Análisis de una guía clínica para el tratamiento y alta precoz en apendicitis aguda complicada / Analysis of a clinical guideline for treatment and early discharge in complicated acute appendicitis

Objetivo: El objetivo de este estudio es evaluar los resultados entérminos de complicaciones infecciosas y estancia hospitalaria de lainstauración de una guía clínica para el tratamiento y alta precoz enpacientes con apendicitis aguda complicada.Material y métodos: Se elaboró una guía para el tratamiento delas apendicitis en función de su grado de severidad. Las complicadas setrataron con ceftriaxona-metronidazol durante 48h, siendo alta si cumplen ciertos criterios clínicos y analíticos. Se realizó un estudio analíticoretrospectivo comparando la incidencia de abscesos intraabdominalespostquirúrgicos (AIA) e infección del sitio quirúrgico (ISQ) en pacientesmenores de 14 años sometidos a la nueva guía (Grupo A), respecto a unacohorte histórica (Grupo B), en la que la pauta de tratamiento era gentamicina-metronidazol 5 días. Además, se realizó un estudio de cohortesprospectivas para evaluar qué antibioterapia (amocilina-clavulánico ocefuroxima-metronidazol) es más eficaz en los pacientes que cumplencriterios de alta precoz. Resultados: Se incluyeron 205 pacientes menores de 14 años en elGrupo A y 109 en el Grupo B. Presentaron AIA un 14,3% en el grupoA, frente al 13,8% en el B (p= 0,83); e ISQ un 1,9% y un 8,25% respectivamente (p= 0,008). Cumplieron criterios de alta precoz el 62,7%de los pacientes del Grupo A. La mediana de estancia disminuyó a de6 a 3 días. Al alta, el 57% recibieron amoxicilina-clavulánico y el 43%cefuroxima-metronidazol, sin hallarse diferencias en términos de ISQ(p= 0,24) ni de AIA (p= 0,12).Conclusiones: El alta precoz disminuye la estancia hospitalariasin aumentar el riesgo de complicaciones infecciosas postquirúrgicas.La amoxicilina-clavulánico es una opción segura para la antibioterapiaoral domiciliaria.(AU)

Objective: The objective of this study was to assess the results of aclinical guideline for the treatment and early discharge of patients withcomplicated acute appendicitis in terms of infectious complicationsand hospital stay. Materials and methods: A guideline for appendicitis treatmentaccording to severity was created. Complicated appendicitis caseswere treated with ceftriaxone-metronidazole for 48h, with dischargebeing approved if certain clinical and blood test criteria were met. Aretrospective analytical study comparing the incidence of postoperative intra-abdominal abscess (IAA) and surgical site infection (SSI) inpatients under 14 years of age to whom the new guideline was applied(Group A) vs. the historical cohort (Group B, treated with gentamicinmetronidazole for 5 days) was carried out. A prospective cohort study toassess which antibiotic therapy (amoxicillin-clavulanic acid or cefuroxime-metronidazole) proved more effective in patients meeting earlydischarge criteria was also conducted.Results: 205 patients under 14 years of age were included in GroupA, whereas 109 patients were included in Group B. IAA was presentin 14.3% of patients from Group A vs. 13.8% from Group B (p=0.83),while SSI was present in 1.9% of patients from Group A vs. 8.25%from Group B (p=0.008). Early discharge criteria were met by 62.7%of patients from Group A. Median hospital stay decreased from 6 to 3days. At discharge, 57% of patients received amoxicillin-clavulanic acid,whereas 43% received cefuroxime-metronidazole, with no differencesbeing found in terms of SSI (p=0.24) or IAA (p=0.12). Conclusions: Early discharge reduces hospital stay without increas-ing the risk of postoperative infectious complications. Amoxicillin-clavulanic acid is a safe option for at-home oral antibiotic therapy.(AU)

Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.

Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.

Formulation and characterization of hydroxyethyl cellulose-based gel containing metronidazole-loaded solid lipid nanoparticles for buccal mucosal drug delivery.

