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.

Effect of a novel herbal vaginal suppository containing myrtle and oak gall in the treatment of vaginitis: a randomized clinical trial.

BACKGROUND: Uncomplicated infections such as candidiasis, bacterial vaginosis (BV), or trichomoniasis are easy to diagnose and treat. However, about 8% of patients will have a more complicated course with failure to respond to treatment or rapid recurrence of symptoms. There are many suggestions in Traditional Persian Medicine like myrtle (Myrtus communis L.) and oak gall (Quercus infectoria G.Olivier) for treatment of vaginitis. OBJECTIVES: A clinical trial was designed to assess the efficacy of a novel herbal suppository, containing myrtle and oak gall (MOGS) in treatment of vaginitis. METHODS: In a parallel randomized clinical trial, 120 women with vaginitis were randomly assigned to MOGS, metronidazole, or placebo. Formulation was simulated from traditional Persian manuscripts and MGOS was prepared after pharmaceutical optimization processing as well as quantification of gallic acid by HPLC. The study was double-blind for MOGS and placebo and single-blind for metronidazole group. RESULTS: MOGS effectively improved vaginal discharge (p = 0.024 for BV and 0.018 for trichomoniasis) and pH (compared to placebo (p = 0.013) and metronidazole (p = 0.001)). Both MOGS and metronidazole could reverse whiff test. Metronidazole was the best medication for making Nugent score negative (p = 0.005) as well as the best therapy according to laboratory findings to treat BV in comparison with placebo (p = 0.021). While for trichomoniasis, MOGS could improve the disease more successfully (p = 0.001). Both MOGS and metronidazole treated mixed vaginitis (p = 0.002). CONCLUSION: MOGS would be a chance for developing new treatment for trichomoniasis.

Testing the regulatory framework in South Africa - a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment. METHODS: Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7-10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment. RESULTS: The  South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24-1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product. CONCLUSION: Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered. TRIAL REGISTRATION: This trial was registered on 17 October 2017 with the South African National Clinical Trial Register ( http://www.sanctr.gov.za/ ; BV-trial1; DOH-27-1117-5579 ).

Carbapenems versus ciprofloxacin/metronidazole for decreasing complications and hospital stay following complicated acute appendicitis surgery: A prospective cohort in an Ecuadorian population.

BACKGROUND: After appendectomy due to complicated acute appendicitis (CAA), there are some alternatives as antibiotic scheme: ciprofloxacin/metronidazole; as well as monoscheme based on carbapenems: ertapenem, meropenem, and imipenem. AIM: This study aims to prove the efficacy of carbapenems versus ciprofloxacin/metronidazole in CAA post-operative management in terms of preventing complications during post-operative period and decreasing hospital stay. MATERIALS AND METHODS: This was an observational, analytical, longitudinal, and prospective cohort study (March 2014-November 2016). Patients were classified into two groups, according to the prescribed antibiotic scheme: some carbapenems or ciprofloxacin/metronidazole. RESULTS: Ninety-eight patients were enrolled. There was an requirement for antibiotic therapy rotation only in the ciprofloxacin/metronidazole (7/49, 14.3%; p = 0.004). Carbapenems reached a mean hospital stay of 4.45 days, in contrast with ciprofloxacin/metronidazole, 8.29 days (p = 0.020). In post-surgical follow-up, there were more cases of curative resolution in the group in the carbapenems group (35/49 vs. 15/49 p < 0.001) as well as a greater number of cases with some late infection in the ciprofloxacin/metronidazole group (1/49 vs. 10/49, p = 0.010). CONCLUSION: In the post-operative management of CAA, carbapenems represent an important indication to be considered as first-line antibiotic therapy.

