPs) can slow cyst growth in Pkd1 knockout (KO) mice. MNP was intravenously administered in adult Pkd1KO mice. Serum and organs were harvested after 8, 24, 48 or 72 h to measure MNP localization, mTOR levels, and rapamycin concentration. Pkd1KO mice were then injected bi-weekly for 6 weeks with RapaMNP, rapamycin, or vehicle to determine drug efficacy on kidney cyst growth. Single MNP injections lead to kidney-preferential accumulation over other organs, specifically in tubules and cysts. Likewise, one RapaMNP injection resulted in higher drug delivery to the kidney compared to the liver, and displayed sustained mTOR inhibition. Bi-weekly injections with RapaMNP, rapamycin or vehicle for 6 weeks resulted in inconsistent mTOR inhibition and little change in cyst index, however. MNPs serve as an effective short-term, kidney-specific delivery system, but long-term RapaMNP failed to slow cyst progression in Pkd1KO mice.
Topics: Animals; Sirolimus; Mice; Polycystic Kidney Diseases; Mice, Knockout; Nanoparticles; Disease Models, Animal; TOR Serine-Threonine Kinases; TRPP Cation Channels; Kidney; Drug Delivery Systems; Male
PubMed: 38956234
DOI: 10.1038/s41598-024-65830-7 -
Scientific Reports Jul 20242K4L is a rationally designed analog of the short α-helical peptide temporin-1CEc, a natural peptide isolated and purified from the skin secretions of the Chinese brown...
2K4L is a rationally designed analog of the short α-helical peptide temporin-1CEc, a natural peptide isolated and purified from the skin secretions of the Chinese brown frog Rana chensinensis by substituting amino acid residues. 2K4L displayed improved and broad-spectrum antibacterial activity than temporin-1CEc in vitro. Here, the antibacterial and anti-inflammatory activities of 2K4L in macrophages, C. elegans and mice were investigated. The results demonstrated that 2K4L could enter THP-1 cells to kill a multidrug-resistant Acinetobacter baumannii strain (MRAB 0227) and a sensitive A. baumannii strain (AB 22933), as well as reduce proinflammatory responses induced by MRAB 0227 by inhibiting NF-κB signaling pathway. Similarly, 2K4L exhibited strong bactericidal activity against A. baumannii uptake into C. elegans, extending the lifespan and healthspan of the nematodes. Meanwhile, 2K4L alleviated the oxidative stress response by inhibiting the expression of core genes in the p38 MAPK/PMK-1 signaling pathway and downregulating the phosphorylation level of p38, thereby protecting the nematodes from damage by A. baumannii. Finally, in an LPS-induced septic model, 2K4L enhanced the survival of septic mice and decreased the production of proinflammatory cytokines by inhibiting the signaling protein expression of the MAPK and NF-κB signaling pathways and protecting LPS-induced septic mice from a lethal inflammatory response. In conclusion, 2K4L ameliorated LPS-induced inflammation both in vitro and in vivo.
Topics: Animals; Caenorhabditis elegans; Mice; Acinetobacter baumannii; Macrophages; Lipopolysaccharides; Shock, Septic; NF-kappa B; Antimicrobial Peptides; Humans; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Inflammation; Anti-Bacterial Agents; Anti-Inflammatory Agents; Oxidative Stress; Mitogen-Activated Protein Kinases; Caenorhabditis elegans Proteins
PubMed: 38956179
DOI: 10.1038/s41598-024-64511-9 -
Scientific Reports Jul 2024Biological agents are getting a noticeable concern as efficient eco-friendly method for nanoparticle fabrication, from which fungi considered promising agents in this...
