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1.
Oper Dent ; 49(3): 336-344, 2024 May 01.
Article En | MEDLINE | ID: mdl-38807319

OBJECTIVE: Tooth color matching is challenging, and digital photocolorimetry using eLABor_aid (eLAB) provides objective evaluation through polarized photographs. However, its comparability with spectrophotometry remains unclear. METHODS AND MATERIALS: Bovine incisor root canals (n=30) were prepared to simulate an incomplete root apex. The teeth were randomly assigned to three groups based on intracanal medication: control (without medication); calcium hydroxide/propylene glycol; and triple-antibiotic paste (n=10 each). Tooth color was assessed using both eLAB and spectrophotometry. Measurements were taken at the crown medio-cervical region on five-time intervals (baseline, 1, 3, 7, and 14 days). Statistical analysis included two-way repeated-measures ANOVA, Sidak post hoc and Pearson's correlation test (α=0.05). RESULTS: No significant differences were observed between the two methods for either medication or follow-ups (p>0.05). Triple-antibiotic paste exhibited higher color variation (p<0.05). After 7 days, all groups presented significant color changes (p<0.05). Moderate to high correlations (R2 from 0.51 to 0.84, p<0.0001) were found between both methods for all groups at all intervals. CONCLUSION: The eLAB is a reliable method for detecting tooth color changes, and its results are comparable to spectrophotometry analysis.


Colorimetry , Spectrophotometry , Cattle , Animals , Spectrophotometry/methods , Colorimetry/methods , Anti-Bacterial Agents , Color , In Vitro Techniques , Calcium Hydroxide , Incisor/anatomy & histology , Propylene Glycol , Tooth Discoloration , Root Canal Irrigants/therapeutic use , Metronidazole/therapeutic use , Ciprofloxacin/therapeutic use , Dental Pulp Cavity/anatomy & histology
2.
J Prim Care Community Health ; 15: 21501319241249645, 2024.
Article En | MEDLINE | ID: mdl-38726585

Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.


Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Humans , Clostridium Infections/prevention & control , Clostridium Infections/diagnosis , Clostridium Infections/therapy , Anti-Bacterial Agents/therapeutic use , Fecal Microbiota Transplantation , Cross Infection/prevention & control , Practice Guidelines as Topic , Fidaxomicin/therapeutic use , Metronidazole/therapeutic use
3.
Sci Rep ; 14(1): 11430, 2024 05 20.
Article En | MEDLINE | ID: mdl-38769330

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.


Anti-Bacterial Agents , Cefixime , Ciprofloxacin , Liver Abscess , Metronidazole , Humans , Ciprofloxacin/administration & dosage , Ciprofloxacin/therapeutic use , Metronidazole/administration & dosage , Metronidazole/therapeutic use , Cefixime/therapeutic use , Cefixime/administration & dosage , Male , Female , Middle Aged , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Liver Abscess/drug therapy , Liver Abscess/microbiology , Treatment Outcome , Double-Blind Method , Drug Therapy, Combination , Drainage , Aged
4.
JAMA Netw Open ; 7(5): e248661, 2024 May 01.
Article En | MEDLINE | ID: mdl-38696172