Local delivery of drug is a promising strategy to manage periodontitis characterized by chronic inflammation of the soft tissue surrounding the teeth. An optimized system should prolong the drug retention time and exhibit controlled drug permeation through the buccal mucosal layer. This study was aimed to develop hydroxyethyl cellulose (HEC)-based gel containing metronidazole (MTZ) loaded in solid lipid nanoparticles (SLNs), and to enhance the antimicrobial activity of MTZ. SLNs were prepared using a combination method of solvent evaporation and hot homogenization. The results showed that the fabricated SLNs, comprising of Precirol (2.93%, w/v), Tween 80 (1.8%, w/v), and the drug:lipid ratio of 19.3% (w/w), were approximately 200 nm in size, with a narrow distribution. The HEC (3%, w/w)-based gel formed a smooth, homogeneous structure and had preferable mechanical and rheological properties. Moreover, the MTZ-loaded SLNs-based HEC gel (equivalent to 1% of MTZ, w/w) exhibited a sustained in vitro drug release pattern, optimal ex vivo permeability, and enhanced in vitro antimicrobial activity after 24 h of treatment. These findings indicate the potential of the MTZ-loaded SLNs-based HEC formulation for local drug delivery at the buccal mucosa in managing periodontal disease.

The influence of pretreatment with PPI on Helicobacter pylori eradication: A systematic review and meta-analysis.

BACKGROUND: In this meta-analysis, we aimed to comprehensively investigate the impact of pretreatment with proton pump inhibitor (PPI) on Helicobacter pylori (H. pylori) eradication and provide novel inspiration to clinical practice. METHODS: Relevant studies were selected through PubMed, Embase, and Cochrane Library from inception to March 2021. Two reviewers performed the selection independently. The primary outcome of the meta-analysis was the eradication rate. A modified Jadad scale was used to evaluate literature quality quantitatively. RESULTS: Ten studies were included in this research. The results showed no significant difference between PPI pretreatment and standard treatment on eradication of H. pylori [relative risk (RR): 1.17, 95% confidence interval (95% CI): 0.0.73-1.88]. There was no significant difference between the PPI pretreatment group and the standard therapy group for conventional triple therapy, PPI and amoxicillin and clarithromycin (RR: 1.29, 95% CI: 0.60-2.77). Similar results were obtained in the therapy strategy of PPI and amoxicillin and metronidazole (RR: 3.01, 95% CI: 0.62-14.74). Interestingly, for the therapy regimen of PPI and clarithromycin and metronidazole, PPI pretreatment indicated superiority on H. pylori eradication rate (RR: 0.48, 95% CI: 0.23-0.97, P < .05). CONCLUSION: PPI pretreatment did not affect the H. pylori eradication rates, regardless of the various types of bacteriostatic antibiotic, except the therapy regimen of PPI and clarithromycin and metronidazole.

Cephalic tetanus manifesting as isolated facial nerve palsy- a case report from rural Armenia.

Cephalic tetanus is a rare clinical form of tetanus, clinically characterized by trismus and cranial nerve palsy involving one or more cranial nerves, facial nerve being the most common. We report a case of cephalic tetanus with left-sided lower motor facial nerve palsy in a 66-year-old non-immunized patient after an untreated laceration injury. The patient had dysphagia, spasm of the muscles of mastication, asymmetry of the left side of the face, cough, shortness of breath, and stiffness of neck muscles. The presentation was unique given that the facial nerve palsy appeared prior to the occurrence of trismus, which misled the initial diagnosis towards Bell's palsy. He was successfully treated with tetanus antitoxin without any adverse events. Although widespread use of tetanus vaccine has led to a dramatic decline in this fatal disease, sporadic disease occurrence is still possible, particularly in individuals without up-to-date vaccinations. In this case report we illustrate the importance of early recognition of cephalic tetanus prior to the development of the full clinical picture. The early initiation of therapy is the key to recovery from this deadly disease. Physicians are encouraged to include cephalic tetanus as a cause of facial nerve palsy in their differential. In particular, paying attention to cases manifesting early after head or neck injury.

Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite.

