Comparison of omeprazole, metronidazole and clarithromycin with omeprazole/amoxicillin dual-therapy for the cure of Helicobacter pylori infection

In this randomized, multicenter trial, we evaluated the effectiveness and side effect profile of a modified omeprazole-based triple therapy to cure Helicobacter pylori infection. The control group consisted of patients treated with standard dual therapy comprising omeprazole and amoxicillin. One hundred and fifty-seven H. pylori infected patients with duodenal ulcers were randomly assigned to receive either a combination of omeprazole 10 mg, clarithromycin 250 mg and metronidazole 400 mg (OCM) given three times daily for 10 days (n = 81),or a combination of omeprazole 20 mg and amoxicillin 1 g (OA) given twice daily for 14 days (n = 76). Prior to treatment and after 2 and 6 weeks, gastric biopsies from the antrum and corpus were obtained for histology and H. pylori culture. H. pylori infection was cured in 97.4% after OCM and in 65.8% after OA in the per-protocol analysis (p < 0.001) (intention-to-treat analysis: 93.4% and 63.2%, respectively). H. pylori was successfully cultured in 122 patients (77%). The overall rate of metronidazole resistance was 19.7% (24/122), no primary resistance to clarithromycin or amoxicillin was found. In the OCM group, all patients infected with metronidazole-sensitive H. pylori strains (n = 51) and those infected with strains of unknown susceptibility to metronidazole (n = 14)were cured (100%), while 77% (10/13) of those harboring metronidazole-resistant. strains were cured of the infection (p = 0.36). Side effects leading to premature termination of treatment occurred in 2.5% of the patients in the OCM group and in 1.4 % of the OA group. We conclude that combined treatment with omeprazole, clarithromycin and a higher dose of metronidazole is highly effective in curing H, pylori infection, Helicobacter pylori omeprazole and that this regimen remains very effective in the presence of metronidazole resistant strains

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

Assessment and analysis of H.pylori infection treatment strategies of St. Vincent Hospital\u27s family and internal medicine clinics

Helicobacter pylori is a gram-negative bacteria that is responsible for causing chronic gastritis, ulcers in the stomach and intestine, and eventually even gastric lymphoma or cancer. Multiple treatment options have been recommended for treating an H. pylori infection based on kidney function, previous antibiotic exposure, and whether or not the infection is recurrent. The most common regimens used at St. Vincent\u27s primary care centers closely mimic the American College of Gastroenterology\u27s clinical guidelines. However, these medications (clarithromycin and levofloxacin) have been associated with high rates of resistance in other countries. The United States has very limited data on H. pylori\u27s resistance rates to these medications and there is not sufficient data to prove the efficacy of these regimens. This project aims to identify what percentage of H. pylori infections diagnosed at St. Vincent\u27s Family Medicine and Internal Medicine clinics are being successfully treated with current, guideline-directed therapy. It also aims to obtain a general understanding of H. pylori resistance rates to clarithromycin and levofloxacin in the Indianapolis area based on treatment failure rates

Impact of creatinine clearance on helicobacter pylori eradication rate in patients with peptic ulcer disease

Introduction. Gastrointestinal complaints are common in patients with kidney failure. The aim of this study was to investigate the effect of creatinine clearance on Helicobacter pylori (HP) eradication rate in patients with peptic ulcer disease. Materials and Methods. In this clinical trial, 132 patients with a range of kidney function (normal to end-stage renal disease) and peptic ulcer disease with HP infection were enrolled and divided into 5 groups by their creatinine clearance. For all patients, a 14-day standard regimen of triple therapy for peptic ulcer was started with omeprazole, 20 mg; clarithromycin, 500 mg; and amoxicillin, 1 g; twice per day. After 6 weeks, HP eradication rate were evaluated and compared between the groups with urea breath test. Results. The mean age of the participants was 44.84 ± 12.20 years and 68 (51.5%) were women. The five groups were not significantly different in terms of age, sex distribution, or body mass index. The results of urea breath test at 6 weeks were positive in 23 patients (17.4%). There was no significant difference in HP eradication rate (negative urea breath test) between the five groups. Conclusions. This study showed no association between the success rate of eradication of HP infection and kidney function. © 2015, Iranian Society of Nephrology. All rights reserved

\u3cem\u3eHelicobacter pylori\u3c/em\u3e infection in Havana, Cuba. Prevalence and \u3cem\u3ecagA\u3c/em\u3e status of the strains

There is a great paucity of information about Helicobacter pylori infection in the countries of the Caribbean basin. Almost no studies have been performed to determine the prevalence, antibiotic resistance or virulence factors of the bacterium. To measure the prevalence of H. pylori infection among patients attending endoscopy in three clinics in Havana, Cuba, to evaluate clarithromycin resistance, and to determine the cagA status of the strains obtained. Endoscopy was performed and biopsies were obtained from 117 successive patients attending the Institute of Oncology, the Institute of Gastroenterology, and the Calixto Garcia Hospital in Havana, Cuba. Biopsies were maintained at –70 ºC before being cultured on three different media (two selective and one non-selective) and incubated for 7 days at 37 °C under a microaerobic atmosphere. The presence of H. pylori was identified by oxidase, catalase and urease activities. DNA was extracted, and PCR was performed with primers H2761676 which amplify a 397 bp fragment of the cagA gene. Clarithromycin susceptibility was measured by the gel diffusion method. The diagnoses of patients were: 1 gastric carcinoma; 19 duodenal ulcers; 8 gastric ulcers; and 89 non-ulcer dyspepsia, including (62) gastritis, (9) hiatal hernia,(2) biliary reflux, (1) gastric polyps, and (15) no abnormality. Among the 117 biopsies tested, 83 were H. pylori positive (70.9%). The cagA status determined for 35 cases gave a positive result in 31 cases (88.5%). Only 3% of the strains were resistant to clarithromycin. The prevalence of Helicobacter pylori infection in the symptomatic population of La Habana is the same as reported for other developing countries. Most strains were cagA positive and are likely harbour the cag pathogenicity island. The low resistance to clarithromycin in the strains studied probably reflects the low degree of use of the antibiotic in this population

