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.

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.

Comparative effectiveness of vancomycin and metronidazole on event-free survival after initial infection in patients with Clostridioides difficile - a German multicentre cohort study (IBIS).

OBJECTIVES: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) following initial infection in patients with Clostridioides difficile (C. difficile) from a German multicentre cohort study. METHODS: The IBIS multicentre cohort enrolled patients with an index episode of CDI between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within ten days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections. RESULTS: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within ten days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event-free. The Cox proportional hazards model revealed differences in EFS for the overall population and both sub-groups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% Cl 0.33-0.65]; non-severe: HR 0.39; [95% Cl 0.24-0.60]; severe: HR 0.52; [95% Cl 0.28-0.95]). CONCLUSIONS: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared to metronidazole across all severity levels.

Comprehensive analysis of flavohemoprotein copy number variation in Giardia intestinalis: exploring links to metronidazole resistance.

BACKGROUND: Giardiasis, caused by the protozoan parasite Giardia intestinalis, often presents a treatment challenge, particularly in terms of resistance to metronidazole. Despite extensive research, markers for metronidazole resistance have not yet been identified. METHODS: This study analysed 28 clinical samples of G. intestinalis from sub-assemblage AII, characterised by varying responses to metronidazole treatment. We focussed on copy number variation (CNV) of the multi-copy flavohemoprotein gene, analysed using digital polymerase chain reaction (dPCR) and next generation sequencing (NGS). Additionally, chromosomal ploidy was tested in 18 of these samples. Flavohemoprotein CNV was also assessed in 17 samples from other sub-assemblages. RESULTS: Analyses revealed variable CNVs of the flavohemoprotein gene among the isolates, with no correlation to clinical metronidazole resistance. Discrepancies in CNVs detected from NGS data were attributed to biases linked to the whole genome amplification. However, dPCR helped to clarify these discrepancies by providing more consistent CNV data. Significant differences in flavohemoprotein CNVs were observed across different G. intestinalis sub-assemblages. Notably, Giardia exhibits a propensity for aneuploidy, contributing to genomic variability within and between sub-assemblages. CONCLUSIONS: The complexity of the clinical metronidazole resistance in Giardia is influenced by multiple genetic factors, including CNVs and aneuploidy. No significant differences in the CNV of the flavohemoprotein gene between isolates from metronidazole-resistant and metronidazole-sensitive cases of giardiasis were found, underscoring the need for further research to identify reliable genetic markers for resistance. We demonstrate that dPCR and NGS are robust methods for analysing CNVs and provide cross-validating results, highlighting their utility in the genetic analyses of this parasite.

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.

Functional determination of site-mutations in rdxA involved in metronidazole resistance of Helicobacter pylori.

Background: Metronidazole (MTZ) is among the first-line drugs against the human gastric pathogen Helicobacter pylori (H. pylori). MTZ is used as a prodrug that is activated by an oxygen-insensitive enzyme NADPH nitroreductase (RdxA). Loss-of-function mutations in rdxA make H. pylori MTZ resistant; however, experimental proof is lacking. Methods: We collected 139 gastric biopsy samples from patients suspected of H. pylori infection in Shanghai, and amplified Hp-specific rdxA gene from 134 samples. All these rdxA genes were sequenced and phylogenetically compared. The effect of mutations on RdxA function was measured by expressing them in Escherichia coli DH5α by using the MTZ sensitivity test. Results: In total, 134 gastric biopsy samples were identified as H. pylori positive. Of the 134 samples, 74 and 6 had point mutations at the various sites or promoter region of rdxA, generating truncated and extended fused proteins, respectively. The remaining 54 were full-length with single nucleotide variation (SNV) compared with the wild-type RdxA from H. pylori, with 49 clustering with hpEastAsia, 3 with hpEurope, and 2 with hpNEAfrica. All 134 rdxA were expressed in E. coli DH5α; 22 and 112 resultant strains showed MTZ-sensitive and MTZ-resistant phenotypes, respectively. Comparative analysis of single nucleotide polymorphisms (SNPs) in the functional and inactivated RdxA revealed 14 novel mutations in RdxA, 5 of which conferred MTZ resistance: S18F, D59S, L62I, S79N, and A187V. Conclusion: The occurrence of MTZ resistance induced by site-mutation of RdxA in patients with H. pylori infection was 83.6% (112/134) in the Shanghai region. The major form of loss-of-function mutation was truncation of RdxA translation at a rate of 58/112 (51.8%). Molecular detection reliably determined the resistance of H. pylori to MTZ. Thus, the functional mutants involved in MTZ resistance facilitate clinical diagnosis and medication based on sequence analysis.

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.

Impacts of storage conditions on the dissolution performance of commercial metronidazole tablets available in Saudi Arabia.

