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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 -
Trials Jun 2023New treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain...
BACKGROUND
New treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain reaction-based methods for antibiotic susceptibility testing are available for detecting H. pylori-specific mutations that confer resistance to clarithromycin and levofloxacin. Several meta-analyses have compared eradication rates for susceptibility-guided versus empirical therapy for H. pylori treatment; however, all have significant limitations and high heterogeneity, and the results are contradictory. The main objective of this trial is to assess whether a sequential strategy based on molecular susceptibility testing-guided therapy for H. pylori has a better eradication rate than empirical therapy.
METHODS
This trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. Men and women who are H. pylori-positive, naïve to treatment, and aged 18-65 years will be recruited. A total of 500 participants will be randomised to receive either empirical therapy or a susceptibility-guided sequential strategy. Bismuth quadruple therapy will be the empirical first-line therapy, and in case of failure, high-dose dual (proton-pump inhibitor + amoxicillin) treatment will be the rescue therapy. For the susceptibility-guided sequential strategy, regimen selection will be based on H. pylori susceptibility to clarithromycin (first-line) and levofloxacin (rescue). A first-line treatment of clarithromycin triple therapy will be selected for clarithromycin-sensitive strains. For clarithromycin resistance, a high-dose dual therapy will be selected. During the rescue treatment, a levofloxacin quadruple regimen will be selected for levofloxacin-sensitive strains, and a furazolidone quadruple regimen will be selected for others. The primary outcome is the first-line eradication rate in both groups, and the overall (including first and rescue therapies) H. pylori eradication rate in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis, and per-protocol analysis.
DISCUSSION
This randomised controlled trial will provide objective and valid evidence about the value of polymerase chain reaction-based molecular methods for antibiotic susceptibility testing in guiding H. pylori eradication.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05549115. Released on 18 September 2022. First posted on 22 September 2022. Enrolment of the first participant on 20 September 2022. The study is retrospectively registered.
Topics: Male; Humans; Female; Helicobacter Infections; Clarithromycin; Helicobacter pylori; Levofloxacin; Prospective Studies; Drug Therapy, Combination; Anti-Bacterial Agents; Proton Pump Inhibitors; Metronidazole; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37337241
DOI: 10.1186/s13063-023-07457-z -
Journal of Microbiology, Immunology,... Feb 2022The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious...
Emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole-resistant Stenotrophomonas maltophilia: Risk factors and antimicrobial sensitivity pattern analysis from a single medical center in Taiwan.
BACKGROUND
The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious problem, but clinical data analysis on this has not been reported.
METHODS
A matched case-control-control study was conducted to investigate risk factors for LTSRSM occurrence in hospitalized patients. For patients with LTSRSM infection/colonization (the case group), two matched control groups were used: control group A with levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) and control group B without S. maltophilia. Besides, tigecycline, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and colistin susceptibilities in collected LTSRSM and levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) isolates were compared.
RESULTS
From January 2014 to June 2016, 129 LTSRSM from cultured 1213 S. maltophilia isolates (10.6%) were identified. A total of 107 LTSRSM infected patients paired with 107 LTSSSM-, and 107 non-S. maltophilia-infected ones were included. When compared with control group A, previous fluoroquinolone and TMP/SMX use was found to be independently associated with LTSRSM occurrence. When compared with control group B, mechanical ventilation, cerebrovascular disease, and previous fluoroquinolone use were risk factors for LTSRSM occurrence. Eighty-five LTSRSM and 85 LTSSSM isolates were compared for antibiotic susceptibilities; the resistance rates and minimum inhibitory concentrations of tigecycline and ceftazidime were significantly higher for LTSRSM than for LTSSSM isolates.
CONCLUSION
The emergence of LTSRSM showing cross resistance to tigecycline and ceftazidime would further limit current therapeutic options. Cautious fluoroquinolone and TMP/SMX use may be helpful to limit such high-level resistant strains of S. maltophilia occurrence.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Risk Factors; Stenotrophomonas maltophilia; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33500210
DOI: 10.1016/j.jmii.2020.12.012 -
Molecules (Basel, Switzerland) Jun 2017The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus,...
