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Scientific Reports May 2022Although 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...
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/1.73m). A daily levofloxacin dose of 1000 mg is suggested to maximise the likelihood of efficacy for adult patients.
Topics: Administration, Intravenous; Adult; Computer Simulation; Databases, Factual; Humans; Kinetics; Levofloxacin
PubMed: 35624222
DOI: 10.1038/s41598-022-12627-1 -
Comparative Study on the Efficacy of Two Perioperative Chemotherapy Regimens for Lumbar Brucellosis.Drug Design, Development and Therapy 2023The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis...
OBJECTIVE
The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis patients with neurological injury.
METHODS
In Beijing Ditan Hospital affiliated with Capital Medical University, 32 patients with lumbar brucellosis spondylitis underwent surgery and triple perioperative chemotherapy (rifampicin, doxycycline, levofloxacin) between 2011 and 2021 due to neurological injury, and 34 patients matched up with the triple group underwent rifampicin, doxycycline, levofloxacin, and ceftriaxone. Both groups were compared in terms of changes in inflammation index, low back/leg pain, lumbar function, neurological function, and adverse drug reactions.
RESULTS
There was no significant difference in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), low back pain visual analogue scale (VAS), leg pain VAS, lumbar Oswestry disability index (ODI) and nerve function injury rate between the two groups before chemotherapy (>0.05). The ESR, CRP at 1 week and 2 weeks after chemotherapy and 1 week, 2 weeks, 1 month postoperatively in the quadruple group were significantly lower than those in the triple group, which is the same to ESR 3 months postoperatively (<0.05). The low back pain VAS, leg pain VAS and lumbar ODI in the quadruple group were significantly lower than those in the triple group at 1 month and 3 months postoperatively (<0.05). The recovery rate of neurological function in the quadruple group was significantly higher than that in the triple group at 3 and 6 months postoperatively (<0.05). Both groups did not experience significantly different perioperative and postoperative adverse reactions (0.05).
CONCLUSION
For lumbar brucellosis spondylitis with neurological injury, quadruple perioperative chemotherapy of rifampicin, doxycycline, levofloxacin and ceftriaxone can significantly reduce perioperative inflammation, and improve low back/leg pain, as well as promoting neurological function recovery in the short term.
Topics: Humans; Low Back Pain; Doxycycline; Rifampin; Levofloxacin; Ceftriaxone; Lumbar Vertebrae; Treatment Outcome; Brucellosis; Inflammation; Spondylitis; Retrospective Studies
PubMed: 38046280
DOI: 10.2147/DDDT.S427477 -
The Turkish Journal of Gastroenterology... Mar 2021It is known that clarithromycin resistance has increased over the years (success rate 60%). The aim of the study was to investigate the importance of regional...
BACKGROUND
It is known that clarithromycin resistance has increased over the years (success rate 60%). The aim of the study was to investigate the importance of regional antimicrobial resistance rates for full accuracy of both diagnosis and treatment of Helicobacter pylori infection.
METHODS
This study was carried out in the University Hospital Department of Gastroenterology. A total of 116 patients were evaluated with upper gastrointestinal endoscopy. Gastric antrum and corpus biopsy samples were taken for the rapid urease test (RUT), culture, and antimicrobial susceptibility testing for the presence of H. pylori. Antimicrobial susceptibilities of isolated H. pylori strains for clarithromycin and levofloxacin were determined by the epsilometer test (E-test). Minimal inhibitory concentration values for clarithromycin and levofloxacin were ≥1 and >1 μg/mL, respectively.
RESULTS
H. pylori infection was considered clinically positive in 93 (80.2%) patients with either the RUT, culture, or histopathological examination. Seventy (60.3%) of the patients had RUT positivity. Sixty (85.7%) of these 70 patients had RUT positivity within the first 20 min. Among the 90 patients, who had a histopathological examination, HLO was positive in 76 (84.4%) patients. Fifty-two (44.8%) out of 116 patients were culture positive. Resistance rates for both clarithromycin and levofloxacin were high. In these 52 culture-positive patients, resistance rates determined for clarithromycin and levofloxacin were 26.9% and 25.5%, respectively.
