Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Indications of Helicobacter pylori Eradication Treatment and Its Influence on Prescriptions and Effectiveness (Hp-EuReg).

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.

Diverticulosis, Adenomas, and Cancer in the Colon: A Systematic Review and Meta-Analysis of Endoscopic Studies.

GOALS: To perform a systematic review and meta-analysis of endoscopic studies to evaluate an association between diverticulosis and neoplastic lesions in the colon. BACKGROUND: Some epidemiological observations suggest an association between diverticulosis and adenoma/cancer in the colon. However, an increased risk of colon neoplastic lesions in diverticulosis subjects was found to be increased in some studies, but not in others, puzzling data interpretation. STUDY: From the retrieved studies, prevalence of adenomas, advanced adenomas, cancer or neoplasia (advanced adenoma or cancer) was compared between subjects with or without diverticulosis, and comparisons in subgroups were also performed. RESULTS: Data of 26 studies with a total of 419,623 patients were eventually considered, including 27,092 patients with diverticulosis. Data analysis found a statistically significant association between diverticulosis and adenomas (OR: 1.88; 95% CI: 1.50-2.25), advanced adenomas (OR: 1.49; 95% CI: 1.02-2.16), and neoplasia (OR: 1.50; 95% CI: 1.11-2.02), but not with cancer alone (OR: 1.01; 95% CI: 0.70-1.47). These associations were confirmed in the subgroup analyses, by considering Caucasian and Asian populations, prospective and retrospective studies, screening or symptoms settings, and between good or fair quality studies. CONCLUSIONS: A statistically significant association between diverticulosis and adenomas, advanced adenomas and neoplasia, but not with cancer alone was found. However, the strength of association seems to be insufficient to impact on clinical practice.

The Auditory Pathway in Congenitally Cytomegalovirus-Infected Human Fetuses.

Congenital cytomegalovirus (CMV) infection is the main cause of non-hereditary sensorineural hearing loss (SNHL). In order to shed light on SNHL pathophysiology, we examined the auditory pathway in CMV-infected fetuses; the temporal lobe, in particular the auditory cortex, and the inner ear. We investigated both inner ears and temporal lobes of 20 human CMV-infected fetuses at 21 weeks of gestation. As a negative group, five fetuses from spontaneous miscarriages without CMV infection were studied. Inner ears and temporal lobes were histologically examined, immunohistochemistry for CMV and CMV-PCR were performed. On the auditory cortex, we evaluated the local microglial reaction to the infection. CMV-positive cells were found in 14/20 brains and the damage was classified as severe, moderate, or mild, according to histological features. Fetuses with severe brain damage had a statistically higher temporal lobe viral load and a higher number of activated microglial cells in the auditory cortex compared to fetuses with mild brain damage (p: 0.01; p: 0.01). In the inner ears, the marginal cells of the stria vascularis were the most CMV positive. In our study, CMV affected the auditory pathway, suggesting a tropism for this route. In addition, in the auditory cortex, microglial activation may favor further tissue damage contributing to hearing loss.

Rescue Therapies for Helicobacter pylori Infection in Foreign Patients Treated in Italy.

MATERIALS AND METHODS: Consecutive foreigner patients with H. pylori infection following at least one therapy failure were enrolled. All patients underwent upper endoscopy with gastric biopsies used for both histologic examination and culture/susceptibility test. Rescue therapies administered accordingly to susceptibility testing were rifabutin-based therapy, levofloxacin-based therapy, sequential. Pylera was prescribed regardless the resistance pattern. RESULTS: A total of 103 (M/F: 27/76, mean age: 41.9 y, range: 18 to 85) were enrolled. The overall resistance rates toward clarithromycin, metronidazole, and levofloxacin were 76.7%, 66%, and 42.7%, respectively, with triple resistance present in 33.9% of bacterial isolates. Eradication rates were 71.4% on 40 patients for rifabutin-based therapy, 82.8% on 42 cases for levofloxacin-based therapy, 75% on 11 patients treated with sequential therapy, and 100% on 10 cases who received Pylera regimen. CONCLUSIONS: To our knowledge, this is the first study assessing H. pylori eradication rates in foreigner patients, who failed at least one therapeutic attempt, managed in Italy. Even by using a culture-based approach, the infection was not cured in a definite number of patients.

Role of MIC levels of resistance to clarithromycin and metronidazole in Helicobacter pylori eradication.

OBJECTIVES: Antimicrobial resistance to clarithromycin and metronidazole significantly affects the cure rate of standard therapies for Helicobacter pylori infection. We tested whether different MIC levels of resistance to these antibiotics play a role in therapeutic efficacy. METHODS: This was a post hoc analysis of data from a therapeutic trial in which patients with antibiotic susceptibility testing (Etest) received first-line sequential therapy. The level of antibiotic resistance was classified according to MIC values into low (MIC from >0.5 to ≤8 for clarithromycin, and from >8 to ≤32 for metronidazole) and high (MIC from >8 to 256 mg/L for clarithromycin, and from >32 to 256 mg/L for metronidazole). RESULTS: Data from 1006 patients were included. There were 520 (51.7%) patients with susceptible strains, 136 (13.5%) with clarithromycin-resistant strains, 144 (14.3%) with metronidazole-resistant strains and 206 (20.5%) with clarithromycin-resistant and metronidazole-resistant strains. In the presence of double resistance, the cure rate was still high (38/41, 92.7%) when MIC levels were low and it was reduced (94/112, 83.9%) only when MIC levels of both antibiotics were high. The cure rates did not significantly differ between patients with single antibiotic-resistant strains, irrespective of MIC values, and those with susceptible strains. CONCLUSIONS: We found that MIC levels of resistance to either clarithromycin or metronidazole play a role in H. pylori therapy outcome and that bacterial resistance becomes relevant in vivo when clarithromycin-resistant and metronidazole-resistant strains have high MIC values for at least one of these antibiotics.

