Nanoparticle-hydrogel composite as dual-drug delivery system for the potential application of corneal graft rejection.

Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60 min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.

Inhalable solid lipid nanoparticles of levofloxacin for potential tuberculosis treatment.

Delivering novel antimycobacterial agents through the pulmonary route using nanoparticle-based systems shows promise for treating diseases like tuberculosis. However, creating dry powder inhaler (DPI) with suitable aerodynamic characteristics while preserving nanostructure integrity and maintaining bioactivity until the active ingredient travels deeply into the lungs is a difficult challenge. We developed DPI formulations containing levofloxacin-loaded solid lipid nanoparticles (SLNs) via spray-drying technique with tailored aerosolization characteristics for effective inhalation therapy. A range of biophysical techniques, including transmission electron microscopy, confocal microscopy, and scanning electron microscopy were used to measure the morphologies and sizes of the spray-dried microparticles that explored both the geometric and aerodynamic properties. Spray drying substantially reduced the particle sizes of the SLNs while preserving their nanostructural integrity and enhancing aerosol dispersion with efficient mucus penetration. Despite a slower uptake rate compared to plain SLNs, the polyethylene glycol modified formulations exhibited enhanced cellular uptake in both A549 and NR8383 cell lines. The percent viability of Mycobacterium bovis had dropped to nearly 0 % by day 5 for both types of SLNs. Interestingly, the levofloxacin-loaded SLNs demonstrated a lower minimum bactericidal concentration (0.25 µg/mL) compared with pure levofloxacin (1 µg/mL), which indicated the formulations have potential as effective treatments for tuberculosis.

The impact of levofloxacin prophylaxis on empiric intravenous antibiotic use in pediatric hematopoietic stem cell transplant recipients.

Levofloxacin prophylaxis during periods of neutropenia in pediatric hematopoietic stem cell transplant (HSCT) may reduce the number of febrile episodes and use of empiric intravenous antibiotics (EIA); however, the literature is conflicting. This retrospective review compared EIA use before and after implementation of levofloxacin prophylaxis at a children's hospital. Levofloxacin prophylaxis was associated with reduced use of certain EIA; however, did not reduce the number of positive blood cultures or clinical deteriorations. Therefore, levofloxacin prophylaxis may have implications for the stewardship of broad-spectrum intravenous antibiotics used in pediatric HSCT.

Chitosan-coated liposome with lysozyme-responsive properties for on-demand release of levofloxacin.

As an anti-infection antibiotic delivery route, a drug-controlled release system based on a specific condition stimulus response can enhance drug stability and bioavailability, reduce antibiotic resistance, achieve on-demand release and improve targeting and utilization efficiency. In this study, chitosan-coated liposomes containing levofloxacin (Lef@Lip@CS) were prepared with lysozyme in body fluids serving as an intelligent "switch" to enable accurate delivery of antibiotics through the catalytic degradation ability of chitosan. Good liposome encapsulation efficacy (64.89 ± 1.86 %) and loading capacity (5.28 ± 0.18 %) were achieved. The controlled-release behavior and morphological characterization before and after enzymatic hydrolysis confirmed that the levofloxacin release rate depended on the lysozyme concentration and the degrees of deacetylation of chitosan. In vitro bacteriostatic experiments showed significant differences in the effects of Lef@Lip@CS before and after enzyme addition, with 6-h inhibition rate of 72.46 % and 100 %, and biofilm removal rates of 51 % and 71 %, respectively. These findings show that chitosan-coated liposomes are a feasible drug delivery system responsive to lysozyme stimulation.

Fluconazole and levofloxacin prophylaxis are ineffective strategies for preventing infections in acute myeloid leukemia patients undergoing chemotherapy.

