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BMJ (Clinical Research Ed.) Nov 2022To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery.
DESIGN
Multicentre, randomised, double blind, placebo controlled trial.
SETTING
11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019.
PARTICIPANTS
926 adults scheduled for elective colorectal surgery.
INTERVENTION
Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision.
MAIN OUTCOME MEASURES
The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery.
RESULTS
Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference -8.6%, 95% confidence interval -13.5% to -3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference -3.2%, 95% confidence interval -6.4% to -0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference -3.4%, -6.7% to -0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference -4.5%, -8.6% to -0.5%).
CONCLUSION
Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02618720.
Topics: Adult; Male; Humans; Middle Aged; Female; Surgical Wound Infection; Colorectal Surgery; Ornidazole; Antibiotic Prophylaxis; Anti-Bacterial Agents; Anti-Infective Agents; Double-Blind Method
PubMed: 36328372
DOI: 10.1136/bmj-2022-071476 -
Chinese Medical Journal Jul 2022High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.
METHODS
This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.
RESULTS
A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (-9.19% in the ITT analysis, - 9.21% in the MITT analysis, and -9.73% in the PP analysis) was greater than the predefined non-inferiority margin of -10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients' compliance were similar between the two groups.
CONCLUSIONS
Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT04678492.
Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Esomeprazole; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Potassium Citrate; Prospective Studies; Proton Pump Inhibitors; Tetracycline; Treatment Outcome
PubMed: 36193978
DOI: 10.1097/CM9.0000000000002289 -
PloS One 2022Furazolidone is a synthetic nitrofuran with a broad spectrum of antimicrobial action and has been widely used in the treatment of Helicobacter pylori (H. pylori)...
BACKGROUND
Furazolidone is a synthetic nitrofuran with a broad spectrum of antimicrobial action and has been widely used in the treatment of Helicobacter pylori (H. pylori) infection. However, its safety profile has not been clarified. Moreover, the drug fever associated with its use is frequently misdiagnosed. The aim of this study was to explore the risk factors of furazolidone-associated fever to increase awareness and stimulate further research on this topic.
METHODS
This was a retrospective case-control study of patients referred to a specialist clinic for furazolidone-containing quadruple regimens for H. pylori infection at a tertiary care hospital located in Eastern China between July 2018 and September 2018. We evaluated adult patients who received furazolidone treatment for Helicobacter pylori infection. The exclusion criteria were as follows: (1) patients were pregnant or breastfeeding; (2) patients received furazolidone treatment not for Helicobacter pylori infection; (3) patients had taken antibiotics or any acid suppressant or non-steroidal anti-inflammatory drug in the last 4 weeks; (4) patients had chronic hepatic, renal, or pulmonary disease. Pertinent information was retrieved from medical records and telephone follow-up. All statistical analysis was performed in SPSS version 22.0.
RESULTS
A total of 1499 patients received furazolidone and met the overall inclusion criterion. Of these 1499 patients, 27 (1.80%) developed drug fever. The mean time between initiation of furazolidone and the onset of fever is 11.00 ± 1.84 days, and the median peak fever was 38.87 ± 0.57°C. We found no differences in age and past drug allergy between the non-fever and fever groups. Through multiple logistic regression analysis, we found two variables as independent risk factors for furazolidone-associated fever, including gender (OR, 3.16; 95% CI, 1.26-7.91; P = 0.014) and clarithromycin (OR, 4.83; 95% CI, 2.17-10.79; P<0.001).
CONCLUSIONS
This retrospective cohort study identified two risk factors for furazolidone-associated fever, which were female and clarithromycin. We also analyzed the characteristics of drug fever during anti-Helicobacter pylori therapy. However, the underlying mechanisms are uncertain and require further research.
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Case-Control Studies; Clarithromycin; Drug Therapy, Combination; Female; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 35395029
DOI: 10.1371/journal.pone.0266763 -
Journal of Infection in Developing... Jan 2023Human trichomoniasis is a widespread sexually transmitted disease and the concern of drug resistance in the parasite is growing. Hence, this study was performed to...