This study aimed to investigate the impact of storage conditions on the dissolution performance of commercial metronidazole (MTZ) tablets available in Saudi Arabia; these were coded as the reference and Test A, Test B, and Test C products. Moreover, the hardness and the disintegration time were measured. The UV spectrophotometrically analytical technique was utilized to quantify MTZ. All the control tablets, which were tested upon receipt, met the USP requirement as not less than 85 % of the labeled amount of MTZ was dissolved in 60 min. The MTZ reference released 91.79 % ± 1.23 after 60 min, while the products A, B, and C released 87.96 % ± 2.60, 93.26 % ± 2.01, and 88.61 % ± 2.04, respectively. The different dissolution parameters calculated for all the control tablets showed that the MTZ products A and B had optimal dissolution performances and were considered similar to the reference product. The product C showed a significantly reduced dissolution performance and was considered different from the reference. The in vitro dissolution of the MTZ tablets stored at 40oC ± 2 oC/75 % RH ± 5 % for 6 months indicated that the tablets maintained compliance with the USP requirement. The MTZ reference released 89.36 % ± 3.64 after 60 min, while the products A, B, and C released 95.79 % ± 3.91, 88.52 % ± 2.52, and 87.79 % ± 5.04, respectively. However, a slight reduction in the percentage released after 30 min (% DE30) and a slight increase in the mean dissolution time (MDT) were observed during the first 3 months of storage under stressed conditions. These changes were more obvious after 6 months of storage under the same conditions. Furthermore, in vitro dissolution of the product C stored at 40oC ± 2 oC/75 % RH ± 5 % for 3 months with further protection against high humidity revealed an improvement in the dissolution parameters due to the similar protective effects exerted by the two packaging forms. Furthermore, the study shows that storage conditions such as humidity and temperature affect in vitro dissolution of MTZ marketed tablets which may have an impact on efficiency and patient safety.

Investigation of the Antitrichomonal Activity of Cinnamaldehyde, Carvacrol and Thymol and Synergy with Metronidazole.

Objective: Trichomonas vaginalis is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980's with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of Cinnamomum zeylanicum (cinnamon) and Thymus vulgaris (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible T. vaginalis strains, and to determine their interaction with metronidazole by checkerboard method. Methods: Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant T. vaginalis reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method. Results: According to in vitro activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol. Conclusion: It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against T. vaginalis isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.

Nitrogen-doped mesoporous activated carbon from Lentinus edodes residue: an optimized adsorbent for pharmaceuticals in aqueous solutions.

In this study, phosphoric acid activation was employed to synthesize nitrogen-doped mesoporous activated carbon (designated as MR1) from Lentinus edodes (shiitake mushroom) residue, while aiming to efficiently remove acetaminophen (APAP), carbamazepine (CBZ), and metronidazole (MNZ) from aqueous solutions. We characterized the physicochemical properties of the produced adsorbents using scanning electron microscopy (SEM), nitrogen adsorption isotherms, and X-ray photoelectron spectroscopy (XPS). MR1, MR2, and MR3 were prepared using phosphoric acid impregnation ratios of 1, 2, and 3 mL/g, respectively. Notably, MR1 exhibited a significant mesoporous structure with a volume of 0.825 cm3/g and a quaternary nitrogen content of 2.6%. This endowed MR1 with a high adsorption capacity for APAP, CBZ, and MNZ, positioning it as a promising candidate for water purification applications. The adsorption behavior of the contaminants followed the Freundlich isotherm model, suggesting a multilayer adsorption process. Notably, MR1 showed excellent durability and recyclability, maintaining 95% of its initial adsorption efficiency after five regeneration cycles and indicating its potential for sustainable use in water treatment processes.

Unveiling the Neurotoxicity of Metronidazole: A Clinical Conundrum.

Metronidazole, a commonly used antiprotozoal agent, has been linked to neurotoxicity in a few individuals. We present the case of a 61-year-old gentleman diagnosed with a liver abscess, who received a total dose of 64 g of metronidazole over a four-week duration. He subsequently developed slurred speech, numbness, and tingling sensation in both feet. His neuroimaging revealed T2 hyperintensities in the bilateral dentate nuclei and withdrawal of the drug led to symptomatic improvement in the patient. Metronidazole is known to produce neurological manifestations with involvement of peripheral nerves and cerebellum commonly. In the present case, the cumulative dose impact of metronidazole on the dentate nucleus was evident.

Single-Arm, Prospective, Interventional Study of Helicobacter pylori Eradication Rescue Therapy with Rifabutin, Metronidazole, and Vonoprazan.

