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Antimicrobial Agents and Chemotherapy Jul 2019Fluoroquinolones are group A drugs in tuberculosis guidelines. We aim to compare the culture conversion between new-generation (levofloxacin and moxifloxacin) and...
Fluoroquinolones are group A drugs in tuberculosis guidelines. We aim to compare the culture conversion between new-generation (levofloxacin and moxifloxacin) and old-generation (ciprofloxacin and ofloxacin) fluoroquinolones, develop pharmacokinetic models, and calculate target attainment for levofloxacin and moxifloxacin. We included three U.S. tuberculosis centers. Patients admitted between 1984 and 2015, infected with drug-resistant tuberculosis, and who had received fluoroquinolones for ≥28 days were included. Demographics, sputum cultures and susceptibility, treatment regimens, and serum concentrations were collected. A time-to-event analysis was conducted, and Cox proportional hazards model was used to compare the time to culture conversion. Using additional data from ongoing studies, pharmacokinetic modelling and Monte Carlo simulations were performed to assess target attainment for different doses. Overall, 124 patients received fluoroquinolones. The median age was 40 years, and the median weight was 60 kg. Fifty-six patients (45%) received old-generation fluoroquinolones. New-generation fluoroquinolones showed a faster time to culture conversion (median 16 versus 40 weeks, = 0.012). After adjusting for isoniazid and clofazimine treatment, patients treated with new-generation fluoroquinolones were more likely to have culture conversion (adjusted hazards ratio, 2.16 [95% confidence interval, 1.28 to 3.64]). We included 178 patients in the pharmacokinetic models. Levofloxacin and moxifloxacin were best described by a one-compartment model with first-order absorption and elimination. At least 1,500 to 1,750 mg levofloxacin and 800 mg moxifloxacin may be needed for maximum kill at the current epidemiologic cutoff values. In summary, new-generation fluoroquinolones showed faster time to culture conversion compared to the old generation. For optimal target attainment at the current MIC values, higher doses of levofloxacin and moxifloxacin may be needed.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Ciprofloxacin; Dose-Response Relationship, Drug; Female; Fluoroquinolones; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Moxifloxacin; Ofloxacin; Retrospective Studies; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Young Adult
PubMed: 31061152
DOI: 10.1128/AAC.00279-19 -
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 -
Therapeutic Advances in Respiratory... Feb 2014Inhaled therapies allow for the targeted delivery of antimicrobials directly into the lungs and have been widely used in the treatment of cystic fibrosis (CF) acute... (Review)
Review
Inhaled therapies allow for the targeted delivery of antimicrobials directly into the lungs and have been widely used in the treatment of cystic fibrosis (CF) acute pulmonary exacerbations. Nebulized levofloxacin solution (MP-376) is a novel therapy that is currently being evaluated in phase I, II, and III clinical trials among patients with stable CF and recent isolation of Pseudomonas aeruginosa from sputum. Phase I studies have investigated the single and multiple-dose pharmacokinetics of MP-376 and shown that it is rapidly absorbed from the lungs and results in low systemic concentrations. A subsequent phase IB study found that MP-376 pharmacokinetics were comparable among adults and children 6-16 years of age. Further phase II studies reported that sputum P. aeruginosa density decreased in a dose-dependent manner among patients who were randomized to MP-376 when compared with patients who received placebo. Improvements in pulmonary function and a decrease in the need for other antipseudomonal antibiotics were also reported for patients who received inhaled levofloxacin. The most common adverse event was dysgeusia (abnormal taste sensation), which was reported by nearly half of the participants who received MP-376. No serious drug-related adverse events were reported. These findings are encouraging; however, data from the two ongoing phase III trials are needed to determine whether MP-376 demonstrates substantial evidence of safety and efficacy as a chronic CF maintenance therapy and therefore may be useful in routine clinical practice.
Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Child; Clinical Trials as Topic; Cystic Fibrosis; Dose-Response Relationship, Drug; Dysgeusia; Humans; Levofloxacin; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 24334337
DOI: 10.1177/1753465813508445 -
Archives of Razi Institute Oct 2022The presence of efflux pumps genes in , such as and , is critical for ciprofloxacin and levofloxacin resistance. This study examined the efflux pump gene expression and...
