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Scientific Reports May 2024Heterojunctions play a crucial role in improving the absorption of visible light and performance of photocatalysts for organic contaminants degradation in water. In this...
Heterojunctions play a crucial role in improving the absorption of visible light and performance of photocatalysts for organic contaminants degradation in water. In this work, a novel type-II-II AgCO/BiWO (AB) heterojunction was synthesized by hydrothermal reaction and in situ-precipitation methods. The mechanisms of charge transfer and carrier separation at the interface of heterojunctions and the influence on the photocatalytic activity were investigated. The degradation of levofloxacin (LEV) under visible light irradiation was employed to evaluate the photocatalytic performance of AB. The results showed that 85.4% LEV was degraded by AB, which was 1.38 and 1.39 times higher than that of BiWO and AgCO, respectively. The work functions of the different crystal planes in the AB heterojunction, which was calculated by density functional theory, are a significant difference. The Fermi energy (E) of AgCO (- 6.005 eV) is lower than BiWO (- 3.659 eV), but the conduction band (CB) is higher. Therefore, using AB heterojunctions as an example, the research explored the mechanism of type-II-II which CB and E of one semiconductor cannot simultaneously surpass those of another material, based on the built-in electric field theory. Through this analysis, a deeper understanding of type-II heterojunctions was achieved, and providing valuable insights into the behavior of this specific heterojunction system.
PubMed: 38724634
DOI: 10.1038/s41598-024-60250-z -
Trials May 2024HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated...
BACKGROUND
HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB.
METHODS
This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events.
DISCUSSION
Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.
Topics: Humans; Rifampin; HIV Infections; Hospitalization; Tuberculosis; Levofloxacin; Treatment Outcome; Clinical Trials, Phase III as Topic; Antitubercular Agents; Equivalence Trials as Topic; Drug Therapy, Combination; Prednisone; AIDS-Related Opportunistic Infections; Time Factors
PubMed: 38720383
DOI: 10.1186/s13063-024-08119-4 -
RSC Advances May 2024Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer...
Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer superlative properties of APIs. Previously, THEDESs of risperidone, fentanyl and levofloxacin with capric acid (CA) were developed by our group. These APIs share cyclic tertiary amine nuclei. Herein, DESs of two drugs bearing cyclic tertiary amine nucleus, namely, droperidol and aripiprazole, in the presence of CA, were investigated as model drugs. Comprehensive analyses were conducted using liquid-state 1D and 2D NMR and differential scanning calorimetry (DSC) to elucidate the regiochemistry and thermodynamic mechanisms bringing about those THEDESs. Everted gut sac technique was used to study the flux of the developed THEDESs. 1D and 2D NMR techniques analyses revealed the importance of cyclic tertiary amine nuclei in forming interactions with CA. This was confirmed by the downfield shift of the protons proximal to the tertiary amine groups compared to the individual drugs. Diffusion NMR analysis (DOSY) showed a significant reduction in the diffusion coefficient of CA in the mixed system compared with CA in isolation. Thermal analysis of the two drugs revealed that the drugs have a low tendency to recrystallise upon melting but rather vitrify from a melt to form an amorphous solid. Interestingly, the superior absorption and flux of the THEDES formulation of droperidol was demonstrated using the ERIS. Collectively, this work provides a green method to attain liquid formulations of APIs with enhanced pharmacokinetic features.
PubMed: 38716106
DOI: 10.1039/d4ra01469c -
Infection and Drug Resistance 2024To compare the epidemiological characteristics and drug resistance of isolated from blood cultures, and to provide data support and a scientific basis for the clinical...
OBJECTIVE
To compare the epidemiological characteristics and drug resistance of isolated from blood cultures, and to provide data support and a scientific basis for the clinical treatment and detection of hospital infections.
METHODS
The Hebei Province Antimicrobial Surveillance Network received 349 strains isolated from blood cultures reported by 83 hospitals, from 2016 to 2021. These strains were identified by MALDI-TOF MS and, the antibiotic sensitivity tests were carried out using the VITEK 2 COMPACT system. The 2023 Institute of Clinical and Laboratory Standardization drug-susceptibility breakpoints were used for drug susceptibility testing and the data were analyzed using WHONET5.6 software.
