Metronidazole Treatment Research Articles

IgA coating of vaginal bacteria is reduced in the setting of bacterial vaginosis (BV) and preferentially targets BV-associated species.

Immunoglobulin (Ig) bacterial coating has been described in the gastrointestinal tract and linked to inflammatory bowel disease; however, little is known about Ig coating of vaginal bacteria and whether it plays a role in vaginal health including bacterial vaginosis (BV). We examined Ig coating in 18 women with symptomatic BV followed longitudinally before, 1 week, and 1 month after oral metronidazole treatment. Immunoglobulin A (IgA) and/or immunoglobulin G (IgG) coating of vaginal bacteria was assessed by flow cytometry, and Ig coated and uncoated bacteria were sorted and characterized using 16S rRNA sequencing. Despite higher levels of IgG compared to IgA in cervicovaginal fluid, the predominant Ig coating the bacteria was IgA. The majority of bacteria were uncoated at all visits, but IgA coating significantly increased after treatment for BV. Despite similar amounts of uncoated and IgA coated majority taxa ( >1% total) across all visits, there was preferential IgA coating of minority taxa (0.2%-1% total) associated with BV including Sneathia, several Prevotella species, and others. At the time of BV, we identified a principal component (PC) driven by proinflammatory mediators that correlated positively with an uncoated BV-associated bacterial community and negatively with an IgA coated protective Lactobacillus bacterial community. The preferential coating of BV-associated species, increase in coating following metronidazole treatment, and positive correlation between uncoated BV-associated species and inflammation suggest that coating may represent a host mechanism designed to limit bacterial diversity and reduce inflammatory responses. Elucidating the role of Ig coating in vaginal mucosal immunity may promote new strategies to prevent recurrent BV.

Frequency and Risk Factor Analysis for Metronidazole-Associated Neurologic Adverse Events.

Little is known about the risk factors and frequency of metronidazole-associated neurological adverse events. To investigate the risk factors and frequency of metronidazole-associated neurological adverse events. This retrospective study contained two parts. First, we investigated metronidazole treatment-associated neurologic adverse events by performing a population-based cohort study using the Korea Adverse Event Reporting System (KAERS) database from January 2011 to December 2020. Second, we conducted a matched case-control study based on a retrospective cohort of patients treated with metronidazole between January 2006 and July 2021 at a tertiary hospital in South Korea. The data analysis was performed from August 2021 to April 2022. In the case-control study, case patients were defined as those diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy during the study period with causal assessment based on the clinical diagnoses and findings from associated tests. In a ratio of 1:3, case patients were compared to a control group of patients prescribed metronidazole without neurologic adverse events matched for age and cumulative dose of metronidazole. Frequency and risk factors for metronidazole-associated neurological adverse events. Overall, 2,309 cases of neurologic adverse events were reported to the KAERS from 2011 to 2020, and the number of reported neurological adverse events showed an increasing trend. Further, 92,838 patients were prescribed metronidazole during the study period at the Severance Hospital; 54 patients were diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy, 40 with central and 28 with peripheral nervous system adverse events. Liver cirrhosis, chronic kidney disease, intravenous administration, and lower body weight were identified as risk factors for these adverse events. The number of reported metronidazole-associated neurological adverse events are increasing. Prolonged metronidazole treatment in patients with the aforementioned factors requires careful examination for neurological adverse events.

Association of Chlamydia trachomatis burden with the vaginal microbiota, bacterial vaginosis, and metronidazole treatment.

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming units (IFU) and Ct genome copy number (GCN), and 16S rRNA gene sequencing was used to determine the composition of the vaginal microbiota. We observed a six-log spectrum of IFU and an eight-log spectrum of GCN in our study participants at their enrollment visit, but BV, as indicated by Amsel's criteria, Nugent scoring, or VALENCIA community state typing, did not predict infectious and total Ct burden, although IFU : GCN increased with Amsel and Nugent scores and in BV-like community state types. Ct burden was, however, associated with the abundance of bacterial species in the vaginal microbiota, negatively with Lactobacillus crispatus and positively with Prevotella bivia. Women diagnosed with BV were treated with metronidazole, and Ct burden was significantly reduced in those who resolved BV with treatment. A subset of women naturally cleared Ct infection in the interim, typified by low Ct burden at enrollment and resolution of BV. Abundance of many BVAB decreased, and Lactobacillus increased, in response to metronidazole treatment, but no changes in abundances of specific vaginal bacteria were unique to women who spontaneously cleared Ct infection.

