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Antimicrobial Agents and Chemotherapy 2014Pharmacokinetic exposure and the MIC of fluoroquinolones are important determinants of their efficacy against Mycobacterium tuberculosis. Population modeling was used to... (Clinical Trial)
Clinical Trial
Pharmacokinetic exposure and the MIC of fluoroquinolones are important determinants of their efficacy against Mycobacterium tuberculosis. Population modeling was used to describe the steady-state plasma pharmacokinetics of moxifloxacin in 241 tuberculosis (TB) patients in southern Africa. Monte Carlo simulations were applied to obtain the area under the unbound concentration-time curve from 0 to 24 h (fAUC0-24) after daily doses of 400 mg or 800 mg moxifloxacin and 800 mg ofloxacin. The MIC distributions of ofloxacin and moxifloxacin were determined for 197 drug-resistant clinical isolates of Mycobacterium tuberculosis. For a specific MIC, the probability of target attainment (PTA) was determined for target fAUC0-24/MIC ratios of ≥53 and ≥100. The PTAs were combined with the MIC distributions to calculate the cumulative fraction of response (CFR) for multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Even with the less stringent target ratio of ≥53, moxifloxacin at 400 mg and ofloxacin at 800 mg achieved CFRs of only 84% and 58% for multidrug-resistant isolates with resistance to an injectable drug, while the 800-mg moxifloxacin dose achieved a CFR of 98%. Using a target ratio of ≥100 for multidrug-resistant strains (without resistance to injectable agents or fluoroquinolones), the CFR was 88% for moxifloxacin and only 43% for ofloxacin, and the higher dose of 800 mg moxifloxacin was needed to achieve a CFR target of >90%. Our results indicate that moxifloxacin is more efficacious than ofloxacin in the treatment of MDR-TB. Further studies should determine the optimal pharmacodynamic target for moxifloxacin in a multidrug regimen and clarify safety issues when it is administered at higher doses.
Topics: Adult; Antitubercular Agents; Female; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Moxifloxacin; Ofloxacin; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 24189253
DOI: 10.1128/AAC.01478-13 -
International Journal of Environmental... Apr 2019Simple, fast, and precise reversed-phase (RP)-high-performance liquid chromatography (HPLC) and two ecofriendly spectrophotometric methods were established and validated...
Simple, fast, and precise reversed-phase (RP)-high-performance liquid chromatography (HPLC) and two ecofriendly spectrophotometric methods were established and validated for the simultaneous determination of moxifloxacin HCl (MOX) and flavoxate HCl (FLX) in formulations. Chromatographic methods involve the separation of two analytes using an Agilent Zorbax SB C18 HPLC column (150 mm × 4.6 mm; 5 µm) and a mobile phase consisting of phosphate buffer (50 mM; pH 5): methanol: acetonitrile in a proportion of 50:20:30 v/v, respectively. Valsartan was used as an internal standard. Analytes were monitored by measuring the absorbance of elute at 299 nm for MOX and 250 nm for FLX and valsartan. Two environmentally friendly spectrophotometric (first derivative and ratio first derivative) methods were also developed using water as a solvent. For the derivative spectrophotometric determination of MOX and FLX, a zero-crossing technique was adopted. The wavelengths selected for MOX and FLX were -304.0 nm and -331.8 nm for the first derivative spectrophotometric method and 358.4 nm and -334.1 nm for the ratio first-derivative spectrophotometric method, respectively. All methods were successfully validated, as per the International Conference on Harmonization(ICH) guidelines, and all parameters were well within acceptable ranges. The proposed analytical methods were successfully utilized for the simultaneous estimation of MOX and FLX in formulations.
Topics: Chromatography, High Pressure Liquid; Flavoxate; Moxifloxacin; Spectrophotometry; Valsartan
PubMed: 30987126
DOI: 10.3390/ijerph16071196 -
Epidemiology of Nontuberculous Mycobacteria in Tuberculosis suspects, Southwest of China, 2017-2022.Frontiers in Cellular and Infection... 2023This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the...