Due to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescence spectroscopic measurements gave 1.9 × 105 M-1 and 1.0 × 104 M-1 as the association constants of the protonated metronidazole inclusion in CB7 and SCX4, whereas the unprotonated guests had values more than one order of magnitude lower, respectively. The preferential binding of the protonated metronidazole resulted in 1.91 pH unit pKa diminution upon encapsulation in CB7, but the complexation with SCX4 led to a pKa decrease of only 0.82 pH unit. The produced protonated metronidazole-SCX4 complex induced nanoparticle formation with protonated chitosan by supramolecular crosslinking of the polysaccharide chains. The properties of the aqueous nanoparticle solutions and the micron-sized solid composite produced therefrom by nano spray drying were unraveled. The results of the present work may find application in the rational design of tailor-made self-assembled drug carrier systems.

Demodex spp / Dermodex spp

Los ácaros ectoparásitos del género Demodex spp (>140 especies) pertenecen a la familia Demodicidae, superfamilia Cheyletoidea, suborden Prostigmata, orden Trombidiformes, superorden Acariformes. Fueron descritos por primera vez en 1841 por Henle y Berger. El término Demodex deriva del griego: demos = grasa y dex = gusano incrustado. Tienen una longitud de 0.2- 0.4 mm, son transparentes y elongados. Su cuerpo se divide en tres secciones principales: 1) gnatosoma, región anterior, en donde se encuentra la apertura bucal; 2) podosoma, región en la que se encuentran sus cuatro pares de patas; y 3) el opistoma, región caudal o cola. Se adquieren poco después del nacimiento y se consideran parte del microbiota normal de muchos mamíferos, así como también del ser humano, en particular de la unidad pilosebácea. Por lo tanto, se ubican principalmente en el rostro, cuero cabelludo y región superior del tronco. Todas estas áreas corporales se caracterizan por la alta secreción sebácea, alimento primordial para el crecimiento y desarrollo de este ácaro; razón por la cual, además, su densidad aumenta durante la pubertad, periodo cuando proliferan las glándulas sebáceas. Dentro de las especies del género, encontramos exclusivamente en humanos, a D. folliculorum (440 µm), habitando frecuentemente el infundíbulo folicular y D. brevis (240 µm), que se localiza predominantemente en los ductos sebáceos y glándulas tarsales a nivel ocular.(AU)

Development of a xanthan gum film for the possible treatment of vaginal infections.

Bacterial vaginosis is a vaginal infection that affects 60% of women of reproductive age worldwide. It is mainly caused by the bacterium Gardnerella vaginalis and is a factor that increases the probability of getting sexually transmitted diseases. We aimed to develop a new pharmaceutical form for the treatment of vaginal infections. We employed the solving-casting method to fabricate a polymeric film with Xanthan gum, a natural polymer produced by the bacterium Xanthomonas campestris, and metronidazole, one of the most commonly used drugs for vaginal infections. In order to characterize the film, we measured pH, dose uniformity, dissolution profile, and the percentage of swelling. Moreover, we performed a thermogravimetric analysis and scanning electron microscopy. The results demonstrated a pH suitable for vaginal application and uniform distribution of the drug in the film. Also, the formulation exhibited a high percentage of swelling and a slow release of the drug in a simulated vaginal fluid medium. All these attributes indicated that the manufactured film has ideal characteristics to be used and administered vaginally. It could be an excellent alternative to treat bacterial vaginosis and also improve user adherence.

Clinical Significance of Postoperative Antibiotic Treatment for Positive Islet Cultures After Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVES: Islet cultures are routinely performed in total pancreatectomy with islet autotransplantation (TPIAT), and the need for empiric antibiotic treatment based on culture results is unknown. We evaluated the effect of postoperative antibiotic treatment for positive islet cultures on clinical infection. METHODS: Seventy-nine patients undergoing TPIAT were reviewed. Prophylactic perioperative ceftriaxone and metronidazole were administered, and transplanted islet preparations included ciprofloxacin. Postoperative antibiotics were not routinely given for positive cultures unless a clinical infection was suspected. The primary end point was 30-day infectious complications. RESULTS: Fifty-one patients (65%) had a positive culture. Overall, 39 patients (87%) had organisms susceptible to our perioperative antibiotic regimen. There was no difference in the infectious complication rate between those with positive compared with negative cultures (16% vs 29%, P = 0.17). Patients with a positive culture had similar 30-day postoperative infectious complication rates whether receiving postoperative antibiotics (n = 7) or not (14% vs 16%, P = 0.91). Only 1 patient had a correlation of clinical and islet cultures. CONCLUSIONS: Beyond prophylactic antibiotics, empiric antibiotic treatment for a positive culture is not warranted and provides a rationale for the abandonment of routine cultures in TPIAT.