CONCLUSION
Clarithromycin or levofloxacin-based treatment regimen may not be an ideal alternative therapy for Turkish patients regardless of culture.
Topics: Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Microbial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Turkey; Urease
PubMed: 34160356
DOI: 10.5152/tjg.2021.20210 -
Journal of Global Antimicrobial... Jun 2023Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name...
OBJECTIVE
Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name medications, especially for antimicrobial drugs. Levofloxacin is a fluoroquinolone antimicrobial drug with excellent antimicrobial activity and wide antimicrobial spectrum, while it is susceptible to drug resistance. Our study aims to evaluate the bioequivalence of generic and brand-name levofloxacin.
METHODS
The pharmacokinetic (PK) parameters (C, AUC, T, and t), pharmacodynamic (PD) parameters (in vitro antibacterial activity and the inhibition of resistant mutation), and PK/PD analysis (the probability of target attainment; the cumulative fraction of response) calculated by Monte Carlo simulation were investigated.
RESULTS
Our results demonstrated that compared with generics, brand-name levofloxacin not only had higher drug content, it also showed higher antimicrobial susceptibility, higher resistance to mutation ability, and higher percentage of each dosage interval wherein plasma concentration of antimicrobial agents exceeded the MPC (mutant prevention concentration to prevent the mutation of 90% strains) against various clinical isolates. Although the differences in AUC between brand-name levofloxacin and generics were not statistically significant (P > 0.05, F test), Monte Carlo simulation results showed cumulative fraction of response values for PK/PD of brand-name medications were higher than generics.
CONCLUSION
Our results indicated that PK or PD equivalence did not imply therapeutic equivalence; thus, we suggest including PK/PD analysis in the bioequivalence evaluation system, which benefits prediction of clinical outcome with high application value.
Topics: Levofloxacin; Monte Carlo Method; Anti-Bacterial Agents; Fluoroquinolones; Anti-Infective Agents
PubMed: 36948495
DOI: 10.1016/j.jgar.2023.03.002 -
Archives of Medical Research Jul 2021Treatments for Helicobacter pylori (H. pylori) eradication include the use of antibiotics and a proton-pump inhibitor. Antibiotic resistance is a major concern for two...
BACKGROUND
Treatments for Helicobacter pylori (H. pylori) eradication include the use of antibiotics and a proton-pump inhibitor. Antibiotic resistance is a major concern for two drugs: levofloxacin and clarithromycin. The aim was to determine the prevalence of levofloxacin resistance (LevoR) and clarithromycin resistance (ClaR) in an urban population in Santiago, Chile.
METHODS
Gastric mucosa biopsies were obtained for DNA isolation from 143 H. pylori-positive individuals aged 18-80 years. Direct sequencing of the quinolone-resistance determining region (QRDR) of the gyrA gene was used to determine LevoR. ClaR was determined using restriction-fragment length polymorphism or 5'exonuclease assay.
RESULTS
The prevalences of LevoR and ClaR were 29 and 27%, respectively. LevoR was higher in women than in men (39 vs. 13%, p <0.001), while no sex difference was observed for ClaR (p = 0.123). The prevalence of LevoR increased with age (p-trend = 0.004) but not for ClaR (p-trend = 0.054). In sex-stratified analyses, both LevoR and ClaR increased with age only among women. Older women (>50 years) had a higher probability to carry LevoR strains as compared to men. The prevalence of dual LevoR and ClaR was 12.6%.
CONCLUSIONS
The prevalence of ClaR and LevoR is high in Santiago, according to International guidelines that recommend avoiding schemes with antibiotic resistance >15%. Our findings provide evidence to re-evaluate current therapies and guide empirical first- and second-line eradication treatments in Chile.
