Development of intestinal colonic drug delivery systems for diverticular disease: A QbD approach.

This study aimed to advance the development of intestinal colon-coated sustained-release matrix tablets of metronidazole for diverticulitis treatment, employing the Quality by Design (QbD) methodology. Comprehensive Risk analysis and Risk evaluation were conducted to assess the potential risks associated with Critical Material Attributes (CMA) and Critical Process Parameters (CPP). Ishikawa diagram, color-coded risk classification and the Risk Priority Number (RPN) were used as tools for risk evaluation. A Design of Experiments (DoE) was executed using a fractional factorial design, incorporating five key factors derived from the Risk analysis and Risk evaluation. Two levels and a central point were established for each factor, resulting in 28 batches of coated tablets. The manufacturing process involved direct compression, followed by a coating process using pH-dependent or time-dependent polymers. Characterization and dissolution studies were conducted on all batches, and the obtained results underwent analysis of variance (ANOVA). The findings demonstrated the robustness and reproducibility of both the direct compression and coating processes. Statistical analysis identified HPMC/chitosan ratio, blending time, coating polymer, and coating weight gain as factors significantly impacting drug release. A Design Space was established to delineate the interplay of these factors, offering insights into various combinations influencing drug release behavior. Thus, the design space for 10 % weight gain formulations includes a range of HPMC/CH ratios between 2.7-3 and mixing times between 10 and 12 min; for 20 % weight gain formulations it includes a range of HPMC/CH ratios up to 2 and mixing times between 10 and 16 min. Multiple Linear Regression between technological and biopharmaceutical variables were optimized facilitating scale-up operations. Batches with a 10 % weight increase and varied HPMC viscosity grades and coating polymers achieve ∼50 % drug release at 24 h; however, batches with a 20 % weight increase along, with either high proportions of HPMC and short blending times or low proportions of HPMC and longer blending times, achieve slow release of metronidazole. This study contributes to optimizing metronidazole colonic delivery systems, enhancing their potential efficacy in diverticulitis treatment.

Investigation of metronidazole resistance-associated mutations and virulence genotypes in helicobacter pylori isolates from the Egyptian population: A cross-sectional study.

INTRODUCTION: This cross-sectional study assesses the prevalence of metronidazole resistance-associated mutations and virulence genotypes in Helicobacter pylori (H. pylori) strains isolated from the Egyptian population. H. pylori infection is a significant public health concern, with antibiotic resistance challenging its eradication. METHODS: Gastric biopsy samples were collected from symptomatic patients referred for upper gastrointestinal endoscopy at selected healthcare facilities. The study included 250 participants with symptoms suggestive of H. pylori infection and aged 18 years or older. Biopsy samples were obtained using standard endoscopic techniques, and H. pylori strains were isolated and identified in the laboratory. Antimicrobial susceptibility testing was conducted using standard methods. Molecular analysis, including polymerase chain reaction (PCR) and sequencing, was performed to identify metronidazole resistance-associated mutations (rdxA and frxA) and virulence genotypes (cagA and vacA). RESULTS: Antimicrobial susceptibility testing revealed that 43.6 % of the isolates were resistant to metronidazole, while 11.8 %, 4.5 %, and 55.4 % were resistant to clarithromycin, amoxicillin, and levofloxacin. Molecular analysis identified rdxA and frxA mutations in 36.3 % and 31.8 % of the isolates, respectively, indicating metronidazole resistance-associated mutations. Additionally, 60.0 % of the isolates were positive for the cagA gene, and 80.0 % had the vacA s1 type, both associated with increased virulence. A significant association was found between metronidazole resistance and the presence of cagA gene, vacA s1 type, rdxA mutation, and frxA mutation. Statistical analysis revealed associations between specific mutations and virulence genotypes with respective odds ratios, indicating higher likelihoods of metronidazole resistance in isolates exhibiting these genetic characteristics. CONCLUSIONS: This study highlights the prevalence of metronidazole resistance and the association between specific mutations and virulence genotypes in H. pylori strains isolated from the Egyptian population. The findings underscore the importance of monitoring antibiotic resistance patterns and understanding the genetic determinants of virulence in H. pylori for effective management and treatment strategies.