INTRODUCTION
Human trichomoniasis is a widespread sexually transmitted disease and the concern of drug resistance in the parasite is growing. Hence, this study was performed to evaluate in vitro antitrichomonal activity of Satureja khuzestanica, carvacrol, thymol, eugenol, and phytochemical evaluation of the S. khuzestanica oil.
METHODOLOGY
Extracts and essential oil of S. khuzestanica, and the components were prepared. Then, susceptibility testing was performed using the microtiter plate method and Trichomonas vaginalis isolates. The minimum lethal concentration (MLC) of the agents was determined in comparison with metronidazole. Also, the essential oil was investigated by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector.
RESULTS
After 48 hours of incubation, carvacrol and thymol were the most effective antitrichomonal agents with MLC of 100 µg/mL, followed by the essential oil and hexanic extract (MLC = 200 µg/mL), then eugenol and methanolic extract (MLC = 400 µg/mL), in comparison with the metronidazole MLC of 6.8 µg/mL. Overall, 33 identified compounds accounted for 98.72% of the total essential oil composition with carvacrol, thymol, and p-cymene being the major constituents.
CONCLUSIONS
The results suggested the potency of S. khuzestanica and its bioactive ingredients against T. vaginalis. Thus, further in vivo studies are required to evaluate the efficacies of the agents.
Topics: Humans; Thymol; Oils, Volatile; Antitrichomonal Agents; Satureja; Eugenol; Metronidazole; Plant Extracts
PubMed: 36795930
DOI: 10.3855/jidc.16360 -
Antimicrobial Agents and Chemotherapy Apr 2023Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor...
Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor efficacy of doxycycline and acquired resistance to azithromycin and moxifloxacin. A recent clinical trial suggested that metronidazole may improve cure rates for women with pelvic inflammatory disease and reduced the detection of M. genitalium when included with standard doxycycline plus ceftriaxone treatment. As data regarding susceptibility of mycoplasmas to nitroimidazoles are lacking in the scientific literature, we determined the susceptibility of 10 M. genitalium strains to metronidazole, secnidazole, and tinidazole. MICs ranged from 1.6 to 12.5 μg/mL for metronidazole, 3.1 to 12.5 μg/mL for secnidazole, and 0.8 to 6.3 μg/mL for tinidazole. None of these agents was synergistic with doxycycline in checkerboard broth microdilution assays. Tinidazole was superior to metronidazole and secnidazole in terms of MIC and time-kill kinetics and was bactericidal (>99.9% killing) at concentrations below reported serum concentrations. Mutations associated with nitroimidazole resistance were identified by whole-genome sequencing of spontaneous resistant mutants, suggesting a mechanism for reductive activation of the nitroimidazole prodrug by a predicted NAD(P)H-dependent flavin mononucleotide (FMN) oxidoreductase. The presence of oxygen did not affect MICs of wild-type M. genitalium, but a nitroimidazole-resistant mutant was defective for growth under anaerobic conditions, suggesting that resistant mutants may have a fitness disadvantage in anaerobic genital sites. Clinical studies are needed to determine if nitroimidazoles, especially tinidazole, are effective for eradicating M. genitalium infections in men and women.
Topics: Male; Female; Humans; Nitroimidazoles; Doxycycline; Metronidazole; Tinidazole; Mycoplasma genitalium; Anti-Bacterial Agents; Mycoplasma Infections; Drug Resistance, Bacterial
PubMed: 37070857
DOI: 10.1128/aac.00006-23 -
Molecules (Basel, Switzerland) Oct 2021Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal,... (Review)
Review
Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antiparasitic Agents; Benzofurans; Hydrophobic and Hydrophilic Interactions; Lichens; Potassium
PubMed: 34641539
DOI: 10.3390/molecules26195995 -
International Journal of Molecular... Sep 2022The colonization of () in human gastric mucosa is highly associated with the occurrence of gastritis, peptic ulcer, and gastric cancer. Antibiotics, including... (Review)
Review
The colonization of () in human gastric mucosa is highly associated with the occurrence of gastritis, peptic ulcer, and gastric cancer. Antibiotics, including amoxicillin, clarithromycin, furazolidone, levofloxacin, metronidazole, and tetracycline, are commonly used and considered the major treatment regimens for eradication, which is, however, becoming less effective by the increasing prevalence of resistance. Thus, it is urgent to understand the molecular mechanisms of pathogenesis and develop alternative therapeutic strategies. In this review, we focus on the virulence factors for colonization and survival within host gastric mucosa and the host antimicrobial responses against infection. Moreover, we describe the current treatments for eradication and provide some insights into new therapeutic strategies for infection.
Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Clarithromycin; Drug Resistance, Bacterial; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Tetracycline; Virulence Factors
PubMed: 36142852
DOI: 10.3390/ijms231810941 -
Microbiology Spectrum Jun 2023The rates of antibiotic resistance of Helicobacter pylori are increasing, and the patterns of resistance are region and population specific. Here, we elucidated the...
The rates of antibiotic resistance of Helicobacter pylori are increasing, and the patterns of resistance are region and population specific. Here, we elucidated the antibiotic resistance pattern of H. pylori in a single center in China and compared short-read- and long-read-based whole-genome sequencing for identifying the genotypes. Resistance rates of 38.5%, 61.5%, 27.9%, and 13.5% against clarithromycin, metronidazole, levofloxacin, and amoxicillin were determined, respectively, while no strain was resistant to tetracycline or furazolidone. Single nucleotide variations (SNVs) in the 23S rRNA and GyrA/B genes revealed by Illumina short-read sequencing showed good diagnostic abilities for clarithromycin and levofloxacin resistance, respectively. Nanopore long-read sequencing also showed a good efficiency in elucidating SNVs in the 23S rRNA gene and, thus, a good ability to detect clarithromycin resistance. The two technologies displayed good consistency in discovering SNVs and shared 76% of SNVs detected in the rRNA gene. Taking Sanger sequencing as the gold standard, Illumina short-read sequencing showed a slightly higher accuracy for discovering SNVs than Nanopore sequencing. There are two copies of the rRNA gene in the genome of H. pylori, and we found that the two copies were not the same in at least 26% of the strains tested, indicating their heterozygous status. Especially, three strains harboring a 2143G/A heterozygous status in the 23S rRNA gene, which is the most important site for clarithromycin resistance, were found. In conclusion, our results provide evidence for an empirical first-line treatment for H. pylori eradication in clinical settings. Moreover, we show that Nanopore sequencing is a potential tool for predicting clarithromycin resistance. Helicobacter pylori resistance has been increasing in recent years. The resistance profile, which is important for empirical treatment, is region and population specific. We found high rates of resistance to metronidazole, clarithromycin, and levofloxacin in H. pylori in our center, while no resistance to tetracycline or furazolidone was found. These results provide a reference for local physicians prescribing antibiotics for H. pylori eradication. Nanopore sequencing recently appeared to be a promising technology for elucidating whole-genome sequences, which generates long sequencing reads and is time-efficient and portable. However, a relatively higher error rate of sequencing reads was also found. In this study, we compared Nanopore sequencing and Illumina sequencing for revealing single nucleotide variations in the 23S rRNA gene, which determines clarithromycin resistance, and we found that although there were a few false discoveries, Nanopore sequencing showed good consistency with Illumina sequencing, indicating that it is a potential tool for predicting clarithromycin resistance.