OBJECTIVES
This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022.
METHODS
We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of strain isolation over 6 years.
RESULTS
The number of samples tested for (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were (MAC) and /, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against and ; linezolid, amikacin, and cefoxitin were effective against /. Over 90% of NTM cases originated from the respiratory tract.
CONCLUSION
The NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and /. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.
Topics: Humans; Aged; Adult; Middle Aged; Nontuberculous Mycobacteria; Clarithromycin; Amikacin; Linezolid; HIV Infections; Moxifloxacin; Retrospective Studies; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous; Tuberculosis; China; Microbial Sensitivity Tests
PubMed: 38029240
DOI: 10.3389/fcimb.2023.1282902 -
International Journal of Infectious... Jul 2017To evaluate the efficacy and safety of the introduction of moxifloxacin into the recommended regimen for tuberculosis (TB) treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the efficacy and safety of the introduction of moxifloxacin into the recommended regimen for tuberculosis (TB) treatment.
METHODS
A meta-analysis was performed of nine eligible studies regarding the effect of moxifloxacin plus the recommended regimen compared to the recommended regimen alone for the treatment of TB.
RESULTS
In the efficacy analysis, the overall odds ratio (OR) for sputum culture conversion was 1.895 (95% confidence interval (CI) 1.355-2.651, p=0.000), indicating that when moxifloxacin is combined with the recommended regimen, the rate of sputum culture conversion is elevated compared to the recommended regimen alone. The overall OR for recurrence was 0.516 (95% CI 0.342-0.920, p=0.022), suggesting that the introduction of moxifloxacin into the recommended regimen reduces TB relapse after treatment. In the safety analysis, the overall OR was estimated to be 1.001 (95% CI 0.855-1.172, p=0.989), demonstrating that adding moxifloxacin to the recommended regimen does not cause more adverse events during TB treatment.
CONCLUSIONS
This meta-analysis suggests that the introduction of moxifloxacin into the recommended regimen for the treatment of non-drug resistant TB improves the clinical outcome by elevating the culture conversion rate and reducing the recurrence rate.
Topics: Antitubercular Agents; Drug Therapy, Combination; Fluoroquinolones; Humans; Moxifloxacin; Recurrence; Sputum; Treatment Outcome; Tuberculosis, Pulmonary
PubMed: 28495364
DOI: 10.1016/j.ijid.2017.05.003 -
PloS One 2023Tuberculosis stands as a prominent cause of mortality in developing countries. The treatment of tuberculosis involves a complex procedure requiring the administration of...
Tuberculosis stands as a prominent cause of mortality in developing countries. The treatment of tuberculosis involves a complex procedure requiring the administration of a panel of at least four antimicrobial drugs for the duration of six months. The occurrence of treatment failure after the completion of a standard treatment course presents a serious medical problem. The purpose of this study was to evaluate antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure. Additionally, it aimed to evaluate the effectiveness of second line drugs such as amikacin, linezolid, moxifloxacin, and the efflux pump inhibitor verapamil against M. tuberculosis isolates associated with treatment failure. We monitored 1200 tuberculosis patients who visited TB centres in Lahore and found that 64 of them were not cured after six months of treatment. Among the M. tuberculosis isolates recovered from the sputum of these 64 patients, 46 (71.9%) isolates were simultaneously resistant to rifampicin and isoniazid (MDR), and 30 (46.9%) isolates were resistant to pyrazinamide, Resistance to amikacin was detected in 17 (26,5%) isolates whereas resistance to moxifloxacin and linezolid was detected in 1 (1.5%) and 2 (3.1%) isolates respectively. Among MDR isolates, the additional resistance to pyrazinamide, amikacin, and linezolid was detected in 15(23.4%), 4(2.6%) and 1(1.56%) isolates respectively. One isolate simultaneously resistant to rifampicin, isoniazid, amikacin, pyrazinamide, and linezolid was also identified. In our investigations, the most frequently mutated amino acid in the treatment failure group was Serine 315 in katG. Three novel mutations were detected at codons 99, 149 and 154 in pncA which were associated with pyrazinamide resistance. The effect of verapamil on the minimum inhibitory concentration of isoniazid and rifampicin was observed in drug susceptible isolates but not in drug resistant isolates. Rifampicin and isoniazid enhanced the transcription of the efflux pump gene rv1258 in drug susceptible isolates collected from the treatment failure patients. Our findings emphasize a high prevalence of MDR isolates linked primarily to drug exposure. Moreover, the use of amikacin as a second line drug may not be the most suitable choice in such cases.
