Broad-spectrum Oral Antibiotics Research Articles

P-327 A multicenter retrospective study of the investigation of detailed immunological inflammatory grading for chronic endometritis and their correlation with the endometrial microbiome

Abstract Study question There exists refractory chronic endometritis which does not respond to antibiotic treatment. This study aims to elucidate its pathogenesis and develop detection methods. Summary answer Through treatment intervention for chronic endometritis (CE), the inflammatory grade decreased overall and the bacteria most associated with endometritis were Lactobacillus iners. What is known already CE and endometrial dysbiosis have been reported to be associated with recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), but there is insufficient data confirming the interrelation between them. Moreover, the diagnosis of CE typically involves single immunohistochemical staining with CD138, but the diagnostic criteria vary across reports (e.g., McQueen’s method, Liu’s method, etc.) and moreover, use of this classical inflammatory assessment methods raises concerns about their sufficiency in evaluating the pathogenesis of endometritis in cases of RPL and RIF. Study design, size, duration A retrospective analysis was conducted on 206 samples of endometrial specimens collected from infertile patients at seven participating assisted reproductive healthcare facilities from 2021 to 2023. Among these, 73 samples (from 48 cases) had undergone both histological examination and simultaneous endometrial microbiome testing, and data on pregnancy outcomes (including implantation success and ongoing pregnancy rate) were collected until December 2023 for these cases. Participants/materials, setting, methods The endometrial specimens from cases with RIF or RPL were obtained through intrauterine aspiration in luteal phase. Immunohistochemical staining using CD138, CD56, and CD8 antibodies was performed. A composite grading for endometritis, based on histological findings and immunohistochemistry intensity, was established (INF grading; grade 0 to 5). Furthermore, a portion of the specimens underwent microbiome analysis using next-generation sequencing targeting the 16SrRNA, exploring correlations between bacterial taxa, abundance, histological findings, and pregnancy outcomes. Main results and the role of chance Among analyzed 48 cases, 11 cases underwent repeated endometrial microbiome analysis post-treatment again, while 7 cases had additional testing without improvement in chronic endometritis (CE) or endometrial dysbiosis. The McQueen’s method diagnosed 27 cases with CE, while the Liu method identified 4 cases. According to our INF grading, 11 cases were classified as endometritis grade 3 or above. Successful embryo implantation was achieved in 18 cases (37.5%), with ongoing pregnancy in 13 cases (27.1%). CE treatment involved broad-spectrum oral antibiotics, mainly doxycycline and metronidazole, resulting in improvement to grade 2 or below in 9 out of 11 cases with INF grade 3 or above. However, clear associations between pregnancy outcomes and INF grades were not apparent, with the most significant correlation found in CE diagnosis using Liu’s method. Analyzing biomarkers for CE through LEfSe (Linear discriminant analysis effect size), both McQueen’s method and INF grading 2 or above were associated with the intrauterine presence of Lactobacillus iners. Estimating endometrial inflammation based on intrauterine Lactobacillus iners presence yielded an AUC of 0.733 for McQueen’s CE and 0.723 for INF grade 2 or above. Limitations, reasons for caution This study is a retrospective analysis, and the treatment protocols and intervention criteria for chronic endometritis vary among different facilities. The number of cases is also limited, and it is desirable to conduct a unified prospective multicenter cohort study with consistent protocols. Wider implications of the findings The combination of the endometrial microbiome testing and detailed inflammatory grading suggests the potential for establishing appropriate treatment intervention strategies and predicting the success rate of infertile treatment. Since Lactobacillus iners tends to colonize extensively in the vaginal environment of East Asian women, it is necessary to explore region-specific measures. Trial registration number not appicable

An Innovative Therapy by Changing the Gut Microbiome for the Dual Post-Operative Complications of the Recurrent Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in the Residual Type II First Branchial Cyst and Facial Nerve Palsy

