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The Science of the Total Environment Jun 2022Drug chirality is attracting increasing attention because the enantiomers of the same chiral pharmaceutical usually exhibit different biological activities, metabolic...
Drug chirality is attracting increasing attention because the enantiomers of the same chiral pharmaceutical usually exhibit different biological activities, metabolic pathways, and toxicities. The ubiquitous presence of microplastics (MPs) can enrich organic pollutants commonly found in the environment. However, knowledge about the enrichment of pharmaceutical enantiomers to MPs is relatively limited. We investigated the occurrence of enantioselectivity of ofloxacin (OFL) and levofloxacin (LEV) in the adsorption processes on polyethylene (PE) and the interactions influenced by environmental factors. The results showed that the adsorption efficiency of OFL was generally 3-5% (p < 0.05) higher than that of LEV, indicating the different affinities of the enantiomers to PE, but the adsorption process of OFL and LEV on PE was both well described by pseudo-first-order kinetics and liner isotherm models. The chirality of OFL and LEV was not affected by sizes of PE particles and solution salinity due to the identical physicochemical properties. An examination of pH effect indicated that OFL showed better acid-base adaptability than LEV. Moreover, the differences in enantiomeric enrichment between OFL and LEV on PE were promoted with increasing UV light exposure time and natural organic matter (NOM) concentrations. Using Fourier transform infrared spectroscopy (FTIR), we demonstrated that the constituents of the functional groups in chiral NOM were greatly related to the enantiomer stereoselectivity of OFL, subsequently affecting their adsorption in a chiral environment. The excitation-emission matrix (EEM) spectra confirmed the enantioselective behaviors of chiral pharmaceuticals under UV light due to the different optical activity and humic acid-like and fulvic acid-like molecular structure of the enantiomers. These findings imply that the enantioselectivity of drug enantiomers should be considered in presence of microplastics, leading to a more accurate environmental fate and risks assessments of chiral pharmaceuticals.
Topics: Adsorption; Levofloxacin; Microplastics; Ofloxacin; Pharmaceutical Preparations; Plastics; Polyethylene; Water Pollutants, Chemical
PubMed: 35157859
DOI: 10.1016/j.scitotenv.2022.153765 -
Molecular Pharmaceutics Jun 2024Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone drug that exists in both hydrated and anhydrous/dehydrated forms. Due to the complexity of such a compound,...
Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone drug that exists in both hydrated and anhydrous/dehydrated forms. Due to the complexity of such a compound, the primary aim of this study was to investigate the amorphization capabilities and solid-state transformations of LVXh when exposed to mechanical treatment using ball milling. Spray drying was utilized as a comparative method for investigating the capabilities of complete LVX amorphous (LVXam) formation. The solid states of the samples produced were comprehensively characterized by powder X-ray diffraction, thermal analysis, infrared spectroscopy, Rietveld method, and dynamic vapor sorption. The kinetics of the process and the quantification of phases at different time points were conducted by Rietveld refinement. The impact of the different mills, milling conditions, and parameters on the composition of the resulting powders was examined. A kinetic investigation of samples produced using both mills disclosed that it was in fact possible to partially amorphize LVXh upon mechanical treatment. It was discovered that LVXh first transformed to the anhydrous/dehydrated form γ (LVXγ), as an intermediate phase, before converting to LVXam. The mechanism of LVXam formation by ball milling was successfully revealed, and a new method of forming LVXγ and LVXam by mechanical forces was developed. Spray drying from water depicted that complete amorphization of LVXh was possible. The amorphous form of LVX had a glass transition temperature of 80 °C. The comparison of methods highlighted that the formation of LVXam is thus both mechanism- and process-dependent. Dynamic vapor sorption studies of both LVXam samples showed comparable stability properties and crystallized to the most stable hemihydrate form upon analysis. In summary, this work contributed to the detailed understanding of solid-state transformations of essential fluoroquinolones while employing greener and more sustainable manufacturing methods.
Topics: Levofloxacin; X-Ray Diffraction; Powders; Kinetics; Drug Compounding; Anti-Bacterial Agents; Calorimetry, Differential Scanning; Crystallization; Chemistry, Pharmaceutical
PubMed: 38662637
DOI: 10.1021/acs.molpharmaceut.4c00008 -
Auris, Nasus, Larynx Aug 2023The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of 1.5% levofloxacin otic solution for the treatment of otitis media in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase III study.
OBJECTIVE
The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media.