Importance: Bacterial vaginosis (BV) is a common cause of vaginal infection. First-line treatments of BV are metronidazole and clindamycin. Due to the increase in antibiotic resistance, effective nonantibiotic treatments for BV are needed. Objective: To examine whether dequalinium chloride, a broad-spectrum antiseptic, is noninferior to oral metronidazole for the treatment of BV. Design, Setting, and Participants: This phase 4, multicenter, triple-blind, double-dummy, parallel, noninferiority randomized clinical trial was conducted from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Participants were premenopausal women 18 years or older with BV from 11 gynecologic practices and 1 hospital in Poland, Slovakia, and the Czech. Intervention: Patients were randomized to treatment with dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg twice daily for 7 days). Double-dummy medication kits contained vaginal and oral tablets with placebo and active medication. Main Outcomes and Measures: The main outcome was the noninferiority margin (of 15 percentage points) in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment (visit 1). Noninferiority was met if the lower 95% CI for the difference in clinical cure rate was less than 15 percentage points at visit 1. Results: A total of 147 women (mean [SD] age, 36.7 [9.0] years) were treated with dequalinium chloride (n = 72) or metronidazole (n = 75). The clinical cure rates at visit 1 were 64 of 69 (92.8%) for dequalinium chloride vs 69 of 74 (93.2%) for metronidazole in the intention-to-treat population, whereas in the per-protocol population, cure rates were 54 of 58 (93.1%) for dequalinium chloride vs 48 of 53 (90.6%) for metronidazole. The treatment differences of -0.5 percentage points (95% CI, -10.8 to 9.8 percentage points; P = .002) in the intention-to-treat population and 2.5 percentage points (95% CI, -9.4 to 14.4 percentage points; P = .001) in the per-protocol population confirmed the noninferiority of dequalinium chloride. The tolerability of dequalinium chloride was rated as very good by 30 of 50 patients (60.0%) but only by 21 of 54 (38.9%) for metronidazole. Three patients in the metronidazole group suspended treatment due to an adverse event. Conclusions and Relevance: This randomized clinical trial showed that dequalinium chloride was not inferior to metronidazole for the treatment of BV. Dequalinium chloride had a similarly high cure rate but with better tolerability and fewer adverse events. With a similar efficacy to metronidazole and clindamycin, dequalinium chloride warrants consideration as first-line treatment for BV to help reduce antibiotic consumption. Trial Registration: EudraCT: 2020-002489-15.


Dequalinium , Metronidazole , Vaginosis, Bacterial , Humans , Female , Metronidazole/therapeutic use , Vaginosis, Bacterial/drug therapy , Adult , Dequalinium/therapeutic use , Treatment Outcome , Double-Blind Method , Middle Aged , Administration, Intravaginal , Anti-Bacterial Agents/therapeutic use , Administration, Oral , Young Adult
5.
Korean J Gastroenterol ; 83(4): 150-156, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38659251

Background/Aims: Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions: Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.


Amoxicillin , Anti-Bacterial Agents , Clarithromycin , Drug Therapy, Combination , Esomeprazole , Helicobacter Infections , Helicobacter pylori , Metronidazole , Adult , Aged , Female , Humans , Male , Middle Aged , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Clarithromycin/administration & dosage , Drug Administration Schedule , Esomeprazole/therapeutic use , Esomeprazole/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Metronidazole/therapeutic use , Pantoprazole/therapeutic use , Proton Pump Inhibitors/therapeutic use , Treatment Outcome
6.
Injury ; 55(6): 111542, 2024 Jun.
Article En | MEDLINE | ID: mdl-38626585

INTRODUCTION: Wound irrigation has been employed as an important surgical step to remove bacteria, devitalized tissues, and foreign bodies from surgical sites to prevent infection and confer to the wound maximum potential of healing. METHOD: A prospective study was conducted at Federal Medical Centre, Gusau, between January 2019- August 2023 to assess the benefit of antibiotics as additives in irrigation of dirty wounds. Seven (7) patients in total were presented with severe cut-throat injuries that require laryngopharyngoplasty. A combination of injection ciprofloxacin and metronidazole were used as additives into 1 L of normal saline, low pressure irrigation was done using 20mls syringe fitted to a broken needle or canular. Dysphagia Outcome and Severity Scale (DOSS) was used to assess return of pharyngeal function. RESULT: The mean time of presentation of the patients was 34 ± 29 h (µ ± standard deviation) and a range of 6-72 h. The mean repair time was 58.3 ± 38.4 h with a range of 24-120 h. Most of the patients (85.7 %) had dysphagia outcome and severity scale of level 5 when per oral feeding was started with steady progress until discharge day. CONCLUSION: Wound irrigation is one of the most crucial steps in treating severe cut-throat injuries. Based on our experience, adding antibiotics to the irrigant has shown potential in the control of local infection, particularly where patients present late.


