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Antimicrobial Agents and Chemotherapy Jul 2019Clinical phenotypic fluoroquinolone susceptibility testing of is currently based on growth at a single critical concentration, which provides limited information for a...
Clinical phenotypic fluoroquinolone susceptibility testing of is currently based on growth at a single critical concentration, which provides limited information for a nuanced clinical response. We propose using specific resistance-conferring mutations in together with population pharmacokinetic and pharmacodynamic modeling as a novel tool to better inform fluoroquinolone treatment decisions. We sequenced the resistance-determining region of 138 clinical isolates collected from India, Moldova, Philippines, and South Africa and then determined each strain's MIC against ofloxacin, moxifloxacin, levofloxacin, and gatifloxacin. Strains with specific single-nucleotide polymorphisms (SNPs) were grouped into high or low drug-specific resistance categories based on their empirically measured MICs. Published population pharmacokinetic models were then used to explore the pharmacokinetics and pharmacodynamics of each fluoroquinolone relative to the empirical MIC distribution for each resistance category to make predictions about the likelihood of patients achieving defined therapeutic targets. In patients infected with isolates containing SNPs associated with a fluoroquinolone-specific low-level increase in MIC, models suggest increased fluoroquinolone dosing improved the probability of achieving therapeutic targets for gatifloxacin and moxifloxacin but not for levofloxacin and ofloxacin. In contrast, among patients with isolates harboring SNPs associated with a high-level increase in MIC, increased dosing of levofloxacin, moxifloxacin, gatifloxacin, or ofloxacin did not meaningfully improve the probability of therapeutic target attainment. We demonstrated that quantifiable fluoroquinolone drug resistance phenotypes could be predicted from rapidly detectable SNPs and used to support dosing decisions based on the likelihood of patients reaching therapeutic targets. Our findings provide further supporting evidence for the moxifloxacin clinical breakpoint recently established by the World Health Organization.
Topics: Antitubercular Agents; Fluoroquinolones; Gatifloxacin; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium tuberculosis; Ofloxacin; Polymorphism, Single Nucleotide
PubMed: 31085512
DOI: 10.1128/AAC.00076-19 -
American Journal of Therapeutics 2015Drug-induced hepatotoxicity is a major cause of hepatocellular injury in patients admitting to emergency services with acute liver failure. Hepatic necrosis may be at...
Drug-induced hepatotoxicity is a major cause of hepatocellular injury in patients admitting to emergency services with acute liver failure. Hepatic necrosis may be at varying degrees from mild elevations in transaminases to fulminant hepatitis, and even death. The case of a 53-year-old female patient with toxic hepatitis due to levofloxacin and multiple organ failure secondary to toxic hepatitis is presented. Patient suffered itching, redness, and rash after receiving a single dose of 750 mg of levofloxacin tablets for pulmonary infection 10 days ago. Skin lesions had regressed within 3 days, but desquamation formed all over the body. After the fifth day of drug intake, complaints of abdominal pain, vomiting, and yellowing in skin color had started. The patient was referred to our emergency department with these complaints 10 days after drug intake. Patient was thought as a candidate for liver transplant, but cardiopulmonary arrest occurred, and the patient died before she could be referred to a transplant center. This case is important because hepatotoxicity and death due to levofloxacin is uncommon in the literature.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Fatal Outcome; Female; Humans; Levofloxacin; Middle Aged
PubMed: 24067876
DOI: 10.1097/MJT.0b013e3182a44055 -
Chinese Medical Sciences Journal =... Jun 2022Objective To explore the clinical significance of the combined application of palpebral margin cleaning and antibiotic eye drops in inhibiting bacterial growth in the... (Randomized Controlled Trial)
Randomized Controlled Trial
Inhibitory Effect of Short-Term Palpebral Margin Cleaning with Antibiotic Eye Drops on Ocular Surface Flora before Cataract Extraction: A New Preoperative Antibacterial Method.
Objective To explore the clinical significance of the combined application of palpebral margin cleaning and antibiotic eye drops in inhibiting bacterial growth in the palpebral margin and conjunctival sacs before cataract extraction. Methods In this study, 61 patients (97 eyes) with age-related cataract who underwent phacoemulsification and intraocular lens implantation were selected, and randomly grouped. In the experimental group, the combined application of palpebral margin cleaning with cotton pads and levofloxacin eye drops was given for three days before the surgery. In the control group, levofloxacin eye drops alone were applied for three consecutive days. Bacteria samples from the conjunctival sac and eyelid margins were cultivated and identified before and three days after taking antimicrobial measures, respectively. Results In the experimental group, the positive rates of the two bacteria samples were 100% (50/50) and 40% (20/50) before and 10% (5/50) and 0% (0/50) after the treatment. In the control group, the positive rates of the two bacteria samples were 97.9% (46/47) and 29.8% (14/47) before and 40.4% (19/47) and 10.6% (5/47) after the treatment. The positive rates between the two groups were not significantly different before taking antimicrobial measures (= 0.485 and 0.395), while they were significantly different after taking antimicrobial measures ( = 0.001 and 0.024). Conclusion Combined application of eyelid and palpebral margin cleaning with cotton pads and antibiotic eye drops before cataract extraction imparted excellent antibacterial effects.