Temporal Changes in Vaginal Microbiota and Genital Tract Cytokines Among South African Women Treated for Bacterial Vaginosis.

The standard treatment for bacterial vaginosis (BV) with oral metronidazole is often ineffective, and recurrence rates are high among African women. BV-associated anaerobes are closely associated with genital inflammation and HIV risk, which underscores the importance of understanding the interplay between vaginal microbiota and genital inflammation in response to treatment. In this cohort study, we therefore investigated the effects of metronidazole treatment on the vaginal microbiota and genital cytokines among symptomatic South African women with BV [defined as Nugent score (NS) ≥4] using 16S rRNA gene sequencing and multiplex bead arrays. Among 56 BV-positive women, we observed short-term BV clearance (NS <4) in a proportion of women six weeks after metronidazole treatment, with more than half of these experiencing recurrence by 12 weeks post-treatment. BV treatment temporarily reduced the relative abundance of BV-associated anaerobes (particularly Gardnerella vaginalis and Atopobium vaginae) and increased lactobacilli species (mainly L. iners), resulting in significantly altered mucosal immune milieu over time. In a linear mixed model, the median concentrations of pro-inflammatory cytokines and chemokines were significantly reduced in women who cleared BV compared to pre-treatment. BV persistence and recurrence were strongly associated with mucosal cytokine profiles that may increase the risk of HIV acquisition. Concentrations of these cytokines were differentially regulated by changes in the relative abundance of BVAB1 and G. vaginalis. We conclude that metronidazole for the treatment of BV induced short-term shifts in the vaginal microbiota and mucosal cytokines, while treatment failures promoted persistent elevation of pro-inflammatory cytokine concentrations in the genital tract. These data suggest the need to improve clinical management of BV to minimize BV related reproductive risk factors.

A Prospective, Open-Label Pilot Study of Concurrent Male Partner Treatment for Bacterial Vaginosis.

Up to 50% of women receiving first-line antibiotics for bacterial vaginosis (BV) experience recurrence within 12 weeks. Evidence suggests that reinfection from an untreated regular sexual partner contributes to recurrence. We conducted a pilot study of 34 heterosexual couples to describe the impact of concurrent partner treatment on the composition of the genital microbiota over a 12-week period. We also determined the acceptability and tolerability of concurrent partner treatment and obtained preliminary estimates of the efficacy of the intervention to inform a randomized controlled trial (RCT). Women received first-line antibiotic treatment for BV (i.e., oral metronidazole or intravaginal clindamycin), and their male partner received oral metronidazole, 400 mg, and 2% clindamycin cream applied topically to penile skin, both twice daily for 7 days. The genital microbiota was characterized at three anatomical sites (women, vaginal; men, cutaneous penile and first-pass urine [representing the urethra]) using 16S rRNA gene sequencing. Immediately posttreatment, concurrent partner treatment significantly reduced the abundance of BV-associated bacteria (false-discovery rate [FDR] corrected P value < 0.05) and altered the overall microbiota composition of all three anatomical sites (P = 0.001). Suppression of BV-associated bacteria was sustained in the majority (81%) of women over the 12-week period (FDR P value < 0.05), despite BV-associated bacteria reemerging at both genital sites in men. In this cohort of women at high risk for recurrence, five recurred within 12 weeks of treatment (17%; 95% confidence interval [CI], 6 to 34%). Importantly, men tolerated and adhered to combination therapy. Our findings provide support for an RCT of combined oral and topical male partner treatment for BV. IMPORTANCE Recurrence of BV following standard treatment is unacceptably high. Posttreatment recurrence is distressing for women, and it imposes a considerable burden on the health care system. Recurrences result in multiple presentations to clinical services and repeated antibiotic use, and the associated obstetric and gynecological sequelae are significant. New treatments to improve long-term BV cure are urgently needed. Here, we used 16S rRNA gene sequencing to investigate changes in the microbiota composition at three genital sites (vagina, penile skin, and male urethra) of heterosexual couples undergoing concurrent partner treatment for bacterial vaginosis (BV). We found that concurrent partner treatment immediately and significantly altered the composition of the genital microbiota of both partners, with a reduction in BV-associated bacteria seen at all three sites. BV cure at 12 weeks posttreatment was higher than expected. These microbiological data provide evidence for continued investigation of partner treatment as a strategy to improve BV cure.