METHODS
This multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial was conducted at 34 institutions in Japan. A total of 202 patients with chronic suppurative otitis media (CSOM) or acute otitis media (AOM) were randomized into either the LVFX group or placebo group. A total of 6-10 drops of 1.5% otic solution of LVFX or its matching placebo were administered in the diseased ear twice daily, in the morning and evening for up to 10 days. Images corresponding to three clinical findings-purulent otorrhea, hyperemia (redness), and granulation tissue formation in the middle ear and tympanic membrane-for each diseased ear were evaluated using digital endoscopy by a blinded central independent review committee (BICRC) at each visit after treatment administration.
RESULTS
In total, the data of 201 participants (LVFX group, 99; placebo group, 102) were analyzed. The proportion of patients with disappearance (improvement rate) of all three clinical findings at the end of treatment or discontinuation by the BICRC was 46.5% (46/99) in the LVFX group and 23.5% (24/102) in the placebo group, and the difference (95% confidence interval) between the groups was 22.0% (8.7, 34.2), with a significantly higher improvement rate in the LVFX group than in the placebo group (p = 0.001; Cochran-Mantel-Haenszel test), demonstrating the efficacy of LVFX. The bacterial eradication rates were 93.9% (77/82) and 12.5% (11/88) in the LVFX and placebo groups, respectively, and the rate was significantly higher in the LVFX group than in the placebo group (p < 0.001). Treatment-related adverse events (AEs) occurred in 5.1% (5/99) and 7.8% (8/102) of the patients in the LVFX and placebo groups, respectively, and no significant difference was noted in incidence rate between the groups.
CONCLUSION
The clinical efficacy of 1.5% LVFX otic solution for CSOM and AOM was demonstrated by the resolution of inflammation in the middle ear and tympanic membrane as well as through the high bacterial eradication rate observed. No deaths or serious treatment-related AEs were observed. The study provided confirmation that 1.5% LVFX otic solution is a safe, well-tolerated, and effective treatment for CSOM and AOM.
Topics: Humans; Anti-Bacterial Agents; Levofloxacin; Otitis Media; Otitis Media, Suppurative; Ear, Middle
PubMed: 36599786
DOI: 10.1016/j.anl.2022.12.013 -
Microbiology Spectrum Jun 2022The activity of two new fluoroquinolones, delafloxacin and finafloxacin, were evaluated against and spp. The MICs of delafloxacin, finafloxacin, and two classical...
The activity of two new fluoroquinolones, delafloxacin and finafloxacin, were evaluated against and spp. The MICs of delafloxacin, finafloxacin, and two classical fluoroquinolones (moxifloxacin and levofloxacin) were tested against 29 and 67 spp. isolates using the broth microdilution method. The molecular mechanisms underlying fluoroquinolone resistance were also investigated. Delafloxacin exhibited low MICs against and spp., including the levofloxacin-resistant isolates. For , delafloxacin showed low MIC value of 1 μg/mL (MIC range, <0.031 -1 μg/mL) compared to 8 μg/mL for finafloxacin, 16 μg/mL for moxifloxacin, and 32 μg/mL for levofloxacin. For and , delafloxacin had low MIC values (, 2 μg/mL; , 4 μg/mL) compared to 16 -32 μg/mL for finafloxacin, 16 μg/mL for moxifloxacin, and 32 - >32 μg/mL for levofloxacin. The two mutations GyrA S153L and ParC S91I were commonly identified in fluoroquinolone-resistant , and ParC S83L was the most frequent mutation identified in fluoroquinolone-resistant spp. Delafloxacin displayed lower MICs against fluoroquinolone-resistant isolates of both and spp. that have mutations in the quinolone resistance determining regions (QRDRs) than the two classical fluoroquinolones. Delafloxacin is a promising fluoroquinolone with low MICs against fluoroquinolone-resistant and spp. Our study confirms the potential clinical use of delafloxacin in treating antimicrobial-resistant and spp. infections. Fluoroquinolone resistance in Mycoplasma hominis and spp. is on the rise globally, which has compromised the efficacy of the currently available antimicrobial agents. This study evaluated the antimicrobial activity of two new fluoroquinolones, delafloxacin and finafloxacin, for the first time, against and spp. clinical isolates. Delafloxacin and finafloxacin displayed different antimicrobial susceptibility profiles against and spp. . Delafloxacin was found to be more effective against and spp. than three classical fluoroquinolones (finafloxacin, moxifloxacin, and levofloxacin). Finafloxacin displayed activity similar to moxifloxacin but superior to levofloxacin against and spp. Our findings demonstrate that delafloxacin is a promising fluoroquinolone with outstanding activity against fluoroquinolone-resistant and spp.
Topics: Anti-Bacterial Agents; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mycoplasma hominis; Ureaplasma; Ureaplasma Infections
PubMed: 35532225
DOI: 10.1128/spectrum.00099-22 -
Revista Espanola de Enfermedades... Jun 2020According to some series, 0.3-1.5% of all cases of acute pancreatitis are drug induced. Acute pancreatitis due to levofloxacin is included in its safety data sheet as an...