Effect of early antibiotic treatment strategy on prognosis of acute pancreatitis

BackgroundAntibiotic use in the early stages of acute pancreatitis is controversial. The purpose of this study was to investigate the effect of early antibiotic application on the prognosis of acute pancreatitis (AP).Materials and methodsClinical data of patients with primary AP admitted to our emergency ward within 72 hours of onset were retrospectively collected from January 2016 to December 2020. We classified patients with acute pancreatitis according to etiology and disease severity, and compared the differences in hospital stay, laparotomy rate, and in-hospital mortality among AP patients who received different antibiotic treatment strategies within 72 hours of onset.ResultsA total of 1134 cases were included, with 681 (60.1%) receiving early antibiotic treatment and 453 (39.9%) not receiving it. There were no significant differences in baseline values and outcomes between the two groups. In subgroup analysis, patients with biliary severe acute pancreatitis (SAP) who received early antibiotics had lower rates of laparotomy and invasive mechanical ventilation, as well as shorter hospital stays compared to those who did not receive antibiotics. In logistic regression analysis, the early administration of carbapenem antibiotics in biliary SAP patients was associated with a lower in-hospital mortality rate. Early antibiotic use in biliary moderate-severe acute pancreatitis (MSAP) reduced hospital stays and in-hospital mortality. Quinolone combined with metronidazole treatment in biliary mild acute pancreatitis (MAP) shortened hospital stays. Early antibiotic use does not benefit patients with non-biliary AP.ConclusionStrategies for antibiotic use in the early stages of AP need to be stratified according to cause and disease severity.

Giardia lamblia Diagnosed During Upper Gastrointestinal Endoscopy: Clinical Manifestation, Histopathologic Findings and the Association With Celiac Disease.

Giardia lamblia may be found incidentally during upper gastrointestinal (GI) endoscopy, including when biopsies are taken for celiac disease (CeD) diagnosis. We aimed to study the clinical presentation and histopathology of G. lamblia and determine its association with CeD. A retrospective case series of pediatric patients diagnosed with G. lamblia based on intestinal biopsies between January 1999 and January 2023. Baseline data; demographics, symptoms, celiac serology, stool testing, macroscopic and histopathologic findings. Follow-up data; treatment and repeated celiac serology. Of 38 patients with G. lamblia , 15 (39.5%) were female, mean age of 6.7 (±4.8 SD) years. Clinical symptoms; GI 19/38 (50%), growth retardation and/or iron deficiency anemia 8/38 (21.1%) or a combination 11/38 (28.9%). Celiac serology was positive in 13/38 (34.2%). Duodenal endoscopic findings; normal (n = 23, 60.5%), nodularity (n = 12, 32.4%), erosions in 2 (5.4%) and scalloping in 1 (2.7%). Histopathology; normal villi 24/38 (63.2%), villous shortening with increased intraepithelial lymphocytes (IEL) 5/38 (13.2%), isolated IEL 3/38 (7.9%) and duodenitis in 6/38 (15.8%). Children with positive CeD serology were younger (4 vs. 8.1 years, P = 0.019), had fewer GI symptoms (23.1% vs. 64%, P = 0.017) and a higher rate of villous shortening with increased IEL (38.5% vs. 0, P < 0.001) versus children with negative serology. On follow-up, metronidazole treatment was recommended to all but was documented to be given in 22/38 (57.9%). Among the 13 children with positive CeD serology, serology normalized in 10 (77%). G. lamblia is a rare histopathologic finding in children. It may be an incidental finding in CeD or may cause false positive celiac serology.

