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Journal of the Medical Association of... Aug 2018Levofloxacin, a fluoroquinolone, is an isomer of ofloxacin with an extensive spectrum of antimicrobial efficacy. In common with other fluoroquinolones, the main...
BACKGROUND
Levofloxacin, a fluoroquinolone, is an isomer of ofloxacin with an extensive spectrum of antimicrobial efficacy. In common with other fluoroquinolones, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with its therapeutic efficacy is the area under the plasma time-concentration curve (AUC)/the minimum inhibitory concentration (MIC) ratios.
OBJECTIVE
To evaluate the population PK and determine the efficacy of various dosage regimens in achieving the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of oral levofloxacin when prescribed as the switching therapy after intravenous levofloxacin treatment.
MATERIAL AND METHOD
The PK studies were conducted in 45 healthy volunteers who received one 500 mg tablet of levofloxacin and PTAs were determined by using a Monte Carlo simulation. The dosage regimens were predicted to achieve CFR greater than or equal to 90% by referral to the MIC distributions database of the European Committee on Antimicrobial Susceptibility Testing.
RESULTS
The population PKs of levofloxacin were; the volume of distribution (V) = 101.71±1.41 L, total clearance (CL) = 8.51±1.43 L/hour and the area under the plasma time-concentration curve from 0 to 24 hours (AUC0-24 ) = 66.19±1.30 mg*hour/L. The predicted CFRs for a target AUC0-24 /MIC ratio of 30 for S. aureus and S. pneumoniae were 83.12% and 92.63%, respectively for 500 mg levofloxacin, and 84.96% and 98.17%, respectively for 750 mg levofloxacin. The predicted CFRs for a target AUC0-24 /MIC ratio of 125 for E. coli and Klebsiella spp. were 84.25% and 88.81%, respectively for 500 mg levofloxacin and 86.00% and 91.34%, respectively for 750 mg levofloxacin.
CONCLUSION
The population PKs of levofloxacin in the present study were similar to the values obtained from the previous study. Both 500 mg qd and 750 mg qd of oral levofloxacin dosage regimens had a high probability of achieving optimal impact against S. pneumoniae, but only the 750 mg qd dosage regimen achieved optimal exposure against Klebsiella spp.
Topics: Anti-Bacterial Agents; Area Under Curve; Escherichia coli; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Monte Carlo Method; Staphylococcus aureus
PubMed: 29947489
DOI: No ID Found -
Alternative Therapies in Health and... Mar 2023Helicobacter pylori (H. pylori) infection has become a global public-health problem, and people living in low-resource settings may be more likely to be infected because... (Observational Study)
Observational Study
CONTEXT
Helicobacter pylori (H. pylori) infection has become a global public-health problem, and people living in low-resource settings may be more likely to be infected because of unhealthy life habits, poor sanitary conditions, and overuse of antibiotics without a prescription.
OBJECTIVES
The study intended to assess the susceptibility of H. pylori to nine antibiotics commonly prescribed for eradication of H. pylori infections among minority people in Yunnan province, China, to provide updated recommendations for H. pylori eradication therapy among adults.
DESIGN
The research team designed a cross-sectional observational study.
SETTING
The study took place in the First Affiliated Hospital of Kunming Medical University, Yunnan Province.
PARTICIPANTS
Participants were 276 people in the Mosuo or Pumi minority population who had lived on the shores of Lugu Lake in Ninglang county, Yunnan province in China for generations.
OUTCOME MEASURES
After completing a questionnaire, all participants underwent 13C-urea breath test, and those with a positive result participated in an antimicrobial-susceptibility test. For each H. pylori isolate, the research team tested the minimum inhibitory concentrations (MICs) of nine commonly used antibiotics: amoxicillin, azithromycin, levofloxacin, clarithromycin, metronidazole, tetracycline, rifampicin, gentamicin, and moxifloxacin.
RESULTS
The research team confirmed that 276 participants were resistant to at least one antibiotic. The resistances rates for moxifloxacin, metronidazole, and levofloxacin were the highest, while that for amoxicillin was the lowest, and no isolates were resistant to gentamicin. Double resistance (33.20%) had the highest proportion of all multiple-resistance patterns. Moreover, the metronidazole resistance rate was higher in females than in males and in nonsmokers than in smokers, and rifampicin resistance was higher in nondrinkers than in drinkers, suggesting that smoking and drinking might be protective against metronidazole and rifampicin resistance.