INTRODUCTION: Acute myeloid leukemia patients are at high risk for infections, which contribute to increased mortality rates of up to 70%. The use of antimicrobial prophylaxis has been shown to significantly lower rates of infection. Therefore, this retrospective study aimed to evaluate the effect of two agents that showed effective results in the literature, levofloxacin and fluconazole, as prophylaxis strategies in AML patients. METHODOLOGY: A total of 85 AML patients' medical records treated with a 7+3 induction chemotherapy protocol in the Cancer Hospital of Uberlândia from 2017 to 2021 were screened and their data was collected. Within these patients, groups for analysis were created based on whether the acting physician included an antibacterial or antifungal prophylaxis protocol during induction. Contingency tables with χ² and odds ratio tests were realized to verify associations between prophylaxis and infection. Additionally, Kaplan-Meier curves with Cox regression were developed to analyze survival. RESULTS: The use of prophylaxis with either fluconazole or levofloxacin did not lower rates of infection, as those who with prophylaxis did not demonstrate significant differences when compared to those without (20.3-29.7%, and 12.3-23.3%, respectively). Patients who suffered a bacterial infection during induction were shown to have lower overall survival, with a similar trend seen in fungal infections. CONCLUSION: Bacterial and fungal infections were associated with higher rates of induction mortality and lower overall survival, and prophylaxis using fluconazole and levofloxacin did not present any significant difference in preventing these infections in this study, contrasting results found in the literature. The individuality of each treatment center should be taken into consideration and future studies should be realized to better determine the most effective methods and agents for prophylaxis.

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis: A Secondary Analysis of the APPAC II Randomized Clinical Trial.

Importance: Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. Objective: To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. Design, Setting, and Participants: This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Interventions: Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. Main Outcomes and Measures: The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. Results: After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. Conclusions and Relevance: This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961.

An adaptive drug-releasing contact lens for personalized treatment of ocular infections and injuries.

This research introduces an innovative solution to address the challenges of bacterial keratitis and alkali burns. Current treatments for bacterial keratitis and alkali burns rely on the frequent use of antibiotics and anti-inflammatory eye drops. However, these approaches suffer from poor bioavailability and fluctuating concentrations, leading to limited efficacy and potential drug resistance. Our approach presents an adaptive drug-releasing contact lens responsive to reactive oxygen species (ROS) at ocular inflammation sites, synchronously releasing Levofloxacin and Diclofenac. During storage, minimal drug release occurred, but over 7 days of wear, the lens maintained a continuous, customizable drug release rate based on disease severity. This contact lens had strong antibacterial activity and biofilm prevention, effectively treating bacterial keratitis. When combined with autologous serum, this hydrophilic, flexible lens aids corneal epithelial regeneration, reducing irritation and promoting healing. In summary, this ROS-responsive drug-releasing contact lens combines antibacterial and anti-inflammatory effects, offering a promising solution for bacterial keratitis and alkali burns.

Population pharmacokinetics and dose optimization of levofloxacin in elderly patients with pneumonia.

AIMS: Levofloxacin is a quinolone antibiotic with a broad antibacterial spectrum. It is frequently used in elderly patients with pneumonia. The pharmacokinetic profile of elderly patients changes with age, but data on the pharmacokinetics of levofloxacin in these patients are limited. The aim of this study was to establish a population pharmacokinetic model of levofloxacin in elderly patients with pneumonia and to optimize individualized dosing regimens based on this newly developed model. METHODS: This is a prospective, open-label pharmacokinetic study in elderly patients with pneumonia. Blood samples were collected using an opportunistic approach. The plasma concentrations of levofloxacin were determined by high-performance liquid chromatography. A population pharmacokinetic model was established using nonlinear mixed-effect model software. Monte Carlo simulations were used for dose simulation and dose optimization. RESULTS: Data from 51 elderly patients with pneumonia were used for the population pharmacokinetic analysis. A one-compartment model with first-order elimination was most suitable for describing the data, and the estimated glomerular filtration rate was the only covariate that had a significant impact on the model. The final model estimated that the mean clearance of levofloxacin in elderly patients with pneumonia was 5.26 L/h. Monte Carlo simulation results showed that the optimal dosing regimen for levofloxacin was 750 mg once a day in elderly patients with pneumonia, with a minimum inhibitory concentration of 2 mg/L. CONCLUSIONS: The population pharmacokinetic model of levofloxacin in elderly patients with pneumonia was established, and the dose optimization of levofloxacin was completed through Monte Carlo simulation.