A very unusual, interesting, and challenging case of a 24-year-old female who was born with three openings in the neck. The patient had chronic abdominal gaseous distention, recurrent abdominal pain, and constipation since early infancy. The patient presented in emergency with acute painful red, hot, and tender swelling in the left upper cervical area. Laboratory studies showed high inflammatory markers and a provisional diagnosis of abscess with a sinus was made. The patient underwent an emergency incision and drainage. Sinus recurred and a sinogram showed it to be a residual cyst in the left submandibular salivary gland. The total cyst excision was attempted with resultant recurrence and grade IV facial nerve palsy. Post-operatively recurrent infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) required several courses of oral and intravenous broad-spectrum antibiotics with several hospital admissions with no resolution in sight. Subsequent ultrasound and magnetic resonance imaging showed a residual infected cyst, cutaneous sinus, and a fistula opening in the left ear canal. A diagnosis of branchial cyst type II of the first brachial cleft remnant with a fistula was established with bilateral branchial fistulas of the second branchial remnants and the associated colorectal hypoganglionosis based on radiological studies. The patient refused any further operative interventions. Therefore, the option of conservative treatment of hypoganglionosis with holobiotics consisting of prebiotics, probiotics and postbiotics, laxatives, dietary changes, lifestyle modifications, and dietary supplements started. All antibiotics were stopped. These therapies resulted in the resolution of residual first branchial remnants and recurrent MRSA infections with the improvement in the facial nerve palsy from grade IV to grade III-IV together with an excellent cosmetic and functional result. The patient is doing well at follow-ups being infection-free for 18 months and repeat contrast-enhanced computed tomogram (CECT) has shown complete resolution of the residual cyst, sinus, and fistula with fibrosis.

Ludwig’s angina in a child: a case report and literature review

BackgroundLudwig’s angina is a diffuse cellulitis in the sub-mandibular space, which extends to the sublingual space. It is an emergency that often occurs in adults as a complication of oral infections. It is rare in children and is particularly life-threatening due to the smaller size, as well as the characteristics in these spaces in a child. This is the case of Ludwig’s angina in a 2-year-old boy, with rapid onset of signs of respiratory discomfort, no dental or systemic etiology, and great evolution.Case presentationA little boy was brought by his mom to the emergency room for the onset a firm swelling in the sub-mental region along with pain and fever, which appeared 3 days prior to the consultation. He was first examined by a pediatrician who prescribed oral broad-spectrum antibiotics (amoxicillin). The symptoms worsened over 48 h, as the little boy presented respiratory discomfort in supine position.He was admitted in the emergency department. Without dysphagia or respiratory distress.The clinical examination showed swelling in the sub-mental and sub-mandibular region with/without trismus or signs of oral infection. The laboratory investigations showed hyper-leukocytosis with a microcytic hypochromic anemia.CRP = 300; HIV test was negative.The computed tomography (CT scan) showed a diffuse abscess in the sub-mental and sub-mandibular and sub-lingual regions.No mediastinal collection was found.The diagnosis of Ludwig’s angina was established.The patient underwent percutaneous surgical drainage of 15 ml of pus, which alleviated his symptoms, the treatment was carried out through broad-spectrum antibiotics, analgesics, and daily cleaning of the wound and change of surgical dressing. Bacteriological exam found gram-positive cocci in chains. The culture showed a Staphylococcus aureus. The patient presented clinical and biological improvement and was discharged after 7 days.Six months follow-up showed a healthy child, without signs of infection or any other complication.ConclusionLudwig’s angina in children -however rare- is a potentially life-threatening, rapidly spreading, bilateral swelling of the sub-mandibular. Its management is based on airway control, drainage of the collection and broad-spectrum intravenous antibiotics, as well as surveillance of the biological parameters.Early diagnosis and appropriate management enhances outcome and decreases mortality significantly.

Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms.

Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention. TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr-/-) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3-/-). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA. Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3-/- mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK. These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.