Bismuth subcitrate, metronidazole and tetracycline – a rare cause of drug-induced liver injury

Drug-induced liver injury (DILI) is a liver condition caused by any drug or toxic substance. The spectrum of DILI manifestations can range from asymptomatic elevation of liver enzymes to acute liver failure. Antibiotics are one of the major causes of DILI. The authors report the case of a 37-year-old male with nausea, right hypochondrium pain and fever with history of bismuth subcitrate, metronidazole and tetracycline combination treatment in the previous five days. DILI was suspected and other aetiologies of acute hepatitis were excluded such as viral, autoimmune or even haemochromatosis and Wilson’s disease. Liver biopsy was performed, being compatible with the diagnosis of DILI; DILI is a diagnosis of exclusion. Bismuth subcitrate, metronidazole and tetracycline combination treatment is a rare cause of DILI.

Vancomycin vs metronidazole use for the treatment of Clostridioides difficile infection in a tertiary care hospital in Saudi Arabia

BackgroundThe 2017 Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) guidelines recommendation for oral vancomycin as preferred treatment was based on studies conducted in North America, Australia, and Europe. According to recent published data, metronidazole remains a reasonable option. No studies have been conducted in Saudi Arabia to compare prescribing patterns before and after the release of the guidelines. Due to low CDI burden in Saudi Arabia, the aim is to assess the effectiveness and outcomes of vancomycin vs metronidazole treatment options. MethodsThis was a retrospective cohort study conducted in a tertiary care hospital in Jeddah which was approved by the Institutional Review Board (IRB 2020–53). Data was collected from January 2017 to April 2020. Eligible patients were adults (>18 years old) diagnosed with CDI who either received oral metronidazole (500 mg 3 times daily) or oral vancomycin (125–500 mg 4 times daily). Patients who received a combination of treatment or who were diagnosed with fulminant CDI were excluded. Demographic data were collected. The primary outcome was to assess treatment response to initial therapy with oral metronidazole versus oral vancomycin. Secondary outcomes included assessing early treatment response, time to discharge after diagnosis, proportion of patients with a positive VRE surveillance culture within 6 months of diagnosis, 30-day recurrence and 30-day all-cause mortality. Chi-square or Fisher's exact test were used to examine differences in categorical variables while student t-test or Mann–Whitney test, were used to examine differences in continuous variables. P value < 0.05 was considered as significant. ResultsA total of 166 patients were included in the analysis. Demographic characteristics were not significantly different between the two groups. There was no difference in treatment response between vancomycin and metronidazole (96.4 % versus 94.3 %, p = 0.682). However, compared with metronidazole, vancomycin treatment was significantly associated with better early response (94.0 % versus 77.8 %, p = 0.008). Other outcomes were not significantly different between the two drug groups for time to discharge after diagnosis (P = 0.522), 30-day recurrence (P > 0.99) and 30-day all-cause mortality (P = 0.782). Of note, the vancomycin versus metronidazole use before the 2017 IDSA guidelines (26 % versus 74 %) was completely reversed after the release of the guidelines (83.3 % versus 16.7 %), p < 0.001). ConclusionThe results of this study demonstrate that vancomycin and metronidazole have comparable outcomes in regards to treatment response for non-fulminant CDI. The study also reveals the high and quick impact of international guidelines on local prescription patterns. Further studies are needed in Saudi Arabia to guide the treatment of CDI.

The Association Between Human Immunodeficiency Virus and Bacterial Vaginosis and Metronidazole Treatment Failure for Trichomonas vaginalis.

Trichomonas vaginalis (TV) is a common sexually transmitted infection. High rates of repeated infections have been observed, particularly among women living with human immunodeficiency virus (HIV). Trichomonas vaginalis frequently cooccurs with bacterial vaginosis (BV). The purpose of this study was to determine if coinfections with TV, BV, and HIV could lead to differential treatment failure outcomes. Data were pooled from 2 prior randomized control trials comparing 2 g oral single-dose versus 500-mg twice daily oral 7-day dose metronidazole for the treatment of TV in HIV infected and HIV uninfected women. Trichomonas vaginalis rates 1-month postcompletion of treatment were compared by arm, HIV and BV status after removing those who had sexual reexposure, and/or did not complete their treatment. Data for 795 subjects were included in the study, of which 76 (9.6%) experienced treatment failure. In the final multivariable model, which included treatment dose, HIV status, and BV status, odds of treatment failure infection in the 7-day dose group were lower than the odds in the single dose group (odds ratio, 040; 95% confidence interval, 0.23-0.68). Treatment failure was lower in the multidose arm compared with single dose for both HIV-infected (4.0% vs 10.3%; P = 0.0568) and HIV-uninfected (7.3% vs 15.4%; P = 0.0037). Neither HIV nor BV was associated with higher treatment failure. Human immunodeficiency virus infection and BV status did not significantly alter the rate of repeat infection for either single dose or 7-day dose metronidazole. Among all women, 7-day metronidazole lowered the odds of treatment failure.

