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The New England Journal of Medicine May 2021Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis.
METHODS
In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months.
RESULTS
Among 2516 participants who had undergone randomization, 2343 had a culture positive for that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group.
CONCLUSIONS
The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).
Topics: Adolescent; Adult; Antibiotics, Antitubercular; Antitubercular Agents; Child; Confidence Intervals; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Moxifloxacin; Mycobacterium tuberculosis; Rifampin; Tuberculosis, Pulmonary; Young Adult
PubMed: 33951360
DOI: 10.1056/NEJMoa2033400 -
Current Pharmaceutical Design 2021Pulmonary infections are an increasing problem in individuals and current therapies are lacking. Liposomes are spherical lipidic vesicles composed of phospholipid and...
BACKGROUND
Pulmonary infections are an increasing problem in individuals and current therapies are lacking. Liposomes are spherical lipidic vesicles composed of phospholipid and cholesterol. Liposomes have numerous advantages, such as biodegradability, biocompatibility, non-immunogenicity, lack of toxicity, controlled release properties and high stability.
OBJECTIVE
This work was carried out to construct a novel liposomal moxifloxacin formulation and examine its antimicrobial effects against Pseudomonas aeruginosa and Staphylococcus aureus.
METHODS
The liposomal moxifloxacin formulation was prepared by the thin-film hydration method. The bilayer was composed of cholesterol and phospholipid at 30:70 molar ratio. To prepare cationic liposomes, 5% cationic agent (CTAB) was added. The liposomes were reduced in size with the bath sonication technique. The liposomal characterizations were tested regarding vesicle size, surface charge and drug encapsulation efficacy. Microdilution method was used to determine the Minimum Inhibitory Concentration (MIC) against Pseudomonas aeruginosa and Staphylococcus aureus of the free drug, neutral and cationic moxifloxacin liposomes.
RESULTS
The size of the liposomes was 50-70 nm. The zeta potential of neutral and cationic vesicles was ∼0 and +22 mV. The MIC values against Pseudomonas aeruginosa of the free drug, neutral and cationic moxifloxacin liposomes were 10, 5 and 2.5, respectively. The MICs against Staphylococcus aureus of the free drug, neutral and cationic moxifloxacin liposomes were 1, 1 and 0.5, respectively.
CONCLUSION
This study demonstrates that the encapsulation of moxifloxacin into liposomes (especially cationic vesicles) could enhance antimicrobial properties.
Topics: Anti-Bacterial Agents; Humans; Liposomes; Microbial Sensitivity Tests; Moxifloxacin; Nanoparticles; Pseudomonas aeruginosa
PubMed: 32611289
DOI: 10.2174/1381612826666200701152618 -
Paediatric Drugs Mar 2022Moxifloxacin is a fluoroquinolone that is commonly used in adults, but not children. Certain clinical situations compel pediatric clinicians to use moxifloxacin, despite...
BACKGROUND/OBJECTIVE
Moxifloxacin is a fluoroquinolone that is commonly used in adults, but not children. Certain clinical situations compel pediatric clinicians to use moxifloxacin, despite its potential for toxicity and limited pharmacokinetics (PK) data. Our objective was to further characterize the pharmacokinetics of moxifloxacin in children.
METHODS
We performed an opportunistic, open-label population PK study of moxifloxacin in children < 18 years of age who received moxifloxacin as part of standard care. A set of structural PK models and residual error models were explored using nonlinear mixed-effects modeling. Covariates with known biological relationships were investigated for their influence on PK parameters.
RESULTS
We obtained 43 moxifloxacin concentrations from 14 participants who received moxifloxacin intravenously (n = 8) or orally (n = 6). The dose of moxifloxacin was 10 mg/kg daily in participants ≤ 40 kg and 400 mg daily in participants > 40 kg. The population mean clearance and mean volume of distribution were 18.2 L/h and 167 L, respectively. The oral absorption was described by a first-order process. The estimated extent of oral bioavailability was highly variable (range 20-91%). Total body weight was identified as a covariate on clearance and volume of distribution, and substantially reduced the random unexplained inter-individual variability for both parameters. No participants experienced suspected serious adverse reactions related to moxifloxacin.