RESULTS
A total of 349 strains were isolated from 2016 to 2021, including 68 strains from secondary hospitals and 281 strains from tertiary hospitals. The ratios of male: female patients with bloodstream infections in all hospitals, secondary hospitals, and tertiary hospitals were 1.49:1 (209/140), 2.09:1 (46/22), and 1.38:1 (163/118), respectively. Most strains were isolated in intensive care units (ICUs), followed by internal medicine departments, accounting for 49.57% (173/349) and 22.92% (80/349), respectively. Regarding the age distribution, most patients were elderly (>65 years, 57.59%, 201/349), with numbers of patients gradually declining with decreasing of age. The resistance rates for levofloxacin, ceftazidime, and sulfamethoxazole decreased over the 6-year period (P<0.05), while there were no significant changes in the resistance rates for meropenem, chloramphenicol, and minocycline (P>0.05). There was no significant difference in drug-resistance rates between secondary and tertiary hospitals (P>0.05).
CONCLUSION
Attention should be paid to bloodstream infections caused by , especially elderly patients and patients admitted to the ICU. The difficult treatment characteristics of bloodstream infections mean that laboratories and clinicians should pay careful attention to drug resistance to provide a basis for their prevention and empirical treatment.
PubMed: 38715964
DOI: 10.2147/IDR.S457314 -
ACS Omega Apr 2024The paper presents the antibacterial and antioxidant activities of silver nanoparticles (AgNPs) when conjugated with two antibiotics levofloxacin and ciprofloxacin as...
Green Synthesis and Characterization of Biologically Synthesized and Antibiotic-Conjugated Silver Nanoparticles followed by Post-Synthesis Assessment for Antibacterial and Antioxidant Applications.
The paper presents the antibacterial and antioxidant activities of silver nanoparticles (AgNPs) when conjugated with two antibiotics levofloxacin and ciprofloxacin as well as biologically synthesized nanoparticles from and . Leaves of and powder of were used in the green synthesis of silver nanoparticles. Ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were used for the characterization of the synthesized silver nanoparticles. Comparison of levofloxacin and ciprofloxacin and their conjugated AgNPs was also studied for antibacterial and antioxidant activity. The synthesis of -AgNPs, turmeric-AgNPs, levofloxacin-AgNPs, and ciprofloxacin-AgNPs was confirmed by UV spectroscopy. An absorption peak value of 400-450 nm was observed, and light to dark brown color indicated the synthesis of AgNPs. -AgNPs revealed high antioxidant activity (80.3 ± 3.14) among all of the synthesized AgNPs. Lev-AgNPs displayed the highest zone of inhibition for , while in , Cip-AgNPs showed high antibacterial activity. Furthermore, AgNPs synthesized using green methods exhibit high and efficient antimicrobial activities against two food-borne pathogens. Biologically synthesized nanoparticles exhibited antibacterial activity against (13.73 ± 0.46 with Tur-AgNPs and 13.53 ± 0.32 with Mor-AgNPs) and (14.16 ± 0.24 with Tur-AgNPs and 13.36 ± 0.77 with Mor-AgNPs) by using a well diffusion method with significant shrinkage and damage of the bacterial cell wall, whereas antibiotic-conjugated nanoparticles showed high antibacterial activity compared to biologically synthesized nanoparticles with 14.4 ± 0.37 for Cip-AgNPs and 13.93 ± 0.2 for Lev-AgNPs for and 13.3 ± 0.43 for Cip-AgNPs and 14.33 ± 0.12 for Lev-AgNPs for . The enhanced efficiency of conjugated silver nanoparticles is attributed to their increased surface area compared to larger particles. Conjugation of different functional groups contributes to improved reactivity, creating active sites for catalytic reactions. Additionally, the precise control over the size and shape of green-synthesized nanoparticles further augments their catalytic and antibiotic activities.
PubMed: 38708285
DOI: 10.1021/acsomega.3c08927 -
ACS Omega Apr 2024Fabric phase sorptive extraction (FPSE) is a simple microextraction technique that allows analytes to be rescued from matrix components while using a small volume of...
Adapting Fabric Phase Sorptive Extraction as an Innovative Multitool for Sample Transfer and Extraction in Pharmacokinetic Analysis Followed by LC-MS Determination of Levofloxacin in Plasma Samples.