According to some series, 0.3-1.5% of all cases of acute pancreatitis are drug induced. Acute pancreatitis due to levofloxacin is included in its safety data sheet as an adverse effect.
Topics: Acute Disease; Humans; Levofloxacin; Pancreatitis
PubMed: 32496110
DOI: 10.17235/reed.2020.6652/2019 -
Future Microbiology Dec 2022Drug repurposing is a viable approach to expediting the tedious conventional drug discovery process, given rapidly increasing bacterial resistance. In this context, we...
Drug repurposing is a viable approach to expediting the tedious conventional drug discovery process, given rapidly increasing bacterial resistance. In this context, we have repurposed pyrvinium pamoate (PP) for its antibacterial activity against . US FDA-approved non-antibiotics were screened against clinically relevant bacterial pathogens to identify antibacterials. The hits were further evaluated utilizing a variety of preclinical parameters, following which efficacy was estimated in isolation and in combination in a murine neutropenic thigh infection model. The screening identified PP exhibiting potent activity against along with concentration-dependent killing. PP also showed a post-antibiotic effect of >22 h and significantly eradicated preformed biofilms and intracellular at 1× and 5× MIC, respectively. PP synergized with levofloxacin both and , resulting in ∼1.5 and ∼0.5 log CFU/g reduction against susceptible and resistant infections, respectively, as compared with untreated control. Pyrvinium potentiates levofloxacin against levofloxacin-resistant
Topics: Mice; Animals; Levofloxacin; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Anti-Bacterial Agents
PubMed: 36314364
DOI: 10.2217/fmb-2022-0159 -
The American Journal of Case Reports Mar 2018BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of...
BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of levofloxacin use. Here, we present a case of severe transaminitis caused by levofloxacin. CASE REPORT A young man in his thirties with a history of asthma, chronic alcoholism, methamphetamine intravenous drug abuse (IVDA), and non-compliant insulin-dependent diabetes mellitus (IDDM) presented to an emergency department with suicidal ideation. Vital signs were stable and the patient was noted to have cellulitis of the right forearm, for which cultures were drawn, and he received IV clindamycin. He was admitted to behavioral medicine for further care. Blood cultures were positive for gram-negative rods and he was transferred to the medicine ward. Cultures eventually grew Brevundimonas diminuta. Clindamycin was discontinued and he was started on levofloxacin. Transaminase levels measured soon after levofloxacin administration showed aminotransferase levels raised to approximately 50 times baseline within a few days. Levofloxacin was discontinued due to concern about drug-induced hepatotoxicity. After discontinuation, transaminase levels decreased immediately. Work-up for other causes of transaminitis revealed no other etiology. CONCLUSIONS Clinicians should remain mindful that levofloxacin can induce hepatotoxicity in rare cases. In patients presenting with acute liver injury who have recently taken levofloxacin, it would be wise to remain cognizant of the possibility of levofloxacin-induced hepatotoxicity.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Humans; Levofloxacin; Liver; Male; Young Adult
PubMed: 29523775
DOI: 10.12659/ajcr.907440 -
Journal of Ayub Medical College,... 2023Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g.,... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy And Cost-Effectiveness, Comparison Of 7-Days Vonoprazan Versus 14-Days Esomeprazole Based Triple Therapies For Treating Helicobacter Pylori Infection In Pakistani Population: A Randomized Clinical Trial.
BACKGROUND
Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g., Gastritis, peptic ulcer disease, adenocarcinoma of the gastric system and mucoid associated lymphoma (MALT). The Objective was to compare the effect of 7-days Vonoprazan based triple therapy and 14-days Esomeprazole based triple therapy on eradication rate, compliance and cost effectiveness in Helicobacter pylori infected patients.
METHODS
This clinical trial was performed in the Department of Pharmacology Army Medical College, National University of Medical Sciences (NUMS) in collaboration with the Gastroenterology Department, Pak Emirates Military Hospital (PEMH) Rawalpindi from December 2022 to March 2023. A total of one hundred and twenty-two patients with dyspepsia symptoms and yielding lab results positive for Helicobacter pylori by stool antigen test were enrolled in the study. They were randomly allocated into two groups. The Esomeprazole group received 14 days of triple therapy orally with Esomeprazole 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. The comparative Vonoprazan group was given 7-days triple therapy orally with Vonoprazan 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. Eradication success was evaluated by stool antigen test four weeks later, as counted from the start of treatment. compliance and cost-effectiveness of both therapies were also assessed.