Background and Objective: Rescue Helicobacter pylori eradication can be challenging. Rifabutin (RBT) demonstrates high activity against Helicobacter pylori and is incorporated into various rescue eradication regimens. This exploratory study was performed to evaluate the efficacy and safety of a rescue regimen comprising RBT, metronidazole (MNZ), and vonoprazan (VPZ). Methods: This prospective, single-center, single-arm, interventional study was performed in Japan. Eligible patients were those who underwent failed primary eradication treatment (7-day treatment with three drugs: VPZ or a proton pump inhibitor [PPI], amoxicillin [AMPC], and clarithromycin) and secondary eradication treatment (7-day treatment with three drugs: VPZ or a PPI, AMPC, and MNZ) and those who were unable to receive first- and second-line therapy because of penicillin allergy. Twenty Helicobacter pylori-positive patients were treated with RBT (150 mg twice daily), MNZ (250 mg twice daily), and VPZ (20 mg twice daily) for 10 days (RBT-MNZ-VPZ therapy). Eradication success was evaluated using the urea breath test. Drug susceptibility test results were available in 16 patients. This study is registered in the Japan Registry of Clinical Trials (jRCT031220504). Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of RBT-MNZ-VPZ therapy were 70% (90% confidence interval [CI]: 49.2%-86.0%) and 72.2% (95% CI: 50.2%-88.4%), respectively. In the MNZ-susceptible subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were 100% (90% CI: 68.8%-100%) and 100% (90% CI: 65.2%-100%). In the MNZ-resistant subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were both 62.5% (90% CI: 28.9%-88.9%). All infections were RBT-susceptible. Conclusions: These findings suggest that RBT-MNZ-VPZ therapy may be a promising rescue regimen, especially in MNZ- and RBT-susceptible infections or patients with penicillin allergy.

A robust and simple non-enzymatic electrochemical sensor based on carbon dots-metal oxide composite for the detection of metronidazole traces in food products.

A facile and simple electrochemical composite sensor, CDs-Ag@Cu2O-GA, prepared from carbon dots stabilized silver nanoparticles and copper oxide, was used as an electrocatalyst and signal amplifier for the non-enzymatic detection of antibiotic traces in food products. The prepared composite demonstrated excellent stability, sensitivity, and cost-effectiveness. The sensor was constructed by modifying a glassy carbon electrode (GCE) with CDs-Ag@Cu2O-GA, and the electroanalytical response was determined for the precise determination of metronidazole (MTZ) drug traces in milk. The analytical response signified fast electron transfer and accessibility of several electroactive sites, producing an amplified response for the reduction of MTZ. The quantitative analysis by the sensor revealed a good linear range (10-110 µM), a low limit of detection (7.1 × 10-7 molL-1), and a high sensitivity (1.5 µA µM-1 cm-2). Furthermore, the sensor displayed excellent potential for practical applications, verified by the good recovery of the drug from spiked milk samples.

The impact of metronidazole on pain persistence after fertility-sparing endometriosis surgery: METROFERT randomized study.

BACKGROUND: Recent studies have shown that a disrupted microbiome is associated with endometriosis. Despite endometriosis affecting 1 in 10 reproductive-aged women, there is a lack of innovative and nonhormonal long-term effective treatments. Studies have reported an approximately 20% to 37.5% persistence of pain after fertility-sparing endometriosis surgery. Metronidazole has been shown to decrease inflammatory markers and the size of endometriosis lesions in animal studies. OBJECTIVE: To determine if modulating the microbiome with oral metronidazole for 14 days after fertility-sparing endometriosis surgery decreases pain persistence postoperatively. STUDY DESIGN: This was a randomized, multicenter, placebo-controlled, double-blind trial. Individuals 18 to 50 years old were prospectively randomized to placebo vs oral metronidazole for 14 days immediately after endometriosis fertility-sparing excision surgery. The primary outcome was binary, subjective pain persistence at 6 weeks postoperatively. Secondary outcomes included quality of life, sexual function, and endometriosis-associated pain scores according to the Endometriosis Health Profile-5, Female Sexual Function Index, and a visual analog scale. RESULTS: One hundred fifty-two participants were approached from October 2020 to October 2023 to enroll in the study. Sixty-four participants were excluded either because they did not meet inclusion or exclusion criteria or because they declined to participate. Eighty-eight participants were randomized in a 1:1 ratio to receive either the oral placebo or metronidazole after endometriosis excision surgery; 18.2% of participants were lost to follow-up or discontinued treatment and this was not significantly different between the 2 arms, yielding a final cohort of 72 participants. Baseline demographics of the 2 study groups were similar. There was no statistically significant improvement in the primary outcome of binary subjective pain persistence between the metronidazole group compared to placebo (84% vs 88%, P=.74) at 6 weeks postoperatively. Further, no significant differences between treatments were detected in the secondary outcomes. CONCLUSION: A postoperative 14-day regimen of oral metronidazole immediately after fertility-sparing endometriosis surgery was not associated with any significant differences between treatment groups in the persistence of endometriosis-related pain symptoms compared to placebo at 6 weeks.