An Unusual Case of Metronidazole-induced Encephalopathy in a Patient with Hereditary Hemorrhagic Telangiectasia.

Metronidazole-induced encephalopathy (MIE) is a rare toxic encephalopathy. We describe a reversible MIE case in a patient with hereditary hemorrhagic telangiectasia (HHT), treated with metronidazole for brain abscess, who developed dizziness, weakness, dysarthria, and severe dysmetria. His Magnetic Resonance Imaging (MRI) brain revealed bilateral, symmetric lesions in bilateral symmetrical regions of increased intensity in the medullary olives, cerebellar dentate nuclei, and the dorsal pons, all characteristic of MIE. Upon metronidazole discontinuation, the patient experienced significant symptom improvement, with subsequent MRI showing resolution of the lesions.

A Retrospective Assessment of Guideline Adherence and Treatment Outcomes From Clostridioides difficile Infection Following the IDSA 2021 Clinical Guideline Update: Clostridioides difficile Infection.

Background: The 2021 update to the Infectious Diseases Society of America Clostridioides difficile infection (CDI) guidelines recommended fidaxomicin as the preferred treatment over vancomycin for patients with initial and recurrent CDI. Few studies have examined how treatment patterns and clinical outcomes of hospitalized CDI patients changed after the postguideline update or contemporary real-world outcomes of fidaxomicin vs vancomycin. Methods: This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections. Results: A total of 45 049 patients with CDI from 779 US hospitals met initial inclusion criteria. Comparing the pre vs post periods, the proportion of patients treated with fidaxomicin increased from 5.9% to 13.7% (P < .001), vancomycin use decreased from 87.9% to 82.9% (P < .001), and metronidazole use decreased from 21.6% to 17.2% (P < .001). When comparing fidaxomicin vs vancomycin in the post period, fidaxomicin was associated with lower CDI recurrence (6.1% vs 10.2%; P < .001) and higher sustained clinical response (91.7% vs 87.8%; P < .001). Ninety-day postdischarge costs were not significantly different between groups. A sensitivity analyses showed similar findings. Conclusions: Since the 2021 guideline update, fidaxomicin use has increased significantly but could be further utilized given its association with better clinical outcomes and no increase in postdischarge costs.

Recurrent Clostridioides difficile infections in solid organ transplant recipients: the international CALIPSO study.

OBJECTIVE: To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. METHODS: Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. RESULTS: 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n=114,59.7%), vancomycin+metronidazole (n=39,20.4%), metronidazole (n=26,13.6%), fidaxomicin (n=9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p<.001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p=.001) were factors independently associated with recurrence. CONCLUSIONS: Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.

Optimization of Minocycline-Containing Bismuth Quadruple Therapy for Helicobacter pylori Rescue Treatment: A Real-World Evidence Study.

BACKGROUND: The optimal dosage of minocycline remains unclear for Helicobacter pylori (H. pylori) eradication. We aimed to evaluate the efficacy and safety of four different regimens with minocycline and metronidazole compared to classical bismuth quadruple therapy for H. pylori rescue treatment. MATERIALS AND METHODS: From March 2021 to March 2024, refractory H. pylori-infected patients with at least two previous treatment failures who received 14-day therapy with b.i.d. proton pump inhibitor 20 mg and bismuth 220 mg, plus tetracycline 400 mg q.i.d and metronidazole 400 mg q.i.d (BQT), or minocycline 50 mg q.i.d and metronidazole 400 mg q.i.d (PBMn4M4), or minocycline 50 mg t.i.d and metronidazole 400 mg t.i.d (PBMn3M3), or minocycline 50 mg b.i.d and metronidazole 400 mg q.i.d (PBMn2M4), or minocycline 50 mg b.i.d and metronidazole 400 mg t.i.d (PBMn2M3) were included in this retrospective study. H. pylori eradication was assessed by 13C-urea breath test at least 6 weeks after treatment. All adverse effects during treatment were recorded. RESULTS: Totally, 823 patients were enrolled: 251 with BQT, 97 with PBMn4M4, 191 with PBMn3M3, 108 with PBMn2M4, and 176 with PBMn2M3. The eradication rates of BQT, PBMn4M4, PBMn3M3, PBMn2M4, and PBMn2M3 were 89.2%, 87.6%, 91.6%, 88.0%, and 91.5%, respectively, by intention-to-treat analysis; 96.1%, 97.7%, 97.8%, 96.9%, and 97.6%, respectively, by modified intention-to-treat analysis; 97.1%, 97.5%, 97.7%, 96.8%, and 97.6%, respectively, by per-protocol analysis. Metronidazole resistance did not affect the efficacy of all groups. PBMn2M3 group achieved the greatest compliance and the fewest moderate and severe adverse events. CONCLUSIONS: The novel bismuth-containing quadruple therapy with a low dose of minocycline and metronidazole is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment with superior safety and compliance. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06332599.