Conjunctival sac bacterial culture of patients using levofloxacin eye drops before cataract surgery: a real-world, retrospective study.

BACKGROUND: The use of antibiotics preoperatively is effective to decrease the incidence of ocular bacterial infections but may lead to high resistance rate, especially on patients with multi-risk clinical factors. This study systematically analyzed real-world data (RWD) of patients to reveal the association between clinical factors and conjunctival sac bacterial load and offer prophylaxis suggestions. METHODS: We retrieved RWD of patients using levofloxacin eye drops (5 mL: 24.4 mg, 4 times a day for 3 days) preoperatively. Retrieved data included information on the conjunctival sac bacterial culture, sex, presence of hypertension and diabetes mellitus (DM), and history of hospital-based surgeries. Data was analyzed using SPSS 24.0. RESULTS: RWD of 15,415 cases (patients) were retrieved. Among these patients, 5,866 (38.1%) were males and 9,549 (61.9%) females. 5,960 (38.7%) patients had a history of hypertension, and 3,493 (22.7%) patients had a history of DM. 7,555 (49.0%) patients had a history of hospital-based operations. There were 274 (1.8%) positive bacterial cultures. Male patients with hypertension and DM may be at increased risk of having positive bacterial cultures (P < 0.05). Staphylococcus epidermidis (n = 56, 20.4%), Kocuria rosea (n = 37, 13.5%), and Micrococcus luteus (n = 32, 11.7%) were the top 3 isolated strains. Most bacterial strains were resistant to various antibiotics except rifampin, and 82.5% (33 of 40 isolates) of Staphylococcus epidermidis isolates had multidrug antibiotic resistance. Numbers of culture-positive Staphylococcus epidermidis isolates in the male group and non-DM group were greater than those in the female and DM groups, respectively. Micrococcus luteus (n = 11, 8.8%) was found less frequently in non-hypertension group than in hypertension group. CONCLUSION: Sex (Male) and the presence of hypertension and DM are risk factors for greater conjunctival sac bacterial loads. We offer a prophylactic suggestion based on the combined use of levofloxacin and rifampin. However, this approach may aggravate risk of multidrug resistance.

Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China.

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.

Synthesis and Characterization of Carbon Dots Coated CaCO3 Nanocarrier for Levofloxacin Against Multidrug Resistance Extended-Spectrum Beta-Lactamase Escherichia coli of Urinary Tract Infection Origin.

The multidrug resistance (MDR) Escherichia coli having Extended-Spectrum Beta-Lactamase (ESBL) genes and the capacity to create a biofilm acts as a major reduction in the therapeutic effectiveness of antimicrobials. In search of a novel nanocarrier (NC) for targeted delivery of antibiotics, carbon dots (CDs) coated calcium carbonate nanocarriers (CCNC) from organic chicken eggshells conjugated with levofloxacin (Lvx) were synthesized. Our main objectives were to explore the antimicrobial, antibiofilm, and NC potential of CDs coated CaCO3 Nanocarrier conjugated with levofloxacin (CD-CCNC-Lvx) to combat biofilm-producing MDR ESBL E. coli of urinary tract infection origin. The synthesized NC system was physiochemically characterized, validating the synthesis of CCNC and CD-CCNC-Lvx with a particle size of 56 and 14 nm, respectively. Scanning electron microscopy (SEM) showed rod shape morphology. X-ray diffraction results discovered crystalline and dispersed nanoparticles. In vitro release drug kinetics illustrated sustained release of Lvx. NC system exhibited strong antibacterial and antibiofilm potential against E. coli with a noticeable low minimal inhibitory concentration (MIC). MIC of CCNC was found to be 30 ± 0.1 µg/mL and CD-CCNC-Lvx was 20 ± 0.1 µg/mL for MDR ESBL-producing E. coli. The synergistic effect of NC upon conjugation with Lvx showed incredible activity with 30 mm zone of inhibition and 68% biofilm inhibition. Flow cytometry analysis revealed treated E. coli cells showed 58.69% reduction in cell viability. SEM images of treated bacterial cells showed morphological changes, which were also confirmed by our flow cytometry findings leading to cell membrane damage in E. coli. NC system also downregulated the blaCTX-M gene in E. coli. The hemolytic analysis proved biocompatibility with human red blood cells (RBCs). It is concluded that CCNC has the potential to be used as NC for target delivery of antibiotics and may combat toxicity of antibiotics as the inhibition of E. coli was noticed at low MIC concentration.