ANTECEDENTES: Tras la cirugía por apendicitis aguda complicada existen varias alternativas de esquema antibiótico, entre las que destacan ciprofloxacino/metronidazol, o bien monoterapia con algún carbapenémico, como ertapenem, meropenem e imipenem. OBJETIVO: Determinar la eficacia de los carbapenémicos en comparación con ciprofloxacino/metronidazol en el manejo posquirúrgico de la apendicitis aguda complicada, en términos de prevención de complicaciones durante el ­posoperatorio y de reducción de la estancia hospitalaria. MÉTODO: Estudio observacional, analítico, longitudinal, prospectivo y de cohorte, de marzo de 2014 a noviembre de 2016. Los pacientes fueron clasificados en dos grupos según el esquema antibiótico prescrito: un carbapenémico o ciprofloxacino/metronidazol. RESULTADOS: Se seleccionaron 98 pacientes. Solo hubo necesidad de rotación de antibiótico en el grupo de ciprofloxacino/metronidazol (7 de 49, 14.3%; p = 0.004). En el grupo de carbapenémico, la media de estancia hospitalaria fue de 4.45 días, y en el grupo de ciprofloxacino/metronidazol fue de 8.29 días (p = 0.020). En el seguimiento posquirúrgico hubo más casos de resolución curativa en el grupo de carbapenémico (35 de 49 vs. 15 de 49; p < 0.001), así como un mayor número de casos con alguna infección tardía en el grupo de ciprofloxacino/metronidazol (1 de 49 vs. 10 de 49; p < 0.001). CONCLUSIÓN: En el manejo posquirúrgico de la apendicitis aguda complicada, los carbapenémicos representan una importante indicación que debe considerarse como antibioticoterapia de primera línea.

Preoperative oral antibiotics and surgical-site infections in colon surgery (ORALEV): a multicentre, single-blind, pragmatic, randomised controlled trial.

BACKGROUND: Previous studies have found that mechanical bowel preparation with oral antibiotics can reduce the incidence of surgical-site infections, but no randomised controlled trial has assessed oral antibiotics alone without mechanical bowel preparation. The aim of this study was to determine whether prophylaxis with oral antibiotics the day before elective colon surgery affects the incidence of postoperative surgical-site infections. METHODS: In this multicentre, pragmatic, randomised controlled trial (ORALEV), patients undergoing colon surgery were recruited from five major hospitals in Spain and 47 colorectal surgeons at these hospitals participated. Patients were eligible for inclusion if they were diagnosed with neoplasia or diverticular disease and if a partial colon resection or total colectomy was indicated. Participants were randomly assigned (1:1) using online randomisation tables to either administration of oral antibiotics the day before surgery (experimental group) or no administration of oral antibiotics before surgery (control group). For the experimental group, ciprofloxacin 750 mg was given every 12 h (two doses at 1200 h and 0000 h) and metronidazole 250 mg every 8 h (three doses at 1200 h, 1800 h, and 0000 h) the day before surgery. All patients were given intravenous cefuroxime 1·5 g and metronidazole 1 g at the time of anaesthetic induction. The primary outcome was incidence of surgical-site infections. Patients were followed up for 1 month after surgery and all postsurgical complications were registered. This study was registered with EudraCT, 2014-002345-21, and ClinicalTrials.gov, NCT02505581, and is closed to accrual. FINDINGS: Between May 2, 2015, and April 15, 2017, we assessed 582 patients for eligibility, of whom 565 were eligible and randomly assigned to receive either no oral antibiotics (n=282) or oral antibiotics (n=282) before surgery. 13 participants in the control group and 16 in the experimental group were subsequently excluded; 269 participants in the control group and 267 in the experimental group received their assigned intervention. The incidence of surgical-site infections in the control group (30 [11%] of 269) was significantly higher than in the experimental group (13 [5%] of 267; χ2 test p=0·013). Oral antibiotics were associated with a significant reduction in the risk of surgical-site infections compared with no oral antibiotics (odds ratio 0·41, 95% CI 0·20-0·80; p=0·008). More complications (including surgical-site infections) were observed in the control group than in the experimental group (76 [28%] vs 51 [19%]; p=0·017), although there was no difference in severity as assessed by Clavien-Dindo score. No differences were noted between groups in terms of local complications, surgical complications, or medical complications that were not related to septic complications. INTERPRETATION: The administration of oral antibiotics as prophylaxis the day before colon surgery significantly reduces the incidence of surgical-site infections without mechanical bowel preparation and should be routinely adopted before elective colon surgery. FUNDING: Fundación Asociación Española de Coloproctología.