Rapid Antimicrobial Susceptibility Test of Helicobacter pylori to Metronidazole via Single-Cell Raman Spectrometry.

BACKGROUND: Metronidazole is a first-line antibiotic to treat Helicobacter pylori infections. However, the Clinical Laboratory Standards Institute guidelines recommend against using antimicrobial susceptibility test (AST) to test metronidazole resistance, due to the unreliable predictive power which can result in treatment failure. OBJECTIVES: The aim of this study was to establish an 8-h, metabolic-phenotype based AST for H. pylori metronidazole susceptibility using D2O-probed Raman microspectroscopy. METHODS: Minimal inhibitory concentration (MIC) measured by conventional AST (E-test) were compared with expedited MIC via metabolic activity (eMIC-MA) for 10 H. pylori isolates. Raman barcodes of cellular-response to stress (RBCS) incorporating protein and carbohydrate Raman bands, were utilized to identify a biomarker to distinguish metronidazole susceptibility. RESULTS: Specifically, eMIC-MA produces metronidazole susceptibility results showing 100% agreement with E-test, and determines the bactericidal dosage for both high- and low-level resistant H. pylori strains. In addition, RBCS not just reliably distinguish between metronidazole-susceptible and -resistant strains, but reveal their distinct mechanisms in bacterial responses to metronidazole. CONCLUSION: The speed, accuracy, low cost, and rich information content that reveals the mode-of-action of drugs suggest the method's value in guiding metronidazole prescriptions for H. pylori eradication and in rapid screening based on drug-resistance mechanism.

Impact of LED radiation intensity on gold nanoparticles photodeposition on TiO2 with physicochemical and photocatalytic characterization.

This study investigates the influence of LED radiation intensity on the photodeposition of gold nanoparticles onto TiO2 substrates, examining their physicochemical properties and photocatalytic activities. Utilizing a range of radiation intensities and wavelengths, TiO2-Au composites were synthesized and characterized through techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive X-ray (EDX), and X-ray photoelectron spectroscopy (XPS). The deposition process, markedly enhanced by shorter wavelengths and higher intensities, efficiently formed gold nanoparticles. This research distinctly highlights observable morphological changes in the nanoparticles; increased radiation intensity not only augmented the size but also altered their shape from spherical to hexagonal. These morphological transformations significantly improve the composites' light absorption and catalytic properties due to the surface plasmon resonance of the gold nanoparticles. Photocatalytic assessments, using metronidazole as a model pollutant, demonstrated that composites prepared with higher LED intensities showed significantly enhanced degradation capabilities compared to those synthesized with lower intensities. The findings underscore that manipulating photodeposition parameters can critically influence the structural and functional properties of TiO2-Au composites, potentially advancing their applications in environmental remediation and solar energy utilization.

Successful Treatment of Angiolymphoid Hyperplasia with Eosinophilia Associated with Scalp Demodicosis Using Cryotherapy and Topical Metronidazole.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign, vasoproliferative tumour. We report a 25-year-old female patient who reported in 2021 to a dermatology clinic in Rustaq, Oman, with multiple, grouped, erythematous dome-shaped papules and nodules of 6 months duration on the left temporo-occipital region. Biopsy findings were consistent with a diagnosis of ALHE with evidence of Demodex mite infestation in the sebaceous ducts. The patient demonstrated significant improvement following 7 weeks of treatment with multiple cryotherapy sessions and topical application of metronidazole gel. This case suggests that scalp demodicosis may represent a novel trigger for the development of ALHE.

