Dose Of Levofloxacin Research Articles

Levofloxacin induces erythrocyte contraction leading to red cell death.

Levofloxacin, a fluoroquinolone, is an extensively used antibiotic effective against both positively and negatively staining bacteria. It works by inhibiting bacterial topoisomerase type II and topoisomerase type IV, resulting in impaired DNA synthesis and bacterial cell death. Eryptosis is another term for apoptotic cell death of erythrocyte marked by cell shrinkage, phosphatidylserine (PS) flipping, and membrane blebbing. The intent of the present research was to look at the eryptotic effect of levofloxacin by exposing erythrocytes to therapeutical doses (7, 14 µM) of levofloxacin for 48 hours. Cell size evaluation, PS subjection to outside, and calcium channel inhibition were carried out to investigate eryptosis. Oxidative stress generated by levofloxacin was measured as a putative mechanism of eryptosis using glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities. Similarly, hemolysis measurements demonstrated levofloxacin's cytotoxic effect. Our findings showed that therapeutic doses of levofloxacin can cause a considerable decline in antioxidant enzymes activities, as well as induce cell shrinkage, PS externalization, and hemolysis in erythrocytes. The role of calcium in triggering erythrocyte shrinkage was also confirmed. In conclusion, our findings showed that the indicated levofloxacin doses caused oxidative stress, which leads to erythrocyte death via eryptosis and hemolysis. These findings emphasize the importance of using levofloxacin with caution and the need for additional research to mitigate these side effects.

Effect of Different Levofloxacin Doses on QTc Interval Prolongation in Multidrug-Resistant Tuberculosis Patients Treated with the 9-Month All-Oral Regimen

Introduction: The World Health Organization (WHO) has recommended the 9-month all-oral regimen for multidrug-resistant tuberculosis (MDR-TB) treatment. This regimen is expected to increase the treatment success rate. Bedaquiline, levofloxacin, and clofazimine are QT-prolonging drugs included in the 9-month all-oral regimen. Bedaquiline and clofazimine are given at the same dose for all patients, while levofloxacine dose is given in 750 mg and 1,000 mg based on the body weight. This study analyzed the correlation between different levofloxacin doses and certain factors on QTc interval prolongation. Methods: This observational retrospective study used the medical records of MDR-TB patients who underwent the 9-month all-oral regimen. Electrocardiography (ECG) for QTc interval measurement was recorded at the baseline before and 2 weeks after treatment. The measured variables included patient demographic data, body mass index (BMI), electrolyte levels, and comorbidities. Results: Thirty MDR-TB patients were included in this study. Gender, diabetes mellitus (DM), and levofloxacin dose did not correlate with QTc interval prolongation at 2 weeks after drug administration (p-values of 0.558, 0.197, and 0.134, respectively). Age, potassium level, magnesium level, calcium level, and baseline QTc interval also did not correlate with QTc interval prolongation at 2 weeks after drug administration (p-values of 0.433, 0.479, 0.705, 0.746, and 0.333, respectively). Multivariate analysis showed that the risk factor associated with QTc interval prolongation at 2 weeks after drug administration was a BMI of 0.013. Conclusion: Different levofloxacin doses did not correlate with QTc interval prolongation in MDR-TB patients treated with the 9-month all-oral regimen. The incidence of QTc interval prolongation was significantly associated with the lower BMI level.

Rapid in vitro activity of telavancin against Bacillus anthracis and in vivo protection against inhalation anthrax infection in the rabbit model.