14-Day High-Dose Amoxicillin- and Metronidazole-Containing Triple Therapy With or Without Bismuth as First-Line Helicobacter pylori Treatment.

BACKGROUND: Amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy had been shown to reliably achieve high eradication rates. The role of individual components remains undefined. AIM: To identify the additional benefit/role of bismuth in amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. METHODS: This was a non-inferiority factorial design trial. Treatment-naive H. pylori-infected subjects were randomly (1:1) assigned to receive 14-day amoxicillin- and metronidazole-containing triple therapy consisting of esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg both thrice daily with or without 220 mg bismuth twice a day. Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. RESULTS: From July 2018 to June 2019, a total of two hundred and sixteen subjects were randomized. Both therapies achieved high eradication rates. Per-protocol with bismuth = 97.9% (94/96, 95% CI 95.1-100%) and without bismuth = 94.7% (90/95, 95% CI 90.3-99.1%) (P = 0.43). Intent-to-treat analysis = 90.7% (98/108, 95% CI 85.2-96.2%) versus 88.9% (96/108, 95% CI 82.8-95.0%) with and without bismuth (P = 0.65). The two regimens were not inferior by intent-to-treat or per-protocol analyses. Metronidazole resistance did not affect the efficacy of either therapy. CONCLUSION: Neither the presence nor absence of bismuth or metronidazole resistance reduced the effectiveness of triple therapy containing esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg thrice daily in this population. The clinical trial was registered with ClinicalTrials.gov, NCT03557437.

Recent progress in Helicobacter pylori treatment.

The main challenge in the field of Helicobacter pylori (H. pylori) infection is antibiotic resistance, which influences the efficacy of eradication regimens. Bismuth-containing quadruple therapy has been confirmed as an effective regimen for eradicating H. pylori, especially in strains with antibiotic resistance. High-dose proton-pump inhibitor-amoxicillin dual therapy could decrease the use of unnecessary antibiotics, which is a promising alternative approach. Adjuvant therapy (specific probiotic or vitamin) also showed good results, although more evidence is needed. Novel anti-H. pylori drugs are needed, and the establishment of the H. pylori database is an effective way to acknowledge the real-time information of H. pylori management. This review provides the recent progress of H. pylori treatment, and further studies are needed to address the role of different regimens in improving H. pylori eradication rate, especially in strains with antibiotics resistance.

Sustained release of antimicrobials from double-layer nanofiber mats for local treatment of periodontal disease, evaluated using a new micro flow-through apparatus.

Periodontal disease is a widespread chronic condition associated with degradation of periodontal tissues that requires more effective approaches for its treatment. Thus, the aim was to develop a nanodelivery system for local application of antimicrobials, with evaluation in vitro using a newly developed micro flow-through apparatus that simulates local in-vivo conditions in the periodontal pocket: small resting volume, and low gingival crevicular fluid flow rate. We successfully developed a double-layer nanofiber mat composed of a chitosan/ poly(ethylene) oxide nanofiber layer with 30% ciprofloxacin, and a poly(ε-caprolactone) nanofiber layer with 5% metronidazole. The precisely designed composition enabled sustained in-vitro release of the antimicrobials according to their specific drug release mechanisms. The rate-limiting step of ciprofloxacin release was its own low solubility at pH 7.4, when there was excess of solid drug present in the delivery system. In contrast, sustained release of metronidazole was due to slow penetration of dissolution medium through the hydrophobic poly(ε-caprolactone) nanofiber layer. The double-layer nanofiber mat developed showed antibacterial activity against Escherichia coli and Aggregatibacter actinomycetemcomitans based on plate antibiogram assays. The antimicrobial concentrations released from the nanofiber mats determined using the developed apparatus were above the minimal inhibitory concentrations against the periodontal pathogens for up to 7 days, which is valuable information for prediction of the efficacy of the nanodelivery system. Although this apparatus was specifically designed for characterization of formulations associated with treatments for periodontal disease, its applicability is much wide, as for development of any delivery system for application at target sites that have similar local conditions.

