-
The Journal of Antibiotics Jul 2022Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis,...
Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC/ MIC results (mg l) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future.
Topics: Anti-Bacterial Agents; Burkholderia cepacia complex; Humans; Levofloxacin; Microbial Sensitivity Tests; Steroids
PubMed: 35562592
DOI: 10.1038/s41429-022-00530-w -
Nephrology (Carlton, Vic.) Jun 2015
Topics: Acute Kidney Injury; Anti-Infective Agents; Biomarkers; Creatinine; Crystallization; Female; Humans; Levofloxacin; Middle Aged; Renal Dialysis; Treatment Outcome
PubMed: 25900386
DOI: 10.1111/nep.12405 -
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 Chemotherapy (Florence,... Nov 2023During the Sars-Cov-2 pandemic, secondary pulmonary infections have increased, especially in critically ill patients, highlighting the need for new therapeutic options....
During the Sars-Cov-2 pandemic, secondary pulmonary infections have increased, especially in critically ill patients, highlighting the need for new therapeutic options. Trimethoprim-sulfamethoxazole (SXT) is the treatment of choice but the increase of resistant strains or adverse drug reactions limited its clinical use. Recently ceftazidime/avibactam (CZA) has been approved for the treatment of multi drug resistant (MDR) Gram-negative bacteria infections, including hospital acquired pneumonia. The aim of this study was to evaluate the activity of ceftazidime/avibactam (CZA) alone and in combination with aztreonam (ATM) against clinical isolates by E-test method. Susceptibility of SXT and levofloxacin (LEV) was also investigated. Our results showed 22% of resistance to CZA, 2% to SXT and 26% to LEV. CZA in combination with ATM demonstrated synergistic activity against 86% of the strains, including all those resistant to CZA. The combination of CZA with ATM provides a new therapeutic option for the treatment of severe respiratory infections in critically ill patients.
Topics: Humans; Aztreonam; Ceftazidime; Stenotrophomonas maltophilia; Critical Illness; Drug Combinations; Azabicyclo Compounds; Levofloxacin; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37615040
DOI: 10.1080/1120009X.2023.2247199 -
Diagnostic Microbiology and Infectious... Apr 2020Increase in Helicobacter pylori resistance to fluoroquinolones has been reported in many countries. The aim of the study was to compare, for the first time to our... (Comparative Study)
Comparative Study
Increase in Helicobacter pylori resistance to fluoroquinolones has been reported in many countries. The aim of the study was to compare, for the first time to our knowledge, levofloxacin and delafloxacin activities against H. pylori, including numerous levofloxacin- and multidrug resistant strains. Minimal inhibitory concentrations (MICs) of six antibiotics against 71 consecutive clinical strains were determined. Delafloxacin MIC and MIC were 0.016 and 0.125 μg/mL versus 0.125 and ≥32 μg/mL, respectively, for levofloxacin. Against the 19 levofloxacin resistant strains, delafloxacin MICs and MICs were 0.094 and 0.38 μg/mL, respectively. Delafloxacin MICs against the 21 strains with double or multidrug resistance were ≤0.75 μg/mL. The low MICs, the activity against levofloxacin resistant and multidrug resistant H. pylori strains and the increased activity of the agent in acidic conditions make delafloxacin worthy of further investigation, aiming at optimizing fluoroquinolone-based eradication regimens.
Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Drug Resistance, Multiple, Bacterial; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Young Adult
PubMed: 31954595
DOI: 10.1016/j.diagmicrobio.2019.114980 -
Applied Biochemistry and Biotechnology Feb 2024Pseudomonas aeruginosa can develop resistance. Therefore, it is necessary to design proper treatment for it. Pseudomonas aeruginosa can develop resistance against...
Pseudomonas aeruginosa can develop resistance. Therefore, it is necessary to design proper treatment for it. Pseudomonas aeruginosa can develop resistance against levofloxacin due to the development of efflux pumps. However, the development of these efflux pumps cannot develop resistance against imipenem. Additionally, the MexCDOprJ efflux system which is responsible for the resistance of Pseudomonas aeruginosa to levofloxacin is highly susceptible to imipenem. The objective of the study was to evaluate the emergence of resistance of Pseudomonas aeruginosa against 750 mg levofloxacin, 250 mg imipenem, and a combination of 750 mg levofloxacin and 250 mg imipenem. An in vitro pharmacodynamic model was selected for the evaluation of the emergence of resistance. Pseudomonas aeruginosa strain 236, Pseudomonas aeruginosa strain GB2, and Pseudomonas aeruginosa strain GB65 were selected. Susceptibility testing of both antibiotics was done by agar dilution methodology. A disk diffusion bioassay was performed for antibiotics. RT-PCR measurement was done for the evaluation of expressions of Pseudomonas aeruginosa genes. Samples were tested at 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, and 30 h. Levofloxacin and imipenem both individually reported a decrease in colony-forming unit per milliliter of strength in the initial stage but in the later stage both develop resistance individually. Levofloxacin with imipenem had no resistance to Pseudomonas aeruginosa during 30 h. Time after the start of development of resistance or decrease in clinical efficacy was higher for levofloxacin and imipenem combination in all strains. The concentration of Pseudomonas aeruginosa at the time after the start of development of resistance or decrease in clinical efficacy was fewer for levofloxacin and imipenem combination. Levofloxacin with imipenem is recommended for the treatment of infection due to Pseudomonas aeruginosa.