CONCLUSION
These data add to the existing literature to support use of moxifloxacin in children in certain situations; however, further prospective studies on the safety and efficacy of moxifloxacin are needed.
Topics: Adult; Child; Humans; Moxifloxacin; Prospective Studies
PubMed: 35284983
DOI: 10.1007/s40272-022-00493-3 -
Journal of Chemotherapy (Florence,... Jul 2023Large data on moxifloxacin activity on anaerobes are old. Moxifloxacin is often used for empiric therapy therefore the knowledge of current epidemiologic data is...
Large data on moxifloxacin activity on anaerobes are old. Moxifloxacin is often used for empiric therapy therefore the knowledge of current epidemiologic data is fundamental. We analyzed 69 anaerobic strains, from a recent multicenter Italian study, for moxifloxacin susceptibility. Using EUCAST criteria 81% of Bacteroides spp. and 48% of anaerobes other than Bacteroides were resistant to moxifloxacin. Using CLSI criteria moxifloxacin resistance rates decrease to 35% for all anaerobes, and to 41% for Bacteroides spp. We reported an alarming increase in moxifloxacin resistance among anaerobes in Italy.
Topics: Humans; Moxifloxacin; Anti-Bacterial Agents; Microbial Sensitivity Tests; Bacteria, Anaerobic; Italy; Drug Resistance, Bacterial
PubMed: 35947127
DOI: 10.1080/1120009X.2022.2106637 -
Pediatric Pulmonology Jul 2023With the increase in macrolide-resistant M. pneumoniae infections, off-label use is difficult to avoid. This study assessed the safety of moxifloxacin in pediatric...
BACKGROUND
With the increase in macrolide-resistant M. pneumoniae infections, off-label use is difficult to avoid. This study assessed the safety of moxifloxacin in pediatric patients with severe refractory M. pneumoniae pneumonia (SRMPP).
METHODS
We retrospectively reviewed the medical records of children with SRMPP between January 2017 and November 2020 at Beijing Children's Hospital. They were divided into the moxifloxacin group and azithromycin group according to whether or not moxifloxacin was used. The clinical symptoms, radiographs of both knees, and cardiac ultrasounds of the children were collected after drug withdrawal for at least 1 year. A multidisciplinary team reviewed all adverse events and determined their relationship with moxifloxacin.
RESULTS
A total of 52 children with SRMPP were included in this study (31 in the moxifloxacin group and 21 in the azithromycin group). In the moxifloxacin group, four patients had arthralgia, one had joint effusion, and seven had heart valve regurgitation. In the azithromycin group, three patients had arthralgia, one had claudication, and one had heart valve regurgitation; no obvious knee abnormalities were observed in the radiographs. No statistically significant differences in clinical symptoms or imaging findings were found between the groups. As for the adverse events, 11 patients in moxifloxacin group were deemed to be doubtfully related and one possibly related to moxifloxacin; in the azithromycin group, four patients were regarded to be doubtfully related to azithromycin and one not related.
CONCLUSION
Moxifloxacin was well tolerated and safe for treating SRMPP in children.
Topics: Child; Humans; Azithromycin; Moxifloxacin; Mycoplasma pneumoniae; Retrospective Studies; Pneumonia, Mycoplasma; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 37098833
DOI: 10.1002/ppul.26426 -
BMC Pulmonary Medicine Jul 2022Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a kind of hypersensitivity drug reaction involving the skin and multiple internal organ... (Review)
Review
BACKGROUND
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a kind of hypersensitivity drug reaction involving the skin and multiple internal organ systems. Moxifloxacin has rarely been reported to be a drug that is associated with DRESS syndrome. Lungs are less frequently involved in DRESS syndrome, but their involvements may herald more serious clinical processes. We present a rare typical case of moxifloxacin-induced DRESS syndrome with lungs involved. Valuable clinical data such as changes in the pulmonary imaging and pulmonary function tests was recorded. This case is important for the differential diagnosis of DRESS syndrome with lungs involved by providing clinical manifestations, CT imaging, pulmonary function tests, and biopsy pathological characteristics. The changes in pulmonary imaging and pulmonary function tests may help us understand the mechanism of DRESS syndrome further.
