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The Pediatric Infectious Disease Journal Apr 2016In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly...
Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.
BACKGROUND
In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis disease or latent infection after multidrug-resistant tuberculosis exposure, to inform future dosing strategies.
METHODS
Blood samples were collected at 0 (RMI only), 1, 2 and 6 hours (50 children, aged 6 months to 15 years) after oral levofloxacin at >6 weeks of treatment. Clinical characteristics and maximal drug concentration (Cmax) of levofloxacin, elimination half-life and area under the curve from 0 to 24 hours (AUC0-24 hours × μg/mL) were correlated to determine the optimal dosage and to examine associations. Population pharmacokinetics and target attainment were modeled. With results from the Federated States of Micronesia, dosages were increased in RMI toward the target Cmax for Mycobacterium tuberculosis, 8-12 µg/mL.
RESULTS
Cmax correlated linearly with per-weight dosage. Neither Cmax nor half-life was associated with gender, age, body mass index, concurrent medications or predose meals. At levofloxacin dosage of 15-20 mg/kg, Cmax ≥8 µg/mL was observed, and modeling corroborated a high target attainment across the ratio of the area under the free concentration versus time curve to minimum inhibitory concentration (fAUCss,0-24/MIC) values.
CONCLUSIONS
Levofloxacin dosage should be 15-20 mg/kg for Cmax ≥8 µg/mL and a high target attainment across fAUCss,0-24/MIC values in children ≥2 years of age.
Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Drug Monitoring; Female; Humans; Infant; Latent Tuberculosis; Levofloxacin; Male; Microbial Sensitivity Tests; Micronesia; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 26658531
DOI: 10.1097/INF.0000000000001022 -
The Brazilian Journal of Infectious... 2023Despite high cure rates, treatment-related mortality in children with acute lymphoblastic leukemia (ALL) remains significant. About 4% of patients die during remission... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety of levofloxacin as an antibiotic prophylaxis in the induction phase of children newly diagnosed with acute lymphoblastic leukemia: an interim analysis of a randomized, open-label trial in Brazil.
BACKGROUND
Despite high cure rates, treatment-related mortality in children with acute lymphoblastic leukemia (ALL) remains significant. About 4% of patients die during remission induction therapy and approximately two-thirds of treatment-related deaths are due to infectious complications.
METHODS
From May 2021 to June 2022, children aged one through 18 years, with a recent diagnosis of ALL, admitted to three pediatric oncology centers in Brazil, were enrolled in this multicenter, open-label, randomized, phase 3 clinical trial. Eligible patients were randomly divided into two groups, based on a 1:1 allocation ratio, to receive, or not, levofloxacin as a prophylactic agent during the induction phase. All patients were treated according to the IC-BFM 2009 chemotherapy protocol. Primary endpoints were carbapenemase-producing Enterobacteriaceae (CPE) colonization, Clostridioides difficile diarrhea, and other adverse events related to the use of levofloxacin. The secondary endpoint was febrile neutropenia during induction. The median follow-up was 289 days.
RESULTS
Twenty patients were included in this trial, 10 in each group (control and levofloxacin). Mild adverse reactions related to levofloxacin were observed in three patients (30%). Three patients had Clostridioides difficile diarrhea, two in the levofloxacin group and one in the control group (p > 0.99). Only one patient presented colonization by CPE. This patient belonged to the levofloxacin group (p > 0.99). Nine patients presented febrile neutropenia, five in the control group and four in the levofloxacin intervention group (p > 0.99), one patient died due to febrile neutropenia.
CONCLUSION
The use of levofloxacin was shown to be safe in the induction phase in children with de novo ALL. The use of this medication did not increase the rate of colonization by CPE nor the rate of diarrhea by C. difficile. All adverse reactions were mild and remitted either spontaneously or after switching medicine administration from oral to intravenous route.
Topics: Humans; Child; Adolescent; Levofloxacin; Antibiotic Prophylaxis; Anti-Bacterial Agents; Clostridioides difficile; Brazil; Febrile Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Diarrhea
PubMed: 36750202
DOI: 10.1016/j.bjid.2023.102745 -
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 -
Journal of Clinical Microbiology Mar 2019In 2019, the Clinical and Laboratory Standards Institute (CLSI) published revisions to the ciprofloxacin and levofloxacin breakpoints. We evaluated the performance of...
