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Environmental Pollution (Barking, Essex... Jan 2023Adsorption and transport of levofloxacin (LEV) and ofloxacin (OFL) enantiomers in a matrix containing goethite and natural organic matter (NOM) were investigated using...
Adsorption and transport of levofloxacin (LEV) and ofloxacin (OFL) enantiomers in a matrix containing goethite and natural organic matter (NOM) were investigated using batch and column experiments. In batch studies, competition and enantioselectivity were observed in the adsorption of LEV and OFL. Enantioselectivity upon adsorption was investigated by comparing changes in the enantiomer fraction (EF) (the ratio of LEV to the sum of LEV and OFL remaining in the solution) after and before adsorption. At pH < 7, there was hardly any selectivity in adsorption of OFL and LEV to goethite. At pH > 7, OFL showed a stronger adsorption than LEV to goethite, and this preference remained when NOM samples of Leonardite humic acid (LHA) and Elliott Soil fulvic acid (ESFA) were added. However, when Suwannee River NOM (SRNOM) was added, the preference was reversed, and LEV was adsorbed more strongly. In single systems, the presence of different types of NOM increased adsorption of LEV and OFL, especially LEV. In column studies, preloaded NOM decreased the transport of LEV and OFL through goethite-coated sand. The EF values in the effluent increased with retention time and reached the largest values (0.59-0.72) at around 1.5 pore volume (PV), and then decreased again, reaching a stable value at 5.0-30.0 PV. Both batch and column experiments showed that, fractionation of LEV and OFL occurred during adsorption and transport in the presence of NOM-goethite complexes, which would eventually affect their environmental fate.
Topics: Levofloxacin; Ofloxacin; Iron Compounds; Adsorption; Humic Substances
PubMed: 36328279
DOI: 10.1016/j.envpol.2022.120542 -
Biomedicine & Pharmacotherapy =... Oct 2021Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the...
Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bone Diseases, Infectious; Female; Fluoroquinolones; Humans; Joint Diseases; Levofloxacin; Male; Middle Aged; Models, Biological; Monte Carlo Method; Ofloxacin; Prospective Studies; Staphylococcus; Young Adult
PubMed: 34435591
DOI: 10.1016/j.biopha.2021.112053 -
The Journal of Antimicrobial... Oct 2016The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not... (Review)
Review
The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not the least important. This review summarizes the available information on pharmacokinetic properties of levofloxacin in relation to microbial susceptibilities, in order to optimize the dose and make general treatment recommendations. A total of 37 studies on adult (32 studies) and paediatric (5 studies) MDR-TB patients were included. Among the 32 adult studies, 19 were on susceptibility of Mycobacterium tuberculosis isolates to levofloxacin by MIC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by MBC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by mutant prevention concentration and 4 were on pharmacokinetics of levofloxacin, and 7 others were included. Likewise, out of five studies on children, two dealt with levofloxacin pharmacokinetic parameters, one reviewed CSF concentrations and two dealt with background information. In adult MDR-TB patients, standard dosing of once-daily 1000 mg levofloxacin in TB treatment did not consistently attain the target concentration (i.e. fAUC/MIC >100 and fAUC/MBC >100) in 80% of the patients with MIC and MBC of 1 mg/L, leaving them at risk of developing drug resistance. However, with an MIC of 0.5 mg/L, 100% of the patients achieved the target concentration. Similarly, paediatric patients failed consistently in achieving given pharmacokinetic/pharmacodynamic targets due to age-related differences, demanding a shift towards once daily dosing of 15-20 mg/kg. Therefore, we recommend therapeutic drug monitoring for patients with strains having MICs of ≥0.5 mg/L and suggest revising the cut-off value from 2 to 1 mg/L.
Topics: Adult; Anti-Bacterial Agents; Antitubercular Agents; Child; Clinical Trials as Topic; Extensively Drug-Resistant Tuberculosis; Humans; Levofloxacin; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 27231277
DOI: 10.1093/jac/dkw164 -
Nephrology (Carlton, Vic.) Jun 2015
Topics: Acute Kidney Injury; Anti-Infective Agents; Biomarkers; Creatinine; Crystallization; Female; Humans; Levofloxacin; Middle Aged; Renal Dialysis; Treatment Outcome
PubMed: 25900386
DOI: 10.1111/nep.12405 -
Scientific Reports Aug 2023Drug-induced liver injury induced by already approved substances is a major threat to human patients, potentially resulting in drug withdrawal and substantial loss of...