Biological agents are getting a noticeable concern as efficient eco-friendly method for nanoparticle fabrication, from which fungi considered promising agents in this field. In the current study, two fungal species (Embellisia spp. and Gymnoascus spp.) were isolated from the desert soil in Saudi Arabia and identified using 18S rRNA gene sequencing then used as bio-mediator for the fabrication of silver nanoparticles (AgNPs). Myco-synthesized AgNPs were characterized using UV-visible spectrometry, transmission electron microscopy, Fourier transform infrared spectroscopy and dynamic light scattering techniques. Their antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae were investigated. In atrial to detect their possible antibacterial mechanism, Sodium dodecyl sulfate (SDS-PAGE) and TEM analysis were performed for Klebsiella pneumoniae treated by the myco-synthesized AgNPs. Detected properties of the fabricated materials indicated the ability of both tested fungal strains in successful fabrication of AgNPs having same range of mean size diameters and varied PDI. The efficiency of Embellisia spp. in providing AgNPs with higher antibacterial activity compared to Gymnoascus spp. was reported however, both indicated antibacterial efficacy. Variations in the protein profile of K. pneumoniae after treatments and ultrastructural changes were observed. Current outcomes suggested applying of fungi as direct, simple and sustainable approach in providing efficient AgNPs.
Topics: Silver; Saudi Arabia; Metal Nanoparticles; Soil Microbiology; Microbial Sensitivity Tests; Anti-Bacterial Agents; Desert Climate; Fungi; Klebsiella pneumoniae; Pseudomonas aeruginosa; Anti-Infective Agents
PubMed: 38956076
DOI: 10.1038/s41598-024-63117-5 -
Pediatric Surgery International Jul 2024The aim of this study was to find statistically valid criteria to preoperatively divide acute appendicitis into simple and complicated to enable surgeons to administer... (Review)
Review
INTRODUCTION
The aim of this study was to find statistically valid criteria to preoperatively divide acute appendicitis into simple and complicated to enable surgeons to administer the most appropriate antibiotic prophylaxis/therapy before surgery.
MATERIALS AND METHODS
We retrospectively reviewed a cohort of patients who underwent appendectomy from January 2022 to December 2023. Patients included were 0-14 years of age. Exclusion criteria included patients who underwent interval appendectomy or concurrent procedures at the same time of appendectomy. We divided patients into two groups: simple (group S) and complicated (group C) appendicitis according to intraoperative finding. Generalized linear model (GLM) with logit function was developed to identify the predictive variables of the type of appendicitis (S vs C) in terms of CRP value, neutrophils percentage and WBC count adjusted for age and sex of patients. Finally, principal component analysis (PCA) was carried out to identify the cutoff value of statistically significant variables found in the previous analysis.
RESULTS
One hundred and twenty patients were eligible (N female = 49, N male = 71) for the study. 74 and 46 patients were included in groups S and C, respectively. In a preliminary analysis using univariate and multivariate GLM, only CRP (p value = < 0.001) and neutrophils percentage (p value = 0.02) were predictive variables for the type of appendicitis. The GLM shows a statistical lower value of CRP (adjusted odds ratio [OR] per unit, 0.17 [95% CI, 0.08-0.39]) and neutrophil percentage (adjusted OR per unit, 0.37 [95% CI, 0.16-0.86]) in the S group compared to C adjusted to age and sex. PCA analysis revealed a P-ROC cutoff of 4.2 mg/dl and 80.1 of CRP value (AUC = 84%) and neutrophil percentage (AUC = 70%), respectively.
CONCLUSIONS
We will perform a prospective study giving preoperative prophylactic cefazolin to patients with a CRP value under 4.2 mg/dl and amoxicillin-clavulanate therapy to patient with CRP value over 4.2 mg/dl.
Topics: Humans; Appendicitis; Female; Male; Retrospective Studies; Child; Appendectomy; Adolescent; Antibiotic Prophylaxis; Child, Preschool; Anti-Bacterial Agents; Infant; Preoperative Care; Acute Disease
PubMed: 38955876
DOI: 10.1007/s00383-024-05753-6 -
Current Microbiology Jul 2024Antimicrobial resistance is a global health issue, in which microorganisms develop resistance to antimicrobial drugs, making infections more difficult to treat. This...