CONCLUSIONS
Most of the Mosuo and Pumi people in Yunnan were resistant to antibiotics. Moxifloxacin, metronidazole, and levofloxacin should no longer be the main medicines for H. pylori, whereas amoxicillin and gentamicin should be recommended to be the first-line clinical therapy for H. pylori eradication regimens.
Topics: Adult; Male; Female; Humans; Anti-Bacterial Agents; Metronidazole; Helicobacter pylori; Levofloxacin; Moxifloxacin; Rifampin; Cross-Sectional Studies; East Asian People; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; China; Helicobacter Infections; Amoxicillin; Gentamicins
PubMed: 36480681
DOI: No ID Found -
Future Microbiology Dec 2022Drug repurposing is a viable approach to expediting the tedious conventional drug discovery process, given rapidly increasing bacterial resistance. In this context, we...
Drug repurposing is a viable approach to expediting the tedious conventional drug discovery process, given rapidly increasing bacterial resistance. In this context, we have repurposed pyrvinium pamoate (PP) for its antibacterial activity against . US FDA-approved non-antibiotics were screened against clinically relevant bacterial pathogens to identify antibacterials. The hits were further evaluated utilizing a variety of preclinical parameters, following which efficacy was estimated in isolation and in combination in a murine neutropenic thigh infection model. The screening identified PP exhibiting potent activity against along with concentration-dependent killing. PP also showed a post-antibiotic effect of >22 h and significantly eradicated preformed biofilms and intracellular at 1× and 5× MIC, respectively. PP synergized with levofloxacin both and , resulting in ∼1.5 and ∼0.5 log CFU/g reduction against susceptible and resistant infections, respectively, as compared with untreated control. Pyrvinium potentiates levofloxacin against levofloxacin-resistant
Topics: Mice; Animals; Levofloxacin; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Anti-Bacterial Agents
PubMed: 36314364
DOI: 10.2217/fmb-2022-0159 -
Current Microbiology May 2023Myroides spp. are rare opportunistic pathogens, but they can be life-threatening because of their multidrug-resistant drug properties and their potential to cause...
Antibacterial and Antibiofilm Activities of Ceragenins Alone and in Combination with Levofloxacin Against Multidrug Resistant Myroides spp. Clinical Isolates from Patients with Urinary Tract Infections.
Myroides spp. are rare opportunistic pathogens, but they can be life-threatening because of their multidrug-resistant drug properties and their potential to cause outbreaks, especially in immunosuppressed patients. In this study, 33 isolates isolated from intensive care patients with urinary tract infections were examined for drug susceptibility. All isolates except three proved to be resistant to the tested conventional antibiotics. The effects of ceragenins, a class of compounds developed to mimic endogenous antimicrobial peptides, were evaluated against these organisms. The MIC values of nine ceragenins were determined, and the most effective ceragenins were CSA-131 and CSA-138. Three isolates that were susceptible to levofloxacin and two isolates resistant to all antibiotics underwent 16 s rDNA analysis, and whereas resistant isolates were identified as M. odoratus, susceptible isolates were identified as M. odoratimimus. CSA-131 and CSA-138 showed rapid antimicrobial effects observed in time-kill analyses. Combinations of ceragenins and levofloxacin caused a significant increase in antimicrobial and antibiofilm activities against M. odoratimimus isolates. In this study, Myroides spp. were found to be multidrug-resistant and have biofilm forming capacity, and ceragenins CSA-131 and CSA-138 were found to be especially effective on both planktonic and biofilm forms of Myroides spp.
Topics: Humans; Levofloxacin; Microbial Sensitivity Tests; Anti-Bacterial Agents; Anti-Infective Agents; Urinary Tract Infections; Flavobacteriaceae; Biofilms
PubMed: 37191731
DOI: 10.1007/s00284-023-03321-0 -
Scientific Reports Aug 2023Drug-induced liver injury induced by already approved substances is a major threat to human patients, potentially resulting in drug withdrawal and substantial loss of...