In 2019, the Clinical and Laboratory Standards Institute (CLSI) published revisions to the ciprofloxacin and levofloxacin breakpoints. We evaluated the performance of disk diffusion and Etest compared to that of reference broth microdilution by use of the revised breakpoints. Fifty-eight isolates with ciprofloxacin MICs of 0.5 μg/ml or 1.0 μg/ml on initial testing were specifically selected for evaluation. These MICs are susceptible by the 2018 breakpoints and not susceptible by the 2019 breakpoints. For ciprofloxacin disk diffusion, the categorical agreement (CA) was 46.6%, with 0 very major errors (VME), 4 major errors (ME) (21.1%), and 27 minor errors (mE) (46.6%) using the 2019 CLSI disk breakpoints. For levofloxacin, the CA was 72.4%, with 0 VME, 0 ME, and 16 mE (27.6%) using the 2019 CLSI disk breakpoints. Using an error rate-bound evaluation method, levofloxacin but not ciprofloxacin disk diffusion yielded an acceptable minor error rate of <40% for isolates with an MIC plus or minus 1 doubling dilution of the intermediate breakpoint. For Etest compared to the reference broth microdilution, the essential agreement was 100% for both ciprofloxacin and levofloxacin and the CA was 81.0% and 65.5%, respectively. No VME or ME were observed by Etest, and 11 minor errors for ciprofloxacin (19.0%) and 20 (34.5%) for levofloxacin were observed. By the error rate-bound method, the minor error rate for ciprofloxacin was acceptable, but minor error rates for levofloxacin remained outside the acceptance range (i.e., 42.6% for isolates with an MIC within 1 dilution of the breakpoint). In general, the disk diffusion and Etest methods performed well with this challenging collection of isolates, although laboratories must be aware of minor errors, particularly for isolates with results near the breakpoint.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Enterobacteriaceae; Levofloxacin; Microbial Sensitivity Tests
PubMed: 30567744
DOI: 10.1128/JCM.01797-18 -
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 -
Scientific Reports Feb 2024The spread of fluoroquinolone (FQ) resistance in Acinetobacter baumannii represents a critical health threat. This study aims to overcome FQ resistance in A. baumannii...
The spread of fluoroquinolone (FQ) resistance in Acinetobacter baumannii represents a critical health threat. This study aims to overcome FQ resistance in A. baumannii via the formulation of polymeric nanoFQs. Herein, 80 A. baumannii isolates were obtained from diverse clinical sources. All A. baumannii isolates showed high resistance to most of the investigated antimicrobials, including ciprofloxacin (CIP) and levofloxacin (LEV) (97.5%). FQ resistance-determining regions of the gyrA and parC genes were the most predominant resistant mechanism, harbored by 69 (86.3%) and 75 (93.8%) of the isolates, respectively. Additionally, plasmid-mediated quinolone resistance genes aac(6')-Ib and qnrS were detected in 61 (76.3%) and 2 (2.5%) of the 80 isolates, respectively. The CIP- and LEV-loaded poly ε-caprolactone (PCL) nanoparticles, F and F, respectively, showed a 1.5-6- and 6-12-fold decrease in the MIC, respectively, against the tested isolates. Interestingly, the time kill assay demonstrated that MICs of F and F completely killed A. baumannii isolates after 5-6 h of treatment. Furthermore, F and F were found to be efficient in overcoming the FQ resistance mediated by the efflux pumps in A. baumannii isolates as revealed by decreasing the MIC four-fold lower than that of free CIP and LEV, respectively. Moreover, F and F at 1/2 and 1/4 MIC significantly decreased biofilm formation by 47-93% and 69-91%, respectively. These findings suggest that polymeric nanoparticles can restore the effectiveness of FQs and represent a paradigm shift in the fight against A. baumannii isolates.
Topics: Ciprofloxacin; Fluoroquinolones; Levofloxacin; Acinetobacter baumannii; Anti-Bacterial Agents; Microbial Sensitivity Tests; Biofilms; Drug Resistance, Bacterial; DNA Gyrase
PubMed: 38326515
DOI: 10.1038/s41598-024-53441-1 -
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 -
International Journal of Molecular... Aug 2022We compared the performance and levofloxacin (Quinsair) lung deposition of three nebulisers commonly used in CF (I-Neb Advance, eFlow rapid, and LC Plus) with the...
We compared the performance and levofloxacin (Quinsair) lung deposition of three nebulisers commonly used in CF (I-Neb Advance, eFlow rapid, and LC Plus) with the approved nebuliser Zirela. The delivered dose, delivery rate, and aerosol particle size distribution (APSD) for each device were determined using the methods described in the Pharmacopeia. High-resolution computed tomography scans obtained from seven adult patients with mild CF were used to generate computer-aided, three-dimensional models of their airway tree to assess lung deposition using functional respiratory imaging (FRI). The eFlow rapid and the LC Plus showed poor delivery efficiencies due to their high residual volumes. The I-Neb, which only delivers aerosols during the inspiratory phase, achieved the highest aerosol delivery efficiency. However, the I-Neb showed the largest particle size and lowest delivery rate (2.9 mg/min), which were respectively associated with a high extrathoracic deposition and extremely long nebulisation times (>20 min). Zirela showed the best performance considering delivery efficiency (159.6 mg out of a nominal dose of 240 mg), delivery rate (43.5 mg/min), and lung deposition (20% of the nominal dose), requiring less than 5 min to deliver a full dose of levofloxacin. The present study supports the use of drug-specific nebulisers and discourages the off-label use of general-purpose devices with the present levofloxacin formulation since subtherapeutic lung doses and long nebulisation times may compromise treatment efficacy and adherence.