Anti-Bacterial Agents , Pharynx , Therapeutic Irrigation , Humans , Therapeutic Irrigation/methods , Prospective Studies , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Male , Adult , Female , Pharynx/injuries , Middle Aged , Wound Healing , Treatment Outcome , Ciprofloxacin/therapeutic use , Ciprofloxacin/administration & dosage , Metronidazole/therapeutic use , Deglutition Disorders , Surgical Wound Infection/prevention & control , Young Adult
7.
Helicobacter ; 29(2): e13076, 2024.
Article En | MEDLINE | ID: mdl-38680067

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).


Anti-Bacterial Agents , Clarithromycin , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Male , Female , Middle Aged , Helicobacter pylori/drug effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Adult , Clarithromycin/therapeutic use , Clarithromycin/administration & dosage , Polymerase Chain Reaction/methods , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage , Aged , Treatment Outcome , Metronidazole/therapeutic use , Metronidazole/administration & dosage , Levofloxacin/therapeutic use , Levofloxacin/administration & dosage , Young Adult
8.
J Antimicrob Chemother ; 79(6): 1320-1328, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38598696

OBJECTIVES: To determine the frequencies and clonal distributions of putative genetic determinants of resistance to antimicrobials applied for treatment of Clostridioides difficile infection (CDI), as documented in the genomic record. METHODS: We scanned 26 557 C. difficile genome sequences publicly available from the EnteroBase platform for plasmids, point mutations and gene truncations previously reported to reduce susceptibility to vancomycin, fidaxomicin or metronidazole, respectively. We measured the antimicrobial susceptibility of 143 selected C. difficile isolates. RESULTS: The frequency of mutations causing reduced susceptibility to vancomycin and metronidazole, respectively, increased strongly after 2000, peaking at up to 52% of all sequenced C. difficile genomes. However, both mutations declined sharply more recently, reflecting major changes in CDI epidemiology. We detected mutations associated with fidaxomicin resistance in several major genotypes, but found no evidence of international spread of resistant clones. The pCD-METRO plasmid, conferring metronidazole resistance, was detected in a single previously unreported C. difficile isolate, recovered from a hospital patient in Germany in 2008. The pX18-498 plasmid, putatively associated with decreased vancomycin susceptibility, was confined to related, recent isolates from the USA. Phenotype measurements confirmed that most of those genetic features were useful predictors of antibiotic susceptibility, even though ranges of MICs typically overlapped among isolates with and without specific mutations. CONCLUSIONS: Genomic data suggested that resistance to therapeutic antimicrobial drugs is rare in C. difficile. Public antimicrobial resistance marker databases were not equipped to detect most of the genetic determinants relevant to antibiotic therapy of CDI.


Anti-Bacterial Agents , Clostridioides difficile , Drug Resistance, Bacterial , Genome, Bacterial , Microbial Sensitivity Tests , Plasmids , Clostridioides difficile/genetics , Clostridioides difficile/drug effects , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/genetics , Plasmids/genetics , Clostridium Infections/drug therapy , Clostridium Infections/microbiology , Vancomycin/pharmacology , Vancomycin/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Genotype , Mutation
9.
Anal Biochem ; 689: 115501, 2024 Jun.
Article En | MEDLINE | ID: mdl-38453048

Vonoprazan and amoxicillin are pharmacological combinations that demonstrate synergistic effects in treating Helicobacter pylori (H. pylori), a global public health concern associated with peptic ulcer disease and gastric cancer. Four spectrophotometric methods were developed, including two univariate techniques (Fourier self-deconvolution and ratio difference) and two multivariate chemometric approaches (partial least squares and principal component regression). These methods provide innovative solutions for effectively resolving and accurately quantifying the overlapping spectra of vonoprazan and amoxicillin. The concentration ranges covered were 3-60 µg ml-1 for vonoprazan and 5-140 µg ml-1 for amoxicillin. To assess the environmental sustainability of the methodologies, various measures such as the Green Analytical Procedure Index (GAPI), National Environmental Method Index (NEMI), Analytical GREEnness Calculator, and Analytical Eco-scale, as well as RGB12 and hexagon toll were implemented. The validation of the developed techniques was carried out in compliance with ICH standards. The present study is highly significant because it is the first time that the mixture has been determined using the current approaches. The comparative analysis demonstrated no significant difference in terms of accuracy and precision compared to reference HPLC method (p = 0.05). The established spectrophotometric methods offer a straightforward, rapid, and cost-effective alternative to complex analytical techniques for determining the vonoprazan and amoxicillin mixture. They show potential for routine analysis in research laboratories and pharmaceutical industries.