Perturbation of maternal gut microbiota in mice during a critical perinatal window influences early neurobehavioral outcomes in offspring

The gut microbiota is increasingly recognized as a key environmental factor that shapes host development and physiology, including neural circuits formation and function. Concurrently, there has been growing concern that early-life antibiotic exposure may alter brain developmental trajectories, increasing the risk for neurodevelopmental disorders such as autism spectrum disorder (ASD). Here, we assessed whether perturbation of the maternal gut microbiota in mice during a narrow critical perinatal window (last week of pregnancy and first three postnatal days), induced by exposure to a commonly used broad-spectrum oral antibiotic (ampicillin), influences offspring neurobehavioral outcomes relevant to ASD. Our results demonstrate that neonatal offspring from antibiotic-treated dams display an altered pattern of ultrasonic communication, which was more pronounced in males. Moreover, juvenile male, but not female, offspring from antibiotic-treated dams showed reduced social motivation and social interaction, as well as context-dependent anxiety-like behavior. However, no changes were observed in locomotor or exploratory activity. This behavioral phenotype of exposed juvenile males was associated with reduced gene expression of the oxytocin receptor (OXTR) and several tight-junction proteins in the prefrontal cortex, a key region involved in the regulation of social and emotional behaviors, as well as a mild inflammatory response in the colon. Further, juvenile offspring from exposed dams also showed distinct alterations in several gut bacterial species, including, Lactobacillus murinus, and Parabacteroides goldsteinii. Overall, this study highlights the importance of the maternal microbiome in early-life, and how its perturbation by a widely used antibiotic could contribute to atypical social and emotional development of offspring in a sex-dependent manner.This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".

Ocular microbiota promotes pathological angiogenesis and inflammation in sterile injury-driven corneal neovascularization

Microbiota promotes or inhibits the pathogenesis of a range of immune-mediated disorders. Although recent studies have elucidated the role of gut microbiota in ocular disease, the effect of ocular microbiota remains unclear. Herein, we explored the role of ocular commensal bacteria in non-infectious corneal inflammation and angiogenesis in a mouse model of suture-induced corneal neovascularization. Results revealed that the ocular surface harbored a microbial community consisting mainly of Actinobacteria, Firmicutes and Proteobacteria. Elimination of the ocular commensal bacteria by oral broad-spectrum antibiotics or topical fluoroquinolone significantly suppressed corneal inflammation and neovascularization. Disease amelioration was associated with reduced numbers of CD11b+Ly6C+ and CD11b+Ly6G+ myeloid cells, not Foxp3+ regulatory T cells, in the spleen, blood, and draining lymph nodes. Therapeutic concentrations of fluoroquinolone, however, did not directly affect immune cells or vascular endothelial cells. In addition, data from a clinical study showed that antibiotic treatment in combination with corticosteroids, as compared with corticosteroid monotherapy, induced faster remission of corneal inflammation and new vessels in pediatric patients with non-infectious marginal keratitis. Altogether, our findings demonstrate a pathogenic role of ocular microbiota in non-infectious inflammatory disorders leading to sight-threatening corneal neovascularization, and suggest a therapeutic potential of targeting commensal microbes in treating ocular inflammation.

Chicken intestinal microbiota modulation of resistance to nephropathogenic infectious bronchitis virus infection through IFN-I

