-
Polymers Jun 2024Pelvic prolapse stands as a substantial medical concern, notably impacting a significant segment of the population, predominantly women. This condition, characterized by...
Pelvic prolapse stands as a substantial medical concern, notably impacting a significant segment of the population, predominantly women. This condition, characterized by the descent of pelvic organs, such as the uterus, bladder, or rectum, from their normal positions, can lead to a range of distressing symptoms, including pelvic pressure, urinary incontinence, and discomfort during intercourse. Clinical challenges abound in the treatment landscape of pelvic prolapse, stemming from its multifactorial etiology and the diverse array of symptoms experienced by affected individuals. Current treatment options, while offering relief to some extent, often fall short in addressing the full spectrum of symptoms and may pose risks of complications or recurrence. Consequently, there exists a palpable need for innovative solutions that can provide more effective, durable, and patient-tailored interventions for pelvic prolapse. We manufactured an integrated polycaprolactone (PCL) mesh, reinforced with nano-hydroxyapatite (nHA), along with drug-eluting poly(lactic-co-glycolic acid) (PLGA) nanofibers for a prolapse scaffold. This aims to offer a promising avenue for enhanced treatment outcomes and improved quality of life for individuals grappling with pelvic prolapse. Solution extrusion additive manufacturing and electrospinning methods were utilized to prepare the nHA filled PCL mesh and drug-incorporated PLGA nanofibers, respectively. The pharmaceuticals employed included metronidazole, ketorolac, bleomycin, and estrone. Properties of fabricated resorbable scaffolds were assessed. The in vitro release characteristics of various pharmaceuticals from the meshes/nanofibers were evaluated. Furthermore, the in vivo drug elution pattern was also estimated on a rat model. The empirical data show that nHA reinforced PCL mesh exhibited superior mechanical strength to virgin PCL mesh. Electrospun resorbable nanofibers possessed diameters ranging from 85 to 540 nm, and released effective metronidazole, ketorolac, bleomycin, and estradiol, respectively, for 9, 30, 3, and over 30 days in vitro. Further, the mesh/nanofiber scaffolds also liberated high drug levels at the target site for more than 28 days in vivo, while the drug concentrations in blood remained low. This discovery suggests that resorbable scaffold can serve as a viable option for treating female pelvic organ prolapse.
PubMed: 38932015
DOI: 10.3390/polym16121667 -
International Journal of Molecular... Jun 2024Bacterial nitroreductase enzymes capable of activating imaging probes and prodrugs are valuable tools for gene-directed enzyme prodrug therapies and targeted cell...
Bacterial nitroreductase enzymes capable of activating imaging probes and prodrugs are valuable tools for gene-directed enzyme prodrug therapies and targeted cell ablation models. We recently engineered a nitroreductase ( NfsB F70A/F108Y) for the substantially enhanced reduction of the 5-nitroimidazole PET-capable probe, SN33623, which permits the theranostic imaging of vectors labeled with oxygen-insensitive bacterial nitroreductases. This mutant enzyme also shows improved activation of the DNA-alkylation prodrugs CB1954 and metronidazole. To elucidate the mechanism behind these enhancements, we resolved the crystal structure of the mutant enzyme to 1.98 Å and compared it to the wild-type enzyme. Structural analysis revealed an expanded substrate access channel and new hydrogen bonding interactions. Additionally, computational modeling of SN33623, CB1954, and metronidazole binding in the active sites of both the mutant and wild-type enzymes revealed key differences in substrate orientations and interactions, with improvements in activity being mirrored by reduced distances between the N5-H of isoalloxazine and the substrate nitro group oxygen in the mutant models. These findings deepen our understanding of nitroreductase substrate specificity and catalytic mechanisms and have potential implications for developing more effective theranostic imaging strategies in cancer treatment.
Topics: Nitroreductases; Nitroimidazoles; Metronidazole; Prodrugs; Escherichia coli Proteins; Positron-Emission Tomography; Escherichia coli; Catalytic Domain; Protein Engineering; Models, Molecular; Aziridines
PubMed: 38928299
DOI: 10.3390/ijms25126593 -
Antibiotics (Basel, Switzerland) Jun 2024is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, is the only... (Review)
Review
is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons and manure pits. Given the rarity of this microorganism and the sparse information in the literature about its way of transmission, the way to diagnose its infections and identify it in the microbiology laboratory, and its public health relevance, the present study aimed to identify all the published cases of , describe the epidemiological, clinical, and microbiological characteristics, and provide information about its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a Pubmed/Medline and Scopus databases search. In total, 14 studies provided data on 17 patients with infections by . The median age of patients was 63 years and 47% were male. The most common types of infection were bone and joint infections, bacteremia, infective endocarditis, and peritonitis. The only isolated species was , and antimicrobial resistance to clindamycin was 50%, but was 0% to the combination of piperacillin with tazobactam, aminopenicillin with a beta-lactamase inhibitor, and metronidazole which were the most commonly used antimicrobials for the treatment of these infections. The overall mortality depends on the type of infection and is notable only for bacteremia, while all other infections had an optimal outcome. Future studies should better assess these infections' clinical and epidemiological characteristics and the mechanisms of the antimicrobial resistance of this microorganism from a mechanistic and genetic perspective.