Metronidazole Modified-Release Therapy Using Two Different Polymeric Systems Gels or Films: Clinical Study for the Treatment of Periodontitis.

This study evaluated the efficacy of semisolid systems (gels) and films containing a combination of metronidazole (MTZ) and metronidazole benzoate after scaling and root-planing (SRP) for periodontitis. In total, 45 patients with stage I or II periodontitis were enrolled and divided into 3 groups: 1-SRP-control; 2-SRP + Film with MTZ; 3-SRP + Gel with MTZ. The pH of gingival crevicular fluid (GCF) before/after treatments, MTZ concentrations, and drug release using high-performance liquid chromatography were investigated. The effects were evaluated by longitudinal monitoring of clinical parameters (probing depth-PD, clinical attachment level-CAL, and bleeding on probing-BP). MTZ and MTZ-benzoate concentrations in the periodontal pocket and pH showed no statistical difference after application. SRP + Gel presented the lowest CAL values. For SRP + Film and SRP + Gel, higher PD values were observed at T0 compared to all groups. A relevant reduction in BP was observed in SRP + Film and SRP + Gel groups at all times compared to T0. Both therapies improved periodontal health compared to SRP alone, reducing PD and BP, and increasing CAL for the gel group, suggesting they are promising for periodontal disease treatment.

Effects of cardanol-based phospholipid analogs on Trichomonas vaginalis.

Trichomonas vaginalis is a protist parasite of the urogenital tract, responsible for human trichomoniasis, an infection sexually transmitted that affects approximately 156 million people worldwide. This pathology is more evident in females and can cause miscarriages, premature births, and infertility. The disease can also lead to a greater predisposition to HIV infection and cervical and prostate cancer. Metronidazole (MTZ) is a drug that treats human trichomoniasis. The data from studies involving human subjects are limited regarding MTZ use during pregnancy. In addition to the toxicity of the treatment, some isolates have become resistant to MTZ. Therefore, searching for new compounds active for treating trichomoniasis becomes necessary. In the present study, we report results obtained using new phospholipid analogs. Two cardanol-based compounds designated LDT117 and LDT134 were active against T. vaginalis with an IC50 of 4.58 and 10.24 µM, respectively. These compounds were not toxic to epithelial cells in culture. Scanning electron microscopy observations revealed a rounding of the cells, a shortening of the flagella, and protrusions on the surface of drug-treated cells. Transmission electron microscopy of treated cells revealed alterations in the plasma membrane with formations of blebs, protrusions, depressions, and vacuoles with myelin figures and vacuolization in the cytoplasm after incubation. Furthermore, after treatments with the compounds LDT117 and LDT134, the parasites presented a positive reaction for TUNEL, indicating death by a mechanism like apoptosis. Given the results obtained, further in vivo studies using animal experimental models are necessary to validate that these compounds are effective for treating human trichomoniasis.

Metronidazole-induced encephalopathy in a patient with spondylodiscitis.

INTRODUCTION: Metronidazole-induced encephalopathy is an uncommon but potentially severe complication of metronidazole treatment. Although the exact pathophysiology remains elusive, proposed hypotheses include RNA binding, neurotoxicity from free radicals, and modulation of neurotransmitter receptors. Most cases demonstrate improvement upon discontinuation of metronidazole, highlighting the importance of early recognition. Magnetic resonance imaging plays a critical role in diagnosing metronidazole-induced encephalopathy, with characteristic imaging findings frequently observed in the dentate nuclei and corpus callosum. CASE SUMMARY: A 63-year-old man treated with metronidazole for lumbar spondylodiscitis developed neurological symptoms consistent with metronidazole-induced encephalopathy. IMAGES: Magnetic resonance imaging revealed characteristic bilateral hyperintense lesions in the cerebellar dentate nuclei, corpus callosum, and brainstem. Prompt recognition and discontinuation of metronidazole led to symptom resolution. CONCLUSION: This case underscores the importance of clinicians and radiologists being aware of this condition and emphasizes the pivotal role of magnetic resonance imagining in establishing the diagnosis.