Topics: Humans; Mycobacterium tuberculosis; Antitubercular Agents; Isoniazid; Pyrazinamide; Rifampin; Linezolid; Amikacin; Moxifloxacin; Tuberculosis, Multidrug-Resistant; Microbial Sensitivity Tests; Verapamil; Mutation
PubMed: 37883448
DOI: 10.1371/journal.pone.0293194 -
Arquivos Brasileiros de OftalmologiaTo determine the release profile of moxifloxacin encapsulated in liposomes in the aqueous humor as a controlled release system for intracameral application.
PURPOSE
To determine the release profile of moxifloxacin encapsulated in liposomes in the aqueous humor as a controlled release system for intracameral application.
METHODS
Liposomes containing moxifloxacin were obtained using the lipid film hydration method and were characterized by particle size and encapsulation efficiency. Female rabbits were used for the in vivo profile release study. Liposomes containing moxifloxacin was injected into the anterior chamber of the right eye of each animal. The rabbits were divided into five groups, and a sample of aqueous humor was collected 2, 4, 8, 24, and 48 h after administration of liposomes containing moxifloxacin administration. Moxifloxacin concentrations in the aqueous humor were analyzed using high-performance liquid chromatography.
RESULTS
The average size of the liposomes containing moxifloxacin was 60.5 ± 0.72 nm with a particle size distribution of 0.307. The encapsulation efficiency of moxifloxacin in liposomes was 92.24 ± 0.24%. The results of an in vivo release study of liposomes containing moxifloxacin, showed that the maximum moxifloxacin concentration was achieved within the first 2 h after administration (5.27 ± 1.09 mg/mL) and was followed by a decrease in intracameral concentration (0.35 ± 0.05 mg/mL) until the 24 h mark.
CONCLUSIONS
The in vivo experiments resulted in liposomes containing moxifloxacin that were homogenous in size and exhibited high drug encapsulation efficiency. The results indicate that liposomes containing moxifloxacin offers a satisfactory aqueous humor release profile after intracameral application.
Topics: Animals; Anti-Bacterial Agents; Aqueous Humor; Biological Availability; Chromatography, High Pressure Liquid; Drug Delivery Systems; Female; Injections, Intraocular; Liposomes; Models, Animal; Moxifloxacin; Rabbits
PubMed: 30231158
DOI: 10.5935/0004-2749.20180090 -
American Journal of Ophthalmology Jul 2021To estimate the association of cefuroxime and moxifloxacin in relation to the occurrence of endophthalmitis following phacoemulsification cataract surgery.
PURPOSE
To estimate the association of cefuroxime and moxifloxacin in relation to the occurrence of endophthalmitis following phacoemulsification cataract surgery.
DESIGN
Retrospective clinical cohort study.
METHODS
We studied patients with noncomplex phacoemulsification cataract surgery in Kaiser Permanente Northern California during 2014-2019. Data were obtained for acute, postoperative endophthalmitis within 90 days of phacoemulsification, including culture and antibiogram results, intracameral and topical antibiotic agent, and dose. In a post hoc analysis, we also examined preoperative anterior chamber depth (ACD) and postoperative anterior chamber volume (ACV).