Nanoparticles encapsulation of Phoenix dactylifera (date palm) mucilage for colonic drug delivery.

Compressed tablet formation from granular drug require binder with Cohesiveness property. Plants mucilage as pharmaceutical excipients are available. In this study, biocompatible date palm mucilage was encapsulated with silver nano particles for sustained drug release to provoke an immune response. Nano formulated mucilage was characterized by UV/VIS, FTIR, XRD, SEM/EDX spectrophotometry. UV/VIS spectra revealed an intense surface plasmon resonance peak at 406 nm for spherical mono dispersed silver nano formulated mucilage resulted from efficient reduction of silver ions to AgNPs. Zeta sizer disclosed the emergence of single peak at 139.7 nm with 100% intensity. Crude mucilage exhibited number of peaks in the region of 4000-500 cm-1 by FT-IR spectroscopy whereas purified as well as nano formulated samples showed somewhat different pattern of peaks in addition to peaks of crude sample. XRD spectra of crude mucilage revealed somewhat regular pattern while purified and modified mucilage displayed irregular structure. In SEM analysis, crude mucilage was appeared as granular that turned into porous network with entangled tiny silver nano spheres. A controlled release of drug levofloxacin hemihydrate was evaluated using crude/ nano formulated mucilage as excipient. Nano formulated mucilage delayed the onset exposure of drug in gastric medium giving recommendations as value added bio binder for drug to the target organ.

Effect of silver nanoparticles on the antibacterial activity of Levofloxacin against methicillin-resistant Staphylococcus aureus.

OBJECTIVE: The paper presents the antibacterial activity of silver nanoparticles (AgNPs) when conjugated with Levofloxacin. The AgNPs used in this study were synthesized from silver nitrate using sodium borohydride as a reducing agent. MATERIALS AND METHODS: Levofloxacin activity was determined by minimum inhibitory concentrations (MICs) and also the erythrocyte hemolytic assay determined the capability of conjugation to cause hemolysis in human erythrocyte. RESULTS: The synthesis of levofloxacin-AgNP conjugates was confirmed by ultraviolet/visible (UV/vis) spectroscopy. A peak absorption value between 400-450 nm for the extract and the color change to dark brown were corresponding to the plasmon absorbance of AgNPs. On the other hand, levofloxacin-AgNPs could be effective against methicillin-resistant Staphylococcus aureus (MRSA). The MICs of levofloxacin and levofloxacin-AgNPs were 12 and 10 µM, respectively. CONCLUSIONS: These findings indicated that levofloxacin-AgNPs had an effective bactericidal activity against the bacterial MRSAs. This conjugation appeared to inhibit bacterial adaptive capabilities, which leads to inhibition of bacterial resistance.

Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study.

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 (R2 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.

Levofloxacin might be safe to use for OSCC patients.

