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International Journal of Pharmaceutical... 2021Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be... (Review)
Review
Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5ÆC and 25ÆC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.
Topics: Administration, Oral; Aged; Child; Chromatography, High Pressure Liquid; Chromones; Drug Compounding; Drug Stability; Drug Storage; Humans; Metronidazole; Suspensions
PubMed: 33798117
DOI: No ID Found -
The Korean Journal of Internal Medicine Jul 2023Tegoprazan, a novel potassium-competitive acid blocker, has shown rapid action and gastric acid inhibition. In this study, we evaluated the efficacy of a...
BACKGROUND/AIMS
Tegoprazan, a novel potassium-competitive acid blocker, has shown rapid action and gastric acid inhibition. In this study, we evaluated the efficacy of a tegoprazan-based, nonbismuth-containing quadruple (concomitant) therapy for the primary eradication of Helicobacter pylori.
METHODS
We conducted a prospective, single-arm, single-center, primitive study to verify the efficacy of a 10-day tegoprazan- based (50-mg dose) concomitant therapy, including amoxicillin (1,000-mg dose), clarithromycin (CLA; 500-mg dose), and metronidazole (MET; 500-mg dose) twice daily as a first-line treatment for H. pylori eradication.
RESULTS
We tested consecutive cultures for antibiotic susceptibility and minimum inhibitory concentrations. We enrolled 84 participants; 79 (94.0%) completed first-line therapy. The overall intention-to-treat and per-protocol eradication rates were 90.5% (95% confidence interval [CI], 82.1-95.8) and 96.2% (95% CI, 83.4-97.6), respectively. Of the 73 participants evaluated for antibiotic resistance, 19 (26.0%), 32 (42.5%), and 8 (11.0%) exhibited CLA, MET, and CLA and MET dual resistance, respectively. Of these, 39 participants (66.1%) exhibited successful eradication after the therapeutic regimen despite antibiotic resistance.
CONCLUSION
The 10-day tegoprazan-based concomitant therapy may be an effective first-line treatment for eradicating H. pylori.
Topics: Humans; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Prospective Studies; Drug Therapy, Combination; Drug Resistance, Bacterial; Amoxicillin; Metronidazole; Clarithromycin; Treatment Outcome
PubMed: 37369525
DOI: 10.3904/kjim.2022.345 -
PloS One 2020Antibiotic administration can be a cause of gastrointestinal disease in horses, creating a disruption in the normal population and function of bacteria found in the...
Antibiotic administration can be a cause of gastrointestinal disease in horses, creating a disruption in the normal population and function of bacteria found in the hindgut. The objective of this study was to describe the changes in the cecal and fecal microbiomes and metabolomes of clinically healthy horses before and after metronidazole administration. Metronidazole (15 mg/kg BID PO) was given to five horses with cecal cannulas. The study was suspended on Day 3 due to adverse gastrointestinal effects. Cecal and fecal samples were obtained before (Days minus52, m28, m14, and 0) and after (Days 7, 14, 28, and 52) metronidazole administration. DNA was extracted from the cecal and fecal samples, and 16S rRNA genes were sequenced. Richness and evenness indices were significantly decreased by metronidazole administration in both cecal and fecal samples, but the overall composition was only significantly changed in fecal samples on Day 3 (ANOSIM, p = 0.008). The most dominant phyla were Bacteroidetes and Firmicutes in all groups examined. In fecal samples, significant changes of the phyla Actinobacteria, Spirochaetes, Lentisphaerae, and Verrucomicrobia occurred on Day 3, which correlated with clinical signs of gastrointestinal disease. The metabolome was characterized by mass spectrometry-based methods and only named metabolites were included in the analysis. Fecal, but not cecal, metabolites were significantly affected by metronidazole. The fecal metabolites affected represent diverse metabolic pathways, such as the metabolism of amino acids, carbohydrates, lipids, nucleic acids and cofactors and vitamins. Metronidazole administration has potential to cause adverse effects in horses, alters the bacterial composition of the horse's cecal and fecal content, and the metabolome of fecal samples.
Topics: Animals; Anti-Bacterial Agents; Biodiversity; Cecum; Feces; Gastrointestinal Microbiome; Horses; Male; Metabolome; Metronidazole; RNA, Ribosomal, 16S
PubMed: 32442163
DOI: 10.1371/journal.pone.0232905 -
Emerging Infectious Diseases Nov 2022The plasmid pCD-METRO confers metronidazole resistance in Clostridioides difficile. We showed high sequence similarity among pCD-METRO plasmids from different isolates...
The plasmid pCD-METRO confers metronidazole resistance in Clostridioides difficile. We showed high sequence similarity among pCD-METRO plasmids from different isolates and identified pCD-METRO and associated metronidazole-resistant isolates in clinical and veterinary reservoirs in the Americas. We recommend using PCR or genomic assays to detect pCD-METRO in metronidazole-resistant C. difficile.