Topics: Aged; Anti-Bacterial Agents; Chile; Clarithromycin; Drug Resistance, Bacterial; Female; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence
PubMed: 33583603
DOI: 10.1016/j.arcmed.2021.01.011 -
Antimicrobial Resistance and Infection... Aug 2020Fluoroquinolone resistance in Pseudomonas aeruginosa typically arises through site-specific mutations and overexpression of efflux pumps. In this study, we investigated...
Fluoroquinolone resistance in Pseudomonas aeruginosa typically arises through site-specific mutations and overexpression of efflux pumps. In this study, we investigated the dynamics of different resistance mechanisms in P. aeruginosa populations that have evolved under fluoroquinolone pressure, as well as the interactions between these mechanisms in evolutionary trajectories. Bacteria of strain ATCC27853 were selected under different concentrations of ciprofloxacin and levofloxacin for six parallel lineages, followed by amplification of four target genes in the quinolone-resistance determining region (QRDR) and Sanger sequencing to identify the mutations. The expression of four efflux pump proteins was evaluated by real-time polymerase chain reaction using the relative quantitation method, with the ATCC27853 strain used as a control. We found that ciprofloxacin killed P. aeruginosa sooner than did levofloxacin. Further, we identified five different mutations in three subunits of QRDRs, with gyrA as the main mutated gene associated with conferring fluoroquinolone resistance. Additionally, we found a larger number of mutations appearing at 2 mg/L and 4 mg/L of ciprofloxacin and levofloxacin, respectively. Moreover, we identified the main efflux pump being expressed as MexCD-OprJ, with initial overexpression observed at 0.25 mg/L and 0.5 mg/L of ciprofloxacin and levofloxacin, respectively. These results demonstrated gyrA mutation and MexCD-OprJ overexpression as the primary mechanism conferring ciprofloxacin and levofloxacin resistance in P. aeruginosa. In addition, we also show that ciprofloxacin exhibited a stronger ability to kill the bacteria while potentially rendering it more susceptible to resistance.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Bacterial; Fluoroquinolones; Levofloxacin; Membrane Transport Proteins; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa
PubMed: 32758289
DOI: 10.1186/s13756-020-00793-8 -
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 -
The American Journal of Case Reports Mar 2018BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of...
BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of levofloxacin use. Here, we present a case of severe transaminitis caused by levofloxacin. CASE REPORT A young man in his thirties with a history of asthma, chronic alcoholism, methamphetamine intravenous drug abuse (IVDA), and non-compliant insulin-dependent diabetes mellitus (IDDM) presented to an emergency department with suicidal ideation. Vital signs were stable and the patient was noted to have cellulitis of the right forearm, for which cultures were drawn, and he received IV clindamycin. He was admitted to behavioral medicine for further care. Blood cultures were positive for gram-negative rods and he was transferred to the medicine ward. Cultures eventually grew Brevundimonas diminuta. Clindamycin was discontinued and he was started on levofloxacin. Transaminase levels measured soon after levofloxacin administration showed aminotransferase levels raised to approximately 50 times baseline within a few days. Levofloxacin was discontinued due to concern about drug-induced hepatotoxicity. After discontinuation, transaminase levels decreased immediately. Work-up for other causes of transaminitis revealed no other etiology. CONCLUSIONS Clinicians should remain mindful that levofloxacin can induce hepatotoxicity in rare cases. In patients presenting with acute liver injury who have recently taken levofloxacin, it would be wise to remain cognizant of the possibility of levofloxacin-induced hepatotoxicity.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Humans; Levofloxacin; Liver; Male; Young Adult
PubMed: 29523775
DOI: 10.12659/ajcr.907440 -
International Wound Journal Jan 2024Chronic prostatitis, which frequently manifests with perineal or urethral ulcers, can have substantial impact on the quality of life experienced by affected individuals.... (Observational Study)
