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International Journal of Molecular... Aug 2022We compared the performance and levofloxacin (Quinsair) lung deposition of three nebulisers commonly used in CF (I-Neb Advance, eFlow rapid, and LC Plus) with the...
We compared the performance and levofloxacin (Quinsair) lung deposition of three nebulisers commonly used in CF (I-Neb Advance, eFlow rapid, and LC Plus) with the approved nebuliser Zirela. The delivered dose, delivery rate, and aerosol particle size distribution (APSD) for each device were determined using the methods described in the Pharmacopeia. High-resolution computed tomography scans obtained from seven adult patients with mild CF were used to generate computer-aided, three-dimensional models of their airway tree to assess lung deposition using functional respiratory imaging (FRI). The eFlow rapid and the LC Plus showed poor delivery efficiencies due to their high residual volumes. The I-Neb, which only delivers aerosols during the inspiratory phase, achieved the highest aerosol delivery efficiency. However, the I-Neb showed the largest particle size and lowest delivery rate (2.9 mg/min), which were respectively associated with a high extrathoracic deposition and extremely long nebulisation times (>20 min). Zirela showed the best performance considering delivery efficiency (159.6 mg out of a nominal dose of 240 mg), delivery rate (43.5 mg/min), and lung deposition (20% of the nominal dose), requiring less than 5 min to deliver a full dose of levofloxacin. The present study supports the use of drug-specific nebulisers and discourages the off-label use of general-purpose devices with the present levofloxacin formulation since subtherapeutic lung doses and long nebulisation times may compromise treatment efficacy and adherence.
Topics: Administration, Inhalation; Adult; Cystic Fibrosis; Humans; Levofloxacin; Lung; Nebulizers and Vaporizers; Respiratory Aerosols and Droplets
PubMed: 36076992
DOI: 10.3390/ijms23179597 -
Diagnostic Microbiology and Infectious... Jul 2023Gepotidacin is a novel agent in development for treatment of gonorrhea and uncomplicated urinary tract infection. This study determined the effect of urine on the in...
Analysis of the effect of urine on the in vitro activity of gepotidacin and levofloxacin against Escherichia coli, Staphylococcus epidermidis, and Staphylococcus saprophyticus.
Gepotidacin is a novel agent in development for treatment of gonorrhea and uncomplicated urinary tract infection. This study determined the effect of urine on the in vitro activity of gepotidacin and levofloxacin against relevant bacteria. Study strains were tested by Clinical and Laboratory Standards Institute broth microdilution and with method variations: CAMHB with 25%, 50%, 100% urine and pH adjusted 100% urine. Mean dilution difference (DD) of urine minimum inhibitory concentration (MICs) were <1 dilution of CAMHB MICs with some exceptions: Gepotidacin mean DD: Escherichia coli and Staphylococcus saprophyticus 100% urine (1.5 and 1.2, respectively) and S. saprophyticus pH 7.3 and 8.1 adjusted 100% urine (1.5 and 1.4, respectively); Levofloxacin mean DD: S. saprophyticus pH 7.3 adjusted 100% urine (1.5) and all species pH 8.1 adjusted 100% urine (1.2-1.8). Effects of urine on gepotidacin and levofloxacin MICs was minimal and not inclusive of all strains. Further analysis is warranted to fully assess the impact of urine on gepotidacin activity.
Topics: Humans; Levofloxacin; Anti-Bacterial Agents; Staphylococcus saprophyticus; Staphylococcus epidermidis; Escherichia coli; Microbial Sensitivity Tests
PubMed: 37201401
DOI: 10.1016/j.diagmicrobio.2023.115946 -
Journal of Veterinary Pharmacology and... Jul 2021The pharmacokinetics of levofloxacin mesylate in healthy adult giant panda is unknown. In this study, the pharmacokinetics of levofloxacin after intramuscular...
The pharmacokinetics of levofloxacin mesylate in healthy adult giant panda is unknown. In this study, the pharmacokinetics of levofloxacin after intramuscular administration at a dose of 2 mg/kg and oral administration at a dose of 3 mg/kg in healthy adult giant pandas was determined. Levofloxacin concentrations in plasma were determined using liquid chromatography. In the levofloxacin intramuscular administration group, the absorption and elimination half-lives of the drug were determined to be 0.123 (range: 0.02) hr and 5.402 (range: 0.70) hr, respectively. In the levofloxacin oral administration group, the absorption and elimination half-lives were determined to be 0.325 (range: 0.02) hr and 7.143 (range: 0.63) hr, respectively. Furthermore, the blood-drug concentration of levofloxacin was found to be above 1 μg/ml after 8 hr of intramuscular administration and above 0.5 μg/ml after 12 hr of oral administration. In this study, HPLC conditions and pretreatment methods of plasma samples were optimized and a detection method was established. Our results indicated that in healthy adult giant pandas, levofloxacin was rapidly absorbed and slowly eliminated. This study will therefore provide to be a guide in veterinary research and will be helpful in the rational use of levofloxacin in giant panda.
Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Levofloxacin; Mesylates; Ursidae
PubMed: 33565110
DOI: 10.1111/jvp.12945 -
AAPS PharmSciTech Nov 2023Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their...
Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their green properties, deep eutectic systems have been heralded as having the potential to be at the forefront of pharmaceutical applications. In this work, capric acid and geranic acid, two examples of medium-chain saturated and polyunsaturated fatty acids, were employed to enhance the pharmaceutical properties and the antibacterial activity of levofloxacin. To this end, levofloxacin formulations with either capric or geranic acid were prepared and characterized using appropriate techniques. Levofloxacin was utilized to create innovative deep eutectic systems in conjunction with capric acid at three different molar ratios: 1:9, 2:8 and 3:7. This was confirmed through a rigorous analysis involving nuclear magnetic resonance, infrared spectroscopy and differential scanning calorimetry. Furthermore, it is noteworthy that geranic acid demonstrated an impressive threefold improvement in levofloxacin's solubility compared to its solubility in aqueous solutions. The antibacterial activity of the novel combinations of levofloxacin with either fatty acid was evaluated using a checkerboard titration assay. Gratifyingly, both formulations exhibited synergistic effects against a panel of levofloxacin-sensitive and resistant Gram-negative bacteria. In conclusion, the observed superior antibacterial activity of levofloxacin illuminates the potential use of fatty acid-based formulations and deep eutectic systems as green and innovative strategies to combat the global antimicrobial resistance problem.
Topics: Levofloxacin; Fatty Acids; Anti-Bacterial Agents; Decanoic Acids; Fatty Acids, Unsaturated; Pharmaceutical Preparations; Solvents
PubMed: 38030950
DOI: 10.1208/s12249-023-02701-w -
Helicobacter Oct 2021The Maastricht V/Florence Consensus Report recommends amoxicillin-fluoroquinolone triple or quadruple therapy as a second-line treatment for Helicobacter pylori... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The Maastricht V/Florence Consensus Report recommends amoxicillin-fluoroquinolone triple or quadruple therapy as a second-line treatment for Helicobacter pylori infection. An important caveat of amoxicillin-fluoroquinolone rescue therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. The study aimed to investigate the efficacies of tetracycline-levofloxacin (TL) quadruple therapy and amoxicillin-levofloxacin (AL) quadruple therapy in the second-line treatment of H. pylori infection.
METHODS
Consecutive H. pylori-infected subjects after the failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (tetracycline 500 mg QID, levofloxacin 500 mg QD, esomeprazole 40 mg BID, and tripotassium dicitrato bismuthate 300 mg QID) or AL quadruple therapy (amoxicillin 500 mg QID, levofloxacin 500 mg QD, esomeprazole 40 mg BID, and tripotassium dicitrato bismuthate 300 mg QID) for 10 days. Post-treatment H. pylori status was assessed 6 weeks after the end of therapy.
RESULTS
The study was early terminated after an interim analysis. In the TL quadruple group, 50 out of 56 patients (89.3%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved only in 39 of 52 patients (69.6%) receiving AL quadruple therapy. Intention-to-treat analysis showed that TL quadruple therapy achieved a markedly higher eradication rate than AL quadruple therapy (95% confidence interval: 4.8% to 34.6%; p = 0.010). Further analysis revealed that TL quadruple therapy had a high eradication rate for both levofloxacin-susceptible and resistant strains (100% and 88.9%). In contrast, AL quadruple therapy yielded a high eradication for levofloxacin-susceptible strains (90.9%) but a poor eradication efficacy for levofloxacin-resistant strains (50.0%). The two therapies exhibited comparable frequencies of adverse events (37.5% vs 21.4%) and drug adherence (98.2% vs 94.6%).
CONCLUSIONS
Ten-day TL quadruple therapy is more effective than AL quadruple therapy in the second-line treatment of H. pylori infection in a population with high levofloxacin resistance.
Topics: Amoxicillin; Anti-Bacterial Agents; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Proton Pump Inhibitors; Tetracycline; Treatment Outcome
PubMed: 34390083
DOI: 10.1111/hel.12840 -
Biodegradation Aug 2021The global presence of antibiotics in the environment has created concerns about the emergence of antibiotic resistance bacteria and potential hazard to humans and the...
