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Proceedings of the National Academy of... Nov 2023Tryptophan and its derivatives perform a variety of biological functions; however, the role and specific mechanism of many tryptophan derivatives in intestinal...
Tryptophan and its derivatives perform a variety of biological functions; however, the role and specific mechanism of many tryptophan derivatives in intestinal inflammation remain largely unclear. Here, we identified that an strain (TMU) isolated from the feces of tinidazole-treated individuals, and indole-3-lactic acid (ILA) in its supernatant, decreased the susceptibility of mice to dextran sulfate sodium-induced colitis. TMU and ILA contribute to the relief of colitis by inhibiting the production of epithelial CCL2/7, thereby reducing the accumulation of inflammatory macrophages in vitro and in vivo. Mechanistically, ILA downregulates glycolysis, NF-κB, and HIF signaling pathways via the aryl hydrocarbon receptor, resulting in decreased CCL2/7 production in epithelial cells. Clinical evidence suggests that the fecal ILA level is negatively correlated with the progression indicator of inflammatory bowel diseases. These results demonstrate that ILA has the potential to regulate intestinal homeostasis by modulating epithelium-macrophage interactions.
Topics: Animals; Mice; Tryptophan; Colitis; Macrophages; Epithelium; Dextran Sulfate; Mice, Inbred C57BL; Intestinal Mucosa
PubMed: 37903267
DOI: 10.1073/pnas.2309032120 -
Medicine Oct 2023Helicobacter pylori (H pylori) can cause gastritis, peptic ulcers, gastric cancer, and many other gastrointestinal diseases. The 14-day neo-dual therapy for H pylori is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Helicobacter pylori (H pylori) can cause gastritis, peptic ulcers, gastric cancer, and many other gastrointestinal diseases. The 14-day neo-dual therapy for H pylori is considered by most countries to have good eradication rates, while the 7- and 10-day studies have been more widely explored, however, we find that their results are different. The applicability of the shorter and less expensive 10-day neo-dual therapy to our country has not yet been confirmed.
METHODS
The patients were divided into 3 groups of 200 each by randomization method. Group A: patients received vonoprazan 20 mg, bid + amoxicillin(1 g), tid, for 14 days. Group B: vonoprazan (20 mg) bid + amoxicillin (1 g) tid, duration of treatment is 10 days, group C: rabeprazole (20 mg) bid + bismuth potassium citrate tablets/tinidazole tablets/clarithromycin tablets, combined package (4.2 g), bid, duration of treatment 14 days. The main comparisons were H pylori eradication rate, adverse drug reaction profile and cost-effect ratio in each group.
RESULTS
The eradication rates of groups A, B, and C were 92.5%, 91.6%, and 80.1%, respectively. There was no significant difference in the eradication rates of groups A and B (P > .05), groups A and B had statistically significantly better eradication rates than group C (P < .05). The incidence of adverse reactions in groups A, B, and C was 9.5%, 8.5%, and 17.0%, respectively. There was no difference in the incidence of adverse reactions between A and B: (P > .05), The incidence of adverse reactions was statistically significantly lower in groups A and B than in group C (P < .05). Logistic regression analysis showed nonsmokers had a higher eradication rate (OR 2.587, 95% CI: 1.377-4.859, P = .003), and taller patients were more likely to have successful eradication (OR 1.052, 95% CI: 1.008-1.097, P = .020). Group B had the lowest cost-benefit analysis results.
CONCLUSION
Group B had an acceptable eradication rate, the lowest incidence of adverse effects, and the lowest cost analysis. Eradication is more likely to be successful in patients who do not smoke and in those who are taller.
Topics: Humans; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Sulfonamides; Treatment Outcome
PubMed: 37832048
DOI: 10.1097/MD.0000000000035610 -
Cureus Jan 2024Recent studies have discussed the role of antibiotic treatment in the conservative management of acute appendicitis and whether antibiotics are a safe option to replace... (Review)
Review
Recent studies have discussed the role of antibiotic treatment in the conservative management of acute appendicitis and whether antibiotics are a safe option to replace appendicectomy, which has been the gold standard treatment of acute appendicitis for many years. The bibliographic databases Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, Medline, and PubMed comparing conservative versus surgical treatment of acute appendicitis were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-one studies consisting of systematic reviews and meta-analyses involving 44,699 participants were identified. At least 17,865 participants were treated with antibiotics. Our studies compare antibiotic versus appendicectomy among acute appendicitis patients ranging from 7 to 94 years of age. In most studies, patients received parenteral antibiotics for a total of one to three days, and oral antibiotics such as oral cephalosporin plus metronidazole, oral amoxicillin/clavulanate, oral fluoroquinolones plus Tinidazole upon hospital discharge for a total of 7 to 10 days. The total course of antibiotics for both parenteral and oral regimes ranged from 2 to 16 days, with 10 days being the commonest duration. The recurrence rate following initial antibiotic treatment at one-year follow-up ranged from 13% to 38%, while the mean duration of recurrence ranged from three to eight months. The majority of the patients with recurrence underwent appendicectomy, while some patients were either given a repeat or different course of antibiotics due to the possible presence of antibiotic resistance; however, only 2.4% of the patients were successfully treated upon completion of the second course of antibiotics. Most of the studies concluded that appendicectomy remains the gold standard treatment for uncomplicated acute appendicitis, given its higher efficacy and lower complication rates. Although antibiotic treatment cannot be routinely recommended, it can be considered an appropriate alternative in selected patients with uncomplicated appendicitis who wish to avoid surgery and also acknowledge the risk of recurrence and the potential need for subsequent surgery at the same time.