Metronidazole Treatment Failure and Persistent BV Lead to Increased Frequencies of Activated T- and Dendritic-Cell Subsets.

Metronidazole (MDZ) treatment failure and bacterial vaginosis (BV) recurrence rates are high among African women. This cohort study identified genital immune parameters associated with treatment response by comparing vaginal microbiota and immune cell frequencies in endocervical cytobrushes obtained from 32 South African women with symptomatic BV pre- and post-metronidazole treatment. Cervical T- and dendritic-cell subsets were phenotyped using multiparameter flow cytometry and the composition of vaginal microbial communities was characterized using 16S rRNA gene sequencing. MDZ treatment led to a modest decrease in the relative abundance of BV-associated bacteria, but colonization with Lactobacillus species (other than L. iners) was rare. At 6 and 12 weeks, MDZ-treated women had a significant increase in the frequencies of CCR5+ CD4+ T cells and plasmacytoid dendritic cells compared to the pre-treatment timepoint. In addition, MDZ non-responders had significantly higher frequencies of activated CD4 T cells and monocytes compared to MDZ responders. We conclude that MDZ treatment failure was characterized by an increased expression of activated T- and dendritic-cell subsets that may enhance HIV susceptibility. These data suggest the need to further assess the long-term impact of MDZ treatment on mucosal immune response and the vaginal microbiota.

SAT066 Leukotriene B4 Receptor 2 Mediates Macrophage Migration To Injured β Cells

Abstract Disclosure: E. Ermis: None. T. Nargis: None. A. Kulkarni: None. S. May: None. S.A. Tersey: None. R.G. Mirmira: None. R.M. Anderson: None. Type 1 diabetes (T1D) is an autoimmune disease, characterized in part by islet inflammation and macrophage infiltration leading to β-cell injury and loss. The inflammatory mediator 12/15-lipoxygenase (12/15-LOX) and its lipid product 12-hydroxyeicosatetraenoic acid (12-HETE) have both been implicated in T1D. 12-HETE activates the low affinity receptor leukotriene B4 receptor 2 (LTB4R2, or simply BLT2), which was reported as a low-affinity receptor for 12-HETE, suggesting that BLT2 may play a proinflammatory role. Here, we used both mouse and zebrafish models to probe the roles of BLT2 in macrophage activation and/or recruitment to pancreatic islets during T1D progression. First, we analyzed Blt2 gene expression in a variety of C57BL/6J mouse tissues. We found Blt2 gene expression in bone marrow derived macrophages and peritoneal macrophages, however we found little to no expression in pancreatic islets. Although Blt2-/- mice showed a significantly reduced expression of Blt2, they exhibited overall normal growth and glucose tolerance. To uncover roles for BLT2 in macrophage function, we first interrogated its involvement in the in vitro polarization of proinflammatory macrophages to the M1-like state using LPS and IFN-γ and the M2-like state using IL-4. Under these conditions, we found no differences between Blt2-/- and wildtype macrophages, as assessed by flow cytometry analysis, suggesting that BLT2 does not play a substantial role in macrophage polarization. Next, to query roles for BLT2 in macrophage migration, we employed the transgenic zebrafish line Tg(mpeg:EGFP) in which macrophages are labeled with green fluorescent protein (GFP). Following zebrafish tailfin injury, we quantified macrophage accumulation at the injury at 6 hours post amputation. Inhibitory treatments of zebrafish larvae with either a chemical BLT2 inhibitor (LY255283) or by knockdown of the blt2a gene using an antisense morpholino, both decreased the number of GFP+ macrophages found at the injury site. Moreover, in the latter approach ectopic expression of blt2a mRNA effectively restored the wild-type phenotype. To determine if BLT2 mediates macrophage migration to injured islets, we employed a transgenic zebrafish model of β-cell injury, Tg(ins:NTR), in which metronidazole treatment rapidly induces β-cell injury. We treated the Tg(mpeg: GFP); Tg(ins: NTR) zebrafish with metronidazole and monitored macrophage migration into injured islets. We observed a significant decrease in macrophage migration towards injured β-cells in blt2a-knockdown zebrafish. Collectively, these results show that BLT2 plays a role in macrophage migration associated with tissue injury, including the islet β cell as seen in T1D. Presentation: Saturday, June 17, 2023