Investigating the removal of some pharmaceutical compounds in hospital wastewater treatment plants operating in Saudi Arabia

The concentrations of 12 pharmaceutical compounds (atenolol, erythromycin, cyclophosphamide, paracetamol, bezafibrate, carbamazepine, ciprofloxacin, caffeine, clarithromycin, lidocaine, sulfamethoxazole and Nacetylsulfamethoxazol (NACS)) were investigated in the influents and effluents of two hospital wastewater treatment plants (HWWTPs) in Saudi Arabia. The majority of the target analytes were detected in the influent samples apart from bezafibrate, cyclophosphamide, and erythromycin. Caffeine and paracetamol were detected in the influent at particularly high concentrations up to 75 and 12 ug/L, respectively. High removal efficiencies of the pharmaceutical compounds were observed in both HWWTPs, with greater than 90 % removal on average. Paracetamol, sulfamethoxazole, NACS, ciprofloxacin, and caffeine were eliminated by between &gt;95 and &gt;99 % on average. Atenolol, carbamazepine, and clarithromycin were eliminated by &gt;86 % on average. Of particular interest were the high removal efficiencies of carbamazepine and antibiotics that were achieved by the HWWTPs; these compounds have been reported to be relatively recalcitrant to biological treatment and are generally only partially removed. Elevated temperatures and high levels of sunlight were considered to be the main factors that enhanced the removal of these compounds

Pertussis post-exposure prophylaxis among household contacts: a cost-utility analysis.

BACKGROUND: Recent pertussis outbreaks have prompted re-examination of post-exposure prophylaxis (PEP) strategies, when immunization is not immediately protective. Chemoprophylaxis is recommended to household contacts; however there are concerns of clinical failure and significant adverse events, especially with erythromycin among infants who have the highest disease burden. Newer macrolides offer fewer side effects at higher drug costs. We sought to determine the cost-effectiveness of PEP strategies from the health care payer perspective. METHODS: A Markov model was constructed to examine 4 mutually exclusive strategies: erythromycin, azithromycin, clarithromycin, or no intervention, stratified by age group of contacts ("infant", "child", and "adult"). Transition probabilities, costs and quality-adjusted life years (QALYs) were derived from the literature. Chronic neurologic sequelae were modeled over a lifetime, with costs and QALYs discounted at 5%. Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars. Deterministic and probabilistic sensitivity analyses were performed to evaluate the degree of uncertainty in the results. FINDINGS: Azithromycin offered the highest QALYs in all scenarios. While this was the dominant strategy among infants, it produced an ICER of $16,963 per QALY among children and$2,415 per QALY among adults. Total QALYs with azithromycin were 19.7 for a 5-kg infant, 19.4 for a 10-year-old child, and 18.8 for a 30-year-old adult. The costs of azithromycin PEP among infants, children and adults were $1,976,$132 and $90, respectively. While results were sensitive to changes in PEP effectiveness (11$379 to $59,644), the choice of strategy remained unchanged. INTERPRETATION: Pertussis PEP is a cost-effective strategy compared with no intervention and plays an important role in contact management, potentially in outbreak situations. From a healthcare payer perspective, azithromycin is the optimal strategy among all contact groups

Formulation and evaluation of floating mucoadhesive alginate beads for targetingHelicobacter pylori

Objectives: There are various obstacles in the eradication of Helicobacter.pylori (H. pylori) infections, including low antibiotic levels and poor accessibility of the drug at the site of the infection. This study describes the preparation and characterisation of novel floating-mucoadhesive alginate beads loaded with clarithromycin (CMN) for delivery to the gastric mucosa to improve the eradication of this micro-organism. Methods: Calcium alginate beads were prepared by ionotropic gelation. The formulation was modified through addition of oil and coating with chitosan in order to improve floating, mucoadhesion and modify drug release. Key findings: SEM confirmed the sphericity of the beads with X-ray microtomography (XμMT) showing the 3D structure of the beads with the layered internal structure of the bead and the even distribution of the drug within the bead. This formulation combined two gastro-retentive strategies and these formulations produced excellent in vitro floating, mucoadhesive and drug release characteristics. Enhanced stability of the beads in phosphate buffer raises a potential for the modified formulations to be targeted to regions of higher pH within the gastrointestinal tract with a higher pH. Drug release from these beads was sustained through an unstirred mucin layer simulating in vivo conditions under which the H. pylori resides in the gastric mucosa. Conclusions: This novel formulation will ensure retention for a longer period in the stomach than conventional formulations and control drug release, ensuring high local drug concentrations, leading to improved eradication of the bacteria

Bismuth-based quadruple therapy following H. Pylori eradication failures: A multicenter study in clinical practice

Background & Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice. Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated. Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported. Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practic

An immunocompromised dialysis patient with skin and bone lesions

Patients with chronic kidney failure have disturbances of immune function involving both innate and adaptive systems. These result in both immunodepression which increases susceptibility to infection and immunoactivation leading to a chronic inflammatory state [1]. Dialysis treatment may further aggravate aspects of this, especially the induction of inflammation. In addition, there is a growing number of patients who have returned to dialysis programmes following transplant failure. Many of these will have been intensively immunosuppressed, often over years or decades. These patients are at particular risk.Non peer reviewedFinal Published versio