The emergence of metronidazole-resistant Prevotella bivia harboring nimK gene in Japan.

We present the identification and characterization of the complete genome of metronidazole (MTZ)-resistant Prevotella bivia strain TOH-2715 [minimum inhibitory concentration (MIC): 8 mg/L], isolated from the urine of an elderly Japanese woman, as well as details of its mobile genetic elements (MGEs) containing antimicrobial resistance (AMR) genes and its relationship with other bacterial species determined using whole-genome sequencing (WGS) data. TOH-2715 possessed two chromosomes with putative MGEs containing AMR genes. Two AMR-related MGE regions were present in chromosome 2. MGE-region 1 (7,821 bp) included Tn6456, where nimK was located, and MGE-region 2 (58.8 Kbp) included the integrative and conjugative element (ICE), where tet(Q) and ermF were located. The genetic structure of the ICE of TOH-2715 was similar to that of CTnDOT-family transposons, where ermF and tet(Q) are located. A search of public databases revealed that nimK was present in Prevotella spp., including P. bivia, and was partially composed of a Tn6456-like element lacking the efflux transporter gene qacE and the Crp/Fnr family transcriptional regulator gene in some cases. Core ICE gene analysis showed that ICEs similar to that of TOH-2715 were present in Prevotella spp. and Bacteroides spp., suggesting horizontal gene transfer among anaerobes. This is the report of WGS analysis of an MTZ-resistant clinical strain of P. bivia (TOH-2715) with Tn6456 encoding nimK. Other submitted genomes have described the presence of nimK, but none of them have described MTZ resistance. Additionally, we described putative MGE regions containing the AMR gene within the genus Prevotella and among anaerobes, raising concerns about the future spread of nimK among anaerobes. IMPORTANCE: Metronidazole (MTZ) is an important antimicrobial agent in anaerobic infections and is widely used in clinical settings. The rate of MTZ resistance in anaerobic bacteria has been increasing in recent years, and the nim gene (nitro-imidazole reductase) is one of the resistance mechanisms. Prevotella bivia is found in humans in the urinary tract and vagina and is known to cause infections in some cases. One of the nim genes, nimK, has recently been discovered in this species of bacteria, but there are no reports of antimicrobial resistance (AMR)-related regions in its whole genome level. In this study, we analyzed the AMR region of nimK-positive P. bivia derived from clinical specimens based on comparisons with other anaerobic genomes. P. bivia was found to be engaged in horizontal gene transfer with other anaerobic bacteria, and the future spread of the nimK gene is a concern.

[A case of metronidazole-induced encephalopathy that is difficult to differentiate from Wernicke encephalopathy].

Herein, we present the case of a 76-year-old man diagnosed with an iliopsoas abscess 3 months prior and consequently administered metronidazole. The patient visited our facility complaining of difficulty in speaking and feeling unsteady when walking. Neurological findings showed dysarthria, nystagmus, and bilateral cerebellar ataxia. Head MRI-FLAIR demonstrated symmetrical hyperintensities in the bilateral cerebellar dentate nuclei, red nucleus, periaqueductal of the midbrain, periventricular third ventricle, and the corpus callosum. Although Wernicke's encephalopathy was among the differential diagnoses based on the imaging findings, the thiamine level was normal and improvement in symptoms and hyperintensity on FLAIR within 5 days of discontinuing metronidazole led to the diagnosis of metronidazole-induced encephalopathy. Although there were many similarities in the imaging findings of metronidazole-induced encephalopathy and Wernicke's encephalopathy, Metronidazole-induced encephalopathy should be initially considered when midbrain red nucleus lesions are observed.

Based on mutated aptamer-smartphone colorimetric detection of metronidazole in milk.