Inhalation anthrax is the most severe form of Bacillus anthracis infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat anthrax when promptly administered, strains engineered for antibiotic resistance could render these drugs ineffective. Telavancin, a semisynthetic lipoglycopeptide antibiotic, was evaluated in this study as a novel therapeutic against anthrax disease. Specifically, the aims were to (i) assess in vitro potency of telavancin against 17 B. anthracis isolates by minimum inhibitory concentration (MIC) testing and (ii) evaluate protective efficacy in rabbits infected with a lethal dose of aerosolized anthrax spores and treated with human-equivalent intravenous telavancin doses (30 mg/kg every 12 hours) for 5 days post-antigen detection versus a humanized dose of levofloxacin and vehicle control. Blood samples were collected at various times post-infection to assess the level of bacteremia and antibody production, and tissues were collected to determine bacterial load. The animals' body temperatures were also recorded. Telavancin demonstrated potent bactericidal activity against all strains tested (MICs 0.06-0.125 μg/mL). Further, telavancin conveyed 100% survival in this model and cleared B. anthracis from the bloodstream and organ tissues more effectively than a humanized dose of levofloxacin. Collectively, the low MICs against all strains tested and rapid bactericidal in vivo activity demonstrate that telavancin has the potential to be an effective alternative for the treatment or prophylaxis of anthrax infection.

Degradation of levofloxacin using electro coagulation residuals-alginate beads as a novel heterogeneous electro-fenton composite

The presence of levofloxacin (LEV) in aqueous solutions can pose health risks to humans, have adverse effects on aquatic organisms and ecosystems, and contribute to the development of antibiotic-resistant bacteria. This study aims to investigate the feasibility of using electrocoagulation residuals (ECRs) as a heterogeneous catalyst in the electro-Fenton process for degrading LEV. By combining electrocoagulation residuals with sodium alginate, ECRs-alginate beads were synthesized as a heterogeneous electro-Fenton composite. The response surface method was employed to investigate the optimization and influence of various operating parameters such as the initial concentration of LEV (10–50 mg/L), voltage (15–35 V), pH (3–9), and catalyst dose (1–9 g/L). The successful incorporation of iron and other metals into the ECRs-alginate beads was confirmed by characterization tests such as EDX and FTIR. By conducting a batch reaction under optimal conditions (initial LEV concentration = 20 mg/L, pH = 4.5, voltage = 30V, and catalyst dose = 7 g/L), a remarkable degradation of 99% for LEV was achieved. Additionally, under these optimal conditions, a high removal efficiency of 92.3% for total organic carbon (TOC) could be attained within 120 min and these findings are remarkable compared to previous studies. The results further indicated that the degradation of levofloxacin (LEV) could be accurately quantified by utilizing the first-order kinetic reaction with a 0.03 min−1 rate constant. The synthesized beads offered notable advantages in terms of being eco-friendly, simple to use, highly efficient, and easily recoverable from the liquid medium after use.

Effects of antibiotics ceftriaxone and levofloxacin on the growth of Protophormia terraenovae (Diptera: Calliphoridae).

Protophormia terraenovae is a colonizer of decomposing bodies and is known to cause pre-mortem myiasis as the female flies lay eggs in uncleaned wounds. In this study the effects of different concentrations of antibiotics levofloxacin and ceftriaxone on maggot development, weight, length, and mortality were examined. The maggot length and weight were significantly increased by therapeutical doses of levofloxacin and ceftriaxone. The maggot development time was significantly decreased in every levofloxacin treatment compared to the control. The time to start pupation was significantly increased in the control compared to the antibiotic treatments. Levofloxacin significantly increased the survivability of the maggots. Every levofloxacin treatment significantly improved the rearing conditions for the maggots. Reaching the third instar was delayed by 24h in the control compared to the Levo 3.57 treatment. The Pupation in the control was delayed by an average of 48h compared to the Levo 3.57 treatment. The significantly reduced development time of the maggots in the antibiotic treatments might lead to an overestimation of the post-mortem interval and therefore an incorrect time of death determination. The improved rearing conditions may be an indication of the potential of a combined application of antibiotics and maggot therapy.

Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.

Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children. Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses. Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax. Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.