Low-dose methotrexate-induced vulvar edema: A case report.

RATIONALE: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate. PATIENT CONCERNS: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp. DIAGNOSES: The patient was diagnosed based on clinical findings for MTX toxic reactions. INTERVENTIONS: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed. OUTCOMES: The vulvar edema and oral cavity ulceration and scalp ulceration healed. LESSONS: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.

Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial.

BACKGROUND: Ceftazidime-avibactam plus metronidazole is effective in the treatment of complicated intra-abdominal infection (cIAI) in adults. This single-blind, randomized, multicenter, phase 2 study (NCT02475733) evaluated the safety, efficacy and pharmacokinetics of ceftazidime-avibactam plus metronidazole in children with cIAI. METHODS: Hospitalized children (≥3 months to <18 years) with cIAI were randomized 3:1 to receive intravenous ceftazidime-avibactam plus metronidazole, or meropenem, for a minimum of 72 hours (9 doses), with optional switch to oral therapy thereafter for a total treatment duration of 7-15 days. Safety and tolerability were assessed throughout the study, along with clinical and microbiologic outcomes, and pharmacokinetics. A blinded observer determined adverse event (AE) causality, and clinical outcomes up to the late follow-up visit. RESULTS: Eighty-three children were randomized and received study drug (61 ceftazidime-avibactam plus metronidazole and 22 meropenem); most (90.4%) had a diagnosis of appendicitis. Predominant Gram-negative baseline pathogens were Escherichia coli (79.7%) and Pseudomonas aeruginosa (33.3%); 2 E. coli isolates were ceftazidime-non-susceptible. AEs occurred in 52.5% and 59.1% of patients in the ceftazidime-avibactam plus metronidazole and meropenem groups, respectively. Serious AEs occurred in 8.2% and 4.5% of patients, respectively; none was considered drug related. No deaths occurred. Favorable clinical/microbiologic responses were observed in ≥90% of patients in both treatment groups at end-of-intravenous treatment and test-of-cure visits. CONCLUSIONS: Ceftazidime-avibactam plus metronidazole was well tolerated, with a safety profile similar to ceftazidime alone, and appeared effective in pediatric patients with cIAI due to Gram-negative pathogens, including ceftazidime-non-susceptible strains.

Combined systemic (fluconazole) and topical (metronidazole + clotrimazole) therapy for a new approach to the treatment and prophylaxis of recurrent candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) is an important pathological and infectious condition that can greatly impact a woman's health and quality of life. Clinical and epidemiological studies show that different types of therapies are able to eliminate the signs and symptoms of mycotic vaginitis in the acute phase, but so far none of these has proved able to significantly reduce the risk of long-term recurrence. In this review, based on the available literature and original data from a preliminary in-vitro microbiological study on the compatibility between fluconazole, clotrimazole and metronidazole a new therapeutic approach to RVVC is discussed and presented. The treatment proposed is a combined scheme using both systemic antimicrobial drug therapy with oral fluconazole 200 mg and topical drug therapy using the association metronidazole 500 mg and clotrimazole 100 mg (vaginal ovules) with adjuvant oral probiotic therapy. In detail, at the time of diagnosis in the acute symptom phase, we propose the following treatment scheme: fluconazole 200 mg on day 1, 4, 11, 26, then 1 dose/month for 3 months at the end of the menstrual cycle; plus metronidazole/clotrimazole ovules 1/day for 6 days the first week, then 1 ovule/day for 3 days the week before the menstrual cycle for 3 months; plus probiotic 1 dose/day for 10 days for 3 months starting from the second month to the end of the menstrual cycle. This scheme aims to address the recurrent infection aggressively from the outset by attempting not only to treat acute symptoms, but also to prevent a new event by countering many of the potential risk factors of recurrence, such as the intestinal Candida reservoir, the mycotic biorhythm, the formation of biofilm, the phenotype switching and the presence of infections complicated by the presence of C. non albicans or G. Vaginalis, without interfering, but rather favoring the restoration of the vaginal lactobacillus species. Future clinical studies will be useful to confirm the proposed scheme.

