Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Mechanical debridement combined with amoxicillin and metronidazole compared with mechanical debridement alone for the treatment of chronic periodontitis: An overview of systematic reviews.

Periodontal mechanical debridement is the most common therapy for the treatment of periodontitis. However, depending on the severity of the disease, mechanical debridement has been recommended in combination with systemic antibiotics. In this study, we performed an overview of systematic reviews using the Friendly Summaries of Body of Evidence using Epistemonikos (FRISBEE) methodology on the effectiveness and safety of mechanical debridement combined with amoxicillin and metronidazole compared to mechanical debridement alone for the treatment of chronic periodontitis. We conducted a systematic search of the Epistemonikos database, extracted data from 10 systematic reviews and re-analyzed data from 23 primary studies to generate a summary of findings (SoF) table. We used RevMan 5.3 and GRADEpro for data analysis and data presentation. The following outcomes were analyzed: probing depth (mean difference (MD): 0.07 mm); clinical attachment level (MD: 0.04 mm); bleeding on probing (MD: 5.06%); and suppuration (MD: 0.31%). There was no evidence of a clinically relevant benefit of periodontal mechanical debridement therapy combined with amoxicillin and metronidazole compared to periodontal mechanical debridement therapy alone for the treatment of chronic periodontitis in the studied periodontal outcomes.

Response to Antibiotic Treatment of Bacterial Vaginosis Predicts the Effectiveness of LACTIN-V (Lactobacillus crispatus CTV-05) in the Prevention of Recurrent Disease.

OBJECTIVES: Live biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment. METHODS: A post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 Food and Drug Administration guidance) 2 days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks. RESULTS: At enrollment, 88% of participants had achieved postantibiotic clinical BV cure. The effect of LACTIN-V on BV recurrence compared with placebo differed by initial clinical BV cure status. The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (95% confidence interval, 0.35-0.77) among participants with initial clinical BV cure after metronidazole treatment and 1.34 (95% confidence interval, 0.47-2.23) among participants without postantibiotic clinical BV cure. Among women receiving LACTIN-V, those who had achieved postantibiotic clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared with women failing to achieve postantibiotic clinical BV cure. CONCLUSIONS: LACTIN-V seems to only decrease BV recurrence in women with clinical cure of BV after initial antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.

Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial.

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Impact of medication dosage on Helicobacter pylori eradication rates among pediatric patients.

OBJECTIVES: Helicobacter pylori rates of eradication to common first-line regimens continue to decline globally. Prescription of the appropriate medication dosage is an important consideration, particularly in the pediatric population due to medication weight-based dosing. Limited data is available on the impact of guideline-recommended weight-based dosing on the successful eradication of H. pylori in children. METHODS: Retrospective study of patients with histologic evidence of H. pylori from two pediatric tertiary care centers in New England. We excluded patients who were not treated or those missing eradication data. We compared the eradication rates of patients prescribed recommended weight-based dosages, duration, and frequency of treatment with those who were not. RESULTS: One hundred forty-four patients were included. The overall eradication rate was 73.6% (106/144). All treatment regimens were properly prescribed for 14 days. There was a high rate of improper weight-based dosing: proton pump inhibitor (PPI) 31.2% (45/144), amoxicillin 31.7% (39/123), metronidazole (MET) 19.4% (12/62), clarithromycin (CLA) 23.9% (22/70), tetracycline 50% (6/12), bismuth 26.1% (6/23). When PPIs were properly weight-dosed, there was a 78.8% eradication rate that dropped to 62.2% with suboptimal dosing (p = 0.036, odds ratio [OR]: 2.26, confidence interval [CI]: 1.04-4.87). When amoxicillin was properly weight-dosed, successful eradication was achieved in 81% versus only 53.8% when improperly dosed (p = 0.002; OR: 3.64, CI: 1.58-8.37). There was no statistically significant impact on eradication rates with improper weight-based dosing of MET, CLA, tetracycline, or bismuth. CONCLUSION: Proper weight-based dosing of amoxicillin and PPI is important for the successful eradication of H. pylori among children in the New England area.

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

Efficacy Assessment of the Co-Administration of Vancomycin and Metronidazole in Clostridioides difficile-Infected Mice Based on Changes in Intestinal Ecology.

