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Frontiers in Cellular and Infection... 2020Amebiasis is a neglected tropical disease which is caused by the protozoan parasite . This disease is one of the leading causes of diarrhea globally, affecting largely... (Review)
Review
Amebiasis is a neglected tropical disease which is caused by the protozoan parasite . This disease is one of the leading causes of diarrhea globally, affecting largely impoverished residents in developing countries. Amebiasis also remains one of the top causes of gastrointestinal diseases in returning international travellers. Despite having many side effects, metronidazole remains the drug of choice as an amebicidal tissue-active agent. However, emergence of metronidazole resistance in pathogens having similar anaerobic metabolism and also in laboratory strains of has necessitated the identification and development of new drug targets and therapeutic strategies against the parasite. Recent research in the field of amebiasis has led to a better understanding of the parasite's metabolic and cellular pathways and hence has been useful in identifying new drug targets. On the other hand, new molecules effective against amebiasis have been mined by modifying available compounds, thereby increasing their potency and efficacy and also by repurposing existing approved drugs. This review aims at compiling and examining up to date information on promising drug targets and drug molecules for the treatment of amebiasis.
Topics: Amebiasis; Drug Development; Dysentery, Amebic; Entamoeba histolytica; Humans; Metronidazole
PubMed: 33718258
DOI: 10.3389/fcimb.2020.628257 -
The Israel Medical Association Journal... Oct 2020Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate...
BACKGROUND
Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates.
OBJECTIVES
To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance.
METHODS
In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen.
RESULTS
No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin.
CONCLUSIONS
The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.
Topics: Academic Medical Centers; Adult; Chi-Square Distribution; Clarithromycin; Cohort Studies; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Female; Helicobacter Infections; Helicobacter pylori; Humans; Israel; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Prevalence; Retrospective Studies; Statistics, Nonparametric
PubMed: 33070487
DOI: No ID Found -
Microbiology Spectrum Jun 2023Bacterial vaginosis (BV) is the most common infection of the lower reproductive tract among women of reproductive age, characterized by a depletion of health-associated...
Bacterial vaginosis (BV) is the most common infection of the lower reproductive tract among women of reproductive age, characterized by a depletion of health-associated and an overgrowth of anaerobes. Metronidazole has been recommended as a first-line therapy for treating BV for decades. Although most cases are cured by the treatment, recurrent infections of BV seriously affect women's reproductive health. Until now, limited information on the vaginal microbiota has been explored at the species level. Here, we adopted a single molecular sequencing approach for the 16S rRNA gene, named FLAST (full-length assembly sequencing technology), to analyze the human vaginal microbiota that improved species-level resolution for taxonomy and identified microbiota alterations in the vaginal tract in response to treatment with metronidazole. Appling high-throughput sequencing, we identified 96 and 189 novel full-length 16S rRNA gene sequences in and , respectively, which had not previously been reported in vaginal samples. Moreover, we found that Lactobacillus iners was significantly enriched in the cured group before metronidazole treatment, and that was maintained in a high frequency after the treatment, suggesting an important role for this species in response to metronidazole treatment. Our research also highlights the importance of the single-molecule paradigm for progressing the field of microbiology and applying these insights to better understand the dynamic microbiota during BV treatment. Subsequent novel treatment approaches should be proposed to improve BV treatment outcomes, optimize the vaginal microbiome, and reduce gynecological and obstetric sequelae. Bacterial vaginosis (BV) is a common infectious disease of the reproductive tract. Metronidazole treatment, as the first line of treatment, frequently fails at recovery of the microbiome. However, the precise types of and other bacteria involved in BV remain unclear, and this has resulted in a failure to identify potential markers to predict clinic outcomes. In this study, we adopted a 16S rRNA gene full-length assembly sequencing technology for the taxonomy analysis and evaluation of vaginal microbiota before and after treatment with metronidazole. We additionally identified 96 and 189 novel 16S rRNA gene sequences in and species, respectively, in vaginal samples, which improves our understanding of the vaginal microbiota. Moreover, we found that the abundance of Lactobacillus iners and Prevotella bivia before treatment was associated with a lack of cure. These potential biomarkers will help to facilitate future studies aimed at improving BV treatment outcomes, optimize the vaginal microbiome, and reduce adverse sexual and reproductive outcomes.
Topics: Female; Humans; Metronidazole; Vaginosis, Bacterial; RNA, Ribosomal, 16S; Vagina; Microbiota; High-Throughput Nucleotide Sequencing
PubMed: 37199621
DOI: 10.1128/spectrum.01706-22 -
Molecules (Basel, Switzerland) Feb 2020We prepared a series of 10 carbamates derivatives based on two common antiprotozoal drugs: metronidazole (-) and secnidazole (-). The compounds were tested in vitro...