BackgroundMammalian intestinal microbiomes are necessary for antagonizing systemic viral infections. However, very few studies have identified whether poultry commensal bacteria play a crucial role in protecting against systemic viral infections. Nephropathogenic infectious bronchitis virus (IBV) is a pathogenic coronavirus that causes high morbidity and multiorgan infection tropism in chickens.ResultsIn this study, we used broad-spectrum oral antibiotics (ABX) to treat specific pathogen free (SPF) chickens to deplete the microbiota before infection with nephropathogenic IBV to analyze the impact of microbiota on IBV infections in vivo. Depletion of the SPF chicken microbiota increases pathogenicity and viral burden following IBV infection. The gnotobiotic chicken infection model further demonstrated that intestinal microbes are resistant to nephropathogenic IBV infection. In addition, ABX-treated chickens showed a severe reduction in macrophage activation, impaired type I IFN production, and IFN-stimulated gene expression in peripheral blood mononuclear cells and the spleen. Lactobacillus isolated from SPF chickens could restore microbiota-depleted chicken macrophage activation and the IFNAR-dependent type I IFN response to limit IBV infection. Furthermore, exopolysaccharide metabolites of Lactobacillus spp. could induce IFN-β.ConclusionsThis study revealed the resistance mechanism of SPF chicken intestinal microbiota to nephropathogenic IBV infection, providing new ideas for preventing and controlling nephropathogenic IBV.39561Y51b4Zm9kk2tsUN9pVideo abstract

Early-Life Exposure to Non-Absorbable Broad-Spectrum Antibiotics Affects the Dopamine Mesocorticolimbic Pathway of Adult Rats in a Sex-Dependent Manner.

Gut microbiota with a stable, rich, and diverse composition is associated with adequate postnatal brain development. Colonization of the infant’s gut begins at birth when parturition exposes the newborn to a set of maternal bacteria, increasing richness and diversity until one to two first years of age when a microbiota composition is stable until old age. Conversely, alterations in gut microbiota by diet, stress, infection, and antibiotic exposure have been associated with several pathologies, including metabolic and neuropsychiatric diseases such as obesity, anxiety, depression, and drug addiction, among others. However, the consequences of early-life exposure to antibiotics (ELEA) on the dopamine (DA) mesocorticolimbic circuit are poorly studied. In this context, we administered oral non-absorbable broad-spectrum antibiotics to pregnant Sprague-Dawley dams during the perinatal period (from embryonic day 18 until postnatal day 7) and investigated their adult offspring (postnatal day 60) to assess methylphenidate-induced conditioned place preference (CPP) and locomotor activity, DA release, DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content in ventral tegmental area (VTA), and expression of key proteins within the mesocorticolimbic system. Our results show that ELEA affect the rats conduct by increasing drug-seeking behavior and locomotor activity induced by methylphenidate of males and females, respectively, while reducing dopamine striatal release and VTA content of DOPAC in females. In addition, antibiotics increased protein levels of DA type 1 receptor in prefrontal cortex and VTA of female rats, and tyrosine hydroxylase in VTA of adult male and female rats. Altogether, these results suggest that ELEA alters the development of the microbiota-gut-brain axis affecting the reward system and the response to abuse drugs in adulthood.

Bioequivalence Study of Two Formulations of Cefixime

Cefixime is a broad-spectrum oral antibiotic used for treating a wide variety of bacterial infections. Study Objective: The objective of this study was to find out whether bioequivalence study of Cefixime 200 mg, Profim® capsule manufactured by PT Promedrahardjo Farmasi Industri in comparison with Cefixime 100 mg, Cefspan® capsule manufactured by PT Dankos Farma, For PT Kalbe Farma Tbk, under license by Astellas Pharma Inc., Osaka – Japan. Methods: The study was conducted using an open-label, randomized, single-dose, two-periods, two-treatments, crossover study under fasting conditions with 8 (eight) days washed-out period between each period. According to the random design, a single oral dose of the test drug or reference drug was administered to 30 healthy male subjects after overnight fasting. The number of subjects who finished the study was twenty-eight (28) healthy male subjects. Serial plasma samples were obtained over a 32 hours period. Plasma concentrations of the drug were determined by LC-MS/MS method. From the Cefixime concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUC0-32h, AUC0-∞, and Cmax, while the statistical interval proposed was 80.00 - 125.00% for AUC0-32h and Cmax with 90% Confidence Interval (CI) with α = 5.00%. The estimation of Tmax and T1/2 in the bioequivalence study was based on a nonparametric statistical procedure on the original data using Wilcoxon Sign Test. Results: The main pharmacokinetic parameters of the test drug Profim® (BN: B051A21P-1)/ reference drug, Cefspan® (BN: KCEFB00038) ratio were as follows: AUC0-32h: 105.86 (95.41 - 117.44) with CV Intra Subjects was 22.72% and Cmax: 105.63 (95.33 - 117.03) with CV Intra Subjects was 22.43 %. Whilst TMAX of the test drug Profim® (BN: B051A21P-1)/ reference drug, Cefspan® (BN: KCEFB00038) were respectively 4.50 (3.50 – 6.00) h and 4.50 (3.00 – 6.00) h; mean T1/2 were respectively 4.18 ± 0.78 h and 4.14 ± 0.56 h; and mean Slope were respectively (-0.17) ± 0.03 h and (-0.17) ± 0.02 h. There is no adverse event that occurred during this study. Conclusion: The present study demonstrated that the evaluated test drug Profim® (BN: B051A21P-1) were bioequivalence in term of both rate and extent of absorption to the reference drug Cefspan® (BN: KCEFB00038).