Natural Skin Care Products as Adjunctive to Prescription Therapy in Moderate to Severe Rosacea

Background: Rosacea is characterized by irritation associated with erythema, telangiectasias and papules/pustules. Whole formula nature-based sensitive skin products are formulated to maintain skin barrier and appropriate hydration that can lead to soothing benefits. Objective: To evaluate the efficacy and tolerability of a regimen consisting of a cleanser containing natural oils, beeswax, and witch hazel and day and night creams containing natural oils, glycerin, and botanical anti-inflammatories (NR); and a synthetic dermatologist-recommended regimen of cetyl alcohol, sodium lauryl sulphate-containing cleanser, and glycerin, polyisobutene-containing lotion (CR) in subjects with rosacea. Methods: 80 female subjects with rosacea who received 6 weeks of 0.75% metronidazole gel, were randomized to receive NR or CR, twice daily, for 4 weeks in conjunction with the gel. Blinded investigator global assessment of rosacea, investigator-rated, and subject-rated overall skin appearance was assessed using a 5-point scale (0=none, 4=severe) at baseline, 2 weeks, and 4 weeks. Noninvasive skin assessments for skin hydration and skin barrier function were made by corneometry and TEWL, respectively. Results: NR resulted in improvement in investigator global assessment of rosacea measures at 4 weeks from baseline (erythema, 28%; telangiectasia, 26%; papules/pustules, 34%: P<0.001) and CR resulted in a 8 to 12% improvement. Differences between treatments were statistically significant. Overall skin appearance measured by the investigator was clinically and statistically improved from baseline by 32% and 12% with NR and CR, respectively. Overall skin appearance measured by subjects was improved by both NR and CR from baseline with no differences between treatments. Both regimens improved barrier function from baseline to week 4 (13%, NR; 14%, CR). NR decreased hydration by 21% from baseline at week 4 while CR increased hydration by 14% (P<0.001 from NR). No clinically significant tolerability issues were reported in either regimen at week 4. Conclusion: NR was effective, well tolerated, and superior to CR in the management of rosacea, concomitantly treated with metronidazole. National Clinical Trial Identifier: NCT03392558 J Drugs Dermatol. 2019;18(2):141-146.

Risk factors of rescue bismuth quadruple therapy failure for Helicobacter pylori eradication.

BACKGROUND AND AIM: Failure of bismuth quadruple therapy for Helicobacter pylori eradication is frequently observed. To increase the eradication rate, comprehensive analyses need to be performed regarding risk factors of bismuth quadruple therapy failure based on complete standard culture and antimicrobial susceptibility testing results. METHODS: Patients with history of failed first therapy who had H. pylori colonies isolated from culture and successful minimum inhibitory concentration (MIC) test were enrolled. Esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapies for 7 or 14 days were given. Eradication rate, treatment compliance, adverse events, and risk factors for the failure of bismuth quadruple therapy were analyzed. RESULTS: A total 54 patients were enrolled. Overall eradication rate in the present study was 88.8%. The eradication rate for cases with metronidazole resistance such as MIC 8-16 µg/mL or 16-32 µg/mL was 92.8% (13/14). For cases with high level metronidazole resistance (MIC > 32 µg/mL), the eradication rate was only 60% (6/10). Multivariate analysis regarding compliance, treatment duration, age > 60, three kinds of metronidazole MICs, tetracycline MIC > 4 µg/mL, adverse events and any other parameters, "metronidazole resistance, high level (MIC > 32 µg/mL)" was the only independent risk factor for eradication failure (P = 0.007). CONCLUSION: For cases with metronidazole resistance at MIC > 32 µg/mL, rescue therapy other than bismuth-containing quadruple therapy is needed.

Intravenous magnesium sulphate infusion as first-line therapy in the control of spasms and muscular rigidity in childhood tetanus.