Fabric phase sorptive extraction (FPSE) is a simple microextraction technique that allows analytes to be rescued from matrix components while using a small volume of samples to analyze complex biological systems. This study used FPSE as a microextraction tool and a sample storage and transfer device. Levofloxacin as a model molecule was applied intravenously (IV) to New Zealand male rabbits. The samples were simultaneously extracted by using FPSE and protein precipitation methods. The final solutions were analyzed using LC-MS equipped with an ACE C18 LC Column (150 mm × 4.6 mm, 5 μm) at 25 °C employed in isocratic elution mode using solution A (0.1% formic acid in water)/solution B (0.1% formic acid in acetonitrile) (80:20, v/v). The total analysis time was less than 15 min. The developed method was validated using the ICH M10 bioanalytical method validation and study sample analysis guidelines. The results obtained using FPSE were statistically identical to those obtained using protein precipitation. The plasma samples applied onto FPSE (10 μL onto 1.0 cm × 1.0 cm Biofluid Sampler) were stored in three different temperatures [refrigerator (2-8 °C), at ambient temperature (20 ± 5 °C), and in the stability cabinet (40 °C, 75% humidity)] and three different storage conditions (Eppendorf tubes, plastic containers, and straw paper envelopes). Levofloxacin in plasma samples adsorbed by FPSE biofluid sampler remained stable at 2-8 °C in Eppendorf tubes for at least 1 week. This study showed that FPSE could be used as a sample storage and transfer device for pharmacokinetic applications that need to work with small sample volumes and discard aggressive cold chains to store and transfer the plasma samples.
PubMed: 38708206
DOI: 10.1021/acsomega.3c09519 -
RSC Advances May 2024Promoting angiogenesis following biomaterial implantation is essential to bone tissue regeneration. Herein, the composite scaffolds composed of zein, whitlockite (WH),...
Promoting angiogenesis following biomaterial implantation is essential to bone tissue regeneration. Herein, the composite scaffolds composed of zein, whitlockite (WH), and levofloxacin (LEVO) were fabricated to augment bone repair by facilitating osteogenesis and angiogenesis. First, three-dimensional composite scaffolds containing zein and WH were prepared using the salt-leaching method. Then, as a model antibiotic drug, the LEVO was loaded into zein/WH scaffolds. Moreover, the addition of WH enhanced the adhesion, differentiation, and mineralization of osteoblasts. The zein/WH/LEVO composite scaffolds not only had significant osteoinductivity but also showed excellent antibacterial properties. The prepared composite scaffolds were then implanted into a calvarial defect model to evaluate their osteogenic induction effects . Micro-CT observation and histological analysis indicate that the scaffolds can accelerate bone regeneration with the contribution of endogenous cytokines. Based on amounts of data and , the scaffolds present profound effects on improving bone regeneration, especially for the favorable osteogenic, intensive angiogenic, and alleviated inflammation abilities. The results showed that the synthesized scaffolds could be a potential material for bone tissue engineering.
PubMed: 38708116
DOI: 10.1039/d4ra00772g -
Heliyon May 2024In this study, ionic liquids (ILs) were used as organic modifiers by introducing montmorillonite nanolayers containing potential C and N active sites between the...
In this study, ionic liquids (ILs) were used as organic modifiers by introducing montmorillonite nanolayers containing potential C and N active sites between the montmorillonite nanolayers. Organically modified montmorillonite (ILs-Mt-p) was further prepared by high-temperature pyrolysis under N and used for the removal of ofloxacin (OFL) by activated peroxymonosulfate (PMS). Combined with XPS and other characterization analyses, it was found that the catalyst materials prepared from different organic modifiers had similar surface functional groups and graphitized structures, but contained differences in the types and numbers of C and N active sites. The catalyst (3CPC-Mt-p) obtained after pyrolysis of montmorillonite modified with cetylpyridinium chloride (CPC) had optimal catalytic performance, in which graphitic C, graphitic N, and carbonyl group (C[bond, double bond]O) could synergistically promote the activation of PMS by electron transfer, and 77.3 % of OFL could be removed within 60 min. The effects of OFL concentration, initial pH, and anions on the effects of OFL removal by the 3CPC-Mt-p/PMS system were further investigated. Satisfactory degradation results were obtained over a wide pH range. Cl promoted the system to degrade OFL, while the presence of SO, HPO and HA showed some inhibition, but overall the 3CPC-Mt-p catalysts had a strong anti-interference ability, showing good application prospects. The quenching experiments and EPR tests showed that O and O in the 3CPC-Mt-p/PMS system were the main reactive oxygen species for the degradation of OFL, and •OH was also involved in the reaction. This study provides ideas for the construction and modulation of active sites in mineral materials such as montmorillonite and broadens the application of montmorillonite composite catalysts in advanced oxidation processes for the treatment of antibiotic wastewater.