One case report of epilepsy and rapidly progressive cognitive impairment after levofloxacin treatment

ObjectiveTo report a case of seizure and rapidly progressive cognitive impairment 20 min after intravenous administration of levofloxacin.Case summaryA 56-year-old woman was admitted to hospital with episodic unconsciousness and unresponsiveness. About 4 days ago, she experienced a loss of consciousness, fell to the floor, and yelled for 2 min, 20 min before the first intravenous dose of levofloxacin. The patient developed symptoms of cognitive impairment after the seizure. Levofloxacin is a synthetic third generation fluoroquinolone used to treat various infectious diseases. Upon admission, the patient was conscious and unresponsive. After 11 days of symptomatic and supportive treatment, the patient was discharged from the hospital with cognition restored to baseline level and no recurrence of seizures 10 months after discharge.DiscussionEpilepsy is a rare adverse reaction to levofloxacin treatment. The patient in this case had infection-related signs before the onset of the disease, and the disease progressed rapidly with fluctuating changes. After ruling out degenerative, infectious, toxic, and autoimmune causes, the patient’s symptoms may be attributed to levofloxacin, and this is the first case of seizure and rapidly progressive cognitive impairment after levofloxacin injection reported in the literature. Clinicians should be aware that unexplained, rapidly progressing cognitive impairment with infection-related signs before onset may be a rare side effect of antibiotics.

Abstract C079: H. pylori eradication for mitigating gastro-duodenal cancers: Modeling pharmacokinetics of levofloxacin niosomes in Sprague-Dawley rats

Abstract Eradication of Helicobacter pylori (H. pylori) and, hence, control of its associated conditions (peptic ulcer, gastric cancer, and lymphoma) still constitute major challenge to therapeutics. H. pylori has been implicated in 60% of gastric and 90 % of duodenal ulcers and has been classified as a Class 1 carcinogen in human by the International Agency for Research on Cancer and the World health Organization (Enerson et al, 2016; Vogiatzi et al, 2007; WHO). It affects 4million people world-wide of which 0.5million is from the US and 70% are of 25-64 y/o (Chung &amp; Shelat, 2017). Presently, gastric cancer is the second leading cause of neoplastic mortality globally (Contreras et al, 2014; Owen et al, 2018). The efficacy of currently used antibiotics (erythromycin, clarithromycin, levofloxacin, and azithromycin) in triple or quadruple combinations with proton pump inhibitor (PPI) is decreasing due to resistance development via lipopolysaccharide modification, increased drug efflux, and reduced porin pathway. Adaptive response by bacteria to specific signal due to antibacterial presence in its environment, leading to up-regulation of the efflux system (MexXY/OprM), and down-regulation of porin pathway (OprD) has been recognized as key factor in the resistance manifestation. In an earlier study, we reported that encapsulation of an anti-H. pylori drug (levofloxacin) molecules in niosomes (nano-size lipid vesicles) improved its molecular assimilation by drug-resistant E. coli and Ps. aeruginosa and produced approximately 50 % reduction in their minimum inhibitory concentrations (MIC) (Jankie et al, 2012). In this study, we investigated the in vivo bioavailability of levofloxacin niosomes administered intraperitoneally to Sprague Dawley rats. Plasma data modelling in Gastroplus PKTM for non-compartmental through 3-compartmental models, using Hooke &amp; Jeeves pattern search, indicated that pure levofloxacin obeyed two-compartment kinetic model, while levofloxacin niosomes demonstrated one-compartmental model. In addition, niosome encapsulation increased drug exposure (AUC) about 5 folds and duration of action (mean residence time, MRT) about 1.6 folds. Thus, niosome encapsulation changed distribution pattern and the values of PK parameter supported 2-compartmental and 1-compartmental models for levofloxacin and its niosomes respectively. The knowledge of in vivo rodent PK generated in this study is vital for the determination of test doses in a higher animal species and, subsequent, for the calculation of thee first in human dose of levofloxacin using allometric equations. Generally, the potential is quite high for niosomes encapsulation to enhance the efficacy of other anti-H. pylori drugs against drug-resistant bacterial strains and needs to be investigated. Citation Format: Amusa S. Adebayo, Satish Jankie. H. pylori eradication for mitigating gastro-duodenal cancers: Modeling pharmacokinetics of levofloxacin niosomes in Sprague-Dawley rats [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C079.