Oral squamous cell carcinoma patients are exhausted against the powerful chemotherapies, radiotherapies after the surgery, and their immune system is devastated during the process and antibiotic usage become inescapable. Although prescribing an antibiotic might be fraught for such as drug interaction and undesirable proliferation danger, studies still look for the new ideas such as antibiotic combinations that might be safe to use. The antiproliferative and apoptotic outcomes of levofloxacin with cisplatin combination as well as their single usage were examined with WST-1, Caspase-3/BCA and Annexin V methods on SCC-15 cells and a healthy cell line (MRC-5). 24 h treatment of 50 mM single levofloxacin, 50 mM single cisplatin and 50 mM levofloxacin-cisplatin combination resulted in viability rates of SCC-15 cells as 90%, 67% and 80.8%, respectively. Caspase-3 enzyme activity was enhanced 0.92-fold for single levofloxacin, 13.05-fold for single cisplatin and 9.73-fold for the combination of levofloxacin-cisplatin, the total apoptotic activity of single levofloxacin, single cisplatin and levofloxacin-cisplatin combination were observed as 4.88%, 21.14%, 16.21%, respectively on SCC-15. The apoptotic effect of cisplatin on MRC-5 has been shown to be suppressed when combined with levofloxacin. Considering the cell viability, caspase-3, and apoptotic activity results, it's conclude that the levofloxacin-cisplatin combination was also effective compared to the only cisplatin treatment on OSCC cells. The combination has shown less toxicity for healthy cells than single cisplatin treatment. Therefore, our apoptotic findings suggest that the different dosage combinations are necessary to understand the interaction for the treatment of tongue squamous cell carcinoma.

Clinical impact of levofloxacin inhalation solution in cystic fibrosis patients in a real-world setting.

BACKGROUND: Levofloxacin inhalation solution is the most recently approved inhaled antibiotic in Europe and Canada for adult cystic fibrosis patients. Its efficacy and safety have been assessed in randomized controlled trials. Our aim was to evaluate real life experience and outcomes in our treatment centre. METHODS: We evaluated the efficacy of inhaled levofloxacin solution in 86 patients with cystic fibrosis in terms of the following outcome parameters: changes in %-predicted forced expiratory volume in one second (FEV1), body-mass index (BMI), and exacerbation rate. We conducted an intraindividual analysis of patients who received levofloxacin inhalation solution twice daily 240 mg for at least 4 weeks. RESULTS: Change in FEV1% predicted for the treatment period was +2.27% (p=0.0027) after 4 weeks. There was no change in BMI for overall group, but exacerbation rate compared to one year before initiation of inhaled levofloxacin decreased significantly (p=0.0024) after 1 year of treatment (3.23 ± 1.39 versus 2.71 ± 1.58). CONCLUSIONS: In patients with cystic fibrosis, inhaled levofloxacin solution has the potential to improve FEV1 and to reduce the number of bronchopulmonary exacerbations.

Population pharmacokinetics of oral levofloxacin in healthy volunteers and dosing optimization for multidrug-resistant tuberculosis therapy.

Levofloxacin is considered a key component of a multidrug-resistant tuberculosis (MDR-TB) regimen. However, there is considerable concern regarding the subtherapeutic concentrations of the currently used doses and the development of drug resistance. Therefore, this study aimed to describe the population pharmacokinetics (PPK) of oral levofloxacin in healthy volunteers and to evaluate the probability of target attainment (PTA) in an attempt to optimize the dosing regimens for MDR-TB therapy. Data of levofloxacin in healthy volunteers from a previous study were used to construct a PPK model. Monte Carlo simulations were performed to derive the PTAs of various regimens. A two-compartment model with linear elimination and transit absorption compartments best described the pharmacokinetics (PK) of levofloxacin. The estimated PK parameters (interindividual variability, %) were: apparent clearance 8.32 L h-1 (22.6%), apparent central volume of distribution 35.8 L (45.2%), apparent peripheral volume of distribution 39.7 L, intercompartmental clearance 40.6 L h-1 (43.8%), absorption rate constant 7.45 h-1 (150%), mean absorption transit time 0.355 h (52.4%), and total number of transit compartments 6.01 (131.9%). Monte Carlo simulations using levofloxacin 750-1000 mg yielded a probability of achieving a target free area under the concentration-time curve/minimum inhibitory concentration (MIC) of 100 at greater than 90% for Mycobacterium tuberculosis with an MIC < 0.5 mg L-1 , while a dose of 1500 mg was required for strains with an MIC of 1 mg L-1 . A higher dose of levofloxacin might be needed to treat tuberculosis. However, further studies on the efficacy and safety of this dose are needed to confirm our findings.