RESULTS
Of 216,141 surgeries, endophthalmitis occurred in 0.020% of moxifloxacin-injected eyes and 0.013% of cefuroxime eyes (relative risk 1.62 with 95% CI 0.82-3.20, P = .16). Of the 34 (0.016%) cases of endophthalmitis, cefuroxime 1 mg was injected into 13 eyes and moxifloxacin 0.1% into 21 eyes. Organisms with antibiograms were identified in 12 (35%) cases. Of these, bacteria recovered from cefuroxime-injected eyes were resistant to cefuroxime in all cases (4/4), with Enterococcus comprising half of these. In eyes injected with moxifloxacin 0.1%, 6 out of 7 organisms were sensitive to moxifloxacin injected with 0.1 mL and in 1 eye injected with 1 mL. Streptococcus was the most common organism recovered (6/9) in moxifloxacin-injected eyes. Preoperative ACD and postoperative calculated ACV were higher in eyes injected with moxifloxacin.
CONCLUSIONS
Endophthalmitis cases with positive cultures were generally related to organism resistance in cefuroxime eyes but to sensitive organisms in moxifloxacin eyes. Moxifloxacin doses may have been insufficient in eyes with larger ACV.
Topics: Anterior Chamber; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Cefuroxime; Endophthalmitis; Eye Infections, Bacterial; Female; Humans; Injections, Intraocular; Lens Implantation, Intraocular; Male; Middle Aged; Moxifloxacin; Phacoemulsification; Retrospective Studies; Treatment Failure
PubMed: 33571472
DOI: 10.1016/j.ajo.2021.02.007 -
Eye & Contact Lens Nov 2018To investigate the diffusion of moxifloxacin through bandage contact lenses (BCLs) versus corneal collagen shields (CSs), the relative ability of BCLs and CSs to release...
OBJECTIVES
To investigate the diffusion of moxifloxacin through bandage contact lenses (BCLs) versus corneal collagen shields (CSs), the relative ability of BCLs and CSs to release moxifloxacin, and the potential of release of moxifloxacin from CSs in the clinical setting.
METHODS
Using an in vitro model, the diffusion of 5% moxifloxacin across BCLs and CSs was compared. Next, the amount of drug release from BCLs and CSs soaked in 0.5% moxifloxacin was measured. Finally, based on a clinical model, CSs were soaked in Vigamox (commercial moxifloxacin) and the total concentration released was detected. Collagen shields remained intact after 24 hr; therefore, enzymatic digestion and mechanical grinding of the CS were performed to determine whether further drug could be released. The concentration of moxifloxacin was measured using a spectrophotometer at set time points up to 24 hr.
RESULTS
In the diffusion assay, 35.7±10.5% diffused through the BCLs and 36.2±11.8% diffused through the CSs (P=0.77). The absorption assay demonstrated at 120 min, a total of 33.3±6.77 μg/mL was released from BCLs compared with 45.8±5.2 μg/mL from the CSs (P=0.0008). In vitro experiments to simulate clinical application of Vigamox-soaked CS found the concentration of moxifloxacin released of 127.7±7.25 μg/mL in 2 mL of phosphate-buffered saline over 24 hr.
CONCLUSIONS
Moxifloxacin diffuses through BCLs and CSs at similar rates; however, CSs have greater capacity to absorb and release moxifloxacin compared with BCLs. Vigamox-soaked CSs released 250 μg of moxifloxacin and may be a useful method to prevent endophthalmitis.