Excessive residue of metronidazole (MNZ) in food is harmful to the human body. There is an urgent demand to develop a portable tool for MNZ detection on-site. In this study, fifteen aptamers were prepared through targeted base mutation. Apt1-3 with the highest enrichment was chosen for further study. Its affinity was characterized by molecular docking simulation, AuNPs colorimetric assay, graphene oxide (GO) fluorescence assay, and exonuclease assay. Kd was determined by GO fluorescence assay (Kd: 92.60 ± 25.59 nM). Its specificity was also characterized by an exonuclease assay. A novel aptasensor was constructed by using the newly identified aptamer combined with the smartphone dark box. The principle of color change is caused by the aggregation state of AuNPs. Smartphones act as reading instruments. The detection can be completed in just a few seconds without the aid of instruments, achieving a detection limit of 0.15 nmol/mL and a range of 6.7-44.4 nmol/mL (R 2 = 0.9810). Therefore, the constructed smartphone colorimetric sensor based on mutant aptamers has important applications in food detection.

From Hemorrhage to Diarrhea: The Comprehensive Clinical Journey of a Patient With Pseudomembranous Colitis.

Pseudomembranous colitis (PC) is an inflammation of the colon primarily caused by the bacterium Clostridium difficile (C. difficile), often following antibiotic use. This case report describes the intricate clinical course of a 48-year-old male farmer with a history of chronic alcoholism, tobacco use, and seizure disorder, who presented with acute onset of left-sided weakness. CT brain revealed an intra-axial hemorrhage in the right gangliocapsular region with significant edema and midline shift. The patient's condition necessitated mechanical ventilation due to a low Glasgow Coma Scale (GCS) score. Complications ensued with the onset of ventilator-associated pneumonia (VAP) on day six, attributed to multi-drug resistant Acinetobacter baumannii, which was managed with meropenem and polymyxin. Following successful weaning from the ventilator, he experienced severe watery diarrhea, high-grade fever, and diffuse abdominal pain on day 13. Subsequent stool tests confirmed PC caused by C. difficile, characterized by diffuse colonic wall-thickening with a water target sign on contrast-enhanced CT (CECT) abdomen. Initial treatment with oral vancomycin and metronidazole was followed by symptomatic treatment. Two weeks later, the patient had a relapse of PC, presenting with multiple episodes of loose stools, which was managed with oral metronidazole alone. Colonoscopy and biopsy confirmed the relapse, showing inflamed colonic mucosa with pseudomembranes. This case highlights the importance of strict infection control, prudent antibiotic use, and close monitoring for these patients. It also suggests the potential role of fecal microbiota transplantation (FMT) for recurrent cases. The patient's recovery demonstrates the effectiveness of meticulous medical management and adherence to infection control protocols in achieving optimal outcomes.

Topical metronidazole after haemorrhoidectomy to reduce postoperative pain: a systematic review.

Excisional haemorrhoidectomy is the gold standard for operating haemorrhoids, but it is accompanied by a significant problem: postoperative pain. Several strategies have been adopted to minimize this condition. Oral metronidazole has been proven to reduce postoperative pain but with some complications. This systematic review was conducted to investigate the effects and general efficacy of topical metronidazole administration and to evaluate its potential superiority over the oral formula. A systematic review of the literature was carried out. Randomized controlled trials published until September 2023 on PubMed, Central, and Web of Science were considered. The primary outcome considered was postoperative pain, which was evaluated using visual analogue scores. The secondary outcomes were analgesic use, return to work, and complications. Six randomized controlled trials were included, with a total of 536 patients. Topical metronidazole was compared with placebo in two studies, with oral formula in three studies, and with placebo and oral administration in one study. Topical metronidazole was found to be effective for treating postoperative pain when compared to a placebo but had no significant advantage over the oral formula. No complications were reported in the studies. Topical and oral metronidazole are effective solutions for postoperative pain after excisional haemorrhoidectomy. No superiority was demonstrated based on the route of administration, and complications were marginal for both formulas. Further studies are required to determine the best metronidazole solution.

Standardization of quantitative PCR (qPCR) method to detect the level of parasitaemia in Babesia gibsoni infected dogs.