Role of autophagy in stress and drug-responsive cell death in Entamoeba histolytica and its cross-talk with apoptosis-inducing factor

Cell death in unicellular protozoan parasite Entamoeba histolytica is not yet reported though it displays several features of autophagic cell death. Autophagic cell death was reported to take place in ancient protozoans under several stresses. Here we report the occurrence of autophagic cell death in the Entamoeba histolytica trophozoites under oxidative stress as well as by the treatment with metronidazole, the most-widely-used drug for amoebiasis treatment and was shown to generate oxidative stress in the trophozoites. The autophagic flux increases during nutrient deprivation and metronidazole treatment and decreases upon oxidative stress. During oxidative stress the autophagy leads to nucleophagy that is ultimately destined to be digested within the lysosomal chamber. The formation of nucleophagosome depends on the apoptosis-inducing factor (AIF) that translocates to the nucleus from cytoplasm upon oxidative stress. It was experimentally proved that ATG8 (Autophagy-related protein 8) binds with the AIF in the nucleus of the trophozoites and helps in ATG8 recruitment and autophagy initiation overall suggesting that oxidative stress-driven AIF translocation to nucleus results in binding with ATG8 and initiates nucleophagy leading to cell death.

Prevalence of Non-Toxigenic Clostridioides difficile in Diarrhoea Patients and Their Clinical Characteristics.

Non-toxigenic Clostridioides difficile (NTCD) has been shown to decrease the risk of recurrent C. difficile infection (CDI) in patients following metronidazole or vancomycin treatment for CDI. Limited data on the prevalence of NTCD strains in symptomatic patients and their clinical characteristics are available. We conducted this study to investigate the prevalence of NTCD in diarrhoea patients and their clinical characteristics. Between July 2017 and June 2018, unduplicated stool specimens were collected from patients with diarrhoea. The characteristics and episodes of C. difficile infection in patients with NTCD and toxigenic strains were compared. Among the 1182 stool specimens collected, 236 (18.5%) were identified as growing C. difficile, and 19.5% of the identified isolates were found to be NTCD. Multivariate analysis showed that community-onset diarrhoea (OR = 4.13, 95% CI 1.07-15.97; p = 0.040), underlying diabetes (OR = 3.64, 95% CI 1.46-9.25; p = 0.006), previous use of glycopeptides (OR = 4.75, 95% CI 1.37-16.42; p = 0.014), and the lack of use of proton pump inhibitors (PPIs) (OR = 3.57, 95% CI 1.39-9.09; p = 0.009) were independently associated with the NTCD group. Although there was no statistical significance, the number of CDI episodes occurring after 90 days tended to be lower in the NTCD group (2.2%) than in the toxigenic group (11.2%). A considerable portion of the C. difficile strains isolated from patients with diarrhoea showed NTCD. Further, more extensive studies are needed to clearly define the protective effects of NTCD strains in patients with diarrhoea.

Mechanistic Assessment of Anise Seeds and Clove Buds against the Neurotoxicity Caused by Metronidazole in Rats: Possible Role of Antioxidants, Neurotransmitters, and Cytokines.