Background: Reports suggest that, in tetanus, magnesium sulphate (MgSO4) alone may control muscle spasms, thereby avoiding sedation and mechanical ventilation. Aim: To study the efficacy and safety of intravenous MgSO4 in controlling spasms and rigidity in children with tetanus. Methods: All children with tetanus consecutively admitted over a 2-year period in a tertiary-care teaching hospital were recruited. In addition to human tetanus immunoglobulin and parenteral metronidazole, patients received MgSO4 100 mg/kg intravenously followed by infusion at 40 mg/kg/hr. The infusion rate was increased by 5 mg/kg/hr every 6 h until cessation of spasms or abolition of the patellar tendon reflex. Efficacy was determined by control of spasms. Time to commencement of feeds, frequency of autonomic instability, the need for ventilatory support, duration of hospitalisation and mortality were also recorded. Results: Twenty-seven children with tetanus aged between 18 months and 10 years were recruited. A contaminated wound was the most common portal of entry of tetanus spores. The incidences of severity were: grade I, 3; grade II, 7; grades IIIa and b, 17. Rigidity and spasms were controlled by magnesium therapy alone in 14 patients. Additional sedation was required for 13 patients (grade II, 1; grade III, 12). Feeding could be commenced early in five patients. Mechanical ventilation was required in eight patients. The mean (SD) duration of hospitalisation was 26.5 (12.0) days. Five patients died (18.5%). Asymptomatic hypocalcaemia was a universal finding and was treated with calcium supplements. Conclusion: MgSO4 alone is effective in mild-to-moderate tetanus but not when it is severe.

Comparison of resorption rate of primary teeth treated with alternative lesion sterilization and tissue repair and conventional endodontic treatment: An in vivo randomized clinical trial.

BACKGROUND: Complete pulpectomy and elimination of wide range of microorganisms from infected primary root canals is not possible through conventional endodontic procedures. Thus, lesion sterilization and tissue repair (LSTR) therapy employing 3Mix tri-antibiotic paste have been used as an alternative endodontic modality for infected primary teeth. AIM: This study aims to evaluate the root resorption rate of endodontically treated mandibular primary molars with conventional endodontic treatment or LSTR therapy and to compare it with their healthy contralateral teeth. MATERIALS AND METHODS: Fifty carious first and second primary mandibular molars from 25 healthy children aged 7-10 years were treated with two different endodontic procedures using LSTR Therapy and conventional endodontic treatment. The resorption rate of these teeth with healthy contralateral teeth was compared clinically and radiographically at 3, 6, 12 and 36 months using Chi-square test. RESULTS: At 12 months, clinically, there was no difference in the outcomes of both groups but radiographically, statistically significant difference (P < 0.001) in root resorption between treated teeth and their controls in both the groups was observed. At 36 months, interradicular bone resorption around the crown of succedaneous teeth and their delayed eruption was noted in LSTR group. CONCLUSIONS: LSTR therapy could be a viable treatment modality for infected/nonvital primary molars with poor prognosis and intended to be maintained for shorter duration in the oral cavity as natural space maintainers.

Efficacy and Tolerability of Two Quadruple Regimens: Bismuth, Omeprazole, Metronidazole with Amoxicillin or Tetracycline as First-Line Treatment for Eradication of Helicobacter Pylori in Patients with Duodenal Ulcer: A Randomized Clinical Trial.

AIM: To evaluate the efficacy and tolerability of tetracycline vs. high-dose amoxicillin in bismuth-based quadruple therapy for Helicobacter pylori(H. pylori) eradication. METHODS: This randomized, open-label clinical trial included 228 patients with H.pylori infection and duodenal ulcer without a history of H.pylori treatment. Patients were randomly divided into two groups. The amoxicillin group received metronidazole 500mg, bismuth subcitrate 240mg, and amoxicillin 1000mg, all three times a day, plus omeprazole 20 mg twice a day, for 14 days. The tetracycline group received metronidazole 500mg three times a day; bismuth subcitrate240mg and tetracycline HCl 500mg, both four times a day; and omeprazole 20 mg twice a day, for 14 days. Evaluation for compliance and drug-relatedadverse effects were evaluated at the end of two weeks. Eight weeks after the end of treatment, the rate of H.pylori eradication was assessed by the C13urease breath test. RESULTS: There were no significant demographic differences between the two groups. Eradication rate was higher with the amoxicillin-containing regimen than the tetracycline-containing regimen: 105/110 (95.51%; 95% confidence interval, 91.5%-99.3%) vs. 88/105 (83.8%; 95%CI, 76.7%-90.8%) by per-protocol analysis (p = 0.005) and 92.9% (95%CI, 88.1%-97.6%) vs. 76.5% (95%CI, 68.7%-84.2%) by intention-to-treat analysis (ITT, p = 0.001). Adverse effects were significant higher in the tetracycline groupthan in the amoxicillin group (65.2% vs. 43.4%; p = 0.001). CONCLUSION: Bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole achieved an acceptable rate of H.pylori infection eradication with good tolerance in patients with duodenal ulcer. This regimen can overcome treatment resistance in areas with high prevalence of metronidazole and clarithromycin resistance. TRIAL REGISTRATION: The Thai Clinical Trial Registry (TCTR) 20170623004.