Synthesis and photodegradation performance of a heterostructure ferromagnetic photocatalyst based on MWCNTs functionalized with (3-glycidyloxypropyl)trimethoxysilane and decorated with tungsten trioxide for metronidazole and acetaminophen degradation in aqueous environments.

The presence of metronidazole (MNZ) and acetaminophen (ACE) in aquatic environments has raised growing concerns regarding their potential impact on human health. Incorporating various patterns into a photocatalytic material is considered a critical approach to achieving enhanced photocatalytic efficiency in the photocatalysis process. In this study, WO3 nanoparticles, which were immobilized onto ferromagnetic multi-walled carbon nanotubes that were functionalized using (3-glycidyloxypropyl)trimethoxysilane (FMMWCNTs@GLYMO@WO3), exhibited remarkable efficiency in removing MNZ and ACE (93% and 97%) in only 15 min. In addition, the new visible-light FMMWCNTs@GLYMO@WO3 nanoparticles as a magnetically separable photocatalyst were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), EDS-mapping, vibrating sample magnetometry (VSM), thermogravimetric analysis (TGA), diffuse reflectance spectroscopy (DRS), high-performance liquid chromatography (HPLC), and total organic carbon (TOC) due to detailed studies (morphological, structural, magnetic and optical properties) of the photocatalyst. In-depth spectroscopic and microscopic characterization of the newly developed ferromagnetic FMMWCNTs@GLYMO@WO3 (III) photocatalyst revealed a spherical morphology, with nanoparticle diameters averaging between 23 and 39 nm. Compared to conventional multiwall carbon nanotube and WO3 photocatalysts, FMMWCNTs@GLYMO@WO3 (III) demonstrated superior photocatalytic activity. Remarkably, it exhibited excellent reusability, maintaining its efficiency over a minimum of five cycles in the degradation of metronidazole (MNZ) and acetaminophen (ACE).

Supramolecular architectures in multicomponent crystals of imidazole-based drugs and trithiocyanuric acid.

The structures of three multicomponent crystals formed with imidazole-based drugs, namely metronidazole, ketoconazole and miconazole, in conjunction with trithiocyanuric acid are characterized. Each of the obtained adducts represents a different category of crystalline molecular forms: a cocrystal, a salt and a cocrystal of salt. The structural analysis revealed that in all cases, the N-H...N hydrogen bond is responsible for the formation of acid-base pairs, regardless of whether proton transfer occurs or not, and these molecular pairs are combined to form unique supramolecular motifs by centrosymmetric N-H...S interactions between acid molecules. The complex intermolecular forces acting in characteristic patterns are discussed from the geometric and energetic perspectives, involving Hirshfeld surface analysis, pairwise energy estimation, and natural bond orbital calculations.

Characterization of a model of liver regeneration: Role of hedgehog signaling in experimental hepatic amoebiasis.

The development of amoebic liver abscess (ALA) leads to liver necrosis, accompanied by an exacerbated inflammatory response and the formation of multiple granulomas. Adequate management of the infection through the administration of treatment and the timely response of the organ to the damage allows the injury to heal with optimal regeneration without leaving scar tissue, which does not occur in other types of damage such as viral hepatitis that may conducts to fibrosis or cirrhosis. The Hedgehog signaling pathway (Hh) is crucial in the embryonic stage, while in adults it is usually reactivated in response to acute or chronic injuries, regeneration, and wound healing. In this work, we characterized Hh in experimental hepatic amoebiasis model, with the administration of treatment with metronidazole, as well as a pathway inhibitor (cyclopamine), through histological and immunohistochemical analyses including an ultrastructure analysis through transmission electron microscopy. The results showed an increase in the percentage of lesions obtained, a decrease in the presence of newly formed hepatocytes, a generalized inflammatory response, irregular distribution of type I collagen accompanied by the presence of fibroblast-type cells and a decrease in effector cells of this pathway. These results constitute the first evidence of the association of the activation of Hh with the liver regeneration process in experimental amebiasis.

Metronidazole-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome With Parvovirus B19 Reactivation: A Pediatric Case.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and rare syndrome that causes life-threatening organ dysfunctions. Here, we present the case of a 10-year-old child who developed a pruritic erythematous eruption, fever, facial edema, and lymphadenopathy seven days after receiving intravenous metronidazole (20 mg/kg/day), vancomycin (50 mg/kg/day), and cefotaxime (200 mg/kg/day). Laboratory tests showed eosinophilia and liver damage as well as positive parvovirus B19 IgM and IgG indicating viral reactivation. Vancomycin was initially discontinued and later reintroduced with no ill effects. The patient was managed with topical corticosteroid emollients and cetirizine and improved within seven days of metronidazole withdrawal. Treatment with cefotaxime was continued and showed no adverse effects.