Long-term use of the nitroimidazole-derived antibiotic metronidazole has been associated with neuronal damage due to its ability to cross the blood-brain barrier. Polyphenol-rich plants, such as anise seeds and clove buds, are suggested to have neuroprotective effects. However, their intracellular protective pathway against metronidazole-induced neurotoxicity remains unexplored. This study aims to evaluate the potential neuroprotective benefits of anise seeds and clove buds and elucidate the proposed metronidazole-induced neurotoxicity mechanism. This study divided rats into six groups, each containing six rats. In Group I, the control group, rats were administered saline orally. Group II rats received 200 mg/kg of metronidazole orally. Group III rats received 250 mg/kg b.w. of anise seed extract and metronidazole. Group IV rats received 500 mg/kg b.w. of anise seed extract (administered orally) and metronidazole. Group V rats received 250 mg/kg b.w. of clove bud extract (administered orally) and metronidazole. Group VI rats were administered 500 mg/kg b.w. of clove bud extract and metronidazole daily for 30 consecutive days. The study evaluated the phenolic compounds of anise seeds and clove buds. Moreover, it assessed the inflammatory and antioxidant indicators and neurotransmitter activity in brain tissues. A histological examination of the brain tissues was conducted to identify neuronal degeneration, brain antioxidants, and apoptotic mRNA expression. The study found that metronidazole treatment significantly altered antioxidant levels, inflammatory mediators, and structural changes in brain tissue. Metronidazole also induced apoptosis in brain tissue and escalated the levels of inflammatory cytokines. Oral administration of metronidazole resulted in a decrease in GABA, dopamine, and serotonin and an increase in ACHE in brain tissue. Conversely, oral administration of anise and clove extracts mitigated the harmful effects of metronidazole. The neurotoxic effects of metronidazole appear to stem from its ability to reduce antioxidants in brain tissue and increase nitric oxide production and apoptosis. The study concludes that neuronal damage caused by metronidazole is significantly mitigated by treatment with anise and clove extracts.

Clostridioides difficile infection in thoroughbred horses in Japan from 2010 to 2021

We encountered 34 Clostridioides difficile (C. difficile) infection (CDI) cases among Thoroughbred horses in Japan from 2010 to 2021. Among them, 79.4% (27/34) either died or were euthanised. The risk factors associated with CDI and mortality among Japanese Thoroughbred horses remain unclear. We used genetic methods to examine C. difficile strains and their relationships with prognosis. Twenty-two (64.7%) cases were hospitalised at the onset of colitis. Outcomes were balanced for hospitalisation rates at the onset of colitis. The mortality rates of cases treated with metronidazole (65.0%) were significantly lower than untreated cases (100%). The predominant genotype of C. difficile isolate was polymerase chain reaction ribotype (RT) 078, isolated from 12 cases (35.3%), followed by RT014 (six cases, 17.6%). Binary toxin (C. difficile transferase [CDT])-positive strains, including all RT078 strains, were isolated from 16 horses. Mortality rates in RT078 strain (75.0%) or CDT-positive strain (83.3%) cases were comparable to that in cases of other types. Sufficient infection control is needed to prevent CDI in Thoroughbred horses. A timely and prompt CDI diagnosis leading to metronidazole treatment would improve CDI outcomes.

The Possible Relation of Demodex and Facial Erythema in Connective Tissue Diseases.

We aimed to investigate the frequency of Demodex infestation and clinical implications in connective tissue disease patients with facial erythema. Patients diagnosed with a connective tissue disease and had facial erythema were consecutively enrolled in the study from 2019-2020. An age and gender matched control group was formed from healthy volunteers. Presence of Demodex was investigated by standardized skin surface biopsy. Number of Demodex mites over 5 per centimeter square was considered meaningful for infestation. Topical or systemic metronidazole treatment was given to the connective tissue disease patients with Demodex infestation. Facial erythema visual analog scale was questioned in patients at treatment onset and one month after. A total of 31 connective tissue disease patients with facial erythema were enrolled. Control group included 31 healthy volunteers. Demographics and comorbidities were similar between groups. Demodex infestation was present in 58.1% of the disease group and in 25.8% of the control group (P=0.01). Pruritus was the most common symptom in patients with infestation. Median (IQR) facial erythema visual analog scale score was 6 (3) at treatment onset and was 2 (2.5) one month later (P<0.001). When evaluating facial cutaneous lesions, Demodex infestation should not be overlooked in a patient group like connective tissue diseases with dysfunctional immune system.