RESULTS
The eradication rate was (95.1%) in the Vonoprazan group with 58 out of 61 patients negative for H. pylori and (93.1%) in Esomeprazole group with 54 patients out of 58 yielding a negative result demonstrating p-value of 0.64. Compliance was 95.0% in the Esomeprazole group with p-value of 0.07. Cost effective ratio for Vonoprazan triple therapy was lower (731.8PKR) than the Esomeprazole group.
CONCLUSION
One two-week Vonoprazan regimen demonstrated improved eradication rate, good compliance, and better tolerability in patients with less cost and a half duration of treatment in comparison with two weeks Esomeprazole regimen, attesting that one week Vonoprazan therapy is more cost efficacious in producing better results.
Topics: Humans; Amoxicillin; Anti-Bacterial Agents; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Levofloxacin; Pakistan; Pyrroles; Sulfonamides; Treatment Outcome
PubMed: 38406904
DOI: 10.55519/JAMC-S4-12110 -
Antimicrobial Agents and Chemotherapy Apr 2022Pathogenic bacteria experience diverse stresses induced by host cells during infection and have developed intricate systems to trigger appropriate responses. Bacterial...
Pathogenic bacteria experience diverse stresses induced by host cells during infection and have developed intricate systems to trigger appropriate responses. Bacterial stress responses have been reported to defend against these stresses and cross-protect bacteria from antibiotic attack. In this study, we aimed to assess whether oxidative stress affects bacterial susceptibility to fluoroquinolone (FQ) and the underlying mechanism. Stenotrophomonas maltophilia, a species with high genetic diversity, is distributed ubiquitously and is an emerging multidrug-resistant opportunistic pathogen. FQs are among the limited antibiotic treatment options for S. maltophilia infection. The minimum inhibitory concentrations (MICs) of 103 S. maltophilia clinical isolates against ciprofloxacin (CIP) and levofloxacin (LVX) were determined using the agar dilution method in Mueller-Hinton plates with or without menadione (MD), a superoxide generator. The resistance rates for ciprofloxacin and levofloxacin were 40% and 18% in the MD-null group and increased to 91% and 23%, respectively, in the MD-treated group. Of the 103 isolates tested, 54% and 27% had elevated MICs against ciprofloxacin and levofloxacin, respectively, in the presence of MD. The involvement of oxidative stress responses in the MD-mediated FQ resistance was further assessed by mutants construction and viability assay. Among the 16 oxidative stress alleviation systems evaluated, and contributed to MD-mediated FQ resistance. The antibiotic susceptibility test is an accredited clinical method to evaluate bacterial susceptibility to antibiotics in clinical practice. However, oxidative stress-mediated antibiotic resistance was not detected using this test, which may lead to treatment failure.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Oxidative Stress; Stenotrophomonas maltophilia
PubMed: 35285252
DOI: 10.1128/aac.02043-21 -
Journal of Infection and Chemotherapy :... Jun 2017Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic...
Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic effect (PAE) of ozenoxacin against Propionibacterium acnes, a major causative bacterium of acne vulgaris. The minimum inhibitory concentrations (MICs) of ozenoxacin against 3 levofloxacin-susceptible strains (MIC of levofloxacin; ≤4 μg/mL) and 3 levofloxacin-resistant strains (MIC of levofloxacin; ≥8 μg/mL) ranged from 0.03 to 0.06 μg/mL and from 0.25 to 0.5 μg/mL, respectively. These MICs of ozenoxacin were almost the same or lower than nadifloxacin and clindamycin. The minimum bactericidal concentrations (MBCs) of ozenoxacin against the levofloxacin-susceptible and -resistant strains were from 0.06 to 8 μg/mL and from 0.5 to 4 μg/mL, respectively. These MBCs were lower than those of nadifloxacin and clindamycin. In time-kill assay, ozenoxacin at 1/4, 1 and 4 times the respective MIC against both levofloxacin-susceptible and -resistant strains showed a concentration-dependent bactericidal activity. Ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains showed more potent and more rapid onset of bactericidal activity compared to nadifloxacin and clindamycin at 4 times the respective MICs. The PAEs of ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains were from 3.3 to 17.1 h, which were almost the same or longer than nadifloxacin and clindamycin. In contrast, the PAEs were hardly induced by any antimicrobial agents against the levofloxacin-resistant strains. The present findings suggest that ozenoxacin has a potent bactericidal activity against both levofloxacin-susceptible and -resistant P. acnes, and a long-lasting PAE against levofloxacin-susceptible P. acnes.
Topics: Aminopyridines; Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Propionibacterium acnes; Quinolones
PubMed: 28389164
DOI: 10.1016/j.jiac.2017.03.004