Pharmacokinetics and optimized dosing of dispersible and non-dispersible levofloxacin formulations in young children.

Levofloxacin is used for treatment and prevention of rifampicin-resistant (RR)-TB in children. Recent data showed higher exposures with 100 mg dispersible compared with non-dispersible tablet formulations with potentially important dosing implications in children. We aimed to verify and better characterize this finding. We conducted a crossover pharmacokinetic trial in children aged ≤5 years receiving levofloxacin RR-TB preventive therapy. Pharmacokinetic sampling was done after 15-20 mg/kg doses of levofloxacin with 100 mg dispersible and crushed 250 mg non-dispersible levofloxacin formulations. A population pharmacokinetic model was developed. Twenty-five children were included, median (IQR) weight and age 12.2 (10.7-15.0) kg and 2.56 (1.58-4.03) years, respectively. A two-compartment model with first-order elimination and transit compartment absorption best described levofloxacin pharmacokinetics. Allometric scaling adjusted for body size, and maturation of clearance with age was characterized. Typical clearance in a 12 kg child was estimated at 4.17 L/h. Non-dispersible tablets had 21.5% reduced bioavailability compared with the dispersible formulation, with no significant differences in other absorption parameters.Dosing simulations showed that current recommended dosing for both formulations result in median exposures below adult-equivalent exposures at a 750 mg daily dose, mainly in children >6 months. Higher levofloxacin doses of 16-30 mg/kg for dispersible and 20-38 mg/kg for crushed non-dispersible tablets may be required in children >6 months. The dispersible paediatric levofloxacin formulation has improved bioavailability compared with the crushed non-dispersible adult formulation, but exposures remain below those in adults. We propose optimized age- and weight-based dosing for levofloxacin, which require further evaluation.

Helicobacter macacae MazF interplays with Escherichia coli homologs and enhances antibiotic tolerance.

Toxin-antitoxin systems are highly variable, even among strains of the same bacterial species. The MazEF toxin-antitoxin system is found in many bacteria and plays important roles in various biological processes such as antibiotic tolerance and phage defense. However, no interplay of MazEF systems between different species was reported. MazEF toxin-antitoxin system of Helicobacter macacae was examined in three Escherichia coli strains with and without endogenous MazEF knockout. In vivo toxicity, antibiotic tolerance, and live/dead staining followed by flowcytometry analysis were performed to evaluate the functionality and interplay of the toxin-antitoxin system between the two species. Controlled ectopic expression of MazF of H. macacae (MazFhm) in E. coli did not affect its growth. However, in endogenous MazEF knockout E. coli strains, MazFhm expression caused a sharp growth arrest. The toxicity of MazFhm could be neutralized by both the antitoxin of MazE homolog of H.macacae and the antitoxin of MazE of E. coli, indicating interplay of MazEF toxin-antitoxin systems between the two species. Induced expression of MazFhm enhanced tolerance to a lethal dose of levofloxacin, suggesting enhanced persister formation, which was further confirmed by live/dead cell staining. The MazEF toxin-antitoxin system of H. macace enhances persister formation and thus antibiotic tolerance in E. coli. Our findings reveal an interplay between the MazEF systems of H. macacae and E. coli, emphasizing the need to consider this interaction while evaluating the toxicity and functionality of MazF homologs from different species in future studies.