Topics: Anti-Bacterial Agents; Bacteria; Cataract; Cataract Extraction; Conjunctiva; Eyelids; Humans; Levofloxacin; Ophthalmic Solutions
PubMed: 35435159
DOI: 10.24920/003901 -
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 -
Spectrochimica Acta. Part A, Molecular... Jan 2022Lipophilicity plays a significant role in the permeability of the drugs through cell membranes and impacts the drug activity in the human body. In this paper, the...
Lipophilicity plays a significant role in the permeability of the drugs through cell membranes and impacts the drug activity in the human body. In this paper, the spectrophotometric method was used to determine the apparent partition coefficients of two amphoteric drugs: ciprofloxacin and levofloxacin. The apparent partition coefficient was determined with the classic shake-flask method with n-octanol according to OECD guidelines. The lipophilicity profiles in a wide range of pH were determined and described quantitatively with the quadratic function. Basing on the macro- and microdissociation constants, the true partition coefficient for both drugs was calculated. Both levofloxacin and ciprofloxacin were lipophilic. The neutral forms, i.e., zwitterionic and uncharged, dominate in the pH relevant to the one in the intestines, the place from which they are absorbed.
Topics: 1-Octanol; Ciprofloxacin; Humans; Hydrogen-Ion Concentration; Levofloxacin; Permeability; Solubility; Water
PubMed: 34500409
DOI: 10.1016/j.saa.2021.120343 -
BMC Infectious Diseases Aug 2023Ralstonia is a genus of Gram-negative opportunistic bacteria that can survive in many kinds of solutions and cause a variety of infections. Ralstonia spp. have... (Review)
Review
BACKGROUND
Ralstonia is a genus of Gram-negative opportunistic bacteria that can survive in many kinds of solutions and cause a variety of infections. Ralstonia spp. have increasingly been isolated and reported to cause infections in recent years, thanks to the development of identification methods such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and gene sequencing. However, infections caused by Ralstonia insidiosa are still rare. Only a few cases of respiratory infections and bloodstream infections have been reported, none of which involved meningitis. To the best of our knowledge, this is the first reported case of meningitis caused by R. insidiosa worldwide. It is necessary to report and review this case.
CASE PRESENTATION
We report a case of meningitis caused by R. insidiosa following lumbar surgery in China. The patient exhibited symptoms of headache, dizziness, and recurrent fever. The fever remained unresolved after empiric antibiotic therapy with intravenous cefotaxime and vancomycin in the initial days. Cerebrospinal fluid (CSF) culture yielded Gram-negative non-fermentative bacteria, which were identified as R. insidiosa. As there was a lack of antibiotic susceptibility testing results, clinical pharmacists conducted a literature review to select appropriate antibiotics. The patient's condition improved after receiving effective treatment with intravenous cefepime and levofloxacin.
CONCLUSIONS
Uncommon pathogens, such as R. insidiosa, should be considered in postoperative central nervous system (CNS) infections, particularly in cases with unsatisfactory results of empiric anti-infective therapy. This is the first reported case of meningitis caused by R. insidiosa worldwide. MALDI-TOF MS provides rapid and accurate identification of this pathogen. The antibiotic susceptibility testing results of R. indiosa may be interpreted based on the breakpoints for Pseudomonas spp., Burkholderia cepacia spp., and Acinetobacter spp. Our case presents a potential option for empiric therapy against this pathogen, at least in the local area. This is crucial to minimize the severity and mortality rates associated with meningitis. Standardized antibiotic susceptibility testing and breakpoints for the Ralstonia genus should be established in the future as cases accumulate. Cefepime and levofloxacin may be potential antibiotics for infections caused by R. indiosa.
Topics: Humans; Cefepime; Levofloxacin; Ralstonia; Anti-Bacterial Agents; Meningitis
PubMed: 37608277
DOI: 10.1186/s12879-023-08506-3 -
Journal of Materials Chemistry. B Sep 2023Carbon dot (CD)-based nanozymes have great potential in antibacterial applications. In order to achieve enhanced broad-spectrum antibacterial capacity, we synthesized...