Septic arthritis of the fingers: is short-term oral antibiotic therapy appropriate?

The management of septic arthritis of the hand is poorly described and there is no consensus. It is based on how septic arthritis of the large joints is managed, despite certain specificities related to the hand, typically involving inpatient management and intravenous antibiotic therapy. The primary objective of this work was to evaluate our postoperative protocol for the management of septic arthritis of the hand with short-term antibiotic therapy. The secondary objective was to determine the risk factors for treatment failure. We conducted a retrospective, descriptive, single-center study and analyzed the medical records of patients managed for septic arthritis of the fingers over a 1-year period from January 2018 to December 2018. We collected patient demographics and all pre-, intra-, and postoperative data. A total of 128 patients were included. The median age was 52.4 years (41–66). An exogenous source of contamination was reported in 98% of cases (animal bite, plant thorn, wound, cyst trituration, etc.). The most frequently isolated microorganism was Staphylococcus aureus (45%), followed by Streptococcus spp. (22%) and Pasteurella spp. (18%). The vast majority of patients (79%) were treated with oral amoxicillin/clavulanic acid. This treatment was continued in 91% of patients after microbiological results were obtained for a median treatment duration of 8 days (7–15). Nine percent of patients failed treatment. The risk factors identified were crush wounds (p = 0.04), initial radiological abnormalities (chondrolysis and/or osteolysis) (p = 0.016) and infection with Pasteurella spp. (p = 0.015). Our study suggests that simplified antibiotic therapy is feasible for the management of septic arthritis of the hand with short duration, broad spectrum oral antibiotics in the absence of identified risk factors.