The presence of efflux pumps genes in , such as and , is critical for ciprofloxacin and levofloxacin resistance. This study examined the efflux pump gene expression and activity in ciprofloxacin and levofloxacin-resistant strains. Twenty clinical samples of wounds and burns were collected. strains were tested using specific culture media. Antibiotic susceptibility testing was done using the disc diffusion method. After determining the disc diffusion method of ciprofloxacin and levofloxacin, Methicillin-resistant (MRSA) isolates were found in ten of the twenty clinical samples. The susceptibility of in the study revealed 40% ciprofloxacin resistance and 20% levofloxacin resistance. The gene expression of and efflux pump genes was assessed using Real-Time PCR. The nor A gene was detected in all ciprofloxacin-resistant pathogens, and gene expression increased in samples treated with ciprofloxacin compared to samples not treated with ciprofloxacin results of a real-time PCR test. The gene was detected in resistant strains, and its expression increased, as was the case with the gene. The fold of gene expression of gene for the ten isolates ranged from (12.082 to 42.81 fold) and also this result was higher than the fold of gene (0.0036-34.05 fold). The research study discovered that efflux pump genes play a crucial role in ciprofloxacin and levofloxacin resistance. Also, when employed as a housekeeping gene in gene expression, the gene produced excellent results.
Topics: Bacterial Proteins; Ciprofloxacin; Gene Expression; Levofloxacin; Methicillin-Resistant Staphylococcus aureus; Multidrug Resistance-Associated Proteins; RNA, Ribosomal, 16S; Staphylococcal Infections; Staphylococcus aureus; Humans
PubMed: 37123124
DOI: 10.22092/ARI.2022.358335.2197 -
Clinical Microbiology and Infection :... May 2006Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide. The treatment of CAP has been complicated by several factors, including... (Review)
Review
Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide. The treatment of CAP has been complicated by several factors, including the expanding spectrum of causative organisms and the rising prevalence of antibiotic resistance among respiratory pathogens. Initial antimicrobial treatment for patients with CAP is usually selected empirically and should provide appropriate coverage against the most common causative organisms, including resistant strains. Respiratory fluoroquinolones, such as levofloxacin, are the only antimicrobials that are highly active against the pathogens most frequently implicated in CAP, including macrolide-resistant and penicillin-resistant pneumococci, Haemophilus influenzae, Legionella spp., and atypical agents. This paper reviews recent studies involving adult patients with CAP that suggest that levofloxacin, as compared with other conventional antibiotic treatments, may be associated with better clinical outcomes.
Topics: Adult; Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Levofloxacin; Ofloxacin; Pneumonia, Pneumococcal; Streptococcus pneumoniae
PubMed: 16669924
DOI: 10.1111/j.1469-0691.2006.01392.x -
International Journal of Clinical... 2022The study's objective was to determine susceptibility in individuals with urinary tract infections and stones to antibiotics and prescribe optimal antimicrobial...
BACKGROUND
The study's objective was to determine susceptibility in individuals with urinary tract infections and stones to antibiotics and prescribe optimal antimicrobial treatment.
METHODS
Nonrepetitive strains were isolated from urine specimens obtained from 317 patients diagnosed with urinary stones from January, 2018, to December, 2021. A VITEK mass spectrometer was used for species identification, and a VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). Susceptibility to imipenem and cefoperazone/sodium sulbactam was tested by the disc diffusion method (K-B method). The antibiotic sensitivity of the strains was analyzed by sex and season.
RESULTS
A total of 317 patients were reviewed: 202 females (63.7%) and 115 males (36.3%). infections were observed during spring (21.8%, = 69), summer (26.2%, = 83), autumn (33.8%, = 107), and winter (18.2%, = 57). infections in females were diagnosed most often during the fall (24.3%, = 77) and during the summer in males (11.0%, = 35) ( = 0.010). Female patients responded best to levofloxacin ( = 0.014), and male patients responded best to sulfamethoxazole ( = 0.023). Seasonal variation in antibiotic sensitivity was confirmed, with significantly higher rates in the winter for cefuroxime ( = 0.002) and sulfamethoxazole ( = 0.002). Significant seasonal increases were also found in levofloxacin sensitivity during the summer ( = 0.005).
CONCLUSIONS
Highly effective antibiotics such as cefoxitin and ceftazidime should be used empirically by considering antibiotic sensitivity changes by sex, season, and year. Regional studies should be conducted frequently.
Topics: Humans; Male; Female; Anti-Bacterial Agents; Proteus mirabilis; Levofloxacin; Urinary Tract Infections; Proteus Infections; Anti-Infective Agents; Cefoperazone; Sulbactam; Sulfamethoxazole; Urinary Calculi; Microbial Sensitivity Tests
PubMed: 36628152
DOI: 10.1155/2022/7273627 -
Molecules (Basel, Switzerland) May 2022Tympanic membrane perforation (TMP), a common disease, often needs a scaffold as the patch to support surgery. Due to the environment of auditory meatus, the patch can...