The global presence of antibiotics in the environment has created concerns about the emergence of antibiotic resistance bacteria and potential hazard to humans and the ecosystem. This work aims to study the removal of levofloxacin, a new generation fluoroquinolone antibiotic from aqueous solutions by enzyme mediated oxidation process and optimization of the conditions thereof by response surface methodology (RSM) using Box-Behnken design (BBD). For this study, experiments were conducted to analyze the effect of independent variables namely, pH, temperature, mediator concentration and antibiotic concentration on the degradation percentage of levofloxacin antibiotic using laccase enzyme derived from Trametes versicolor. The residual levofloxacin concentration was determined using high performance liquid chromatography (HPLC). On applying the quadratic regression analysis, among the main parameters, it was found that the percentage degradation was significantly affected by all the four variables. The predicted values for percentage degradation of levofloxacin were close to the experimental values obtained and the R (0.95) indicated that the regression was able to give a good prediction of response for the percentage degradation of levofloxacin in the studied range. The optimal conditions for the maximum degradation (99.9%) as predicted by the BBD were: temperature of 37 °C, pH of 4.5, mediator concentration of 0.1 mM and levofloxacin concentration of 5 μg mL. The findings of the study were further extended to study the effect of partially purified enzymes isolated from Pleurotus eryngii, Pleurotus florida and Pleurotus sajor caju on the degradation of levofloxacin at concentrations ranging from as low as 0.1 to as high as 50 µg mL in synthetic wastewater utilizing the optimized conditions generated by BBD. A maximum degradation of 88.8% was achieved with the partially purified enzyme isolated from Pleurotus eryngii at 1 µg mL levofloxacin concentration which was at par with the commercial laccase which showed 89% degradation in synthetic wastewater at the optimized conditions. The biodegradation studies were conducted using only 2 units of laccase. Thus, the expensive commercial laccase can be effectively replaced by crude laccase isolated from indigenous macrofungi such as P. eryngii, P. florida and P. sajor caju as a cost effective alternative to degrade levofloxacin present in contaminated wastewater using as low as 2 units of enzyme for a 72 h treatment period.
Topics: Anti-Bacterial Agents; Biodegradation, Environmental; Ecosystem; Humans; Laccase; Levofloxacin; Pleurotus; Polyporaceae; Trametes
PubMed: 34014411
DOI: 10.1007/s10532-021-09946-x -
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 -
International Journal of Antimicrobial... Sep 2019Staphylococcus aureus may invade and persist intracellularly in prosthetic joint infections (PJIs). Despite optimized treatments with levofloxacin plus rifampin, the...
Intraosteoblastic activity of levofloxacin and rifampin alone and in combination against clinical isolates of meticillin-susceptible Staphylococcus aureus causing prosthetic joint infection.
BACKGROUND
Staphylococcus aureus may invade and persist intracellularly in prosthetic joint infections (PJIs). Despite optimized treatments with levofloxacin plus rifampin, the intracellular reservoir may lead to infection relapse. This study assessed the intracellular activity of levofloxacin and rifampin in an in-vitro model of human osteoblastic infection.
METHODS
Ten meticillin-susceptible S. aureus strains were used to infect osteoblastic MG63 cells. Osteoblasts were challenged with rifampin and levofloxacin at cortical and cancellous bone concentrations. Efficacy was measured as the intracellular counts of colony-forming units (logCFU) compared with untreated controls. The emergence of small colony variants (SCVs) was determined, and the results were stratified according to the patient's prognosis (six cured and four with persistence/relapse).
RESULTS
All regimes led to a significant decrease in CFU count compared with controls (1-2 logCFU). Levofloxacin was the most effective treatment at both cortical and cancellous bone concentrations (-2.4 to -1.9 logCFU, respectively). The addition of rifampin to levofloxacin did not improve performance (-1.9 logCFU for cortical concentration and -1.8 log CFU for cancellous concentration). An increase in SCVs was observed in the presence of rifampin. The efficacy of antimicrobials was higher and the formation of SCVs was lower against strains belonging to PJIs with a favourable outcome.
CONCLUSIONS
Levofloxacin plus rifampin had good intracellular activity against S. aureus. However, from the intracellular perspective, the addition of rifampin to levofloxacin showed no benefit but could account for an increased number of SCVs.
Topics: Anti-Bacterial Agents; Cell Line; Colony Count, Microbial; Humans; Levofloxacin; Microbial Sensitivity Tests; Microbial Viability; Models, Theoretical; Osteoarthritis; Osteoblasts; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus
PubMed: 31254616
DOI: 10.1016/j.ijantimicag.2019.06.018 -
Colloids and Surfaces. B, Biointerfaces Jul 2022Levofloxacin is the levo-enantiomer of ofloxacin (a fluoroquinolone class of antibacterial drug). Cyclodextrins (CDs) including hydroxypropyl-β-cyclodextrin (HPβCD)...