Application of Ti-based mixed metal oxide electrodes towards electrochemical mineralization of Metronidazole: Evaluation of influencing factors and removal by-products

BackgroundThe treatment of Metronidazole (MTZ) as a persistent pharmaceutical waste in the water is a significant challenge. To reduce the adverse effect of MTZ in water, we tested a novel SiO2-incorporated MMO-Ti/IrO2-Ta2O5 electrode via the electrochemical oxidation (EO) method. MethodsThe electrode was characterized by scanning electron microscopy, energy dispersive spectrum, atomic force microscopy, and cyclic voltammetry analyses. Structural characterization results were represented high resistance, compact surface, and better electrocatalytic properties for Ti/IrO2-Ta2O5-SiO2 electrode. The influence of critical operational parameters, including applied current density, initial pH, initial concentration of MTZ, and electrolysis time, was detected on electrocatalytic removal efficiency. Significant findingsIt was recognized that the high electrocatalytic power of SiO2-incorporated MMO-Ti/IrO2-Ta2O5 electrode gives a high amount of •OH during the removal process. At optimum conditions (pH = 7, J = 200 mA/cm2, [MTZ]0 = 40 mg/L, t = 80 min), 98.76% MTZ removal efficiency was achieved. Besides, comparison analysis was performed with SiO2-incorporated MMO-Ti/IrO2-Ta2O5 electrode and Ti/IrO2-Ta2O5, so results point out the higher total organic carbon removal of about 78.90% and 54.30% with SiO2-incorporated MMO-Ti/IrO2-Ta2O5 than Ti/IrO2-Ta2O5, respectively. Furthermore, MTZ removal intermediates formed during the electrocatalytic oxidation process were identified by the gas chromatography–mass spectrometry technique.

Risk factors for recurrent healthcare-facility associated Clostridioides difficile infection in a Swedish setting

ObjectiveThe objectives were to determine the risk factors for recurrent healthcare facility-associated Clostridioides difficile infection (HCF-CDI) in a high CDI incidence, low antibiotic use setting and to determine if length of cefotaxime exposure is a risk factor for recurrent HCF-CDI. MethodsThe risk factors for recurrent HCF-CDI were evaluated with a retrospective nested case control study based on chart reading. The risk factors were evaluated univariately and multivariately. Length of risk antibiotic exposure was evaluated further in a subanalysis. ResultsRisk factors for recurrent HCF-CDI were renal insufficiency (25.4% of cases compared to 15.4% of controls p = 0.006) and metronidazole treatment of initial CDI episode (88.4% compared to 71.7% p = 0.01). Exposure to cefotaxime and risk for recurrent CDI showed a dose-dependent relationship (linear by linear p = 0.028). ConclusionsRenal insufficiency and metronidazole treatment were independent risk factors for recurrent HCF-CDI in our setting. The relationship between cefotaxime exposure and risk for recurrent HCF-CDI, dose-dependent, could be evaluated further in a setting with high cefotaxime use.

Single-Molecule Approach to 16S rRNA for Vaginal Microbiome Signatures in Response to Metronidazole Treatment.

Bacterial vaginosis (BV) is the most common infection of the lower reproductive tract among women of reproductive age, characterized by a depletion of health-associated Lactobacillus and an overgrowth of anaerobes. Metronidazole has been recommended as a first-line therapy for treating BV for decades. Although most cases are cured by the treatment, recurrent infections of BV seriously affect women's reproductive health. Until now, limited information on the vaginal microbiota has been explored at the species level. Here, we adopted a single molecular sequencing approach for the 16S rRNA gene, named FLAST (full-length assembly sequencing technology), to analyze the human vaginal microbiota that improved species-level resolution for taxonomy and identified microbiota alterations in the vaginal tract in response to treatment with metronidazole. Appling high-throughput sequencing, we identified 96 and 189 novel full-length 16S rRNA gene sequences in Lactobacillus and Prevotella, respectively, which had not previously been reported in vaginal samples. Moreover, we found that Lactobacillus iners was significantly enriched in the cured group before metronidazole treatment, and that was maintained in a high frequency after the treatment, suggesting an important role for this species in response to metronidazole treatment. Our research also highlights the importance of the single-molecule paradigm for progressing the field of microbiology and applying these insights to better understand the dynamic microbiota during BV treatment. Subsequent novel treatment approaches should be proposed to improve BV treatment outcomes, optimize the vaginal microbiome, and reduce gynecological and obstetric sequelae. IMPORTANCE Bacterial vaginosis (BV) is a common infectious disease of the reproductive tract. Metronidazole treatment, as the first line of treatment, frequently fails at recovery of the microbiome. However, the precise types of Lactobacillus and other bacteria involved in BV remain unclear, and this has resulted in a failure to identify potential markers to predict clinic outcomes. In this study, we adopted a 16S rRNA gene full-length assembly sequencing technology for the taxonomy analysis and evaluation of vaginal microbiota before and after treatment with metronidazole. We additionally identified 96 and 189 novel 16S rRNA gene sequences in Lactobacillus and Prevotella species, respectively, in vaginal samples, which improves our understanding of the vaginal microbiota. Moreover, we found that the abundance of Lactobacillus iners and Prevotella bivia before treatment was associated with a lack of cure. These potential biomarkers will help to facilitate future studies aimed at improving BV treatment outcomes, optimize the vaginal microbiome, and reduce adverse sexual and reproductive outcomes.