Mechanistic investigation of levofloxacin adsorption on Fe (III)-tartaric acid/xanthan gum/graphene oxide/polyacrylamide hydrogel: Box-Behnken design and Taguchi method for optimization

Fe (III)-tartaric acid/xanthan gum/graphene oxide/polyacrylamide (FXM) hydrogel was synthesized and probed its effectiveness in removing levofloxacin from water. The hydrogel (FXM) was characterized by instrumental techniques. Brunauer-Emmett-Teller (BET) analysis showed a surface area of 161.85 m2/g and Barrett-Joyner-Halenda (BJH) analysis provided pore size of 3.41 nm, indicating mesoporous nature. The adsorption experiments (batch mode) showed the adsorption capacity of 154.83 mg/g in a short equilibrium time (∼2 min). The controllable factors (adsorbent dose, pH and initial concentration of levofloxacin) were optimized by response surface methodology (RSM) and Taguchi technique. Various isotherm models were employed to correlate the equilibrium data; Freundlich isotherm model fitted well with equilibrium data as compared to other models based on high R2 values (0.9975–0.9980) and low values of χ2 (0.004–0.005) for non-linear analysis. Classical kinetic and fractal-like kinetic equations were applied to fit the experimental data. The experimental data best fit with fractal-like pseudo first order equation and heterogeneity parameter was 0.531. Mechanism of adsorption of levofloxacin on FXM was discussed based on XPS analysis and ΔG° values. Reusability experiments were executed in five adsorption–desorption cycles and percent removal varied from 98.00 to 82.25%, demonstrating high potential of FXM for re-use.

The effect of different doses of levofloxacin on leukocyte dynamics in chicken blood

The article deals with research into the effect of different doses of levofloxacin (fluoroquinolone class drug) on chicken blood parameters. Male Hisex Brown chickens were divided into 3 groups, one of them was control, the other two were experimental, the latter received the drug at concentrations 600 mg/L and 200 mg/L. The fluoroquinolone was administered via drinking water 5 consecutive days. We evaluated the following hematological parameters of chickens: leukocyte count (direct count in Goryaev's chamber) and leukogram (count in stained blood smears). The results of our research state that the administration of levofloxacin at concentration 600 mg/L causes transitory leukocytosis, lymphopenia and pseudoeosinophilia, but that does not imply a heavy toxic effect on chicken organism as by the end of the research the parameters were already within the normal range. The administration of levofloxacin at concentration 200 mg/L similarly caused a brief increase in pseudoeosinophil number and a decrease in lymphocyte number in chicken blood but they were not generally marked which would prove the negative effect of levofloxacin.

Comparison of Single Versus Multiple Doses of Fluoroquinolone (Levofloxacin) for Prophylaxis in Prostate Biopsy

Objective: To assess the efficacy of Levofloxacin 500 mg orally for prophylaxis in transrectal prostate biopsy guided by ultrasonography compared to three dosages. Study design: A comparative study Place and Duration: this study was done in Murshid Hospital and Health Care Centre Karachi from September 2021 to September 2022 Methodology: A total of 615 patients having the typical indications for prostate biopsy performed under transrectal ultrasonography guidance (increased PSA, abnormal digital rectal examination) were included in this study. Overall 425 patients were considered qualified for participation; using Graph Pad Prism 6.0, patients were assigned to one of two groups using random assignment, 205 individuals in Group A were given one oral dosage of 500 mg of levofloxacin 60 to 120 minutes before the procedure, Likewise, 220 patients in Group B received Levofloxacin (500 mg) once per 24 hours for two days before to the procedure as well as the day of it. Results: Patients in Group A were given orally a single dose of levofloxacin 500 mg there were 205 patients in this group. These individuals were diagnosed with diabetes mellitus (DM) at a rate of 43.9%, febrile urinary tract infections at a rate of 4.3%, and sepsis at a rate of 0.97%.In this group, 65.80cc,was the average prostate volume, and 90.17% were overweight.A total of 220 patients in groupB who received orally three doses of levofloxacin 500 mg, with an average age of 67.45 years and a PSA mean of 21.26 ng/mL; 31.8% of patients had diabetes mellitus, &amp; 4.45% had a febrile urinary tract infection (FUTI). In this group, no patients had sepsis, 75.61 cc was the mean prostate volume, and 72.74% of the patients were overweight, as in Group A. Conclusion: Because of how effective it is, a single dose of levofloxacin containing 500 milligrams is an excellent option for prophylaxis in patients who are going to have a transrectal prostate biopsy. Keywords: transrectal biopsy, flroquinolone, prophylaxis