Topics: Humans; Levofloxacin; Imipenem; Pseudomonas aeruginosa; Microbial Sensitivity Tests; Anti-Bacterial Agents; Pseudomonas Infections
PubMed: 37178250
DOI: 10.1007/s12010-023-04516-8 -
Journal of Infection and Chemotherapy :... Jun 2017Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic...
Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic effect (PAE) of ozenoxacin against Propionibacterium acnes, a major causative bacterium of acne vulgaris. The minimum inhibitory concentrations (MICs) of ozenoxacin against 3 levofloxacin-susceptible strains (MIC of levofloxacin; ≤4 μg/mL) and 3 levofloxacin-resistant strains (MIC of levofloxacin; ≥8 μg/mL) ranged from 0.03 to 0.06 μg/mL and from 0.25 to 0.5 μg/mL, respectively. These MICs of ozenoxacin were almost the same or lower than nadifloxacin and clindamycin. The minimum bactericidal concentrations (MBCs) of ozenoxacin against the levofloxacin-susceptible and -resistant strains were from 0.06 to 8 μg/mL and from 0.5 to 4 μg/mL, respectively. These MBCs were lower than those of nadifloxacin and clindamycin. In time-kill assay, ozenoxacin at 1/4, 1 and 4 times the respective MIC against both levofloxacin-susceptible and -resistant strains showed a concentration-dependent bactericidal activity. Ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains showed more potent and more rapid onset of bactericidal activity compared to nadifloxacin and clindamycin at 4 times the respective MICs. The PAEs of ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains were from 3.3 to 17.1 h, which were almost the same or longer than nadifloxacin and clindamycin. In contrast, the PAEs were hardly induced by any antimicrobial agents against the levofloxacin-resistant strains. The present findings suggest that ozenoxacin has a potent bactericidal activity against both levofloxacin-susceptible and -resistant P. acnes, and a long-lasting PAE against levofloxacin-susceptible P. acnes.
Topics: Aminopyridines; Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Propionibacterium acnes; Quinolones
PubMed: 28389164
DOI: 10.1016/j.jiac.2017.03.004 -
International Journal of... 2020Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum...
BACKGROUND
Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum peak concentration (C) and total area under the concentration time curve (AUC). Pharmacokinetic exposures can be measured to personalize dosing to reach targets, but this practice requires venepuncture, chromatographic or mass spectrometry equipment, and technical expertise. We sought to demonstrate the accuracy of using urine colorimetry as a more feasible estimation of levofloxacin exposure.
METHOD
A colorimetric method using bromocresol green was tested on spiked urine samples with levofloxacin measured using a spectrophotometer. This method was tested in urine samples of healthy volunteers given one 750 mg dose of levofloxacin with urine collected at 0-4 h, 4-8 h, and 8-24 h intervals, and concomitant serum samples were collected and analyzed by high-performance liquid chromatography. Validation of this assay was done in a cohort of people living with human immunodeficiency virus (PLWH), initiating a levofloxacin containing MDR-TB regimen.
RESULTS
Urine colorimetry was reproducible in spiked samples and the calibration was curve linear for levofloxacin concentrations ranging from 7.8 μg/ml to 250 μg/ml, with r = 0.98. In healthy volunteers, correlation between urine absorbance values and serum AUC was highest in urine collected between 4 and 8 h (r = 0.91, P = 0.01), yet in PLWH, urine collected between 0 and 4 h had highest correlation (r = 0.66, P = 0.05). The area under the receiver operating characteristics curve was >0.8 in the derivation, as well as the validation cohort for the urine absorbance values identifying people with total serum exposure below target.
CONCLUSION
Urine colorimetry was highly sensitive in predicting target serum concentrations. Colorimetric methods to determine levofloxacin in urine may improve the feasibility of therapeutic drug monitoring and personalized dose adjustment in TB endemic settings.