Multi Drug Resistance (MDR) Urinary Tract Infection: An Evidence Based Study

Background: Urinary tract infections are the most frequently reported infections that drive the use of antibiotics around the world. UTI is the 4th most common healthcare-associated infection. Multidrug-resistant (MDR) organisms are predominantly bacteria that are resistant to one or more classes of antimicrobials. The increasing rise in the incidence of MDR-UTI has resulted in increased morbidity, mortality, and treatment cost of the patients. Thus, it is important to highlight the magnitude of the problem, identify the risk factors that result in MDR-UTI, and to take appropriate measures to control its occurrence. Objective: To determine the magnitude of the multidrug-resistant bacteria, their antibiotic-resistant profile, andtheir effect on the treatment cost of the patients Methods: It is a descriptive study conducted in the Department of Urology at the Institute of Kidney Diseases (IKD) from Jan 2019 till 30th March 2020. A total of 54 patients with multi-drug resistant UTI were included in the study irrespective of age and gender. All the data was recorded on a structured pro-forma and was analyzed on SPSS. Results: A total of 3190 patients were operated on from Jan 2019 till 30th March 2020. Out of which 54 patients (1.6 %) developed MDR-UTI. Among them,38 were male and 16 females. The mean age of the patients was 41 ± 18.4. Urolithiasis with infections was found most frequent, in 32 (59.3%) patients. All patients were on broad-spectrum oral antibiotics and had a history of urethral catheterization before the development of MDR-UTI. The most common procedure was Emergency cystoscopy and DJ stent 15 (27.8%). Followed by Percutaneous nephrostomy in 8 (14.8%). Regarding co-morbidities, 38(68.5%) patients had none, 3 patients had diabetes and 6 patients were having Diabetes and Hypertension. Pseudomonas aeruginosa was found most frequent microorganisms in 34 (63%) patients while E.coli in 10 (18.5%) and Klebsiella in 5 (9.3%) patients. Colistin was found sensitive in 36 patients (66.7%). The mean hospital stay in MDR-UTI is 9.28± 5.17 days as compared to 2.1 days in routine cases. Approximately a 4-fold increase was observed in medicines alone in the management of MDR UTI. We recorded 1 mortality (1.9%), case of MDR urosepsis. Linear regression revealed previous use of antibiotics; catheterization, old age, and endo-urological procedures in an emergency as independent risk factors for MDR-UTI. Conclusion: MDR-uti is an emerging local problem. pseudomonas aeruginosa is the most frequently found microorganism in the present setup. it is associated with significant morbidity and very high treatment cost. Keywords: Urinary Tract Infection, Multidrug Resistance, Micro-Organism, Urology, Antimicrobials

Investigations on Antibacterial Potency of Azadirachta Indica Leaf Extracts against Some Resistant Bacteria

Resistance to antibiotics in pathogens responsible for causing infectious diseases has become a matter of great public health concern internationally and India is no exception to it. Widespread use and availability of practically all the antimicrobials across the counter and incompletion of the dose is supposed to be one of the major reasons for this. It is observed that some plant extracts seem to potentiate the activity of antibiotics against resistant bacterial strains. So the objective of the study was to use some natural products as an alternate to the conventional treatment against antibiotic resistance. The effects of crude extracts of leaves of Azadirachta indica against resistant strains of pathogenic S. aureus, E. coli and K. Pneumoniae were investigated using the agar well diffusion method. It was observed that the growth of all the isolates were inhibited to varying degrees with gram-positive more susceptible than gram-negative bacteria. Hexane extract was more effective, producing larger zones of growth inhibition sizes and smaller MIC, than the aqueous and ethyl acetate extracts. The MIC values ranged from 0.5 - 4 mg/ml. The ability of the crude extracts to inhibit the growth of such resistant pathogenic bacterial strains that were used in this study is an indication that the neem leaves extract has the potential and can be used as a source for new broad spectrum oral antibiotics. The result obtained in this study validates the use of the neem leaves extract in traditional medicine to treat infectious conditions.

Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial

To compare the rates of negative test results for chronic endometritis (CE) between subjects who did and did not receive antibiotic treatment. Prospective, single-blind randomized controlled trial. Tertiary hysteroscopic center in a university teaching hospital. A total of 132 women with CE confirmed with immunohistochemical study with CD138 epitope. Women randomized to antibiotic therapy received oral levofloxacin 500 mg and tinidazole 1,000 mg daily for 14 days. Women randomized to the control group did not receive any treatment. A repeated endometrial biopsy was performed 4 to 8 weeks after the initial biopsy to determine whether CE was still present. The rate of negative test results for CE (from positive to negative). The CE rate of negative test results in the treatment group (89.3%) after one course of antibiotic treatment was significantly higher than that in the control group (12.7%). Among subjects who attempted pregnancy, there was no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (43.2%, 5.4%) and the control arm (25.7%, 14.3%). Among subjects randomized, there was also no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (27.1%, 3.4%) and the control arm (16.4%, 9.1%). A course of broad-spectrum oral antibiotic therapy for 14 days is effective in the treatment of CE in >89.8% of cases. However, it is not yet clear whether treatment improved pregnancy outcomes. NCT02648698.