Topics: Humans; Clarithromycin; Metronidazole; Levofloxacin; Helicobacter pylori; Helicobacter Infections; Furazolidone; Microbial Sensitivity Tests; Anti-Bacterial Agents; Tetracycline; Drug Resistance, Microbial; Nucleotides; RNA, Ribosomal, 23S; Drug Resistance, Bacterial
PubMed: 37067452
DOI: 10.1128/spectrum.04522-22 -
American Journal of Obstetrics and... Feb 2020Vaginitis is one of the most common causes of patient visits to gynecologists, primary care providers, and urgent care centers. However, many women leave without a clear... (Review)
Review
Vaginitis is one of the most common causes of patient visits to gynecologists, primary care providers, and urgent care centers. However, many women leave without a clear diagnosis or experience recurrent symptoms despite treatment. The 3 most common etiologies of vaginitis are trichomonas, bacterial vaginosis, and vulvovaginal candidiasis, which account for an estimated 70% of cases. The remaining 30% may be related to other causes of vaginitis, including atrophic vaginitis, desquamative inflammatory vaginitis, and vaginal erosive disease. The purpose of this review is to describe the noncandidal causes of acute and recurrent vaginitis, with the goal of improving the likelihood of accurate diagnosis as well as efficient and effective therapy. We excluded candidal vaginitis from our review because there was a recently published review on this topic in the Journal. The clinical presentation and evaluation of patients with symptoms of vaginitis can be triaged into 1 of 2 diagnostic pathways: noninflammatory and inflammatory vaginitis. The most common noninflammatory cause is bacterial vaginosis. Features such as irritation, purulent discharge, and the presence of polymorphonuclear neutrophils are more suggestive of an inflammatory process. Trichomoniasis is the most common cause of inflammatory vaginitis. Other well-described forms of inflammatory vaginitis include atrophic vaginitis, desquamative inflammatory vaginitis, and erosive disease. We present a review of the pathogenesis, symptoms, examination findings, diagnostic testing, and treatment for each of these causes of noncandidal vaginitis.
Topics: Administration, Intravaginal; Administration, Oral; Anti-Infective Agents; Anti-Inflammatory Agents; Atrophic Vaginitis; Candidiasis, Vulvovaginal; Clindamycin; Dehydroepiandrosterone; Diagnosis, Differential; Estrogen Replacement Therapy; Estrogens; Female; Humans; Hydrocortisone; Inflammation; Lichen Planus; Metronidazole; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Pemphigus; Tamoxifen; Tinidazole; Trichomonas Vaginitis; Vaginitis; Vaginosis, Bacterial
PubMed: 31513780
DOI: 10.1016/j.ajog.2019.09.001 -
Gynecologic and Obstetric Investigation 2022The aim of this study was to investigate the effectiveness of ornidazole in inhibiting the progression of endometriosis in a rat model.
OBJECTIVE
The aim of this study was to investigate the effectiveness of ornidazole in inhibiting the progression of endometriosis in a rat model.
DESIGN
This was an in vivo experiment, including the ornidazole group (n = 16) and a control group (n = 14). Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days.
MATERIALS AND METHODS
Surgical induction of endometriosis was performed in Sprague Dawley rats via autologous endometrial transplantation. Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Once the rats were euthanized (ornidazole group, n = 16; control group, n = 14), histological signatures and the volumes of endometriosis lesions were assessed. Cells positive for the inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were counted. Angiogenesis was identified by assessing vascular endothelial growth factor (VEGF) and microvessel density.
RESULTS
The median lesion volume was lower in the ornidazole group (20.2 mm3; range, 5.7-53.3 mm3) than in the control group (81.3 mm3; range, 32.8-122.2 mm3; p = 0.007). Median IL-1β cell counts were 5.3 (range, 4.5-6.4) for ornidazole and 11.7 (range, 9.4-15.4) for control (p < 0.001). Mean IL-6 cell counts were 5.6 ± 1.8 for ornidazole and 11.3 ± 4.1 for control (p < 0.001). Median TNF-α cell counts were 5.7 (range, 4.5-7.2) for ornidazole and 12.1 (range, 10.0-15.9) for control (p < 0.001). Median VEGF cell counts were 8.1 (range, 6.5-11.4) for ornidazole and 18.3 (range, 14.2-21.0) for control (p = 0.001). Median microvessel density values were 11.3/HPF (range, 7.7-21.8) for ornidazole and 28.7/HPF (range, 13.1-48.2) for control (p = 0.012).
LIMITATIONS
This study is a short period and small sample size experiment. In this study, multiple drug concentrations were not used. We did not use in vitro models to assess the anti-inflammatory and antiangiogenic effects of ornidazole on endometriosis, and the specific anti-inflammatory and antiangiogenic mechanisms associated with ornidazole need to be further investigated.
CONCLUSION
Ornidazole restricts the growth of endometriosis in rats, possibly by exerting anti-inflammatory and antiangiogenic effects.
Topics: Animals; Female; Rats; Anti-Inflammatory Agents; Disease Models, Animal; Drinking Water; Endometriosis; Interleukin-6; Ornidazole; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A
PubMed: 36265450
DOI: 10.1159/000527515