PubMed: 38384640
DOI: 10.7759/cureus.52697 -
PeerJ 2023Efficacy of . ) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of in Fujian, China.
BACKGROUND AND AIM
Efficacy of . ) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of in Fujian, China.
METHODS
-infected patients in four centers were enrolled in the study from Oct 2019 to Jan 2022. The bacteria were isolated, cultured and identified from the biopsy of patients' gastric mucosa samples. Antimicrobial susceptibility testing was performed by a modified broth microdilution method for to seven guideline-recommended antibiotics and seven potential choices for eradication.
RESULTS
A total of 205 strains were isolated. The resistance rates of amoxicillin (AMX), amoxicillin and clavulanate potassium (AMC), cefixime (CFM), gentamicin (GEN), tetracycline (TET), doxycycline (DOX), azithromycin (AZM), clarithromycin (CLR), levofloxacin (LVFX), sparfloxacin (SPFX), metronidazole (MTZ), tinidazole (TID), rifampicin (RFP) and furazolidone (FZD) were 11.22%, 12.20%, 7.32%, 12.20%, 4.88%, 4.39%, 44.39%, 43.90%, 30.24%, 21.46%, 40.98%, 45.85%, 5.37% and 10.24%, respectively. The rates of pan-sensitivity, single, double, triple and multiple resistance for seven guideline-recommended antibiotics were 32.68%, 30.24%, 13.17%, 7.76%, and 14.15%, respectively. The main double-resistance patterns were CLR+MTZ (10/205, 5%) and CLR+LVFX (9/205, 4%). The main triple-resistance pattern was CLR+MTZ+ LVFX (15/205, 7%).
CONCLUSIONS
In Fujian, the prevalence of resistance to AZM, CLR, LVFX, SPFX, MTZ, and TID was high, whereas that to AMX, AMC, GEN, CFM, TET, DOX, RFP and FZD was relatively low. CFM and DOX are promising new choices for eradication.
Topics: Humans; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Microbial Sensitivity Tests; Metronidazole; Clarithromycin; Amoxicillin; Tetracycline; Drug Resistance, Bacterial; Furazolidone; Cefixime; Doxycycline; Levofloxacin
PubMed: 37456872
DOI: 10.7717/peerj.15611 -
Parasites & Vectors Sep 2023The emergence and spread of drug resistance in Trichomonas vaginalis parasites has become an important concern in trichomoniasis treatment. Fast and reliable growth...
BACKGROUND
The emergence and spread of drug resistance in Trichomonas vaginalis parasites has become an important concern in trichomoniasis treatment. Fast and reliable growth assessment is critical for validating in vitro drug susceptibility and high-throughput screening of newly developed drugs.
METHODS
Modified media without yeast extract were evaluated for their ability to support the growth of T. vaginalis parasites. The potential of the nucleic acid-binding dye SYBR Green I for detecting T. vaginalis drug resistance was characterized, and seeding parasite concentration and incubation time were optimized. The fluorescence assay based on SYBR Green I was further validated in four T. vaginalis isolates with different susceptibilities to the antibiotics metronidazole, tinidazole, ornidazole and secnidazole, and compared with the traditional method that detects minimum lethal concentrations (MLCs).
RESULTS
A modified medium consisting of RPMI 1640 and Tryptone Plus as replacements for yeast extract and tryptone, respectively, in traditional trypticase-yeast extract-maltose (TYM) medium exhibited similar performance as TYM medium in maintaining T. vaginalis growth, while it showed much lower background fluorescent signals. The T. vaginalis SYBR Green I-based fluorescence (TSF) drug assay was found to have to satisfy one of two conditions to demonstrate the 50% inhibitory concentration of metronidazole for the sensitive isolate TV-334: (i) a seeding density of 3 × 10 parasites/ml and an incubation time of 48 h; or (ii) a seeding density of 1 × 10 parasites/ml and an incubation time of 72 h. Subsequent validation experiments revealed that the 48-h incubation/3 × 10 parasites/ml seeding density condition had a greater sensitivity to detect drug resistance than the 72-h condition. The TSF assay also exhibited high efficiency in identifying parasite drug resistance, as evidenced by its strong correlation with the standard MLC assay results (P = 0.003).