We prepared a series of 10 carbamates derivatives based on two common antiprotozoal drugs: metronidazole (-) and secnidazole (-). The compounds were tested in vitro against a set of two amitochondriate protozoa: and . Compounds 1-10 showed strong antiprotozoal activities, with potency values in the low micromolar-to-nanomolar range, being more active than their parent drugs. Metronidazole carbamate (1) was the most active of the series, with nanomolar activities against G. duodenalis (IC = 460 nM) and T. vaginalis (IC = 60 nM). The potency of compound 1 was 10 times greater than that of metronidazole against both parasites. None of compounds showed in vitro cytotoxicity against VERO cells tested at 100 µM. Molecular dynamics of compounds 1-10, secnidazole, and metronidazole onto the ligand binding site of pyruvate-ferredoxin oxidoreductase of T. vaginalis and the modeled -tubulin of G. duodenalis revealed putative molecular interactions with key residues in the binding site of both proteins implicated in the mode of action of the parent drugs.
Topics: Antiprotozoal Agents; Carbamates; Giardia lamblia; Giardiasis; Metronidazole; Trichomonas Infections; Trichomonas vaginalis
PubMed: 32059495
DOI: 10.3390/molecules25040793 -
International Journal of Infectious... Feb 2021We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number... (Observational Study)
Observational Study
Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection - An observational cohort study.
PURPOSE
We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number and disease severity.
METHODS
An observation cohort study included 271 CDI patients hospitalised between 2013-2016. Univariate logistic regression was used to evaluate the association between patients' clinical outcome (sustained clinical cure or recurrence) in a 60-day follow-up and the antibiotic regimen used (oral metronidazole, oral vancomycin, combination of oral vancomycin and metronidazole, oral fidaxomicin). Subgroup analyses, based on CDI episode number and severity, were performed.
RESULTS
In the overall population, fidaxomicin was superior to metronidazole, vancomycin or their combination, for a sustained clinical response and in the prevention of recurrent CDI (rCDI). In the subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence and non-severe cases. In the oral treatment of severe CDI, fidaxomicin had a similar treatment outcome to vancomycin and none of the antibiotic treatments were superior in the prevention of rCDI. Fidaxomicin, vancomycin, or a combination of metronidazole and vancomycin, had similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple rCDI.
CONCLUSION
Fidaxomicin was superior to metronidazole or vancomycin for the treatment of the initial episode, first recurrence, and non-severe CDI.
Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Cohort Studies; Female; Fidaxomicin; Hospitalization; Humans; Logistic Models; Male; Metronidazole; Middle Aged; Recurrence; Treatment Outcome; Vancomycin
PubMed: 33188906
DOI: 10.1016/j.ijid.2020.11.004 -
Journal of Veterinary Science Nov 2023Antibiotic beads are used to treat local bacterial infections by delivering high drug concentrations to infected tissue.
BACKGROUND
Antibiotic beads are used to treat local bacterial infections by delivering high drug concentrations to infected tissue.
OBJECTIVES
This study examined the elution characteristics of metronidazole from metronidazole-calcium sulfate (MCa) and metronidazole-calcium-potassium sulfate (MCaK) beads over 20 days and the antibacterial efficacy of the beads after storage.
METHODS
The MCa and MCaK beads were prepared by mixing 250 mg of metronidazole and 10 g of calcium sulfate hemihydrate with water and a 3% potassium sulfate solution, respectively. The beads were placed in phosphate-buffered saline for the elution study. The metronidazole eluents were determined using high-performance liquid chromatography. The microstructures were examined by scanning electron microscopy (SEM), and the antimicrobial activity was evaluated by a microbioassay.
RESULTS
For the 20-day study, the total amount of metronidazole released was greater in the MCa beads than in the MCaK beads by 6.61 ± 0.48 mg (89.11% ± 3.04%) and 4.65 ± 0.36 mg (73.11% ± 4.38%), respectively. The amounts of eluted drugs from the MCa and MCaK beads were higher than the minimum inhibitory concentration at 0.5 µg/mL against anaerobic bacteria at both 20 days and 14 days. SEM showed that calcium crystals on the outer surface had dissolved after elution, and thinner calcium crystals were prominent in the MCaK beads. The MCa and MCaK beads exhibited antibacterial activity after setting, followed by storage at room temperature or 4°C for 21 days.
CONCLUSIONS
The MCa beads could release more drug than the MCaK beads, but all eluted metronidazole amounts were effective in controlling bacterial infections. Both metronidazole beads could be stored at ambient temperature or in a refrigerator.