Amoxicillin , Helicobacter Infections , Sulfonamides , Humans , Amoxicillin/therapeutic use , Anti-Bacterial Agents , Clarithromycin/therapeutic use , Metronidazole/therapeutic use , Proton Pump Inhibitors/therapeutic use , Drug Therapy, Combination , Retrospective Studies , Pyrroles
10.
Vet Med Sci ; 10(3): e1432, 2024 05.
Article En | MEDLINE | ID: mdl-38527006

BACKGROUND: Trichomonas gallinae is a parasite that causes canker and severe loss and death, especially in young pigeons. Metronidazole (MTZ) is the recommended drug for treating avian trichomoniasis. Due to drug resistance, non-chemical alternatives, such as medicinal plant extracts, are also considered possible therapies for this disease. OBJECTIVES: This study compares the antitrichomonal effects of MTZ with extracts of Camellia sinensis and Ziziphus vulgaris on T. gallinae in vitro. METHODS: Samples of T. gallinae were taken from infected pigeons. Multi-well plates with different concentrations (5, 10, 25, 50 and 100 µg/mL) of plant extracts were used for the in vitro study. RESULTS: The minimum inhibitory concentration (MIC) of C. sinensis extract was 25 µg/mL over 24 h, compared to 50 µg/mL for MTZ. The MIC value of the Z. vulgaris extracts was 50 µg/mL. CONCLUSIONS: The results suggest that the extracts of Z. vulgaris and C. sinensis, as potential natural agents, could have anti-avian trichomoniasis properties. This study also shows that MTZ, C. sinensis and Z. vulgaris are equally effective in preventing the growth of T. gallinae trophozoites in the culture.


Camellia sinensis , Trichomonas Infections , Trichomonas , Ziziphus , Animals , Trichomonas Infections/drug therapy , Trichomonas Infections/veterinary , Antitrichomonal Agents/pharmacology , Antitrichomonal Agents/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Columbidae
12.
Pediatr Infect Dis J ; 43(6): e214-e217, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38451881

The European Society for Clinical Microbiology and Infectious Diseases recommends 3rd generation cephalosporins and metronidazole for empirical treatment of community-acquired brain abscesses. In 53 retrospectively analyzed pediatric patients with community-acquired brain abscesses at a German University Hospital Staphylococcus aureus was identified as a relevant pathogen (21%). Therefore, it may be reasonable to cover S. aureus when selecting empirical therapy.


Anti-Bacterial Agents , Brain Abscess , Community-Acquired Infections , Staphylococcal Infections , Staphylococcus aureus , Humans , Retrospective Studies , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Brain Abscess/microbiology , Brain Abscess/drug therapy , Child , Male , Female , Anti-Bacterial Agents/therapeutic use , Child, Preschool , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Adolescent , Staphylococcus aureus/drug effects , Infant , Germany/epidemiology , Metronidazole/therapeutic use
13.
Am Surg ; 90(7): 1960-1962, 2024 Jul.
Article En | MEDLINE | ID: mdl-38537664

Surgical site infections (SSIs) remain a significant cause of morbidity and mortality in patients undergoing traumatic exploratory laparotomy. The goal of this study was to compare antibiotic usage and subsequent outcomes in patients undergoing traumatic exploratory laparotomy. A retrospective chart analysis and a chi-square test of independence were performed to examine the relation between preoperative cefoxitin versus ceftriaxone and metronidazole and the rate of SSI development. 323 patients were analyzed, 111 patients receiving cefoxitin and 212 patients receiving ceftriaxone and metronidazole. The proportion of patients who developed SSI was 16.2% for the cefoxitin group and 9.9% for the ceftriaxone and metronidazole group, X2 (1, N = 323) = 2.7, P = .098, thus displaying no statistical difference in the development of SSIs between patients in the cefoxitin group when compared to the ceftriaxone and metronidazole group.