Antimicrobial resistance is a global health issue, in which microorganisms develop resistance to antimicrobial drugs, making infections more difficult to treat. This threatens the effectiveness of standard medical treatments and necessitates the urgent development of new strategies to combat resistant microbes. Studies have increasingly explored natural sources of new antimicrobial agents that harness the rich diversity of compounds found in plant species. This pursuit holds promise for the discovery of novel treatments for combating antimicrobial resistance. In this context, the chemical composition, antibacterial, and antibiofilm activities of the essential oil from Croton urticifolius Lam. leaves (CuEO) were evaluated. CuEO was extracted via hydrodistillation, and its chemical constituents were identified via gas chromatography-mass spectrometry (GC/MS). The antibacterial activity of CuEO was evaluated in a 96-well plate via the microdilution method, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined. The effect of CuEO on biofilm formation was assessed by quantifying the biomass using crystal violet staining and viable cell counting. In addition, alterations in the cellular morphology of biofilms treated with CuEO were examined using scanning electron microscopy (SEM) and laser confocal microscopy. GC/MS analysis identified 26 compounds, with elemicine (39.72%); eucalyptol (19.03%), E-caryophyllene (5.36%), and methyleugenol (4.12%) as the major compounds. In terms of antibacterial activity, CuEO showed bacteriostatic effects against Staphylococcus aureus ATCC 700698, S. aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, and Escherichia coli ATCC 11303, and bactericidal activity against S. aureus ATCC 700698. In addition, CuEO significantly inhibited bacterial biofilm formation. Microscopic analysis showed that CuEO damaged the bacterial membrane by leaching out the cytoplasmic content. Therefore, the results of this study show that the essential oil of C. urticifolius may be a promising natural alternative for preventing infections caused by bacterial biofilms. This study is the first to report the antibiofilm activity of C. urticifolius essential oil.
Topics: Biofilms; Oils, Volatile; Croton; Anti-Bacterial Agents; Microbial Sensitivity Tests; Plant Leaves; Staphylococcus aureus; Gas Chromatography-Mass Spectrometry; Plant Extracts; Cell Membrane
PubMed: 38955831
DOI: 10.1007/s00284-024-03779-6 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead... (Review)
Review
Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead to increased exposure of populations to antimicrobials, the antimicrobial resistance of pathogens has accelerated and resulted in weakened clinical infection treatment effects. This article reviews the main mechanisms and driving factors of the production and spread of antimicrobial resistance from the perspective of "One Health"and discusses methods and strategies for controlling antimicrobial resistance from multiple dimensions. It also looks forward to the prospects of research and prevention of drug resistance to explore antimicrobial resistance prevention and control strategies based on "One Health".
Topics: Humans; One Health; Public Health; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 38955741
DOI: 10.3760/cma.j.cn112150-20231127-00379 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of e from respiratory specimen sources. A...
To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of e from respiratory specimen sources. A total of 35 strains of meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly B, with a carrying rate of 74.2%; tetracycline resistance genes were mainly M, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants A and C were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, , 1, , , and r_0594, and seven virulence factors, E, A, B, l, and A. Overall, isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by from respiratory tract speciments of elderly patients.
Topics: Streptococcus agalactiae; Humans; Aged; Anti-Bacterial Agents; Middle Aged; Microbial Sensitivity Tests; Aged, 80 and over; Adult; Child; Adolescent; Child, Preschool; Infant; Young Adult; Infant, Newborn; Drug Resistance, Bacterial; Streptococcal Infections
PubMed: 38955738
DOI: 10.3760/cma.j.cn112150-20231214-00446 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024
Review
Topics: Humans; Pneumonia, Mycoplasma; China; Mycoplasma pneumoniae; Child; Macrolides; Anti-Bacterial Agents; Child, Preschool; Drug Resistance, Bacterial
PubMed: 38955692
DOI: 10.3760/cma.j.cn112140-20240407-00247