Drug-induced liver injury induced by already approved substances is a major threat to human patients, potentially resulting in drug withdrawal and substantial loss of financial resources in the pharmaceutical industry. Trovafloxacin, a broad-spectrum fluoroquinolone, was found to have unexpected side effects of severe hepatotoxicity, which was not detected by preclinical testing. To address the limitations of current drug testing strategies mainly involving 2D cell cultures and animal testing, a three-dimensional microphysiological model of the human liver containing expandable human liver sinusoidal endothelial cells, monocyte-derived macrophages and differentiated HepaRG cells was utilized to investigate the toxicity of trovafloxacin and compared it to the structurally-related non-toxic drug levofloxacin. In the model, trovafloxacin elicited vascular and hepatocellular toxicity associated with pro-inflammatory cytokine release already at clinically relevant concentrations, whereas levofloxacin did not provoke tissue injury. Similar to in vivo, cytokine secretion was dependent on a multicellular immune response, highlighting the potential of the complex microphysiological liver model for reliably detecting drug-related cytotoxicity in preclinical testing. Moreover, hepatic glutathione depletion and mitochondrial ROS formation were elucidated as intrinsic toxicity mechanisms contributing to trovafloxacin toxicity.
Topics: Animals; Humans; Levofloxacin; Endothelial Cells; Hepatitis; Fluoroquinolones; Drug-Related Side Effects and Adverse Reactions; Cytokines
PubMed: 37587168
DOI: 10.1038/s41598-023-40004-z -
Journal of Clinical Pharmacy and... Jun 2021In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in...
WHAT IS KNOWN AND OBJECTIVE
In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in carrying out the diagnosis and treatment of refractory Mycoplasma pneumoniae pneumonia in children. Levofloxacin is suitable for treating infectious diseases in various systems but limited in children due to arthropathy issues in weight-bearing joints. This study aimed to evaluate the efficacy and safety of levofloxacin in children with macrolide-resistant Mycoplasma pneumoniae pneumonia.
METHODS
We retrospectively enrolled six confirmed cases of refractory Mycoplasma pneumoniae pneumonia who were admitted in the paediatric respiratory ward of Shandong provincial hospital Affiliated to Shandong first Medical University between 1st January 2020 and 29th February 2020. Levofloxacin was given to the patients through the intravenous or oral route as per the following dosages :<5 years, 8-10 mg/kg q12 h; >5 years, 8-10 mg/kg, qd for 10 days. The clinical data were collected and analysed.
RESULTS AND DISCUSSION
The average age of the enrolled cases was six years and nine months (range, four years, and seven months to eleven years and seven months). All cases were found to be drug-resistant and were treated with azithromycin combined with antibacterial drugs. Levofloxacin was used in the patient's refractory to macrolide antibiotics. The temperature of five cases returned to normal 1-2 days after treatment with levofloxacin, and the imaging of the four cases showed expected improvements. The gastrointestinal symptoms, neurological manifestations, joint symptoms, blood parameters, liver and kidney functions, and exercise conditions of the children were closely monitored. The follow-up time of the patients ranged from one week to five months. No drug-related adverse reactions were observed in patients during treatment or during follow-up.
WHAT IS NEW AND CONCLUSION
The clinical symptoms and imaging significantly improved after treatment with levofloxacin, and no drug-related adverse reactions were observed. Levofloxacin proved to be an effective and safe drug in the treatment of children with macrolide-resistant mycoplasma pneumonia. This study will provide a reference for evaluating the efficacy and safety of levofloxacin in the paediatric population.
Topics: Anti-Bacterial Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Female; Humans; Levofloxacin; Macrolides; Male; Pneumonia, Mycoplasma; Retrospective Studies
PubMed: 33403672
DOI: 10.1111/jcpt.13331 -
Ecotoxicology and Environmental Safety Jul 2023Excessive antibiotics transferred into the aquatic environment may affect the development of amphibians. Previous studies on the aquatic ecological risk of ofloxacin...