CONCLUSIONS
This study presents a robust TSF assay that has the potential to facilitate high-throughput, automated in vitro anti-trichomoniasis susceptibility testing for drug resistance monitoring and drug development. In comparison to the standard MLC method, this assay offers the advantages of reduced labor and elimination of subjective examination.
Topics: Animals; Trichomonas vaginalis; Drug Evaluation, Preclinical; Metronidazole; Trichomonas Infections
PubMed: 37723582
DOI: 10.1186/s13071-023-05919-6 -
PloS One 2023The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient...
The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected in Cameroon. Each sample was then analyzed by HPLC and disintegration tests. Seven additional samples from the nitro-imidazole (secnidazole, ornidazole, tinidazole) and the fluoroquinolone (levofloxacin, ofloxacin, norfloxacin, moxifloxacin) families were analyzed to mimic falsified medicines. Placebo samples that contained only inert excipients were also tested to mimic falsified samples without active pharmaceutical ingredient (API). The three screening tools implemented were: a simplified visual inspection checklist, a low-cost handheld near infrared (NIR) spectrophotometer and paper analytical devices (PADs). Overall, 61.1% of the samples that failed disintegration and assay tests also failed the visual inspection checklist test. For the handheld NIR, one-class classifier models were built to detect the presence of ciprofloxacin and metronidazole, respectively. The APIs were correctly identified in all the samples with sensitivities and specificities of 100%. However, the importance of a representative and up-to-date spectral database was underlined by comparing models built with different calibration set spanning different variability spaces. The PADs were used only on ciprofloxacin samples and detected the API in all samples in which the presence of ciprofloxacin was confirmed by HPLC. However, these PADs were not specific to ciprofloxacin since they reacted like ciprofloxacin to other fluoroquinolone compounds. The advantages and drawbacks of each screening tool were highlighted. They are promising means in the frame of early detection of SF medicines and they can increase the speed of decision about SF medicines in the context of pharmaceutical post-marketing surveillance.
Topics: Humans; Metronidazole; Counterfeit Drugs; Substandard Drugs; Ciprofloxacin; Levofloxacin; Product Surveillance, Postmarketing
PubMed: 37566594
DOI: 10.1371/journal.pone.0289865 -
United European Gastroenterology Journal Feb 2024Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful...
BACKGROUND
Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication.
AIM
To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg).
METHODS
Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022.
RESULTS
Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness.
CONCLUSIONS
We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.
Topics: Adult; Humans; Proton Pump Inhibitors; Helicobacter pylori; Metronidazole; Clarithromycin; Levofloxacin; Bismuth; Prospective Studies; Drug Therapy, Combination; Anti-Bacterial Agents; Helicobacter Infections; Amoxicillin; Tetracycline; Registries
PubMed: 38050339
DOI: 10.1002/ueg2.12476 -
Sexually Transmitted Diseases Jun 2023The only drugs approved by the US Food and Drug Administration for oral treatment of trichomoniasis belong to the 5-nitroimidazole group. Most individuals infected with...
In Vitro Testing of Trichomonas vaginalis Drug Susceptibility: Evaluation of Minimal Lethal Concentrations for Metronidazole and Tinidazole That Correspond With Treatment Failure.
BACKGROUND
The only drugs approved by the US Food and Drug Administration for oral treatment of trichomoniasis belong to the 5-nitroimidazole group. Most individuals infected with Trichomonas vaginalis can be cured with a standard treatment of metronidazole or tinidazole, but it is estimated that more than 159,000 people fail treatment each year. Although a minimal lethal concentration (MLC) corresponding to treatment failure has been reported for metronidazole, the MLC for tinidazole associated with treatment failure has not been determined. We conducted a study using T. vaginalis isolates from women with reported treatment success or failure to determine these values.
METHODS
We measured MLCs of 47 isolates obtained from women who had failed metronidazole treatment, 33 isolates from women who had failed tinidazole treatment, and 48 isolates from women successfully cured with metronidazole. The cutoff was calculated as the 95th percentile of MLCs of susceptible isolates for each drug.
RESULTS
Our data confirmed that the MLC previously associated with metronidazole treatment failure is ≥50 μg/mL and identified the MLC associated with tinidazole treatment failure as ≥6.3 μg/mL. For metronidazole, the agreement between laboratory result and treatment outcome was 93.7%; for tinidazole, this agreement was 88.9%.
CONCLUSIONS
The T. vaginalis susceptibility assay is useful for determining whether 5-nitroimidazole treatment failure in persons with trichomoniasis can be attributed to drug resistance. These results are useful for establishing interpretive guidance of test results, and MLC levels can help guide appropriate patient treatment.
Topics: Female; Humans; Metronidazole; Trichomonas vaginalis; Tinidazole; Trichomonas Vaginitis; Pharmaceutical Preparations; Drug Resistance; Trichomonas Infections; Treatment Failure; In Vitro Techniques
PubMed: 36849257
DOI: 10.1097/OLQ.0000000000001788