ATYPICAL VARIANT OF GRANULOMATOSIS WITH POLYANGIITIS WITH EOSINOPHILIA

ATYPICAL VARIANT OF GRANULOMATOSIS WITH POLYANGIITIS WITH EOSINOPHILIA

Differential Performance and Lung Deposition of Levofloxacin with Different Nebulisers Used in Cystic Fibrosis.

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.

Point-of-care diagnostics for therapeutic monitoring of levofloxacin in human plasma utilizing electrochemical sensor mussel-inspired molecularly imprinted copolymer

• Fabrication of MIP electrochemical sensor to personalize the Levofloxacin dose. • Bio-inspired molecularly imprinted copolymer was synthesized utilizing Levodopa as a monomer. • Molecularly imprinted copolymer was electropolymerized on Au-NPs decorated pencil graphite electrode as a substrate. • The sensor was employed successfully for levofloxacin detection in spiked human plasma. Therapeutic drug monitoring is mandatory for drugs with narrow therapeutic index and is an integral part of the patient care standards, where drug concentration is measured in biological fluids to “ personalize ” patient’s dosage. In this work a disposable electrochemical sensor has been developed for Levofloxacin (LEV) determination in human plasma. The selected substrate was pencil graphite electrode (PGE). To enhance the sensor performance, the PGE has been modified with Au-NPs via electrochemical deposition. To achieve high selectivity towards levofloxacin, the PGE/Au-NPs electrode has been further modified with molecularly imprinted copolymer; poly( l -dopa)/poly( o -phenylenediamine), by anodic electropolymerization of the corresponding monomers. The Levodopa not only acts as a functional monomer but moreover, a substrate for mussel-inspired polymer. The sensor surface has been characterized using both scanning electron microscopy (SEM) imaging and X-ray photoelectron spectroscopy (XPS) to investigate the morphology and elemental composition of the modified PGE, respectively. To optimize the sensor performance, experimental variables were studied and tuned to improve the outcomes. The sensor has a linear response in two concentration windows (1.0 × 10 −6 –1.0 × 10 −4 mol/L) and (1.0 × 10 −4 –1.0 × 10 −2 mol/L) Levofloxacin, with a limit of detection of 4.62 × 10 −7 mol/L. Selectivity, repeatability, and low manufacturing cost are some benefits of the proposed sensor. The sensor was successfully used to determine Levofloxacin in Tavanic® tablets and spiked plasma samples.

Population pharmacokinetics and dose optimization of intravenous levofloxacin in hospitalized adult patients

Although levofloxacin has been used for the last 25 years, there are limited pharmacokinetic data to guide levofloxacin dosing in adult patients. This study aimed to develop a population pharmacokinetic model of levofloxacin for adult hospitalized patients and define dosing regimens that attain pharmacokinetic/pharmacodynamic target associated with maximum effectiveness. Blood samples were drawn from 26 patients during one dosing interval. Population pharmacokinetic modelling and dosign simulations were performed using Pmetrics®. Pathogen minimum inhibition concentration (MIC) distribution data from the European Committee on Antimicrobial Susceptibility Testing database was used to analyse fractional target attainment (FTA). A two-compartment model adequately described the data. The final model included estimated glomerular filtration rate (eGFR) to describe clearance. The population estimate for clearance was 1.12 L/h, while the volume of distribution in the central compartment and peripheral compartments were 27.6 L and 28.2 L, respectively. Our simulation demonstrated that an area under free concentration–time curve to MIC ≥ 80 was hardly achieved for pathogens with MIC ≥ 1 mg/L. Low FTA against Pseudomonas aeruginosa and Streptococcus pneumoniae were observed for patients with higher eGFR (≥ 80 mL/min/1.73m2). A daily levofloxacin dose of 1000 mg is suggested to maximise the likelihood of efficacy for adult patients.