Anti-Bacterial Agents , Cefoxitin , Ceftriaxone , Laparotomy , Metronidazole , Surgical Wound Infection , Humans , Metronidazole/therapeutic use , Metronidazole/administration & dosage , Surgical Wound Infection/prevention & control , Retrospective Studies , Cefoxitin/therapeutic use , Cefoxitin/administration & dosage , Ceftriaxone/therapeutic use , Male , Female , Adult , Anti-Bacterial Agents/therapeutic use , Laparotomy/adverse effects , Laparotomy/methods , Middle Aged , Antibiotic Prophylaxis/methods , Preoperative Care/methods , Treatment Outcome , Abdominal Injuries/surgery , Abdominal Injuries/complications
14.
Sci Rep ; 14(1): 5277, 2024 03 04.
Article En | MEDLINE | ID: mdl-38438389

Antibiotic resistance is recognised as one of the biggest global threats to human and animal health. Understanding the influence of antibiotics on the canine microbiome is important to know the potential mid-to-long term effects on dysbiosis and mitigate side-effects such as antibiotic-associated diarrhoea. In this study, metronidazole was prescribed to 22 dogs for suspected giardiasis after exhibiting gastrointestinal symptoms such as diarrhoea and/or vomiting. Faecal samples were collected before, during seven days of treatment, and six months post-cessation. Faecal microbiota was assessed with 16S rRNA sequencing. Shannon diversity was reduced for up to three days after the treatment ended, and an altered community persisted for four to six weeks. All dogs recovered to a similar microbiome composition as pre-treatment. Immediately after receiving metronidazole, an increase in the relative abundance of the genera Lactobacillus, Bifidobacterium, and Enterococcus was observed. This may be due to antibiotic resistance commonly exhibited by these organisms. One-to-two weeks post-cessation, several other genera that were sensitive to the antibiotic recovered in abundances, with taxa belonging to the Erysipelotrichaceae family particularly driving composition change. Many of the bacteria initially reduced were associated with carbohydrate fermentation. This suggests scope exists to explore interventions to augment gastrointestinal health and support the re-establishment of the microbiome.


Metronidazole , Microbiota , Humans , Dogs , Animals , Metronidazole/pharmacology , Metronidazole/therapeutic use , RNA, Ribosomal, 16S/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Diarrhea
15.
Bioorg Chem ; 146: 107288, 2024 May.
Article En | MEDLINE | ID: mdl-38521013

Nitroimidazole compounds are well-known bioactive substances, and the structural activity relationship has been reported whereby the position of the nitro group within the imidazole ring has a large influence on the activity. This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds). The in vitro trypanocidal tests show good results for both AC and AD hybrid compounds against both epimastigote and trypomastigote forms of T. cruzi. In silico studies showed positive data for most of the synthesised compounds and, in general present low toxicological risks. The AC compounds present lower ClogP (lipophilicity) values than those found for the AD series and higher TPSA (topological polar surface area) values, suggesting lower lipophilicity may be related to the presence of the triazole connector. The AD series compounds have higher Drug Score values than the AC series derivatives, suggesting better general properties for a pharmacological action.


Chagas Disease , Trypanocidal Agents , Trypanosoma cruzi , Humans , Chagas Disease/drug therapy , Eugenol , Metronidazole/pharmacology , Metronidazole/therapeutic use , Structure-Activity Relationship , Triazoles/therapeutic use , Trypanocidal Agents/chemistry , Guaiacol/chemical synthesis , Guaiacol/chemistry , Guaiacol/pharmacology
16.
Eur J Gastroenterol Hepatol ; 36(5): 545-553, 2024 May 01.
Article En | MEDLINE | ID: mdl-38477847

OBJECTIVE: Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics. BASIC METHODS: Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates. MAIN RESULTS: In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021. PRINCIPAL CONCLUSION: Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.