Observational Study
Chronic prostatitis, which frequently manifests with perineal or urethral ulcers, can have substantial impact on the quality of life experienced by affected individuals. Present treatment approaches primarily target the alleviation of symptoms and control of complications. In patients with chronic prostatitis, this investigation examined the potential synergistic effects of tamsulosin and levofloxacin on urinary function and urethral and perineal wounds healing. This cross-sectional observational study was carried out at Chongqing Western Hospital, China, from February to November 2023. The participants comprised 88 males aged 40-75 years who had been clinically diagnosed with chronic prostatitis and complications that accompany the wound healing process. The participants were equally distributed into two groups: one assigned to the treatment group, which received a daily combination of levofloxacin (500 mg) and tamsulosin (0.4 mg) and other to receive conventional care. The wound healing rate and improvement in urinary function were the primary outcomes evaluated monthly for 9 months. Patient satisfaction and symptom amelioration were secondary outcomes, in addition to the surveillance of adverse effects. In comparison to the control, treatment group exhibited significantly higher rate of wound closure (78.08% at 1 month and 79.38% at 9 months) and urinary function improvement (66.69% at 1 month and 67.95% at 9 months). In addition, the treatment group exhibited a greater degree of symptom amelioration; however, a rise in adverse effects was observed. In every domain, patient satisfaction scores were significantly higher in the treatment group. Thus the combination of tamsulosin and levofloxacin improved urinary function and wound repair in patients with chronic prostatitis, while also exhibiting tolerable profile of adverse effects.
Topics: Male; Humans; Tamsulosin; Levofloxacin; Prostatitis; Quality of Life; Cross-Sectional Studies; Sulfonamides; Chronic Disease
PubMed: 38272823
DOI: 10.1111/iwj.14656 -
Expert Opinion on Drug Safety Nov 2019: Ciprofloxacin, levofloxacin, and moxifloxacin belong to the fluoroquinolone class of antibiotics and are amongst the most commonly prescribed antibiotics. In 2018 and... (Review)
Review
An evaluation of reports of ciprofloxacin, levofloxacin, and moxifloxacin-association neuropsychiatric toxicities, long-term disability, and aortic aneurysms/dissections disseminated by the Food and Drug Administration and the European Medicines Agency.
: Ciprofloxacin, levofloxacin, and moxifloxacin belong to the fluoroquinolone class of antibiotics and are amongst the most commonly prescribed antibiotics. In 2018 and 2019, Food and Drug Administration (FDA) and the European Medicine Agency (EMA) requested that manufacturers harmonize FQ safety information related to neuropsychiatric, aortic dissection, and long-term disability. The authors hypothesize that FDA and EMA epidemiologists support a strong association between these drugs and the three toxicities. : Studies of FQ-associated neuropsychiatric toxicity, long-term disability, and aortic ruptures/dissections. Clinical sources include FDA Advisory Committee documents, a 2014 Citizen Petition filed with the FDA requesting safety information additions to FQ labels for neuropsychiatric toxicities (partially granted in 2018), an under-review Citizen Petition under review by the FDA requesting a FQ Risk Evaluation and Mitigation Strategy, and safety notifications from the EMA. : FDA and the EMA report state that neuropsychiatric toxicity, long-term disability, and aortic dissections//aneurysms occur with all FQs. Disability and neuropsychiatric toxicity can occur after one dose or several months after FQs. United States' and European' regulators warn physicians not to prescribe FQs for uncomplicated acute urinary tract infection, sinusitis, or bronchitis, unless other possible choices are tried first, as risks outweigh benefits in these settings.
Topics: Aortic Dissection; Animals; Anti-Bacterial Agents; Aortic Aneurysm; Aortic Rupture; Ciprofloxacin; Disability Evaluation; European Union; Humans; Levofloxacin; Moxifloxacin; Neurotoxicity Syndromes; United States; United States Food and Drug Administration
PubMed: 31500468
DOI: 10.1080/14740338.2019.1665022