To Determine the Efficacy of Antibiotic Prophylaxis in patients Undergoing Flexible Cystoscopy

Background: Flexible cystoscopy is a commonly performed intervention in urology practice. It has both diagnostic and therapeutic value and has an added advantage of being used as an outpatient procedure. However one of the common complication associated with it, is the development of Urinary tract infection (UTI) because of its minimally invasive nature. Aim: To determine the efficacy of antibiotic prophylaxis in patients undergoing flexible cystoscopy. Methods: A randomized control study was performed in total 144 patients selected for flexible cystoscopy. Patients were divided into Group A (Antibiotic group) and Control Group B. Group A received a single dose of Levofloxacin 500mg one hour before procedure, while no antibiotic prophylaxis was given to Group B. Primary outcome was development of UTI, which was assessed by subjective symptoms of UTI, results of urine culture and routine urine examination at 1st week after the procedure Results: After 1 week of procedure, 5 patients (6.9%) in Group A and 7 patients (9.7%) in Group B developed UTI. 3 patients (4.1%) in Group A and 6 patients (8.3%) in Group B developed asymptomatic bacteriuria after 1 week. 64 patients (88.9%) in Group A and 59 patients (81.9%) in Group B did not develop UTI after 1 week of procedure Conclusion: Prophylactic use of antibiotics before flexible cystoscopy has no effect in reducing the frequency of post procedure urinary tract infections Keywords: Urinary Tract Infection UTI), Cystoscopy, Antibiotic prophylaxis

Oral levofloxacin: population pharmacokinetics model and pharmacodynamics study in bone and joint infections.

This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.

Evaluation of Levofloxacin Prescription Pattern and Appropriateness Rate in the Outpatient Setting; A Cross-Sectional Study from Iran (2018-2019)

Background: Levofloxacin is prescribed widely as a first-line or alternative treatment option for different infectious diseases. The inappropriate use of this agent has increased the risk of antibiotic resistance, which has convinced researchers to address this issue by designing antibiotic prescription pattern studies.&#x0D; Aim: This study aimed to evaluate levofloxacin's prescription pattern and appropriateness in the outpatient setting in Iran.&#x0D; Methodology: This cross-sectional study included all admitted prescriptions containing levofloxacin from October 2018 to June 2019. Data regarding the demographics, clinical and laboratory presentations, preexisting comorbidities, dose and duration of levofloxacin, and the prescribers medical specialty were collected by reviewing the patient's prescriptions or history taking. The pattern and appropriateness of prescriptions were evaluated according to the assessment tool based on accepted international guidelines.&#x0D; Results: A total of 300 eligible patients (median age: 56.5 years; 56.7% male) were included in the study. Respiratory tract infections were the most common indication for levofloxacin prescription (55.6%); more than half of them were related to community-acquired pneumonia (29.6%). The inappropriateness rate for levofloxacin prescription was 55.3 %, of which 12.6% were related to community-acquired pneumonia, 9.6% skin infections, 8.4% rhinosinusitis, and 6.6% Urinary tract infection. Only 54 (18.0%) patients received levofloxacin with an appropriate indication, dose, and duration, indicating its rational use.&#x0D; Conclusion: This study found that more than half of all levofloxacin prescriptions in the outpatient setting are inappropriate, contributed mainly to respiratory tract diseases. Interventions that target these health care providers are essential to improve prescribing of this valuable antibiotic.