Gastritis , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Bismuth/pharmacology , Bismuth/therapeutic use , Turkey/epidemiology , Anti-Bacterial Agents , Amoxicillin/therapeutic use , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Metronidazole/therapeutic use , Tetracycline/therapeutic use , Drug Resistance, Microbial , Levofloxacin/therapeutic use , Gastritis/drug therapy
17.
Sci Rep ; 14(1): 5947, 2024 03 11.
Article En | MEDLINE | ID: mdl-38467719

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.


Clostridium Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia , Adult , Humans , Vancomycin/therapeutic use , Metronidazole/therapeutic use , Retrospective Studies , Poland , Prospective Studies , Graft vs Host Disease/etiology , Leukemia/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Clostridium Infections/drug therapy , Clostridium Infections/etiology
18.
J Clin Periodontol ; 51(5): 610-630, 2024 May.
Article En | MEDLINE | ID: mdl-38342946

AIM: This Bayesian network meta-analysis of randomized controlled trials assessed the effect of adjuvant periodontal treatment in both periodontal and HbA1c outcomes in adult individuals with type 2 diabetes (T2DM). MATERIALS AND METHODS: A systematic search was done up to February 2023 comparing sub-gingival debridement (SD) in combination with local or systemic adjuvant treatment with SD alone for individuals with T2DM. The primary outcomes were changes in absolute HbA1c levels and full-mouth probing depth reported at 3- to 6-month post-treatment. RESULTS: Seventy-two eligible publications evaluating 27 adjuvant treatments were retrieved. The combination of SD and systemic antibiotic metronidazole or SD and antioxidant alpha lipoic acid provided, respectively, 1.4% (95% credible interval [CrI] 0.48; 2.20) and 2.4% (95% CrI 1.50; 3.30) more significant improvement on HbA1c levels, and 0.89 mm (95% CrI 0.23; 1.50) and 0.92 mm (95% CrI 0.02; 0.92) greater periodontal probing depth reductions. Other adjuvant treatments provided added benefit to the periodontal outcomes without discernible effects on HbA1c. CONCLUSIONS: Adjuvant use of metronidazole or alpha lipoic acid was the best adjunct option to provide clinically meaningful HbA1c levels and probing depth reductions. However, no strong recommendation can be drawn due to the scarcity of studies for each adjuvant treatment and the low certainty of the resultant evidence.


Diabetes Mellitus, Type 2 , Thioctic Acid , Adult , Humans , Metronidazole/therapeutic use , Diabetes Mellitus, Type 2/complications , Dental Scaling , Root Planing , Glycated Hemoglobin , Network Meta-Analysis , Bayes Theorem , Thioctic Acid/therapeutic use
19.
Obes Surg ; 34(4): 1196-1206, 2024 Apr.
Article En | MEDLINE | ID: mdl-38400943

PURPOSE: To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS). METHODS: Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated. RESULTS: HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (-14.6 ± 27.5 mg/dL HP-treated vs -22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (-13.7 ± 29.4 mg/dL HP-treated vs -26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023). CONCLUSIONS: Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS.


Bariatric Surgery , Helicobacter Infections , Helicobacter pylori , Obesity, Morbid , Humans , Retrospective Studies , Prospective Studies , Obesity, Morbid/surgery , Helicobacter Infections/drug therapy , Amoxicillin/therapeutic use , Clarithromycin/therapeutic use , Omeprazole/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Weight Loss , Drug Therapy, Combination , Anti-Bacterial Agents/therapeutic use
20.
Ann Clin Microbiol Antimicrob ; 23(1): 21, 2024 Feb 24.
Article En | MEDLINE | ID: mdl-38402175

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.


Pregnancy Complications, Infectious , Urinary Tract Infections , Pregnancy , Female , Humans , Anti-Bacterial Agents/therapeutic use , Metronidazole/therapeutic use , Pregnancy Complications, Infectious/drug therapy , Cephalosporins/therapeutic use , World Health Organization , Urinary Tract Infections/drug therapy
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