Prolapse Surgery: What Kind of Antibiotic Prophylaxis Is Necessary?

INTRODUCTION: The aim of this study was to assess whether antibiotic prophylaxis or therapy is sufficient for laparoscopic or vaginal prolapse surgery with mesh. METHODS: This is a single-center prospective study. The study was divided into 3 groups. Protocol A: metronidazole (15 mg/kg) and piperacillin-tazobactam (2 g) 1 h before surgery and, for postoperative treatment, gentamycin (160 mg) 1 h before surgery in a single dose. Metronidazole and piperacillin-tazobactam were administered until hospital discharge. Protocol B: gentamycin and piperacillin-tazobactam in the same manner as group A. Protocol C: clindamycin (600 mg) and gentamicin (160 mg) 1 h before surgery in a single dose. RESULTS: We included 87 consecutive patients who underwent prolapse surgery involving mesh prostheses: 57 by the laparoscopic approach and 30 by the vaginal route. Of these, 30 patients were included in protocol A, 30 in protocol B, and 27 in protocol C. There were no statistically significant differences among the 3 protocols regarding any postoperative complications, except for urinary tract infections that were more in the vaginal approach than in the laparoscopic route, in protocol A (p = 0.002). CONCLUSIONS: One-shot prophylaxis can be successfully used in prolapse surgery regardless of the surgical approach.

Chlorhexidine, clotrimazole, metronidazole and combination therapy in the treatment of vaginal infections.

This was a clinical trial study that aimed to investigate the efficacy of vaginal chlorhexidine gel in the treatment of vulvovaginal candidiasis, bacterial vaginosis, and nonspecific vaginitis. The study population included patients who complained of vaginal discharge and presented to our University Gynecology Clinic. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) software. The student t-test and Mann-Whitney U test were used to analyze the quantitative and ordinal data, respectively. In order to analyze the qualitative data, the Chi-square or Fischer's exact tests were used. The mean satisfaction score in the vulvovaginal candidiasis patients who received chlorhexiine vaginal gel was 9.06 and 8.29 in the patients who received clotrimazole vaginal cream. The Mann-Whitney test did not show a statistically significant difference between mean scores of VAS in these two groups with vulvovaginal candidiasis (P=0.027). Among the patients with bacterial vaginosis, the mean satisfaction score was 8.91 in the chlorhexidine vaginal gel group and 8.72 in the metronidazole tablet group (P=0.607). In the nonspecific vaginitis group, the mean satisfaction score was 8.83 in the chlorhexidine vaginal gel group and 9.17 in the combination group (metronidazole + clotrimazole vaginal cream)(P=0.401). The highest mean visual analog scale score (VAS) score was documented in the combination therapy group. We found that chlorhexidine vaginal gel is a more effective method for the treatment and improvement of vaginal infections. The benefits of chlorhexidine gel have a positive therapeutic effect as a single drug in nonspecific vaginitis, rather than simultaneous administration of two agents.

Fabrication of multifunctional mucoadhesive buccal patch for drug delivery applications.