The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R₄W₄] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 µg/mL against Methicillin-resistant (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R₄W₄] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of [R₄W₄K]-levofloxacin-Q and [R₄W₄K]-levofloxacin. The carboxylic acid group of levofloxacin or levofloxacin-Q was conjugated with the amino group of β-alanine attached to lysine in the presence of 2-(1-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and ,-diisopropylethylamine (DIPEA) for 3 h to afford the products. Antibacterial assays were conducted to determine the potency of conjugates [R₄W₄K]-levofloxacin-Q and [R₄W₄K]-levofloxacin against MRSA and . Although levofloxacin-Q was inactive even at a concentration of 128 µg/mL, [R₄W₄K]-levofloxacin-Q conjugate and the corresponding physical mixture showed MIC values of 8 µg/mL and 32 µg/mL against MRSA and , respectively, possibly due to the activity of the peptide. On the other hand, [R₄W₄K]-levofloxacin conjugate (MIC = 32 µg/mL and MIC = 128 µg/mL) and the physical mixture (MIC = 8 µg/mL and 32 µg/mL) was less active than levofloxacin (MIC = 2 µg/mL and 4 = µg/mL) against MRSA and , respectively. The data showed that the conjugation of levofloxacin with [R₄W₄K] significantly reduced the antibacterial activity compared to the parent analogs, while [R₄W₄K]-levofloxacin-Q conjugate was more significantly potent than levofloxacin-Q alone.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Bacterial; Ethylamines; Humans; Klebsiella pneumoniae; Levofloxacin; Methicillin-Resistant Staphylococcus aureus; Peptides, Cyclic; Triazoles; Urea
PubMed: 28594345
DOI: 10.3390/molecules22060957 -
Auris, Nasus, Larynx Aug 2023The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of 1.5% levofloxacin otic solution for the treatment of otitis media in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase III study.
OBJECTIVE
The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media.
METHODS
This multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial was conducted at 34 institutions in Japan. A total of 202 patients with chronic suppurative otitis media (CSOM) or acute otitis media (AOM) were randomized into either the LVFX group or placebo group. A total of 6-10 drops of 1.5% otic solution of LVFX or its matching placebo were administered in the diseased ear twice daily, in the morning and evening for up to 10 days. Images corresponding to three clinical findings-purulent otorrhea, hyperemia (redness), and granulation tissue formation in the middle ear and tympanic membrane-for each diseased ear were evaluated using digital endoscopy by a blinded central independent review committee (BICRC) at each visit after treatment administration.
RESULTS
In total, the data of 201 participants (LVFX group, 99; placebo group, 102) were analyzed. The proportion of patients with disappearance (improvement rate) of all three clinical findings at the end of treatment or discontinuation by the BICRC was 46.5% (46/99) in the LVFX group and 23.5% (24/102) in the placebo group, and the difference (95% confidence interval) between the groups was 22.0% (8.7, 34.2), with a significantly higher improvement rate in the LVFX group than in the placebo group (p = 0.001; Cochran-Mantel-Haenszel test), demonstrating the efficacy of LVFX. The bacterial eradication rates were 93.9% (77/82) and 12.5% (11/88) in the LVFX and placebo groups, respectively, and the rate was significantly higher in the LVFX group than in the placebo group (p < 0.001). Treatment-related adverse events (AEs) occurred in 5.1% (5/99) and 7.8% (8/102) of the patients in the LVFX and placebo groups, respectively, and no significant difference was noted in incidence rate between the groups.
CONCLUSION
The clinical efficacy of 1.5% LVFX otic solution for CSOM and AOM was demonstrated by the resolution of inflammation in the middle ear and tympanic membrane as well as through the high bacterial eradication rate observed. No deaths or serious treatment-related AEs were observed. The study provided confirmation that 1.5% LVFX otic solution is a safe, well-tolerated, and effective treatment for CSOM and AOM.