Excessive antibiotics transferred into the aquatic environment may affect the development of amphibians. Previous studies on the aquatic ecological risk of ofloxacin generally ignored its enantiomers. The purpose of this study was to compare the effects and mechanisms of ofloxacin (OFL) and levofloxacin (LEV) on the early development of Rana nigromaculata. After 28-day exposure at environmental levels, we found that LEV exerted more severe inhibitory effects on the development of tadpoles than OFL. According to the enrichment results of differentially expressed genes in the LEV and OFL treatments, LEV and OFL had different effects on the thyroid development of tadpoles. dio2 and trh were affected by the regulation of dexofloxacin instead of LEV. At the protein level, LEV was the main component that affected thyroid development-related protein, while dexofloxacin in OFL had little effect on thyroid development. Furthermore, molecular docking results further confirmed that LEV was a major component affecting thyroid development-related proteins, including DIO and TSH. In summary, OFL and LEV regulated the thyroid axis by differential binding to DIO and TSH proteins, thereby exerting differential effects on the thyroid development of tadpoles. Our research is of great significance for comprehensive assessment of chiral antibiotics aquatic ecological risk.
Topics: Animals; Ofloxacin; Levofloxacin; Larva; Thyroid Gland; Molecular Docking Simulation; Anti-Bacterial Agents; Ranidae; Hypothalamus; Thyrotropin
PubMed: 37178612
DOI: 10.1016/j.ecoenv.2023.114985 -
The Journal of Antibiotics Jul 2022Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis,...
Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC/ MIC results (mg l) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future.
Topics: Anti-Bacterial Agents; Burkholderia cepacia complex; Humans; Levofloxacin; Microbial Sensitivity Tests; Steroids
PubMed: 35562592
DOI: 10.1038/s41429-022-00530-w -
Minerva Urology and Nephrology Jun 2023On March 11 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on... (Review)
Review
BACKGROUND
On March 11 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on musculoskeletal and nervous system, with quinolone (QN) and fluoroquinolone (FQ) antibiotics. Aim of this study was to evaluate the effect of the EMA warning on the rate of AEs after QN and FQ treatments, reported in the EudraVigilance (EV) database.
METHODS
EV database is the system for managing and analyzing information on suspected AEs to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We retrospectively explored the effect of FQs and QNs on musculoskeletal and nervous system from the EMA warning up to now (21 months) and compared these results with the 21 months before the EMA warning.
RESULTS
Main part of AEs in EV database were reported for ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin. Ciprofloxacin total AEs before 21 months till 12 months of EMA warning were 2763. 12 months before EMA Warning they were 2935. Twelve months after EMA Warning they were 3419. Between 12 months till 21 months they were 3174. Musculoskeletal disorders were respectively 574 (21% of the total) 21 months before, 558 (19%) 12 months before, 1048 (31%) after 12 months, 540 (17%) after 21 months of EMA Warning. Nervous system disorders were respectively 606 (22% of the total) 21 months before, 517 (18%) 12 months before, 680 (20%) after 12 months, 560 (18%) after 21 months of EMA Warning (respectively OR 1,16 95%CI 1,10 -1,22, P 0,12 ; OR 0,76 95%CI 0,69-0,83, P 0,27 ; OR 1,01 95%CI 0,96-1,06 P 0,05).
CONCLUSIONS
Our analysis clearly showed no significant differences before and after EMA warning, opening new insights in the role of the EMA warning in clinical practice.
Topics: Fluoroquinolones; Quinolones; Retrospective Studies; Ciprofloxacin; Levofloxacin
PubMed: 36940165
DOI: 10.23736/S2724-6051.23.05169-8 -
Journal of Oncology Pharmacy Practice :... Oct 2016Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated... (Review)
Review
INTRODUCTION
Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery.
METHODS
The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery.
RESULTS
There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39).
CONCLUSIONS
Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications.
Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Febrile Neutropenia; Female; Humans; Leukocyte Count; Levofloxacin; Male; Middle Aged; Retrospective Studies
PubMed: 26227319
DOI: 10.1177/1078155215597558