Mucoadhesive buccal patch is a promising dosage form for a successful oral drug delivery, which provides unique advantages for various applications such as treatment of periodontal disease and postdental surgery disorders. The aim of this study is to synthesize a novel multifunctional mucoadhesive buccal patch in a multilayer reservoir design for therapeutic applications. The patches were fabricated through simultaneous electrospinning of chitosan/poly(vinylalcohol) (PVA)/ibuprofen and electrospraying of phenylalanine amino acid nanotubes (PhNTs) containing metronidazole into the electrospun mats through a layer-by-layer process. An electrospun poly(caprolactone) (PCL) was used as an impermeable backing layer to protect the mucoadhesive component from tongue movement and drug loss. Buccal patches were characterized using scanning electron microscopy (SEM) and field emission scanning electron microscopy (FESEM) and also evaluated in terms of physicomechanical parameters such as pH, weight, thickness, tensile strength, folding endurance, and mucoadhesive properties. The swelling index of the patches was examined with respect to the PVA/chitosan ratio. The effect of genipin addition to the electrospinning solution was also studied on mucoadhesive and swelling properties. The cell viability of buccal patches was assessed by methylthiazolydiphenyl-tetrazolium bromide test on L929 fibroblast cell line. The patch with an optimal amount of mucoadhesive polymers (PVA/chitosan 80:20) and crosslinking agent (0.05 g) indicated an ideal hemostatic activity along with antibacterial properties against Streptococcus mutans bacteria. The synthesized multifunctional mucoadhesive patch with a novel composition and design has a great potential for oral therapeutic applications.

Early Life Antibiotics Influence In Vivo and In Vitro Mouse Intestinal Epithelium Maturation and Functioning.

BACKGROUND & AIMS: The use of antibiotics (ABs) is a common practice during the first months of life. ABs can perturb the intestinal microbiota, indirectly influencing the intestinal epithelial cells (IECs), but can also directly affect IECs independent of the microbiota. Previous studies have focused mostly on the impact of AB treatment during adulthood. However, the difference between the adult and neonatal intestine warrants careful investigation of AB effects in early life. METHODS: Neonatal mice were treated with a combination of amoxicillin, vancomycin, and metronidazole from postnatal day 10 to 20. Intestinal permeability and whole-intestine gene and protein expression were analyzed. IECs were sorted by a fluorescence-activated cell sorter and their genome-wide gene expression was analyzed. Mouse fetal intestinal organoids were treated with the same AB combination and their gene and protein expression and metabolic capacity were determined. RESULTS: We found that in vivo treatment of neonatal mice led to decreased intestinal permeability and a reduced number of specialized vacuolated cells, characteristic of the neonatal period and necessary for absorption of milk macromolecules. In addition, the expression of genes typically present in the neonatal intestinal epithelium was lower, whereas the adult gene expression signature was higher. Moreover, we found altered epithelial defense and transepithelial-sensing capacity. In vitro treatment of intestinal fetal organoids with AB showed that part of the consequences observed in vivo is a result of the direct action of the ABs on IECs. Lastly, ABs reduced the metabolic capacity of intestinal fetal organoids. CONCLUSIONS: Our results show that early life AB treatment induces direct and indirect effects on IECs, influencing their maturation and functioning.

Colonic delivery of metronidazole-loaded capsules for local treatment of bacterial infections: A clinical pharmacoscintigraphy study.

Drug delivery to the colon offers great promise for local treatment of colonic diseases as it allows bypassing systemic absorption in the small intestine, thereby increasing luminal drug concentrations in the colon. The primary objective of this in vivo pharmaco-scintigraphy study was to assess the colon drug targeting accuracy of a metronidazole benzoate colonic drug delivery system intended for local treatment of Clostridioides difficile infections. Additionally, it was assessed if the concept of mucoadhesion would increase colonic residence time and promote higher drug bioavailability. Two different capsule formulations were designed and tested in healthy human subjects. Capsules contained either non-mucoadhesive (NM) or mucoadhesive (M) microgranules, both loaded with 100 mg metronidazole benzoate (antibiotic prodrug) and 5 mg samarium oxide (scintigraphy tracer). Filled capsules were coated with a colonic-targeting technology consisting of two functional layers, which allow for accelerated drug release mediated by the intestinal pH in combination with colonic bacteria. Coated capsules were neutron-activated to yield the radioisotope 153Sm prior to administration to 18 healthy subjects. Gamma-scintigraphy imaging was combined with the measurement of drug plasma levels. Formulation NM showed high colon-targeting accuracy. Initial capsule disintegration within the targeted ileocolonic region was observed in 8 out of 9 subjects (89%) with colonic arrival times in the range of 3.5-12 h and reduced systemic exposure. In contrast, the mucoadhesive formulation M showed some inconsistency regarding the site of initial capsule disintegration (targeting accuracy 56%). Variability of drug release was attributed to self-adhesion and agglomeration of the mucoadhesive microparticles within the capsule. Accurate ileocolonic delivery of metronidazole-loaded microgranules was achieved following oral administration of colonic-targeted capsules. Delayed drug release from NM microparticles in the colon leads to a reduced systemic exposure compared to immediate-release data from literature and presumably elevated drug concentrations in the colonic lumen. This approach offers promising options for the local treatment of colonic diseases.