Vancomycin (VAN) and metronidazole (MTR) remain the current drugs of choice for the treatment of non-severe Clostridioides difficile infection (CDI); however, while their co-administration has appeared in clinical treatment, the efficacy varies greatly and the mechanism is unknown. In this study, a CDI mouse model was constructed to evaluate the therapeutic effects of VAN and MTR alone or in combination. For a perspective on the intestinal ecology, 16S rRNA amplicon sequencing and non-targeted metabolomics techniques were used to investigate changes in the fecal microbiota and metabolome of mice under the co-administration treatment. As a result, the survival rate of mice under co-administration was not dramatically different compared to that of single antibiotics, and the former caused intestinal tissue hyperplasia and edema. Co-administration also significantly enhanced the activity of amino acid metabolic pathways represented by phenylalanine, arginine, proline, and histidine, decreased the level of deoxycholic acid (DCA), and downregulated the abundance of beneficial microbes, such as Bifidobacterium and Akkermansia. VAN plays a dominant role in microbiota regulation in co-administration. In addition, co-administration reduced or increased the relative abundance of antibiotic-sensitive bacteria, including beneficial and harmful microbes, without a difference. Taken together, there are some risks associated with the co-administration of VAN and MTR, and this combination mode should be used with caution in CDI treatment.

Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis: A Secondary Analysis of the APPAC II Randomized Clinical Trial.

Importance: Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. Objective: To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. Design, Setting, and Participants: This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Interventions: Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. Main Outcomes and Measures: The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. Results: After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. Conclusions and Relevance: This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

Association Between First-time Neurologic Events and Metronidazole Treatment: A Case-time Control Study.

PURPOSE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. FINDINGS: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. IMPLICATIONS: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

Morbidity After Mechanical Bowel Preparation and Oral Antibiotics Prior to Rectal Resection: The MOBILE2 Randomized Clinical Trial.

Importance: Surgical site infections (SSIs)-especially anastomotic dehiscence-are major contributors to morbidity and mortality after rectal resection. The role of mechanical and oral antibiotics bowel preparation (MOABP) in preventing complications of rectal resection is currently disputed. Objective: To assess whether MOABP reduces overall complications and SSIs after elective rectal resection compared with mechanical bowel preparation (MBP) plus placebo. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 3 university hospitals in Finland between March 18, 2020, and October 10, 2022. Patients aged 18 years and older undergoing elective resection with primary anastomosis of a rectal tumor 15 cm or less from the anal verge on magnetic resonance imaging were eligible for inclusion. Outcomes were analyzed using a modified intention-to-treat principle, which included all patients who were randomly allocated to and underwent elective rectal resection with an anastomosis. Interventions: Patients were stratified according to tumor distance from the anal verge and neoadjuvant treatment given and randomized in a 1:1 ratio to receive MOABP with an oral regimen of neomycin and metronidazole (n = 277) or MBP plus matching placebo tablets (n = 288). All study medications were taken the day before surgery, and all patients received intravenous antibiotics approximately 30 minutes before surgery. Main Outcomes and Measures: The primary outcome was overall cumulative postoperative complications measured using the Comprehensive Complication Index. Key secondary outcomes were SSI and anastomotic dehiscence within 30 days after surgery. Results: In all, 565 patients were included in the analysis, with 288 in the MBP plus placebo group (median [IQR] age, 69 [62-74] years; 190 males [66.0%]) and 277 in the MOABP group (median [IQR] age, 70 [62-75] years; 158 males [57.0%]). Patients in the MOABP group experienced fewer overall postoperative complications (median [IQR] Comprehensive Complication Index, 0 [0-8.66] vs 8.66 [0-20.92]; Wilcoxon effect size, 0.146; P < .001), fewer SSIs (23 patients [8.3%] vs 48 patients [16.7%]; odds ratio, 0.45 [95% CI, 0.27-0.77]), and fewer anastomotic dehiscences (16 patients [5.8%] vs 39 patients [13.5%]; odds ratio, 0.39 [95% CI, 0.21-0.72]) compared with patients in the MBP plus placebo group. Conclusions and Relevance: Findings of this randomized clinical trial indicate that MOABP reduced overall postoperative complications as well as rates of SSIs and anastomotic dehiscences in patients undergoing elective rectal resection compared with MBP plus placebo. Based on these findings, MOABP should be considered as standard treatment in patients undergoing elective rectal resection. Trial Registration: ClinicalTrials.gov Identifier: NCT04281667.

Surgical Site Infections in Trauma Exploratory Laparotomies Preoperative Ceftriaxone and Metronidazole Versus Cefoxitin.

Surgical site infections (SSIs) remain a significant cause of morbidity and mortality in patients undergoing traumatic exploratory laparotomy. The goal of this study was to compare antibiotic usage and subsequent outcomes in patients undergoing traumatic exploratory laparotomy. A retrospective chart analysis and a chi-square test of independence were performed to examine the relation between preoperative cefoxitin versus ceftriaxone and metronidazole and the rate of SSI development. 323 patients were analyzed, 111 patients receiving cefoxitin and 212 patients receiving ceftriaxone and metronidazole. The proportion of patients who developed SSI was 16.2% for the cefoxitin group and 9.9% for the ceftriaxone and metronidazole group, X2 (1, N = 323) = 2.7, P = .098, thus displaying no statistical difference in the development of SSIs between patients in the cefoxitin group when compared to the ceftriaxone and metronidazole group.

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.

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.

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.

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.