Carbon dot (CD)-based nanozymes have great potential in antibacterial applications. In order to achieve enhanced broad-spectrum antibacterial capacity, we synthesized Co-doped drug-based CDs (Co-Lvx-CDs) using levofloxacin and vitamin B12 as precursors by mimicking the catalysis of antibacterial activity of natural enzymes. The Co-Lvx-CDs retained not only the effective functional groups of the traditional antibiotic levofloxacin but also achieved oxidase-like and peroxidase-like activities to generate reactive oxygen species (ROS) through Co doping. Additionally, the Co-Lvx-CDs had superb fluorescence properties and could be applied in information encryption. The CDs were validated to have a broad-spectrum bactericidal effect against Gram-positive and -negative bacteria, compensating for the limitations of levofloxacin while also having enhanced sterilization ability. Importantly, the proposed Co-Lvx-CDs provide a new idea for the design of multifunctional CD-based nanozymes with preconceived outcomes.
Topics: Levofloxacin; Carbon; Anti-Bacterial Agents; Catalysis
PubMed: 37545365
DOI: 10.1039/d3tb01376f -
Letters in Applied Microbiology Sep 2022Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of...
Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the development of novel antimicrobials effective against multidrug-resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Levofloxacin; Meropenem; Metal Nanoparticles; Microbial Sensitivity Tests; Plant Extracts; Pseudomonas Infections; Pseudomonas aeruginosa; Reactive Oxygen Species; Silver
PubMed: 35687297
DOI: 10.1111/lam.13759 -
Journal of Hazardous Materials Jun 2022Herein, a flower-shaped fluorescent probe was proposed for hydrogen peroxide (HO) and levofloxacin (LVF) sensing based on MoOx QDs@Co/Zn-MOFs with porous structure. Both...
Herein, a flower-shaped fluorescent probe was proposed for hydrogen peroxide (HO) and levofloxacin (LVF) sensing based on MoOx QDs@Co/Zn-MOFs with porous structure. Both MoOx QDs and Co/Zn-MOFs exhibited peroxidase-like properties, and the combination of them greatly aroused the synergistic catalytic capabilities between them. In o-Phenylenediamine (OPD)-HO system, MoOx QDs@Co/Zn-MOFs efficiently catalyzed HO to produce •OH and then oxidized OPD to its oxidation product (OxOPD). The OxOPD could not only emit blue fluorescence, but also inhibit the fluorescent intensity of MoOx QDs through fluorescence resonance energy transfer (FRET). Moreover, when introducing LVF into the system, the fluorescent intensities of MoOx QDs increased along with the aggregation of themselves while that of OxOPD remained unchanged, which was explained by the joint behavior of FRET and photo-induced electron transfer (PET) instead of the conventional aggregation-induced emission enhancement (AIEE). With these observation, the proposed probe was employed for HO and LVF determination in biological samples with the limit of detection (LOD) of 32.60 pmol/L and 0.85 μmol/L, respectively, suggesting the method holds great promises for trace HO and LVF monitoring in eco-environment.
Topics: Fluorescent Dyes; Hydrogen Peroxide; Levofloxacin; Limit of Detection; Quantum Dots
PubMed: 35286934
DOI: 10.1016/j.jhazmat.2022.128605 -
Biomacromolecules Sep 2023Herein, we demonstrate the feasibility of a three-dimensional printed chitosan (CS)-poly(vinyl alcohol) (PVA)-gelatin (Gel) hydrogel incorporating the antimicrobial drug...
Herein, we demonstrate the feasibility of a three-dimensional printed chitosan (CS)-poly(vinyl alcohol) (PVA)-gelatin (Gel) hydrogel incorporating the antimicrobial drug levofloxacin (LEV) as a potential tissue engineering scaffold. Hydrogels were prepared by physically cross-linking the polymers, and the printability of the prepared hydrogels was determined. The hydrogel with 3% w/v of CS, 3% w/v of PVA, and 2% w/v of Gel presented the best printability, producing smooth and uniform scaffolds. The integrity of 3D-printed scaffolds was improved via a neutralization process since after testing three different neutralized agents, i.e., NH vapors, EtOH/NaOH, and KOH solutions. It was proved that the CS/PVA/Gel hydrogel was formed by hydrogen bonds and remained amorphous in the 3D-printed structures. Drug loading studies confirmed the successful incorporation of LEV, and its in vitro release continued for 48 h. The cytotoxicity/cytocompatibility tests showed that all prepared scaffolds were cytocompatible.
Topics: Tissue Engineering; Chitosan; Levofloxacin; Gelatin; Hydrogels; Printing, Three-Dimensional
PubMed: 37604780
DOI: 10.1021/acs.biomac.3c00362