Levofloxacin is the levo-enantiomer of ofloxacin (a fluoroquinolone class of antibacterial drug). Cyclodextrins (CDs) including hydroxypropyl-β-cyclodextrin (HPβCD) are generally used as a chiral selector for the enantioseparation of some drugs including levofloxacin or as a drug/food nanocarrier for the efficacy improvement of many pharmaceuticals. We hypothesized that the cyclodextrin inclusion is potentially able to further improve the antibacterial activity of levofloxacin. To test this hypothesis, the levofloxacin/HPβCD inclusion complex was prepared by the freeze-drying method and characterized by phase solubility diagram, differential scanning calorimetry (DSC), X-ray diffractometry (XRD), UV-Vis spectrophotometer, and H NMR spectroscopy, confirming the successful HPβCD inclusion of levofloxacin. The in vitro antibacterial effects of HPβCD, levofloxacin, and the levofloxacin/HPβCD inclusion complex against four different bacterial strains in liquid media and on agar plates were determined/compared (an MIC of 0.5-1.0 μg/mL for the inclusion complex compared with that of 1.0-2.0 μg/mL for free levofloxacin in liquid). Moreover, the in vivo antibacterial effects of levofloxacin and levofloxacin/HPβCD inclusion complex were tested by using a skin scald model in mice infected with Staphylococcus aureus, and decreased amounts of both bacteria and leukocytes were detected in scalded skin after the inclusion complex treatment. The data revealed that the levofloxacin/HPβCD inclusion complex had an enhanced antibacterial activity compared with free levofloxacin. It implies that cyclodextrins (e.g. HPβCD) may have a beneficial role when using as a chiral selector or as a drug nanocarrier for levofloxacin and that the levofloxacin/HPβCD inclusion complex has the potential of being developed into a pharmaceutical for antibacterial therapies.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Anti-Bacterial Agents; Calorimetry, Differential Scanning; Cyclodextrins; Levofloxacin; Mice; Solubility
PubMed: 35490541
DOI: 10.1016/j.colsurfb.2022.112514 -
International Journal of Environmental... Apr 2022The Chinese community-acquired pneumonia (CAP) Diagnosis and Treatment Guideline 2020 recommends quinolone antibiotics as the initial empirical treatment options for...
The Chinese community-acquired pneumonia (CAP) Diagnosis and Treatment Guideline 2020 recommends quinolone antibiotics as the initial empirical treatment options for CAP. However, patients with pulmonary tuberculosis (PTB) are often misdiagnosed with CAP because of the similarity of symptoms. Moxifloxacin and levofloxacin have inhibitory effects on mycobacterium tuberculosis as compared with nemonoxacin, resulting in delayed diagnosis of PTB. Hence, the aim of this study is to compare the cost-effectiveness of nemonoxacin, moxifloxacin and levofloxacin in the treatment of CAP and to determine the value of these treatments in the differential diagnosis of PTB. Primary efficacy data were collected from phase II-III randomized, double-blind, multi-center clinical trials comparing nemonoxacin to moxifloxacin (CTR20130195) and nemonoxacin to levofloxacin (CTR20140439) for the treatment of Chinese CAP patients. A decision tree was constructed to compare the cost-utility among three groups under the perspective of healthcare system. The threshold for willingness to pay (WTP) is 1-3 times GDP per capita ($11,174-33,521). Scenarios including efficacy and cost for CAP patients with a total of 6% undifferentiated PTB. Sensitivity and scenario analyses were performed to test the robustness of basic analysis. The costs of nemonoxacin, moxifloxacin, and levofloxacin were $903.72, $1053.59, and $1212.06 and the outcomes were 188.7, 188.8, and 188.5 quality-adjusted life days (QALD), respectively. Nemonoxacin and moxifloxacin were dominant compared with levofloxacin, and the ICER of moxifloxacin compared with nemonoxacin was $551,643, which was much greater than WTP; therefore, nemonoxacin was the most cost-effective option. Regarding patients with PTB who were misdiagnosed with CAP, taking nemonoxacin could save $290.76 and $205.51 when compared with moxifloxacin and levofloxacin and resulted in a gain of 2.83 QALDs. Our findings demonstrate that nemonoxacin is the more economical compared with moxifloxacin and levofloxacin, and non-fluoroquinolone antibiotics are cost-saving and utility-increasing compared to fluoroquinolones in the differential diagnosis of PTB, which can help healthcare system in making optimal policies and help clinicians in the medication of patients.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cost-Benefit Analysis; Fluoroquinolones; Humans; Levofloxacin; Moxifloxacin; Pneumonia; Quinolones; Randomized Controlled Trials as Topic; Tuberculosis, Pulmonary
PubMed: 35457683
DOI: 10.3390/ijerph19084816