Topics: Humans; Anti-Bacterial Agents; Levofloxacin; Otitis Media; Otitis Media, Suppurative; Ear, Middle
PubMed: 36599786
DOI: 10.1016/j.anl.2022.12.013 -
Journal of Biomedical Science Oct 2018In the face of rising prevalence of antibiotic resistance, susceptibility testing to provide personalized treatment is recommended prior to eradication therapy for... (Review)
Review
In the face of rising prevalence of antibiotic resistance, susceptibility testing to provide personalized treatment is recommended prior to eradication therapy for Helicobacter pylori (H. pylori). Yet, population specific treatment according to the local prevalence of antibiotic resistance may be an alternative if susceptibility testing is not available. In this article, we reviewed the global prevalence of primary antibiotic resistance and the efficacies of commonly used regimens in antibiotic susceptible and resistance strains. We then constructed a model to predict the efficacies of these regimens and proposed an algorithm to choose the optimal first-line and rescue therapies according to the prevalence of antibiotic resistance. Clarithromycin-based therapy (triple, sequential, concomitant, and hybrid therapies) for 14 days remains the treatment of choice in regions with low clarithromycin resistance (≤15%) and bismuth quadruple therapy may be an alternative therapy. In regions with high clarithromycin resistance (> 15%), bismuth quadruple therapy is the treatment of choice and non-bismuth quadruple therapy may be an alternative. Either levofloxacin-based therapy or bismuth quadruple therapy may be used as second-line rescue therapy for patients fail after clarithromycin-based therapies, whereas levofloxacin-based therapy may be used for patients fail after bismuth quadruple therapy. Susceptibility testing or genotypic resistance should be determined after two or more eradication failures. However, empirical therapy according to prior medication history to avoid the empirical reuse of levofloxacin and clarithromycin may be an acceptable alternative after consideration of cost, patient preference, and accessibility. Rifabutin-based therapy for 14 days may serve as the fourth-line therapy. New antibiotics specific for H. pylori are highly anticipated.
Topics: Algorithms; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Resistance, Microbial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Models, Theoretical
PubMed: 30285834
DOI: 10.1186/s12929-018-0471-z -
PloS One 2023Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics...
Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli O157:H7). Results indicated that L. enzymogenes CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to E. coli (O157:H7). The combination of L. enzymogenes CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with L. enzymogenes CFS restored its antibacterial activity against MRSA. The MTT assay revealed that L. enzymogenes CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, L. enzymogenes bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Levofloxacin; Peptide Hydrolases; Cefixime; Escherichia coli; Virulence; Anti-Bacterial Agents; Methicillin; Staphylococcus aureus; Gentamicins; Microbial Sensitivity Tests
PubMed: 36893145
DOI: 10.1371/journal.pone.0282705 -
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 -
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 -
International Journal of Infectious... Sep 2022To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage.
OBJECTIVES
To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage.
METHODS
Children aged 1-15 years with tuberculosis who received levofloxacin-based treatment for at least 7 days were enrolled. First, five children were enrolled to receive the WHO-recommended dosage (15-20 mg/kg/day), then an additional five children received a dosage higher than the WHO-recommended dosage (20-30 mg/kg/day). Blood samples were collected at predose and postdose 1, 2, 4, 6, 8, and 12 hours. A target of the ratio of the free area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was 100.
RESULTS
The median (interquartile range) age was 9.6 (4.9-10.5) and 12.0 (10.1-12.3) years in the WHO dosage and higher-than-WHO dosage groups, respectively. The median (interquartile range) duration of antituberculosis treatment was 24 (8-24) weeks. The geometric mean (95% confidence interval) of fAUC/MIC was 60.4 (43.5-84.0) and 103.2 (70.1-151.8) in the WHO and higher-than-WHO dosage groups, respectively. There was no adverse event of QT prolongation or any other grade 3 or 4 adverse events.
CONCLUSION
Levofloxacin at a higher dose of 20-30 mg/kg/day could achieve the fAUC/MIC target in children.
Topics: Antitubercular Agents; Child; Humans; Levofloxacin; Pilot Projects; Tuberculosis; World Health Organization
PubMed: 35842213
DOI: 10.1016/j.ijid.2022.07.029