CASE PRESENTATION
We report a case of a 47-year-old woman who was treated with oral moxifloxacin for community-acquired pneumonia. The patient subsequently developed a cough, fever, liver injury, skin rash, hematologic abnormalities, and shortness of breath (SOB) followed by pharyngeal herpes and peripheral neuritis. These symptoms, clinical lab index, and CT scan of the lungs improved after the withdrawal of moxifloxacin. The probability of moxifloxacin-induced DRESS syndrome was rated as "Definite", with 7 scores graded by RegiSCAR. A literature search was also performed with "fluoroquinolones," "moxifloxacin," "ciprofloxacin," "levofloxacin," "delafloxacin," and "DRESS" or "drug-induced hypersensitivity syndrome (DIHS)" as the keywords that were put into PubMed. The overall pulmonary involvement was approximately 9.1% (1/11). It is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. We summarized detailed clinical data, including pulmonary imaging and pulmonary function changes.
CONCLUSION
This is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. Prompt recognition and correct diagnosis can promote appropriate treatment and accelerate recovery. This case is important for us as a reference in the differential diagnosis of DRESS syndrome and helps us further understand the mechanism of DRESS syndrome.
Topics: Drug Hypersensitivity Syndrome; Eosinophilia; Female; Fluoroquinolones; Humans; Middle Aged; Moxifloxacin; Pneumonia
PubMed: 35854287
DOI: 10.1186/s12890-022-02064-1 -
Journal of Pharmaceutical Sciences Sep 2020In this monograph, literature data is reviewed to evaluate the feasibility of waiving in vivo bioequivalence testing and instead applying the Biopharmaceutics... (Review)
Review
In this monograph, literature data is reviewed to evaluate the feasibility of waiving in vivo bioequivalence testing and instead applying the Biopharmaceutics Classification System (BCS) based methods to the approval of immediate-release solid oral dosage forms containing moxifloxacin hydrochloride as the sole active pharmaceutical ingredient. To facilitate the feasibility decision, solubility and permeability and dissolution characteristics in the context of the BCS, therapeutic index, therapeutic use, pharmacokinetic parameters, bioequivalence/bioavailability issues, drug-excipient interactions and other relevant data were taken into consideration. Moxifloxacin is a BCS class I drug with a wide therapeutic index. Bioequivalence risks arising from the presence of different excipients in the formulation and due to manufacturing variables were deemed to be low. The risks can be further reduced if the choice of excipients is limited to those present in products already approved in International Conference on Harmonisation or associated countries and if the results of in vitro dissolution studies comply with the specifications stipulated in the appropriate biowaiver guidelines. Under these conditions, we conclude that a BCS-based biowaiver can be recommended for moxifloxacin immediate-release solid oral dosage forms.
Topics: Administration, Oral; Biological Availability; Biopharmaceutics; Dosage Forms; Moxifloxacin; Permeability; Solubility; Therapeutic Equivalency
PubMed: 32534881
DOI: 10.1016/j.xphs.2020.06.007 -
Journal of Cataract and Refractive... May 2019
Topics: Cataract; Endophthalmitis; Humans; Moxifloxacin; Triamcinolone Acetonide
PubMed: 31030793
DOI: 10.1016/j.jcrs.2019.01.037 -
The American Journal of Case Reports Apr 2022BACKGROUND Black hairy tongue (BHT) is a relatively uncommon acquired benign condition, with a prevalence ranging from 0.6% to 11.3%. It presents as a superficial black...