Topics: Humans; Metronidazole; Clostridioides difficile; Ribotyping; Clostridium Infections; Clostridioides; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 36286226
DOI: 10.3201/eid2811.220615 -
Frontiers in Cellular and Infection... 2023The increasing prevalence of antibiotic resistance in cases of () infection has emerged as a significant global issue. This study offers a comprehensive examination of...
BACKGROUND
The increasing prevalence of antibiotic resistance in cases of () infection has emerged as a significant global issue. This study offers a comprehensive examination of the alterations in drug resistance exhibited by in the Nanjing region of China during the preceding five years. Another important objective is to investigate the influence of levofloxacin medication history on genotypic and phenotypic resistance.
METHODS
This research screened 4277 individuals diagnosed with infection between April 2018 and May 2023. The phenotype and genotypic resistance were evaluated using the Kirby-Bauer disk diffusion and PCR method.
RESULTS
The most recent primary resistance rates for metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone, and tetracycline were recorded at 77.23% (2385/3088), 37.24% (1150/3088), 27.72% (856/3088), 0.52% (16/3088), 0.19% (6/3088), and 0.06% (2/3088), respectively. For the recent five years, we observed a notable upsurge in the rate of metronidazole resistance and a slight elevation of clarithromycin and levofloxacin resistance. The documented resistance rates to single-drug, dual-drug, triple-drug, and quadruple-drug regimens were 35.39%, 28.32%, 25.72%, and 0.21%, respectively. The prevalence of multidrug-resistant strains escalated, rising from 37.96% in 2018 to 66.22% in 2023. The rate of phenotypic and genotypic resistance rate (57.10% and 65.57%) observed in strains obtained from patients without a levofloxacin treatment history was significantly lower than the rate in strains obtained from those with a history of levofloxacin treatment (88.73% and 94.74%). The prevailing mutations were primarily N87K (52.35%, 345/659), accompanied by D91N (13.96%, 92/659), and closely followed by D87G (10.77%, 71/659). For mutations, the 91-amino acid mutants exhibit a higher likelihood of discrepancies between phenotypic and genotypic resistance than the 87-amino acid mutants.
CONCLUSION
The extent of antibiotic resistance within remains substantial within the Nanjing region. If levofloxacin proves ineffective in eradicating during the initial treatment, its use in subsequent treatments is discouraged. The employment of levofloxacin resistance genotype testing can partially substitute conventional antibiotic sensitivity testing. Notably, predicting phenotypic resistance of levofloxacin through PCR requires more attention to the mutation type of to improve prediction accuracy.
Topics: Humans; Clarithromycin; Metronidazole; Helicobacter pylori; Levofloxacin; Anti-Bacterial Agents; Helicobacter Infections; Drug Resistance, Microbial; China; Amino Acids; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 38089809
DOI: 10.3389/fcimb.2023.1294379 -
Clinical Therapeutics Apr 2021Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this...
PURPOSE
Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth.
METHODS
An open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100 mg/d) was administered orally with or without triple-antibiotic therapy (1500 mg/d metronidazole, 2000 mg/d tetracycline, and 1200 mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24 h after the last dose. Safety assessments were performed.
FINDINGS
Eleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUC and C at steady state geometric mean ratios (90% CIs) were 0.78 (0.73-0.83) and 0.75 (0.68-0.82) for tegoprazan; 0.77 (0.68-0.88) and 0.84 (0.72-0.98) for tegoprazan metabolite M1; 1.03 (0.98-1.08) and 1.08 (0.99-1.18) for metronidazole; 0.63 (0.56-0.70) and 0.64 (0.56-0.74) for tetracycline; and 1.55 (0.99-2.44) and 1.38 (0.72-2.66) for bismuth, respectively. All reported adverse events were mild.
IMPLICATIONS
Changes in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257.
Topics: Anti-Bacterial Agents; Benzene Derivatives; Bismuth; Cross-Over Studies; Drug Therapy, Combination; Healthy Volunteers; Helicobacter Infections; Helicobacter pylori; Humans; Imidazoles; Male; Metronidazole; Republic of Korea; Tetracycline
PubMed: 33637332
DOI: 10.1016/j.clinthera.2021.01.026 -
Journal of Clinical Laboratory Analysis Apr 2023Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations,... (Review)
Review
Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations, efflux pumps, and biofilms. Gene mutations such as nucleic acid synthesis-related gene mutations, rRNA coding gene mutations, and cell wall synthesis-related gene mutations are the most important mechanisms by which H. pylori evades bactericidal effects. These mechanisms are also closely related to the biological activity of the efflux pump systems and biofilms. Activation of the efflux pump system and biofilm formation both lead to the emergence of MDR strains, further increasing the difficulty of eradication therapy. In this review, the status of antibiotic resistance in H. pylori from different regions and countries is summarized and compared, and H. pylori resistance profiles and their changing trends in the clinic are described. Then, research progress on biomolecular mechanisms underlying antibiotic resistance, diagnostic methods, and treatment strategies are introduced and discussed. Challenges resulting from increasing resistance, potential solutions to combat increasing resistance, and future directions are discussed to help clinicians and researchers better address the emergence and spread of resistant H. pylori strains and optimize drug regimens. With the rate of H. pylori resistance to commonly used antibiotics increasing, more attention should be given to the selection of antibiotics and to monitoring resistance when antibiotics are used for clinical eradication treatment. Individualized precise eradication treatment under the guidance of drug susceptibility testing will become the mainstream method of treatment in the future.