The present investigation aimed to quantitatively assess the level of parasitemia in dogs using qPCR.The dogs selected for this study were infected with the haemoprotozoan parasite Babesia gibsoni. In the study, dogs diagnosed with babesiosis were divided into two groups (n = 12) and subjected to distinct treatment strategies. The first group received clindamycin-metronidazole-doxycycline (CMD) therapy, while the second group was treated with a combination of buparvaquone-azithromycin (BPV-AZM). The level of parasitemia in the infected dogs was determined using an absolute quantification-based qPCR method. This assessment was conducted both prior to initiating the treatment and on the 10th day following the commencement of the treatment protocols. On the tenth day after the initiation of treatment, the CMD group exhibited a lower level of parasitemia in comparison to the BPV-AZM group. In the CMD treated groups, the mean parasitemia decreased from 4.9E + 06 to 3.4E + 06, indicating a reduction in parasitic load. Conversely, in the BPV-AZM treatment groups, the mean parasitemia increased from 1.62E + 06 to 2.87E + 06, suggesting an increase in parasitic load. On the 10th day, the CMD-treated group demonstrated a statistically significant decline in the level of parasitemia, with a P-value of ≤0.001. This indicates a strong and significant reduction in parasitic load following the CMD treatment. Therefore, the absolute quantification-based qPCR method could effectively assess the initial treatment response by measuring the level of parasitemia.

Mechanochemical synthesis of novel metronidazole cocrystal: Structure characterization and pharmaceutical properties study.

A new cocrystalline form of metronidazole (MET) with propyl gallate (PRO), referred to as MET-PRO, has been successfully synthesized and characterized. Structural characterization reveals that MET and PRO are present in a 1:1 ratio within the cocrystal lattice, with one water molecule equivalent incorporated into the structure. This arrangement facilitates the formation of MET-PRO heterodimers and multiple stable units, collectively constructing a three-dimensional supramolecular network. The solubility and permeability of the current cocrystal, along with the parent drug MET, are evaluated under physiological pH conditions. Experimental findings reveal that MET within the cocrystal exhibits a 1.54-2.37 folds increase in solubility and approximately a threefold improvement in permeability compared to its standalone form. Intriguingly, these concurrent enhancements in the physicochemical properties of MET lead to augmented antibacterial activity in vitro, evidenced by a reduction in minimum inhibitory concentration. Even more intriguingly, the enhanced physicochemical properties observed in vitro for the current cocrystal translate into tangible pharmacokinetic benefits in vivo, characterized by prolonged half-life and enhanced bioavailability. Consequently, this research not only introduces a fresh crystal structure for antibacterial medication but also presents approach for optimizing drug properties across in vitro and in vivo settings, while concurrently bolstering the antibacterial effectiveness of MET through pharmaceutical cocrystallization techniques.

New functions of pirin proteins and a 2-ketoglutarate: Ferredoxin oxidoreductase ortholog in Bacteroides fragilis metabolism and their impact on antimicrobial susceptibility to metronidazole and amixicile.

The understanding of how central metabolism and fermentation pathways regulate antimicrobial susceptibility in the anaerobic pathogen Bacteroides fragilis is still incomplete. Our study reveals that B. fragilis encodes two iron-dependent, redox-sensitive regulatory pirin protein genes, pir1 and pir2. The mRNA expression of these genes increases when exposed to oxygen and during growth in iron-limiting conditions. These proteins, Pir1 and Pir2, influence the production of short-chain fatty acids and modify the susceptibility to metronidazole and amixicile, a new inhibitor of pyruvate: ferredoxin oxidoreductase in anaerobes. We have demonstrated that Pir1 and Pir2 interact directly with this oxidoreductase, as confirmed by two-hybrid system assays. Furthermore, structural analysis using AlphaFold2 predicts that Pir1 and Pir2 interact stably with several central metabolism enzymes, including the 2-ketoglutarate:ferredoxin oxidoreductases Kor1AB and Kor2CDAEBG. We used a series of metabolic mutants and electron transport chain inhibitors to demonstrate the extensive impact of bacterial metabolism on metronidazole and amixicile susceptibility. We also show that amixicile is an effective antimicrobial against B. fragilis in an experimental model of intra-abdominal infection. Our investigation led to the discovery that the kor2AEBG genes are essential for growth and have dual functions, including the formation of 2-ketoglutarate via the reverse TCA cycle. However, the metabolic activity that bypasses the function of Kor2AEBG following the addition of phospholipids or fatty acids remains undefined. Overall, our study provides new insights into the central metabolism of B. fragilis and its regulation by pirin proteins, which could be exploited for the development of new narrow-spectrum antimicrobials in the future.