Topics: Animals; Metronidazole; Calcium Sulfate; Calcium; Anti-Bacterial Agents; Bacterial Infections
PubMed: 37904636
DOI: 10.4142/jvs.23166 -
World Journal of Gastroenterology Jul 2019() is the causative agent of gastritis, peptic ulcer disease, mucosa associated lymphoid tissue lymphoma and gastric cancer (GC). While this bacterium infects 50% of... (Review)
Review
() is the causative agent of gastritis, peptic ulcer disease, mucosa associated lymphoid tissue lymphoma and gastric cancer (GC). While this bacterium infects 50% of the world's population, in Africa its prevalence reach as high as 80% as the infection is acquired during childhood. Risk factors for acquisition have been reported to be mainly due to overcrowding, to have infected siblings or parent and to unsafe water sources. Despite this high prevalence there still does not exist an African guideline, equivalent to the Maastricht V/Florence Consensus Report of the European Helicobacter and Microbiota Study Group for the management of this infection. In this continent, although there is a paucity of epidemiologic data, a contrast between the high prevalence of infection and the low incidence of GC has been reported. This phenomenon is the so-called "African Enigma" and it has been hypothesized that it could be explained by environmental, dietary and genetic factors. A heterogeneity of data both on diagnosis and on therapy have been published. In this context, it is evident that in several African countries the increasing rate of bacterial resistance, mainly to metronidazole and clarithromycin, requires continental guidelines to recommend the appropriate management of . The aim of this manuscript is to review current literature on infection in Africa, in terms of prevalence, risk factors, impact on human health, treatment and challenges encountered so as to proffer possible solutions to reduce transmission in this continent.
Topics: Africa; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Gastroenterology; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Metronidazole; Practice Guidelines as Topic; Prevalence; Risk Factors; Stomach Neoplasms
PubMed: 31333310
DOI: 10.3748/wjg.v25.i25.3183 -
Nature Communications Jan 2020Metronidazole was until recently used as a first-line treatment for potentially life-threatening Clostridioides difficile (CD) infection. Although cases of metronidazole...
Metronidazole was until recently used as a first-line treatment for potentially life-threatening Clostridioides difficile (CD) infection. Although cases of metronidazole resistance have been documented, no clear mechanism for metronidazole resistance or a role for plasmids in antimicrobial resistance has been described for CD. Here, we report genome sequences of seven susceptible and sixteen resistant CD isolates from human and animal sources, including isolates from a patient with recurrent CD infection by a PCR ribotype (RT) 020 strain, which developed resistance to metronidazole over the course of treatment (minimal inhibitory concentration [MIC] = 8 mg L). Metronidazole resistance correlates with the presence of a 7-kb plasmid, pCD-METRO. pCD-METRO is present in toxigenic and non-toxigenic resistant (n = 23), but not susceptible (n = 563), isolates from multiple countries. Introduction of a pCD-METRO-derived vector into a susceptible strain increases the MIC 25-fold. Our finding of plasmid-mediated resistance can impact diagnostics and treatment of CD infections.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; DNA, Bacterial; Drug Resistance, Bacterial; Feces; Gene Dosage; Gene Transfer, Horizontal; Humans; Metronidazole; Plasmids; Polymorphism, Single Nucleotide; Replicon
PubMed: 32001686
DOI: 10.1038/s41467-020-14382-1 -
Antimicrobial Agents and Chemotherapy Jan 2024The intestinal parasites and are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat...
The intestinal parasites and are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and antiamebic activities of the rediscovered nitroimidazole compound, fexinidazole, and its sulfone and sulfoxide metabolites. Fexinidazole is equally active against and trophozoites, and both metabolites were 3- to 18-fold more active than the parent drug. Fexinidazole and its metabolites were also active against a metronidazole-resistant strain of . and cell extracts exhibited decreased residual nitroreductase activity when metabolites were used as substrates, indicating nitroreductase may be central to the mechanism of action of fexinidazole. In a cell invasion model, fexinidazole and its metabolites significantly reduced the invasiveness of trophozoites through basement membrane matrix. A q.d. oral dose of fexinidazole and its metabolites at 10 mg/kg for 3 days reduced infection significantly in mice compared to control. The newly discovered antigiardial and antiamebic activities of fexinidazole, combined with its FDA-approval and inclusion in the WHO Model List of Essential Medicines for the treatment of human African trypanosomiasis, offer decreased risk and a shortened development timeline toward clinical use of fexinidazole for treatment of giardiasis or amebiasis.
Topics: Mice; Animals; Humans; Giardiasis; Metronidazole; Nitroimidazoles; Amebiasis; Giardia lamblia; Entamoeba histolytica; Nitroreductases
PubMed: 38063401
DOI: 10.1128/aac.00731-23 -
BMC Microbiology Dec 2022Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter...
BACKGROUND
Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota.
AIM
The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors.
METHODS
Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database.
RESULTS
The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group.
CONCLUSIONS
Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.
Topics: Humans; Helicobacter Infections; Metronidazole; Minocycline; Helicobacter pylori; Gastrointestinal Microbiome; Anti-Bacterial Agents; RNA, Ribosomal, 16S; Phylogeny; Drug Therapy, Combination
PubMed: 36581836
DOI: 10.1186/s12866-022-02732-6