BACKGROUND Black hairy tongue (BHT) is a relatively uncommon acquired benign condition, with a prevalence ranging from 0.6% to 11.3%. It presents as a superficial black hairy carpet-like lingual growth. The exact etiology of BHT remains unclear, and both extrinsic and intrinsic factors are potentially contributive. Several types of antibiotics are also associated with BHT, but no English reports of moxifloxacin-induced BHT exist. Here, we report the first case of moxifloxacin-induced BHT. CASE REPORT A 69-year-old woman presented with a brown and hairy tongue. She was taking prednisolone for mixed connective tissue disease and developed right finger flexor tenosynovitis, which was complicated by osteomyelitis due to Mycobacterium chelonae. Based on the susceptibility results, she was treated with tobramycin, imipenem, and clarithromycin for 6 weeks, and then switched to moxifloxacin and clarithromycin. Within 10 days, she developed brown discoloration on the dorsum of the tongue, with carpet-like elongated filiform lingual papillae. The diagnosis of BHT was made. After stopping moxifloxacin, improvement was seen within 2 days, and her right finger has shown no signs of recurrence for 12 months. CONCLUSIONS Clinicians should be vigilant against agents and lifestyles that can precipitate BHT, especially moxifloxacin. It is essential to counsel patients before such treatments to avoid patient anxiety or treatment changes.
Topics: Aged; Female; Humans; Clarithromycin; Moxifloxacin; Tongue; Tongue, Hairy
PubMed: 35466283
DOI: 10.12659/AJCR.936235 -
Biochemical and Biophysical Research... Nov 2022Fluoroquinolones are one of the most frequently prescribed antibiotics. However, their use increases the risk of Aortic aneurysm and dissection (AAD). The mechanism...
Fluoroquinolones are one of the most frequently prescribed antibiotics. However, their use increases the risk of Aortic aneurysm and dissection (AAD). The mechanism underlying this effect remains unclear. AAD are caused by weakening of the aortic wall and loss of vascular smooth muscle cells. Osteopontin is involved in the occurrence and development of AAD. The aim of the present study was to examine the role of moxifloxacin, a fluoroquinolone, in the occurrence of AAD using a moderate-severity AAD mouse model. Four-week-old male C57BL/6J mice were fed a high-fat diet. At 8 weeks of age, the mice were infused with saline or angiotensin II (1000 ng kg min) via osmotic minipumps for 4 weeks, and then orally administered water (vehicle) or moxifloxacin (30 and 100 mg kg day) for another 3 weeks. Moxifloxacin (30 and 100 mg kg day) induced AAD and elastin degradation in aortic tissues, as revealed by hematoxylin and eosin staining and elastica-van Gieson staining. Additionally, immunohistochemical staining and Western blot analyses showed that moxifloxacin 100 mg kg day decreased the protein expression of smooth muscle protein 22α, one of the markers of the contractile phenotype of vascular smooth muscle cells, in aortic tissues compared to vehicle and moxifloxacin 30 mg kg day. Furthermore, moxifloxacin (100 mg kg day) increased the protein expression of osteopontin and matrix metalloproteinases-2 in the aortic tissues when compared to control. Moxifloxacin may induce the onset of AAD and weakening of the aortic media by increasing the expression of osteopontin and matrix metalloproteinase-2 and decreasing that of smooth muscle protein 22α in aortic tissue.
Topics: Aortic Dissection; Angiotensin II; Animals; Anti-Bacterial Agents; Aortic Aneurysm; Disease Models, Animal; Elastin; Eosine Yellowish-(YS); Hematoxylin; Male; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Moxifloxacin; Muscle Proteins; Myocytes, Smooth Muscle; Osteopontin; Rubber; Water
PubMed: 36087537
DOI: 10.1016/j.bbrc.2022.08.080