Manganese dioxide (MnO2)/Fullerene-C60-Modified Electrodes for the Voltammetric Determination of Rifaximin

Rifaximin (RFX) is a broad-spectrum oral antibiotic with bactericidal actions against Gram-negative and Gram-positive bacteria. In the present work, a sensitive voltammetric assay for the RFX in pharmaceutical formulations is designed using nanostructured working electrodes. Surface functionalization with manganese dioxide (MnO2)/fullerene-C60 nanocomposite exhibited the highest electrochemical responses with a sharp oxidation peak at about 336 mV that was obtained using the differential pulse voltammetry (DPV). The cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were applied, while the electrode matrix composition including types of nanomaterials, electroanalytical parameters, and pH effect were optimized. To that end, using the DPV, high sensitivity was obtained from the linear calibration curve ranged from 0.8 to 31.5 µg·mL−1 with the correlation coefficient of 0.99, limit of detection of 0.76 µg·mL−1 and limit of quantification of 2.31 µg·mL−1. Accordingly, the designed approach is offering a potential applicability towards the RFX determination in pharmaceutical preparations and its quality control.

Gaps in the implementation of COVID-19 mitigation measures could lead to development of new strains of antimicrobial resistant pathogens: Nigerian perspective.

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a new virus that is responsible for COVID-19, a disease that complicate health conditions and results in death. The total diversion of attention of government and health care workers (HCWs) to prevent the escalation of the pandemic disease has placed a great barrier to diagnosis and treatment of other illnesses that share common symptoms with COVID-19, and that has consequently enabled the endemic practice of self-antimicrobial medication to increase in Nigeria. Development of secondary infections in COVID-19 and in other conditions, caused by antibiotic resistant pathogens could make them more deadly now or in the future. The mitigation strategies adopted in Nigeria and its States, which include enforcing social distancing, partial or total lockdown, and restricting access to health care facilities for non COVID-19 patients, have further increased the demand of antimicrobial agents from unauthorized outlets in communities for inappropriate use. A cross-sectional survey of 162 randomly selected individuals that visited medical stores and 170 medical store owners to evaluates the level of self-medication with five oral broad spectrum antibiotics and antimalaria during the lockdown revealed an increase (68.5%) in practice of self-medication with at least one of the antimicrobial and emergence of new abusers. Blind treatment of symptoms of malaria and common cold without diagnosis and health care consultation was nearly 100%. Irrational use of sanitizers, disinfectants and other cidal agents that can fuel antimicrobial resistance has drastically increased in communities. Exposure of microorganisms in the environment without caution to large volume of fumigants is increasing on daily basis. We strongly recommend that while mitigating SARS-CoV-2 virus spread, efficacious and feasible technological, social, economic and behavioral interventions that will also control the evolution and spread antimicrobial resistant microorganisms should be applied.

Pharmacokinetics and bioequivalence study of two formulations of Cefixime Suspension ‎

Cefixime is a broad-spectrum oral antibiotic used for treating a wide variety of bacterial infections. This investigation was aimed to study the pharmacokinetics and bioequivalence of a new generic suspension containing 100 mg cefixime trihydrate per 5 ml as a test product against the reference formulation Suprax® suspension after administration to 28 Arabic healthy male adult subjects under fasting condition. Ten milliliters of each formulation (equivalent to 200 mg cefixime) were administered

GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity.

Rationale: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear.Methods: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces.Results: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate.Conclusion: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity.