Antibacterial Efficacy and Discoloration Potential of Endodontic Topical Antibiotics.

INTRODUCTION: The optimal concentration for the use of endodontic topical antibiotics is not known. The aims of this study were to determine the minimum bactericidal concentrations (MBCs) and minimum inhibitory concentrations (MICs) of metronidazole, ciprofloxacin, minocycline, Augmentin (GlaxoSmithKline, Research Triangle Park, NC), and tigecycline against common endodontic pathogens and to evaluate ex vivo the antibacterial efficacy and discoloration effect of triple antibiotic paste (TAP), Augmentin, and tigecycline at different concentrations using a slow-release hydrogel scaffold. METHODS: Using the Epsilometer test method (Etest; bioMérieux USA, St Louis, MO), MICs and MBCs of selected antibiotics were determined against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus intermedius, and Enterococcus faecalis. Biofilms of these bacterial species were then grown in extracted single-rooted teeth anaerobically for 3 weeks. Root canals were filled with TAP, Augmentin, and tigecycline at concentrations of 1 or 0.1 mg/mL in a degradable hydrogel scaffold or pure TAP at 1 g/mL for 7 days. Coronal discoloration was evaluated spectrophotometrically at 1, 2, and 3 weeks after dressing. RESULTS: MIC/MBC data showed significant efficacy of tigecycline, Augmentin, and minocycline compared with the other antibiotics (P < .05). Significant differences were found when comparing the log10 colony-forming units of all experimental groups (P < .05). TAP at 1 g/mL had no bacterial growth but caused the greatest discoloration. Hydrogel mixtures with TAP, Augmentin, or tigecycline at 1 mg/mL significantly reduced bacterial growth and the number of positive samples compared with those at 0.1 mg/mL (P < .05) with minimal discoloration. CONCLUSIONS: TAP, Augmentin, and tigecycline in a hydrogel at 1 mg/mL reduced bacterial growth significantly with minimal color change.

Bismuth improves efficacy of proton-pump inhibitor clarithromycin, metronidazole triple Helicobacter pylori therapy despite a high prevalence of antimicrobial resistance.

BACKGROUND: Helicobacter pylori (H. pylori) eradication has become increasingly difficult especially for penicillin allergy patients. AIMS: To evaluate the efficacy of adding bismuth or high-dose metronidazole to an H. pylori eradication regimen containing a proton-pump inhibitor, clarithromycin, and metronidazole in patients allergic to penicillin. METHODS: Pilot study in which penicillin-allergic, treatment-naive subjects were randomized (1:1) to 14-day esomeprazole (20 mg q12h), clarithromycin (500 mg q12h), and high dose of metronidazole (400 mg q6h) with (BECM group) or without (ECM group) bismuth (600 mg q12h). Eradication was confirmed by 13 C-urea breath test 6 weeks after therapy. Antimicrobial susceptibility was assessed by the agar dilution method. Adverse events were recorded. RESULTS: Sixty-six subjects were randomized, four were lost to follow-up and eight violated the protocol. The eradication rates were 63.6% (95% CI: 47.2%-80.0%) for ECM vs 84.8% (95% CI 72.6%-97.1%) (p = .049) for BECM by intention-to-treat, 67.7% (95% CI 51.3%-84.2%) vs 90.3% (95% CI 79.9%-100%) (p = .029) by modified ITT, and 70% (95% CI 53.6%-86.4%) vs 96% (95% CI 88.3%-100%) (P = .033) by per-protocol. Metronidazole, clarithromycin, and dual-resistant rates were 74.2%, 24.2%, and 18.2%, respectively. The cure rates were significantly improved by the addition of bismuth for both clarithromycin-resistant isolates (100% vs 25%, P = .024) and metronidazole-resistant isolates (94.7% vs 63.6%, P = .043). Adverse events were reported by 45.5% of subjects in ECM group and 48.5% in the BECM group (P = .805). CONCLUSIONS: This prospective trial demonstrated that while high-dose metronidazole could not completely overcome metronidazole resistance, bismuth was additive and improved the overall cure rates by 21%-26%.