Topics: Administration, Inhalation; Adult; Cystic Fibrosis; Humans; Levofloxacin; Lung; Nebulizers and Vaporizers; Respiratory Aerosols and Droplets
PubMed: 36076992
DOI: 10.3390/ijms23179597 -
Annals of Clinical Microbiology and... Jan 2023Maternal rectovaginal colonization with group B Streptococcus (GBS) or Streptococcus agalactiae is the most common pathway for this disease during the perinatal period.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Maternal rectovaginal colonization with group B Streptococcus (GBS) or Streptococcus agalactiae is the most common pathway for this disease during the perinatal period. This meta-analysis aimed to summarize existing data regarding maternal colonization, serotype profiles, and antibiotic resistance in China.
METHODS
Systematic literature reviews were conducted after searching 6 databases. Meta-analysis was applied to analyze colonization rate, serotype, and antimicrobial susceptibility of GBS clinical isolates in different regions of China. Summary estimates are presented using tables, funnel plots, forest plots, histograms, violin plots, and line plots.
RESULTS
The dataset regarding colonization included 52 articles and 195 303 pregnant women. Our estimate for maternal GBS colonization in China was 8.1% (95% confidence interval [CI] 7.2%-8.9%). Serotypes Ia, Ib, III, and V account for 95.9% of identified isolates. Serotype III, which is frequently associated with the hypervirulent clonal complex, accounts for 46.4%. Among the maternal GBS isolates using multilocus sequence typing (MLST), ST19 (25.7%, 289/1126) and ST10 (25.1%, 283/1126) were most common, followed by ST12 (12.4%, 140/1126), ST17 (4.8%, 54/1126), and ST651 (3.7%, 42/1126). GBS was highly resistant to tetracycline (75.1% [95% CI 74.0-76.3%]) and erythromycin (65.4% [95% CI 64.5-66.3%]) and generally susceptible to penicillin, ampicillin, vancomycin, ceftriaxone, and linezolid. Resistance rates of GBS to clindamycin and levofloxacin varied greatly (1.0-99.2% and 10.3-72.9%, respectively). A summary analysis of the bacterial drug resistance reports released by the China Antimicrobial Resistance Surveillance System (CARSS) in the past 5 years showed that the drug resistance rate of GBS to erythromycin, clindamycin, and levofloxacin decreased slowly from 2018 to 2020. However, the resistance rates of GBS to all 3 antibiotics increased slightly in 2021.
CONCLUSIONS
The overall colonization rate in China was much lower than the global colonization rate (17.4%). Consistent with many original and review reports in other parts of the world, GBS was highly resistant to tetracycline. However, the resistance of GBS isolates in China to erythromycin and clindamycin was greater than in other countries. This paper provides important epidemiological information, to assist with prevention and treatment of GBS colonization in these women.
Topics: Female; Pregnancy; Humans; Clindamycin; Streptococcal Infections; Levofloxacin; Streptococcus agalactiae; Multilocus Sequence Typing; Anti-Bacterial Agents; Erythromycin; Tetracycline; Drug Resistance, Bacterial; China; Microbial Sensitivity Tests
PubMed: 36639677
DOI: 10.1186/s12941-023-00553-7 -
BMJ (Clinical Research Ed.) Aug 2015To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane Library, PubMed, and Embase without language or date restrictions.
STUDY SELECTION
Full text reports of randomised controlled trials that compared different eradication treatments for H pylori among adults.
RESULTS
Of the 15,565 studies identified, 143 were eligible and included. Data on 14 kinds of treatments were available. Of 91 possible comparisons for the efficacy outcome, 34 were compared directly and the following treatments performed better: seven days of concomitant treatment (proton pump inhibitor and three kinds of antibiotics administered together), 10 or 14 days of concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment (standard triple treatment which is probiotic supplemented), 10 or 14 days of levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and antibiotic administered together), 14 days of hybrid treatment (proton pump inhibitor and amoxicillin used for seven days, followed by a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days), and 10 or 14 days of sequential treatment (five or seven days of a proton pump inhibitor plus amoxicillin, followed by five or seven additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin). In terms of tolerance, all treatments were considered tolerable, but seven days of probiotic supplemented triple treatment and seven days of levofloxacin based triple treatment ranked best in terms of the proportion of adverse events reported.
CONCLUSION
Comparison of different eradication treatments for H pylori showed that concomitant treatments, 10 or 14 days of probiotic supplemented triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days of hybrid treatment, and 10 or 14 days of sequential treatment might be better alternatives for the eradication of H pylori.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Nitroimidazoles; Probiotics; Proton Pump Inhibitors
PubMed: 26290044
DOI: 10.1136/bmj.h4052