2-Day versus C-reactive protein guided antibiotherapy with levofloxacin in acute COPD exacerbation: A randomized controlled trial.

INTRODUCTION: Duration of antibiotic treatment in acute exacerbation of COPD (AECOPD) is most commonly based on expert opinion. Biomarker guided strategy is increasingly recommended to limit unnecessary antibiotic use. We performed a randomized controlled study to evaluate the efficacy of 2-day versus C-reactive protein (CRP)-guided treatment with levofloxacin in patients with AECOPD. METHODS: Patients with AECOPD were randomized to receive oral levofloxacin daily for 7 days unless the serum CRP level decreased by at least 50% from the baseline value or levofloxacin for two days; thereafter, oral placebo tablet was prescribed according to the CRP. The primary outcome measure was cure rate, and secondary outcome included need for additional antibiotics, intensive care unit (ICU) admission, exacerbation rates and exacerbation free interval (EFI) within one-year follow-up. RESULTS: In intention to treat (ITT) analysis, cure rate was 76.1% (n = 118) and 79.3% (n = 123) respectively in 2-day and CRP-guided groups. In per protocol (PP) analysis, cure rate was 73% (n = 92) and 70.4% (n = 88) respectively in 2-day and CRP-guided groups. The difference between the two groups was not significant. The need for additional antibiotics and ICU admission rates were not significantly different between the two groups. One-year exacerbation rate was 27% (n = 42) in 2-day group versus 30.3% (n = 47) in CRP-guided group (p = 0.53); the EFI was 125 days (interquartile range, 100-151) versus 100 days (interquartile range, 78-123) in 2-day and CRP-guided groups respectively (p = 0.45). No difference in adverse effects was detected. CONCLUSION: Levofloxacin once daily for 2 days had similar efficacy compared to CRP-guided in AECOPD. This short course treatment decreased antibiotic consumption which would improve patient compliance and reduce adverse effects.

Pharmacokinetic/pharmacodynamic evaluation of the antimicrobial therapy of pneumococcal invasive disease in adults in post-PCV13 vaccine period in Madrid, Spain.

The objective of our study was to evaluate by pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the antimicrobials used for the treatment of invasive pneumococcal disease (IPD) in adults, including meningitis, are adequate considering the susceptibility profile of S. pneumoniae in Spain after the implantation of PVC13 vaccine. Pharmacokinetic parameters of benzylpenicillin and cefotaxime were obtained from the literature, and susceptibility data of invasive S. pneumoniae strains recovered in 2017 (post-PCV13 vaccination period) were provided by the Public Health Regional Laboratory of Madrid. We have also studied levofloxacin because it is used to treat pneumococcal pneumonia previously to be diagnosed as bacteremic pneumonia. Monte Carlo simulation was used to estimate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). All doses of benzylpenicillin except 2 mU q6h provide a high probability of treatment success for MIC values ≤ 1 mg/L; 4 mU q4h is even useful for MIC values up to 4 mg/L. This high dose, used for the treatment of meningitis, also provides high probability of treatment success for MIC ≤ 0.5 mg/L. At the susceptibility EUCAST breakpoint (≤ 0.5 mg/L), cefotaxime provides a high rate of PD target achievement, even at the lowest dose (1 g q8h). For meningitis, 2 g q6h ensures probabilities of target attainment ≥90% for MIC up to 1 mg/L. Our study confirms that after the implementation of PCV13 vaccine, the treatment with benzylpenicillin and cefotaxime provides high probability of the therapy success of IPD, including meningitis.