In Vitro and In Vivo Activities of DS-2969b, a Novel GyrB Inhibitor, against Clostridium difficile.

DS-2969b is a novel GyrB inhibitor that is currently under clinical development for the treatment of Clostridium difficile infection (CDI). In this study, the in vitro and in vivo activities of DS-2969b were evaluated. DS-2969b inhibited the supercoiling activity of C. difficile DNA gyrase. DS-2969b showed potent in vitro activity against C. difficile clinical isolates with a MIC90 of 0.06 µg/ml, which was 2-, 32-, and 16-fold lower than the MIC90s of fidaxomicin, vancomycin, and metronidazole, respectively. DS-2969b did not select spontaneously resistant mutants of various C. difficile strains at 4× MIC, and the frequency of resistance development was less than 4.8 × 10-9 In a hamster CDI model, 5-day oral administration of DS-2969b conferred complete protection from recurrence and mortality at 0.3 mg/kg of body weight once a day, in contrast to a 50% survival rate with fidaxomicin at 3 mg/kg once a day and 0% with vancomycin at a 50-mg/kg/dose twice a day. Even a single oral administration of 1 mg/kg of DS-2969b in the CDI model exhibited 100% animal survival without recurrence. DS-2969b was also efficacious by 5-day subcutaneous administration in the CDI model. DS-2969b showed similar levels of fecal excretion after intravenous and oral administrations in rats. These data support further development of DS-2969b as a drug for oral and intravenous treatment of CDI.

Pylera and sequential therapy for first-line Helicobacter pylori eradication: a culture-based study in real clinical practice.

BACKGROUND AND AIMS: Italian guideline suggests 10-day sequential or bismuth-based quadruple therapies for first-line Helicobacter pylori treatment. Comparison between these regimens is lacking. We assessed the efficacy of these therapies in clinical practice and evaluated the role of primary bacterial resistance toward clarithromycin and metronidazole. PATIENTS AND METHODS: Consecutive patients with H. pylori infection were enrolled. Bacterial culture with antibiotics susceptibility testing was attempted in all cases. Patients received either a sequential therapy with esomeprazole 40 mg for 10 days plus amoxicillin 1000 mg for the first 5 days followed by clarithromycin 500 mg and tinidazole 500 mg (all twice daily) for the remaining 5 days, or bismuth-based therapy with esomeprazole 20 mg twice daily and Pylera 3 tablets four times daily for 10 days. H. pylori eradication was assessed by using C-urea breath test. RESULTS: A total of 495 patients were enrolled. Following sequential (250 patients) and quadruple (245 patients) therapies, the eradication rate were 92 and 91%, respectively, at intention-to-treat analysis and 96 and 97%, respectively, at per protocol analysis. Overall, the pattern of bacterial resistance did not significantly affect the cure rate, but the presence of clarithromycin and metronidazole dual resistance tended to reduce the success rate of both sequential (84.8 vs. 90.1%; P=0.4) and quadruple (85 vs. 94.1%; P=0.06) therapies. Adverse events occurred more frequently with the quadruple than with sequential therapy (56.9 vs. 25.8%; P<0.001). CONCLUSION: In our country, sequential and bismuth-based quadruple therapy achieved similarly high eradication rates as first-line treatments for H. pylori infection in clinical practice.