PubMed: 38707273
DOI: 10.1016/j.heliyon.2024.e29896 -
Cureus Apr 2024Background Despite preventive measures and varying antibiotic recommendations, bacterial infections continue to pose a significant threat to individuals undergoing...
Background Despite preventive measures and varying antibiotic recommendations, bacterial infections continue to pose a significant threat to individuals undergoing hematopoietic stem cell transplantation (HSCT). Levofloxacin prophylaxis is commonly used, but the optimal timing for initiation is debated. This study aims to assess infection outcomes based on timing of levofloxacin prophylaxis (initiation at the first day of conditioning vs. after infusion of stem cells) in autologous and allogeneic HSCT patients. Methods We compared infectious episodes, responsible pathogens, and clinical outcomes based on the implementation of levofloxacin prophylaxis in patients receiving autologous or allogeneic HSCT procedures. This retrospective single-center study involved a review of the medical records of autologous and allogeneic HSCT patients treated at our adult stem cell transplantation unit between 2018 and 2020. The study included 23 patients who underwent autologous HSCT and 12 patients who underwent allogeneic HSCT. We compared the demographic data, febrile neutropenia, proven bacterial infections, and 30-day survival among the autologous and allogeneic transplant groups, including those who received oral levofloxacin 500 mg/day prophylaxis. Results Positive blood cultures (26.1% vs. 75%; p = 0.011), mean neutrophil engraftment (10.6±1.2 vs. 14.8±1.3; p<0.001), and mean platelet engraftment (11.2±1.1 vs. 15.4±3.2; p = 0.004) were all lower in autologous transplant patients versus their allogeneic counterparts. When each type of HSCT was evaluated within the same type, there were no observed differences in infection frequency, infection type, or 30-day mortality between the patient groups with different levofloxacin initiation times. Conclusion Healthcare professionals should choose the most appropriate timing for initiating levofloxacin prophylaxis based on individual patient factors and clinical circumstances while considering the cost-effectiveness implications. Further research with a larger sample size and prospective design is needed to support our findings.
PubMed: 38707020
DOI: 10.7759/cureus.57598 -
Malaria Journal May 2024Drug repurposing offers a strategic alternative to the development of novel compounds, leveraging the known safety and pharmacokinetic profiles of medications, such as... (Review)
Review
BACKGROUND
Drug repurposing offers a strategic alternative to the development of novel compounds, leveraging the known safety and pharmacokinetic profiles of medications, such as linezolid and levofloxacin for tuberculosis (TB). Anti-malarial drugs, including quinolones and artemisinins, are already applied to other diseases and infections and could be promising for TB treatment.
METHODS
This review included studies on the activity of anti-malarial drugs, specifically quinolones and artemisinins, against Mycobacterium tuberculosis complex (MTC), summarizing results from in vitro, in vivo (animal models) studies, and clinical trials. Studies on drugs not primarily developed for TB (doxycycline, sulfonamides) and any novel developed compounds were excluded. Analysis focused on in vitro activity (minimal inhibitory concentrations), synergistic effects, pre-clinical activity, and clinical trials.
RESULTS
Nineteen studies, including one ongoing Phase 1 clinical trial, were analysed: primarily investigating quinolones like mefloquine and chloroquine, and, to a lesser extent, artemisinins. In vitro findings revealed high MIC values for anti-malarials versus standard TB drugs, suggesting a limited activity. Synergistic effects with anti-TB drugs were modest, with some synergy observed in combinations with isoniazid or pyrazinamide. In vivo animal studies showed limited activity of anti-malarials against MTC, except for one study of the combination of chloroquine with isoniazid.
CONCLUSIONS
The repurposing of anti-malarials for TB treatment is limited by high MIC values, poor synergy, and minimal in vivo effects. Concerns about potential toxicity at effective dosages and the risk of antimicrobial resistance, especially where TB and malaria overlap, further question their repurposing. These findings suggest that focusing on novel compounds might be both more beneficial and rewarding.
Topics: Drug Repositioning; Tuberculosis; Antimalarials; Antitubercular Agents; Mycobacterium tuberculosis; Humans; Animals
PubMed: 38702649
DOI: 10.1186/s12936-024-04967-2