Differences in Vaginal Microbiota, Host Transcriptome, and Proteins in Women With Bacterial Vaginosis Are Associated With Metronidazole Treatment Response.

BACKGROUND: Bacterial vaginosis (BV) treatment failures and recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. METHODS: Women with BV (Bronx, New York and Thika, Kenya) received 7 days of oral metronidazole at enrollment (day 0) and underwent genital tract sampling of microbiome (16S ribosomal RNA gene sequencing), transcriptome (RNAseq), and immune mediator concentrations on day 0, 15, and 35. RESULTS: Bronx participants were more likely than Thika participants to clinically respond to metronidazole (19/20 vs 10/18, respectively, P = .0067) and by changes in microbiota composition and diversity. After dichotomizing the cohort into responders and nonresponders by change in α-diversity between day 35 and day 0, we identified that transcription differences associated with chemokine signaling (q = 0.002) and immune system process (q = 2.5 × 10-8) that differentiated responders from nonresponders were present at enrollment. Responders had significantly lower levels of CXCL9 in cervicovaginal lavage on day 0 (P < .007), and concentrations of CXCL9, CXCL10, and monocyte chemoattractant protein 1 increased significantly between day 0 and day 35 in responders vs nonresponders. CONCLUSIONS: Response to metronidazole is characterized by significant changes in chemokines and related transcripts, suggesting that treatments that promote these pathways may prove beneficial.

Three is a crowd: Clinical outcomes of a twice daily versus a thrice daily metronidazole dosing strategy from a multicenter study.

This was a multicenter, retrospective study of patients with anaerobic bacteremia comparing metronidazole 500 mg every 8 h versus 500 mg every 12 h. Of 782 patients reviewed, 85 met inclusion criteria. There was no significant difference in mortality, length of stay, or escalation of therapy between dosing strategies.

Improving metronidazole prescription practices in surgical patients: a full cycle audit.

INTRODUCTION: Metronidazole is commonly prescribed for intra-abdominal infections. Oral metronidazole has high bioavailability (>95%) and intravenous metronidazole should be reserved for patients not suitable for oral preparations. METHODS AND MATERIALS: This full cycle audit evaluated the type of metronidazole preparation prescribed in adult emergency surgical patients requiring first-line empirical antimicrobial therapy for intra-abdominal infections. The criterion for audit was the proportion of patients who were prescribed intravenous metronidazole when the oral route was available. The first cycle included all consecutive eligible patients between 20 April and 14 May 2020. After an intervention phase educating prescribers about the similar pharmacokinetic properties of oral and intravenous metronidazole, clinical practice was reaudited between 22 June and 16 July 2020. Data were collected by case note and drug chart review. RESULTS: A total of 54 patients were included in the first audit cycle. Of these, 11 (20.4%) were prescribed oral metronidazole and 43 (79.6%) were prescribed intravenous metronidazole. In the majority of cases (35/43, 81.4%), intravenous metronidazole was prescribed in the absence of clear contraindications to the oral preparation. Of the 61 patients included in the reaudit cycle, 23 (37.7%) were prescribed oral metronidazole and 38 (62.3%) were prescribed intravenous metronidazole. The proportion of patients prescribed intravenous metronidazole despite being suitable for oral preparation decreased from 81.4% in the first cycle to 34.2% (13/38) in the reaudit cycle (risk ratio 0.42, 95% CI: 0.26 to 0.67, p<0.0001). Prescribing oral metronidazole when suitable saved up to £10.53/day per patient. CONCLUSION: This full cycle audit led to a significant improvement in the use of oral metronidazole in suitable patients, as well as a considerable reduction in healthcare costs.