PubMed: 38927236
DOI: 10.3390/antibiotics13060570 -
Scientific Reports Jun 2024The aim of this study is to introduce a dental capping agent for the treatment of pulp inflammation (pulpitis). Nanohydroxyapatite with Elaeagnus angustifolia L. extract...
The aim of this study is to introduce a dental capping agent for the treatment of pulp inflammation (pulpitis). Nanohydroxyapatite with Elaeagnus angustifolia L. extract (nHAEA) loaded with metronidazole (nHAEA@MTZ) was synthesized and evaluated using a lipopolysaccharide (LPS) in vitro model of pulpitis. nHAEA was synthesized through sol-gel method and analyzed using Scanning Electron Microscopy, Transmission Electron Microscopy, and Brunauer Emmett Teller. Inflammation in human dental pulp stem cells (HDPSCs) induced by LPS. A scratch test assessed cell migration, RT PCR measured cytokines levels, and Alizarin red staining quantified odontogenesis. The nHAEA nanorods were 17-23 nm wide and 93-146 nm length, with an average pore diameter of 27/312 nm, and a surface area of 210.89 m/g. MTZ loading content with controlled release, suggesting suitability for therapeutic applications. nHAEA@MTZ did not affect the odontogenic abilities of HDPSCs more than nHAEA. However, it was observed that nHAEA@MTZ demonstrated a more pronounced anti-inflammatory effect. HDPSCs treated with nanoparticles exhibited improved migration compared to other groups. These findings demonstrated that nHAEA@MTZ could be an effective material for pulp capping and may be more effective than nHAEA in reducing inflammation and activating HDPSCs to enhance pulp repair after pulp damage.
Topics: Plant Extracts; Humans; Pulpitis; Metronidazole; Dental Pulp; Durapatite; Nanoparticles; Green Chemistry Technology; Drug Carriers; Stem Cells; Cell Movement; Cells, Cultured
PubMed: 38926433
DOI: 10.1038/s41598-024-65582-4 -
PloS One 2024Antibiotic self-medication is one of the common causes of antibiotic resistance of bacterial organisms. The COVID-19 pandemic introduced a new paradigm shift and...
BACKGROUND
Antibiotic self-medication is one of the common causes of antibiotic resistance of bacterial organisms. The COVID-19 pandemic introduced a new paradigm shift and significantly influenced healthcare behaviors, including an increase in antibiotic self-medication, which contributes to antibiotic resistance. This study was aimed at determining the prevalence of antibiotic self-medication and the possible associated factors during the peak of the COVID-19 pandemic among adult residents of Tema in Ghana from April to July 2021.
METHODS
Using a cross-sectional design, 400 adults were randomly selected and surveyed using a researcher-assisted questionnaire. Data were analyzed with IBM® SPSS® Statistics Version 22.0, considering associations significant at a 95% confidence interval (p < 0.05).
RESULTS
Of the 400 respondents, (76%) 304 had practiced antibiotic self-medication within the previous 12 months during the COVID-19 pandemic. Significant factors associated with antibiotic self-medication included gender, age, marital status, education, occupation, and National Health Insurance Scheme subscription. Convenience and avoiding long hospital queues were primary non-medical reasons for antibiotic self-medication, while previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection were the medical reasons for antibiotic self-medication. Commonly self-administered antibiotics were azithromycin (34%), amoxicillin/clavulanic acid (22%), and metronidazole (16%) for perceived respiratory tract and gastrointestinal tract infections.
CONCLUSIONS
The high prevalence of antibiotic self-medication observed during the COVID-19 pandemic underscores the need for enhanced public education and stricter enforcement of regulations governing antibiotic sales. The non-medical and medical factors of convenience, avoiding long hospital queues, previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection which motivated antibiotic self-medication practices require the implementation of antimicrobial stewardship interventions.
Topics: Humans; Self Medication; Male; Female; Adult; Cross-Sectional Studies; COVID-19; Anti-Bacterial Agents; Middle Aged; Ghana; Young Adult; SARS-CoV-2; Surveys and Questionnaires; Pandemics; Aged; Adolescent
PubMed: 38917123
DOI: 10.1371/journal.pone.0305602 -
Microbiology Spectrum Jun 2024The aim of the present study was first to isolate from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of...
The aim of the present study was first to isolate from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia. positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for . Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8% = 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.IMPORTANCEAntibiotic resistance in has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%-19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns.
PubMed: 38916348
DOI: 10.1128/spectrum.00401-24 -
Scientific Reports Jun 2024Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the...
Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the prevalence of antibiotic resistance in H. pylori bacteria in Palestine. We enlisted 91 individuals suffering from dyspepsia, comprising 49 females and 42 males. These participants underwent esophagogastroduodenoscopy procedures with gastric biopsies. These biopsies were subsequently subjected to microbiological assessments and tested for their susceptibility to various antimicrobial drugs. Among the 91 patients, 38 (41.7%) exhibited the presence of H. pylori. Notably, Ciprofloxacin displayed the highest efficacy against H. pylori, followed by Levofloxacin, Moxifloxacin, and Amoxicillin, with resistance rates of 0%, 0%, 2.6%, and 18.4%, respectively. On the contrary, Metronidazole and Clarithromycin demonstrated the lowest effectiveness, with resistance percentages of 100% and 47.4%, respectively. The outcomes of this investigation emphasize that H. pylori strains within the Palestinian patient group exhibit substantial resistance to conventional first-line antibiotics like clarithromycin and metronidazole. However, alternative agents such as fluoroquinolones and amoxicillin remain efficacious choices. Consequently, we recommend favoring quinolone-based treatment regimens for H. pylori infections and adopting a more judicious approach to antibiotic usage among the Palestinian population.
Topics: Humans; Helicobacter pylori; Female; Male; Helicobacter Infections; Cross-Sectional Studies; Anti-Bacterial Agents; Adult; Prevalence; Middle Aged; Drug Resistance, Bacterial; Hospitals, University; Microbial Sensitivity Tests; Amoxicillin; Clarithromycin; Metronidazole; Levofloxacin
PubMed: 38914675
DOI: 10.1038/s41598-024-63982-0 -
JAMA Internal Medicine Jun 2024Current approaches to classify the hepatotoxic potential of medications are based on cumulative case reports of acute liver injury (ALI), which do not consider the size...
IMPORTANCE
Current approaches to classify the hepatotoxic potential of medications are based on cumulative case reports of acute liver injury (ALI), which do not consider the size of the exposed population. There is little evidence from real-world data (data relating to patient health status and/or the delivery of health care routinely collected from sources outside of a research setting) on incidence rates of severe ALI after initiation of medications, accounting for duration of exposure.
OBJECTIVE
To identify the most potentially hepatotoxic medications based on real-world incidence rates of severe ALI and to examine how these rates compare with categorization based on case reports.
DESIGN, SETTING, AND PARTICIPANTS
This series of cohort studies obtained data from the US Department of Veterans Affairs on persons without preexisting liver or biliary disease who initiated a suspected hepatotoxic medication in the outpatient setting between October 1, 2000, and September 30, 2021. Data were analyzed from June 2020 to November 2023.
EXPOSURES
Outpatient initiation of any one of 194 medications with 4 or more published reports of hepatotoxicity.
MAIN OUTCOMES AND MEASURES
Hospitalization for severe ALI, defined by either inpatient: (1) alanine aminotransferase level greater than 120 U/L plus total bilirubin level greater than 2.0 mg/dL or (2) international normalized ratio of 1.5 or higher plus total bilirubin level greater than 2.0 mg/dL recorded within the first 2 days of admission. Acute or chronic liver or biliary disease diagnosis recorded during follow-up or as a discharge diagnosis of a hospitalization for severe ALI resulted in censoring. This study calculated age- and sex-adjusted incidence rates of severe ALI and compared observed rates with hepatotoxicity categories based on cumulative published case reports.
RESULTS
The study included 7 899 888 patients across 194 medication cohorts (mean [SD] age, 64.4 [16.4] years, 7 305 558 males [92.5%], 4 354 136 individuals [55.1%] had polypharmacy). Incidence rates of severe ALI ranged from 0 events per 10 000 person-years (candesartan, minocycline) to 86.4 events per 10 000 person-years (stavudine). Seven medications (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) exhibited rates of 10.0 or more events per 10 000 person-years, and 10 (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) had rates between 5.0 and 9.9 events per 10 000 person-years. Of these 17 medications with the highest observed rates of severe ALI, 11 (64%) were not included in the highest hepatotoxicity category when based on case reports.
CONCLUSIONS AND RELEVANCE
In this study, incidence rates of severe ALI using real-world data identified the most potentially hepatotoxic medications and can serve as a tool to investigate hepatotoxicity safety signals obtained from case reports. Case report counts did not accurately reflect the observed rates of severe ALI after medication initiation.
PubMed: 38913369
DOI: 10.1001/jamainternmed.2024.1836 -
Microbiology Spectrum Jun 2024Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional...
Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a -based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted = 0.0006), with most of this increase attributable to . Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as . Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.
PubMed: 38912808
DOI: 10.1128/spectrum.03501-23 -
Gut Jun 2024This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for infection in patients with penicillin...
BACKGROUND AND AIMS
This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for infection in patients with penicillin allergy.
METHODS
In this randomised controlled trial, treatment-naïve adults with infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects.
RESULTS
300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010).
CONCLUSIONS
VT dual therapy demonstrated efficacy and safety as a first-line treatment for infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT.
TRIAL REGISTRATION NUMBER
ChiCTR2300074693.
PubMed: 38906695
DOI: 10.1136/gutjnl-2024-332640