Apoptosis‐inducing factor‐like protein‐mediated stress and metronidazole‐responsive programmed cell death pathway in Entamoeba histolytica

Apoptosis-inducing factor (AIF) is the major component of the caspase-independent cell death pathway that is considered to be evolutionarily ancient. Apoptosis is generally evolved with multicellularity as a prerequisite for the elimination of aged, stressed, or infected cells promoting the survival of the organism. Our study reports the presence of a putative AIF-like protein in Entamoeba histolytica, a caspase-deficient primitive protozoan, strengthening the concept of occurrence of apoptosis in unicellular organisms as well. The putative cytoplasmic EhAIF migrates to the nucleus on receiving stresses that precede its binding with DNA, following chromatin degradation and chromatin condensation as evident from both in vitro and in vivo experiments. Down-regulating the EhAIF expression attenuates the apoptotic features of insulted cells and increases the survival potency in terms of cell viability and vitality of the trophozoites, whereas over-expression of the EhAIF effectively enhances the phenomena. Interestingly, metronidazole, the most widely used drug for amoebiasis treatment, is also potent to elicit similar AIF-mediated cell death responses like other stresses indicating the AIF-mediated cell death could be the probable mechanism of trophozoite-death by metronidazole treatment. The occurrence of apoptosis in a unicellular organism is an interesting phenomenon that might signify the altruistic death that overall improves the population health.

The association between symptom or microscopy based diagnosis of bacterial vaginosis (BV) and response to treatment in women with recurrent BV.

Bacterial vaginosis (BV) is a common condition, yet accurate diagnosis remains a challenge. We explored symptom and microscopy-based diagnosis of BV and assessed the influence of these diagnostic approaches on treatment response. BV diagnosis based on patient-reported symptoms, and vaginal swab gram stain microscopy at local laboratories and a central laboratory were compared for women recruited into the VITA trial in England. Multivariable analysis was used to assess the association between the method of diagnosis and symptom resolution 2weeks after metronidazole treatment. 517 women presenting with vaginal discharge (470/517 [91%]) and/or malodour (440/517 [85%]) were included. The accuracy of patients' vaginal symptoms compared to local laboratory microscopy for BV diagnosis were -discharge, sensitivity 90% and specificity 5%; malodour, sensitivity 84% and specificity 12%, and compared to a central laboratory diagnosis were -discharge, sensitivity 91% and specificity 8%; malodour, sensitivity 88% and specificity 18%. 143/204 (70%) participants reported symptom resolution after treatment and this was associated with a positive baseline local laboratory diagnosis (adjusted relative risk-aRR 1.64 [1.02 to 2.64]), but not with a positive central laboratory diagnosis (aRR 1.14 [0.95 to 1.37]). Symptom resolution occurred in 75% (83/111) of women who were symptom positive/central laboratory BV positive compared to 65% (58/89) who were symptom positive/microscopy negative. Symptoms correlated poorly with microscopy-based BV diagnosis but two-thirds of women with a symptom positive/microscopy negative diagnosis experienced symptom resolution following metronidazole treatment. Further studies are needed to determine the optimal investigation and treatment for microscopy-negative women with typical BV symptoms.