Rare Spontaneous Development of Nasal Septal Abscess in End-stage Kidney Disease

The spontaneous development of a nasal septal abscess in patients with chronic kidney disease is hardly described in the literature. A 58-year-old man with long-standing type 2 diabetes mellitus and a history of rectal adenocarcinoma was admitted for resection of tumor recurrence. He was initiated on hemodialysis post-operatively due to worsening kidney function. He was discharged on thrice-weekly dialysis but was readmitted two months after for progressive shortness of breath. Further examination revealed severe nasal congestion from a nasal septal abscess which prompted mouth-breathing. Incision and drainage and anterior nasal packing were done, and the patient was discharged improved on broad-spectrum oral antibiotics. This case report highlights the possibility of developing nontraumatic nasal infections in patients with chronic kidney disease due to compromised host defenses.

Antibiotic-mediated gut dysbiosis alters innate-like T cell frequency and phenotype in tumor-bearing mice

Abstract Innate-like T cells bind to non-peptide antigens in a TCR-dependent manner and are not MHC-restricted. This subpopulation of T cells consists of mucosal associated invariant T cells (MAIT), natural killer T cells (NKT), and gamma delta (γδ) T cells. Innate-like T cells can recognize microbially-derived antigens and interact with gut commensals to help maintain intestinal homeostasis. Additionally, they are implicated in tumour immunity as producers of cytokines and cytotoxic molecules. Thus, innate-like T cells may serve as an intermediary between the gut microbiota and tumor development. Using syngeneic mouse tumour models and flow cytometric analysis, we aim to evaluate the relationships between gut microbiota modulation, tumour growth, checkpoint inhibitor response, and innate-like T cell phenotype. Gut dysbiosis was induced using broad spectrum oral antibiotics two weeks prior to subcutaneous injection of MC38 colon adenocarcinoma cells. Mice with palpable tumours were treated twice with anti-PD-L1 during the experiment. Compared to vehicle control, tumor size reduction in response to anti-PD-L1 was not significantly altered with antibiotic treatment. The following observations were noted in antibiotic-treated mice. The frequency of γδ T cells was decreased in the tumour, blood, and spleen. MAIT, NKT, and γδ T cells in the spleen had lower expression of tissue localization-associated markers, CD103 and CXCR6. MAIT cell activation state, characterized by CD25 and CD69 expression, was also elevated in the spleen. These findings suggest that changes to the immune landscape of tumor-bearing mice due to antibiotic-driven dysbiosis is characterized by alterations in innate-like T cell abundance and phenotype.

Cost of inappropriate antimicrobial use for upper respiratory infection in Japan

BackgroundAntibiotics are often prescribed inappropriately to patients with upper respiratory infection (URI) in ambulatory care settings; however, the economic burden of such prescription has not been quantitatively assessed. Here, we aimed to evaluate the additional cost of antimicrobial prescription for URI at the population level in Japan.MethodsWe conducted a retrospective observational survey using longitudinal claims data between 2013 and 2016 obtained from JMDC Claims Database, which contains data from 5·1 million corporate employees and family members under the age of 65 years. Appropriateness of antibiotic prescription was assessed by a panel of six infectious disease physicians according to ICD-10 code in JMDC Claims Database. Total additional cost of antibiotic prescription for URI at the national level was estimated by weighting of age-structured population data.ResultsThe annual additional cost of inappropriate antibiotic prescription for URI was estimated at 423·6 (95% CI: 416·8–430·5) million USD in 2013, 340·9 (95% CI: 335·7–346·2) million USD in 2014, 349·9 (95% CI: 344·5–355·3) million USD in 2015, and 297·1 (95% CI: 292·4–301·9) million USD in 2016. Three classes of broad-spectrum oral antibiotics (third-generation cephalosporins, macrolides, and fluoroquinolones) accounted for > 90% of the total additional cost.ConclusionsAlthough a decreasing trend was observed, annual additional costs of inappropriate antibiotic prescriptions for URI could be a substantial economic burden in Japan. Appropriately prescribing broad-spectrum oral antibiotics might be an important issue to reduce unnecessary medical costs in Japanese ambulatory care.