Topics: Antitubercular Agents; Colorimetry; Drug Monitoring; Female; Humans; Levofloxacin; ROC Curve; Tuberculosis, Multidrug-Resistant
PubMed: 33323657
DOI: 10.4103/ijmy.ijmy_186_20 -
Microbiology Spectrum Oct 2022Pseudomonas aeruginosa (PA) biofilm infection is clinically prevalent and difficult to eradicate. In the present work, we aimed to evaluate the and efficacy of...
Pseudomonas aeruginosa (PA) biofilm infection is clinically prevalent and difficult to eradicate. In the present work, we aimed to evaluate the and efficacy of colistin (COL)-based combinations against PA biofilm. MICs and fractional inhibitory concentration indexes (FICIs) of four antibiotics (COL, amikacin, levofloxacin, and meropenem) to bioluminescent strain PAO1, carbapenem-resistant PAO1 (CRPAO1), and clinically isolated strains were assessed. Minimal biofilm eradication concentrations (MBECs) of monotherapy and combinations were examined by counting the live bacteria in biofilm, accompanied by visual confirmation using confocal laser-scanning microscopy. An animal biofilm infection model was established by implanting biofilm subcutaneously, and the therapeutic effect was evaluated according to the change in luminescence through a live animal bio-photonic imaging system. , even combined with 4 or 8 mg/L COL, meropenem needed to reach 128 or 256 mg/L to eradicate the biofilm. Moreover, 2 mg/L COL combined with 32 mg/L amikacin or 4-8 mg/L levofloxacin could kill the PAO1 and CRPAO1 in biofilm within 24 h. , COL combined with amikacin or levofloxacin could shorten the eradication time of biofilm than monotherapy. For PAO1 biofilm, combination therapy could eradicate the biofilm in all mice on the 5th day, whereas monotherapy only eradicated biofilms in almost half of the mice. For CRPAO1 biofilm, the biofilm eradication rate on the 6th day in the COL+ amikacin, amikacin, or COL alone regimen was 90%, 10%, or 40%, respectively. COL combined with levofloxacin did not show a better effect than each individual antibiotic. COL-based combinations containing levofloxacin or amikacin were promising choices for treating PA biofilm infection. Infections associated with PA biofilm formation are extremely challenging. When monotherapy fails to achieve optimal efficacy, combination therapy becomes the last option. After evaluating multiple drug combinations through a series of experiments and , we confirmed that colistin-based combinations containing levofloxacin or amikacin were promising choices for treating PA biofilm infection. The efficacy of these combinations derives from the different bactericidal mechanisms and the bacterial susceptibility to each antibiotic. This study provided a new regimen to solve the incurable problem of biofilm by using COL combined with other antibiotics.
Topics: Mice; Animals; Colistin; Amikacin; Levofloxacin; Pseudomonas aeruginosa; Meropenem; Drug Resistance, Multiple, Bacterial; Pseudomonas Infections; Biofilms; Anti-Bacterial Agents; Microbial Sensitivity Tests; Carbapenems; Drug Combinations
PubMed: 36102678
DOI: 10.1128/spectrum.01468-22 -
Journal of Chromatographic Science Aug 2017Simple, economic and environmental friendly high-performance liquid chromatography methods for levofloxacin and minocycline quantification in biomimetic media were...
Simple, economic and environmental friendly high-performance liquid chromatography methods for levofloxacin and minocycline quantification in biomimetic media were developed and validate including their stability at body temperature, an often neglected evaluation parameter. Both methods are similar only differing in the wavelength setting, i.e., for levofloxacin and minocycline quantification the UV detection was set at 284 and at 273 nm, respectively. The separation of both antibiotics was achieved using a reversed-phase column and a mobile phase consisting of acetonitrile and water (15:85) with 0.6% triethylamine, adjusted to pH 3. As an internal standard for levofloxacin quantification, minocycline was used and vice versa. The calibration curves for both methods were linear (r = 0.99) over a concentration range of 0.3-16 μg/mL and 0.5-16 μg/mL for levofloxacin and minocycline, respectively, with precision, accuracy and recovery in agreement with international guidelines requirement. Levofloxacin revealed stability in all media and conditions, including at 37°C, with exception to freeze-thaw cycle conditions. Minocycline presented a more accentuated degradation profile over prolonged time courses, when compared to levofloxacin. Reported data is of utmost interest for pharma and biomaterials fields regarding the research and development of new local drug-delivery-systems containing either of these two antibiotics, namely when monitoring the in vitro release studies of those systems.
Topics: Calibration; Chromatography, High Pressure Liquid; Culture Media; Drug Stability; Levofloxacin; Limit of Detection; Linear Models; Minocycline; Reproducibility of Results
PubMed: 28444354
DOI: 10.1093/chromsci/bmx033