Tympanic membrane perforation (TMP), a common disease, often needs a scaffold as the patch to support surgery. Due to the environment of auditory meatus, the patch can be infected by bacteria that results in failure; therefore, the ideal scaffold may combine biomimetic and antibacterial features. In this work, gelatin was used as the electrospinning framework, genipin as the crosslinking agent, and levofloxacin as an antibacterial in order to prepare the scaffold for TMP. Different contents of levofloxacin have been added to gelatin/genipin. It was found that, with the addition of levofloxacin, the gelatin/genipin membranes exhibit improved hydrophilia and enhanced tensile strength. The antibacterial and cell-cultured experiments showed that the prepared antibacterial membranes had excellent antibacterial properties and good biocompatibility, respectively. In summary, levofloxacin is a good group for the gelatin/genipin scaffold because it improves the physical properties and antibacterial action. Compared with different amounts of levofloxacin, a gelatin/genipin membrane with 1% levofloxacin is more suitable for a TM.
Topics: Anti-Bacterial Agents; Gelatin; Iridoids; Levofloxacin; Nanofibers; Tissue Scaffolds; Tympanic Membrane
PubMed: 35566258
DOI: 10.3390/molecules27092906 -
Antimicrobial Agents and Chemotherapy Jun 2022Antibiotic resistance is the most important factor leading to failed Helicobacter pylori eradication therapy, and personalized treatment based on antibiotic...
Antibiotic resistance is the most important factor leading to failed Helicobacter pylori eradication therapy, and personalized treatment based on antibiotic susceptibility is becoming increasingly important. To strengthen the understanding of antibiotic genotypic resistance of H. pylori and identify new antibiotic resistance loci, in this study, we identified phenotypic resistance information for 60 clinical isolates and compared the concordance of phenotypic and genotypic resistance using whole-genome sequencing (WGS). Clarithromycin and levofloxacin genotypic resistance was in almost perfect concordance with phenotypic resistance, with kappa coefficients of 0.867 and 0.833, respectively. All strains with the R16H/C mutation and truncation in were metronidazole resistant, with 100% specificity. For other genes of concern, at least one phenotypically sensitive strain had a previous mutation related to antibiotic resistance. Moreover, we found that the A1378G mutation of HP0399 and the A149G mutation of might contribute to tetracycline resistance and multidrug resistance, respectively. Overall, the inference of resistance to clarithromycin and levofloxacin from genotypic resistance is reliable, and WGS has been very helpful in discovering novel H. pylori resistance loci. In addition, WGS has also enhanced our study of strain lineages, providing new ways to understand resistance information and mechanisms.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Microbial Sensitivity Tests
PubMed: 35652644
DOI: 10.1128/aac.02188-21 -
Analytical Sciences : the International... Aug 2006A novel, rapid and sensitive analytical method is described for determination of ofloxacin and levofloxacin by enhanced chemiluminescence (CL) with flow-injection...
A novel, rapid and sensitive analytical method is described for determination of ofloxacin and levofloxacin by enhanced chemiluminescence (CL) with flow-injection sampling. The method is based on the CL reaction of the Ce(IV)-Na2S2O4-ofloxacin/levofloxacin-H2SO2 system. The enhanced CL mechanism was developed and the optimum conditions for CL emission were investigated. The CL intensity was correlated linearly (r = 0.9988) with the concentration of ofloxacin (or levofloxacin) in the range of 1.0 x 10(-8) - 1.0 x 10(-7) g ml(-1) and 1.0 x 10(-7) - 6.0 x 10(-6) g ml(-1). The detection limit (S/N = 3) is 7 x 10(-9) g ml(-1). The relative standard derivation (RSD, n = 11) is 2.0% for ofloxacin at 4 x 10(-7) g ml(-1) and for levofloxacin at 6 x 10(-7) g ml(-1). This method has been successfully applied for the determination of ofloxacin and levofloxacin in pharmaceutical preparations and biological fluids with satisfactory results.
Topics: Anti-Infective Agents, Urinary; Cerium; Chemistry Techniques, Analytical; Chemistry, Pharmaceutical; Flow Injection Analysis; Humans; Levofloxacin; Luminescence; Models, Chemical; Ofloxacin; Pharmaceutical Preparations; Sensitivity and Specificity; Urinalysis
PubMed: 16896259
DOI: 10.2116/analsci.22.1145 -
Annals of Family Medicine 2014Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug...
PURPOSE
Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin.
METHODS
We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days.
RESULTS
During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82).
CONCLUSIONS
Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.
Topics: Adult; Aged; Anti-Bacterial Agents; Arrhythmias, Cardiac; Azithromycin; Death, Sudden, Cardiac; Female; Humans; Levofloxacin; Male; Middle Aged; Risk Factors; United States; Veterans
PubMed: 24615307
DOI: 10.1370/afm.1601