Drug-induced liver injury induced by already approved substances is a major threat to human patients, potentially resulting in drug withdrawal and substantial loss of financial resources in the pharmaceutical industry. Trovafloxacin, a broad-spectrum fluoroquinolone, was found to have unexpected side effects of severe hepatotoxicity, which was not detected by preclinical testing. To address the limitations of current drug testing strategies mainly involving 2D cell cultures and animal testing, a three-dimensional microphysiological model of the human liver containing expandable human liver sinusoidal endothelial cells, monocyte-derived macrophages and differentiated HepaRG cells was utilized to investigate the toxicity of trovafloxacin and compared it to the structurally-related non-toxic drug levofloxacin. In the model, trovafloxacin elicited vascular and hepatocellular toxicity associated with pro-inflammatory cytokine release already at clinically relevant concentrations, whereas levofloxacin did not provoke tissue injury. Similar to in vivo, cytokine secretion was dependent on a multicellular immune response, highlighting the potential of the complex microphysiological liver model for reliably detecting drug-related cytotoxicity in preclinical testing. Moreover, hepatic glutathione depletion and mitochondrial ROS formation were elucidated as intrinsic toxicity mechanisms contributing to trovafloxacin toxicity.
Topics: Animals; Humans; Levofloxacin; Endothelial Cells; Hepatitis; Fluoroquinolones; Drug-Related Side Effects and Adverse Reactions; Cytokines
PubMed: 37587168
DOI: 10.1038/s41598-023-40004-z -
Microbiology Spectrum Jun 2022The activity of two new fluoroquinolones, delafloxacin and finafloxacin, were evaluated against and spp. The MICs of delafloxacin, finafloxacin, and two classical...
The activity of two new fluoroquinolones, delafloxacin and finafloxacin, were evaluated against and spp. The MICs of delafloxacin, finafloxacin, and two classical fluoroquinolones (moxifloxacin and levofloxacin) were tested against 29 and 67 spp. isolates using the broth microdilution method. The molecular mechanisms underlying fluoroquinolone resistance were also investigated. Delafloxacin exhibited low MICs against and spp., including the levofloxacin-resistant isolates. For , delafloxacin showed low MIC value of 1 μg/mL (MIC range, <0.031 -1 μg/mL) compared to 8 μg/mL for finafloxacin, 16 μg/mL for moxifloxacin, and 32 μg/mL for levofloxacin. For and , delafloxacin had low MIC values (, 2 μg/mL; , 4 μg/mL) compared to 16 -32 μg/mL for finafloxacin, 16 μg/mL for moxifloxacin, and 32 - >32 μg/mL for levofloxacin. The two mutations GyrA S153L and ParC S91I were commonly identified in fluoroquinolone-resistant , and ParC S83L was the most frequent mutation identified in fluoroquinolone-resistant spp. Delafloxacin displayed lower MICs against fluoroquinolone-resistant isolates of both and spp. that have mutations in the quinolone resistance determining regions (QRDRs) than the two classical fluoroquinolones. Delafloxacin is a promising fluoroquinolone with low MICs against fluoroquinolone-resistant and spp. Our study confirms the potential clinical use of delafloxacin in treating antimicrobial-resistant and spp. infections. Fluoroquinolone resistance in Mycoplasma hominis and spp. is on the rise globally, which has compromised the efficacy of the currently available antimicrobial agents. This study evaluated the antimicrobial activity of two new fluoroquinolones, delafloxacin and finafloxacin, for the first time, against and spp. clinical isolates. Delafloxacin and finafloxacin displayed different antimicrobial susceptibility profiles against and spp. . Delafloxacin was found to be more effective against and spp. than three classical fluoroquinolones (finafloxacin, moxifloxacin, and levofloxacin). Finafloxacin displayed activity similar to moxifloxacin but superior to levofloxacin against and spp. Our findings demonstrate that delafloxacin is a promising fluoroquinolone with outstanding activity against fluoroquinolone-resistant and spp.
Topics: Anti-Bacterial Agents; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mycoplasma hominis; Ureaplasma; Ureaplasma Infections
PubMed: 35532225
DOI: 10.1128/spectrum.00099-22 -
Environmental Pollution (Barking, Essex... Jan 2023Adsorption and transport of levofloxacin (LEV) and ofloxacin (OFL) enantiomers in a matrix containing goethite and natural organic matter (NOM) were investigated using...