Topics: Anti-Bacterial Agents; Bandages; Collagen; Contact Lenses, Hydrophilic; Drug Delivery Systems; Endophthalmitis; Humans; Moxifloxacin; Ophthalmic Solutions
PubMed: 28945653
DOI: 10.1097/ICL.0000000000000421 -
Medicine Jun 2020Moxifloxacin, a fourth generation fluoroquinolone, which has good antibacterial activity against both Gram-positive cocci and Gram-negative bacteria. To date, there are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Moxifloxacin, a fourth generation fluoroquinolone, which has good antibacterial activity against both Gram-positive cocci and Gram-negative bacteria. To date, there are no meta-analysis to evaluate the efficacy and safety of moxifloxacin for multi-drug resistant tuberculosis (MDR-TB) treatment. This meta-analysis to explore the efficacy and safety of the moxifloxacin in treatment of MDR-TB in adults.
METHODS
Databases of PubMed, Embase, Embase, Ovid, and Google Scholar databases were investigated for eligible literatures from their establishments to August, 2019. Included studies were selected according to precise eligibility criteria: MDR-TB confirmed by the clinical diagnostic criteria (at least 2 or more first-line drugs resistant to isoniazid and rifampicin). Study design was limited to retrospective studies, randomized controlled trials, or prospective cohort studies; the control group was treated with other drugs or no moxifloxacin. Statistical analysis was performed by RevMan 5.3 software.
RESULTS
Eight studies with a total of 1447 patients were finally eligible for the final systematic review and meta-analysis. Moxifloxacin regimen was related to a significantly elevated treatment success rate compared with levofloxacin or conventional therapy regimen (OR = 1.94; 95% CI = 1.16-3.25, P = .01). No significant difference of sputum culture conversion rate (OR = 1.15; 95% CI = 0.82-1.60; P = 0.43) was found between 2 groups. In addition, there was no significant difference in the increased risks of gastrointestinal trouble (OR = 1.28; 95% CI = 0.98-1.68; P = .05), hepatotoxicity (OR = 0.91; 95% CI = 0.64-1.30; P = .6), dermatologic abnormalities (OR = 1.11; 95% CI = 0.74-1.67; P = .62), and vision change (OR = 1.47; 95% CI = 0.74-2.89; P = .27) between the moxifloxacin-containing regimens and control group.
CONCLUSIONS
This meta-analysis revealed that the addition of moxifloxacin to the recommended regimen significantly improved the rate of treatment success in the treatment of MDR-TB, with no additional adverse moxifloxacin events.
Topics: Adult; Antitubercular Agents; Drug Therapy, Combination; Humans; Moxifloxacin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 32569195
DOI: 10.1097/MD.0000000000020648 -
Journal of Infection in Developing... Oct 2018Moxifloxacin is a fourth generation widely used fluoroquinolone antibiotic. There are three cases of moxifloxacin-induced neutropenia reported in the literature and we...
Moxifloxacin is a fourth generation widely used fluoroquinolone antibiotic. There are three cases of moxifloxacin-induced neutropenia reported in the literature and we report the fourth case. A 26-year-old man with pneumonia was treated with moxifloxacin because of penicillin allergy. On the second day of therapy, leukopenia [White blood cell (WBC) count 2.7×10³/μL] and neutropenia (neutrophils 1.21×10³/μL) occurred. Rothia mucilaginosa was isolated in sputum culture. On the fourth day of hospitalization moxifloxacin treatment was stopped and clarithromycin 500 mg PO twice daily was started. Leukopenia and neutropenia resolved one day after discontinuation of moxifloxacin that WBC and neutrophil count rose 4.5×10³/μL and 1.97×10³/μL, respectively. On the sixth day of hospitalization, WBC and neutrophil count was 4.3×10³/μL and 2.29×10³/μL, respectively. The immunomodulatory effects of moxifloxacin may result in the changes of WBC count like leukopenia with neutropenia. Moxifloxacin induced neutropenia may be more common and is an important adverse effect. More observational studies about safety profiles of moxifloxacin are needed.
Topics: Adult; Anti-Bacterial Agents; Humans; Male; Moxifloxacin; Neutropenia
PubMed: 32004163
DOI: 10.3855/jidc.10212