Topics: Humans; Helicobacter pylori; Helicobacter Infections; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Anti-Bacterial Agents; Drug Resistance, Bacterial; Clarithromycin; Metronidazole
PubMed: 37088871
DOI: 10.1002/jcla.24885 -
International Journal of Molecular... May 2024Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new...
Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)AgNO], [(MTZ)Ag]SO, [Ag(MCZ)NO], [Ag(MCZ)BF], [Ag(MCZ)SbF] and [Ag(MCZ)ClO] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC values against the A375 line were demonstrated by [Ag(MCZ)NO] and [(MTZ)AgNO]. The compound [(MTZ)AgNO] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.
Topics: Humans; Melanoma; Miconazole; Silver; Antineoplastic Agents; Metronidazole; Cell Line, Tumor; Coordination Complexes; Cell Survival; Skin Neoplasms
PubMed: 38791121
DOI: 10.3390/ijms25105081 -
ChemMedChem Nov 2022From four focused compound libraries based on the known anticoccidial agent robenidine, 44 compounds total were synthesised and screened for antigiardial activity. All...
From four focused compound libraries based on the known anticoccidial agent robenidine, 44 compounds total were synthesised and screened for antigiardial activity. All active compounds were counter-screened for antibiotic and cytotoxic action. Of the analogues examined, 21 displayed IC <5 μM, seven with IC <1.0 μM. Most active were 2,2'-bis{[4-(trifluoromethoxy)phenyl]methylene}carbonimidic dihydrazide hydrochloride (30), 2,2'-bis{[4-(trifluoromethylsulfanyl)phenyl]methylene}carbonimidic dihydrazide hydrochloride (32), and 2,2'-bis[(2-bromo-4,5-dimethoxyphenyl)methylene]carbonimidic dihydrazide hydrochloride (41) with IC =0.2 μM. The maximal observed activity was a 5 h IC value of 0.2 μM for 41. The clinically used metronidazole was inactive at this timepoint at a concentration of 25 μM. Robenidine off-target effects at bacteria and cell line toxicity were removed. Analogue 41 was well tolerated in mice treated orally (100 mg/kg). Following 5 h treatment with 41, no Giardia regrowth was noted after 48 h.
Topics: Animals; Mice; Robenidine; Guanidine; Guanidines; Metronidazole; Anti-Bacterial Agents
PubMed: 36085254
DOI: 10.1002/cmdc.202200341 -
Annals of Clinical Microbiology and... May 2022Antimicrobial resistance of H. pylori can lead to treatment failure. Importantly, several studies have reported on heteroresistance, i.e. the presence of resistant and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antimicrobial resistance of H. pylori can lead to treatment failure. Importantly, several studies have reported on heteroresistance, i.e. the presence of resistant and susceptible H. pylori populations in the same sample and/or a difference in the susceptibility patterns between biopsy samples. This meta-analysis aims to provide comprehensive data on the prevalence of metronidazole and clarithromycin heteroresistance and the approaches to their detection.
MATERIAL AND METHODS
A systematic review was performed after the search of MEDLINE, Scopus and Web of Science. The study outcomes were the weighted pooled prevalence of heteroresistance to clarithromycin and metronidazole in H. pylori positive samples and/or isolates with a subanalysis by continent.
RESULTS
A total of 22 studies that had investigated 3852 H. pylori positive patients were included in the meta-analysis. Heteroresistance to clarithromycin was reported in 20 studies, with a weighted pooled prevalence of 6.8% (95% CI 5.1-8.6; 3654 H. pylori positive patients; the substantial heterogeneity I = 55.6%). Heteroresistance to metronidazole was reported in 12 studies, with a weighted pooled prevalence of 13.8% (95% CI 8.9-18.6; 1670 H. pylori positive patients; the substantial heterogeneity I = 60.9%). The weighted pooled prevalence of clarithromycin heteroresistance was similar in Asia and Europe (p = 0.174584), however, metronidazole heteroresistance was detected more often in Europe (p < 0.00001). Clarithromycin heteroresistance was detected more often by phenotype rather than by using genotyping methods (12 vs 8 studies), whereas heteroresistance to metronidazole was detected only by phenotype.
CONCLUSION
The prevalence of heteroresistance to clarithromycin and/or metronidazole is not negligible and can be detected in approximately 7 and 14% of H. pylori positive samples, respectively. These findings highlight the need to raise the awareness of gastroenterologists and microbiologists to the heteroresistance to clarithromycin and metronidazole in patients with a H. pylori infection.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Microbial Sensitivity Tests
PubMed: 35596211
DOI: 10.1186/s12941-022-00509-3