Adsorption and transport of levofloxacin (LEV) and ofloxacin (OFL) enantiomers in a matrix containing goethite and natural organic matter (NOM) were investigated using batch and column experiments. In batch studies, competition and enantioselectivity were observed in the adsorption of LEV and OFL. Enantioselectivity upon adsorption was investigated by comparing changes in the enantiomer fraction (EF) (the ratio of LEV to the sum of LEV and OFL remaining in the solution) after and before adsorption. At pH < 7, there was hardly any selectivity in adsorption of OFL and LEV to goethite. At pH > 7, OFL showed a stronger adsorption than LEV to goethite, and this preference remained when NOM samples of Leonardite humic acid (LHA) and Elliott Soil fulvic acid (ESFA) were added. However, when Suwannee River NOM (SRNOM) was added, the preference was reversed, and LEV was adsorbed more strongly. In single systems, the presence of different types of NOM increased adsorption of LEV and OFL, especially LEV. In column studies, preloaded NOM decreased the transport of LEV and OFL through goethite-coated sand. The EF values in the effluent increased with retention time and reached the largest values (0.59-0.72) at around 1.5 pore volume (PV), and then decreased again, reaching a stable value at 5.0-30.0 PV. Both batch and column experiments showed that, fractionation of LEV and OFL occurred during adsorption and transport in the presence of NOM-goethite complexes, which would eventually affect their environmental fate.
Topics: Levofloxacin; Ofloxacin; Iron Compounds; Adsorption; Humic Substances
PubMed: 36328279
DOI: 10.1016/j.envpol.2022.120542 -
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 -
Infectious Disorders Drug Targets 2021Acute pyelonephritis is among the most common bacterial infections. Options for initial treatment of pyelonephritis include an extended-spectrum cephalosporin or a... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Acute pyelonephritis is among the most common bacterial infections. Options for initial treatment of pyelonephritis include an extended-spectrum cephalosporin or a fluoroquinolone. This study aimed to compare the clinical outcomes of patients receiving ceftriaxone to those who received levofloxacin for the treatment of acute pyelonephritis.
METHODS
In this randomized, open-label trial, hospitalized adults with acute pyelonephritis were treated with ceftriaxone (1g IV every 12 hours) or levofloxacin (750 mg IV daily) for at least 7 days. Clinical and microbiological characteristics were compared among patients treated with ceftriaxone and levofloxacin.
RESULTS
A total of 59 patients were randomized, 30 to the ceftriaxone group and 29 to the levofloxacin group. The clinical response was that 68.0% of patients in the ceftriaxone group and 56.0% of patients in the levofloxacin group were cured. The microbiological response, i.e. pathogen eradication rates was 68.7% in the ceftriaxone group and 21.4% in the levofloxacin group. (P value=0.00028) Escherichia coli was the most common pathogen (n = 31), followed by Klebsiella pneumoniae (n = 21). High resistance rates were detected for cotrimoxazole (55%), ciprofloxacin (48%), and ceftriaxone (34.4%) in isolated E.coli. Likewise, all K. pneumoniae isolates were resistant to ciprofloxacin.
CONCLUSION
This study indicates that ceftriaxone was more effective than levofloxacin in the treatment of acute pyelonephritis, on the basis of microbiological response, but there were no statistically significant differences between the treatment groups in the rates of clinical cure. The resistance of uropathogens to the most used antibiotics was relatively high. Choosing the treatment regimen based on susceptibility testing results and shortening the duration of the therapy are now recommended to be the most important approaches to decrease the spread of antibiotic resistance worldwide.
Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Humans; Iran; Levofloxacin; Pyelonephritis; Urinary Tract Infections
PubMed: 32720608
DOI: 10.2174/1871526520999200727154214 -
Helicobacter Jun 2023Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data...
BACKGROUND
Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance.
METHODS
Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed.
RESULTS
We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement.
CONCLUSION
H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.
Topics: Humans; Female; Aged; Clarithromycin; Metronidazole; Helicobacter pylori; Levofloxacin; Helicobacter Infections; Retrospective Studies; Furazolidone; Microbial Sensitivity Tests; Anti-Bacterial Agents; Amoxicillin; Tetracycline; Drug Resistance, Microbial; Drug Resistance, Bacterial
PubMed: 37042045
DOI: 10.1111/hel.12960