Antibiotic resistance pattern of Helicobacter pylori strains isolated in Italy during 2010-2016.

PURPOSE: Bacterial resistance toward the most used antibiotics is increasing in Helicobacter pylori strains worldwide. Emergence of multidrug resistance significantly affects the efficacy of standard therapy regimens. Therefore, monitoring for primary antimicrobial resistance is essential for H. pylori management in clinical practice. METHODOLOGY: H. pylori isolates obtained from patients consecutively observed in a single center were tested for primary resistance by using E-test method. Bacterial strains showing MIC values >0.5, >8 and >1 mg/L toward clarithromycin, metronidazole and levofloxacin, respectively, were considered resistant. The trend of antibiotic prevalence, either single or combined, during 2010-2016 was assessed. RESULTS: Antibiotic susceptibility data were available in 1424 (82.3%) out of 1730 tested patients. The overall resistance for all the three antibiotics showed an increasing trend from 2010 to 2013 (clarithromycin: from 19% to 35.6%; metronidazole: from 33.6% to 45.3%; levofloxacin: from 19% to 29.7%; p < .001), when a plateau until 2016 was observed (clarithromycin: 35.9%; metronidazole: 40.2%; levofloxacin: 29.3%). A similar trend occurred for clarithromycin-metronidazole combined resistance rate (2010: 11.4%; 2013: 28.2%; 2016: 21.9%). CONCLUSION: Our data suggest that prevalence of primary resistance in H. pylori isolates toward the most frequently used antibiotics probably reached a plateau in the last years.

Rescue therapy with bismuth quadruple regimen in patients with Helicobacter pylori -resistant strains.

BACKGROUND: Bismuth quadruple therapy (BQT) is the recommended rescue therapy for Helicobacter pylori (H. pylori) infection. This study aimed to assess the efficacy and safety of a 10-day BQT regimen in patients who failed previous therapies and were infected with multiresistant H. pylori strains MATERIALS AND METHODS: Helicobacter pylori-infected patients underwent endoscopy, culture, and susceptibility test for clarithromycin, metronidazole, and levofloxacin. Treatment with three-in-one capsule (Pylera®) four times daily and esomeprazole 20 mg twice daily for 10 days was administered. Treatment-emergent adverse events (TEAEs) were registered. RESULTS: A total of 116 patients with persistent H. pylori infection following at least one eradication therapy attempt were treated. Overall, resistance toward clarithromycin was detected in 80% of strains, toward metronidazole in 70%, and levofloxacin in 47.5%, with dual or triple resistance in 72.5% of cases. An eradication rate of 81.0% (95% CI: 73.0-87.1) and 87.0% (95% CI: 79.4-92.1) at ITT and PP analyses, respectively, was achieved. The cure rate remained high until it was used as fourth-line regimen, while it dropped to low values (<67%) in those patients with more than 4 therapy failures. A total of 65.7% (95% CI: 56.4-74.0) patients complained of TEAEs. CONCLUSIONS: Our data found that bismuth-based quadruple regimen is effective as rescue therapy for curing patients infected with multiresistant H. pylori strains.

Antimicrobial Resistance of Genital Mycoplasma and Ureaplasma: A Multicentre Study Over a 5-Year Period in Italy (2017-2021).

Updated data on genital Mollicutes prevalence and antimicrobial susceptibility can help provide guidance for antibiotic stewardship and set up effective strategies for infection control policies. In this multicentre study, we assessed the prevalence and the resistance profile of Mycoplasma hominis (MH) and Ureaplasma species (U. parvum/U. urealyticum), analyzing data from 21,210 subjects who provided urogenital samples for Mollicutes detection by culture over a 5-year period (2017-2021) in two high-density urban areas in the North of Italy (i.e., Bologna and Lecco). Overall prevalence of Mollicutes infection was 22.3%, with women showing a significantly higher detection rate than men (p < 0.00001). The prevalence decreased with age (highest prevalence <30 years) and over the years considered. Ureaplasma strains were much more frequently detected (62.3%) compared to MH (8.3%) and to mixed infections (29.4%). Ureaplasma species showed high levels of ciprofloxacin resistance (39.5%), whereas MH strains were nonsusceptible to azithromycin and roxithromycin in about 60% of cases. Over time, a significant decrease of resistance to azithromycin and doxycycline was detected (p < 0.0001 and 0.0004, respectively), in parallel with an important increase of ciprofloxacin-resistance levels (p < 0.0001). Overall, our results revealed that minocycline and josamycin can be first-line drugs for Mollicutes empirical treatment.

Mollaret's Meningitis due to Herpes Simplex Virus 2: A Case Report and Review of the Literature.

Mollaret's meningitis is a rare neurological disorder characterized by recurrent episodes of aseptic lymphocytic meningitis, often associated with herpes simplex virus 2 (HSV-2) infection. We report the case of a 39 y.o. Italian woman who experienced four episodes of aseptic lymphocytic meningitis between 2004 and 2023, diagnosed as Mollaret's meningitis. In each episode, the patient presented with fever, severe headache and photophobia. In two episodes cutaneous vesicles in the left gluteal area preceding meningitis symptoms were also reported. A diagnostic evaluation included a physical-chemical analysis and a real-time PCR of the cerebrospinal fluid (CSF). The CSF presented pleocytosis with lymphocytic predominance and a positive HSV-2 load, with a peak of 1234 copies/mL. The patient was treated successfully with acyclovir, and the symptoms resolved without neurological sequelae. This case highlights the importance of comprehensive diagnostic testing and vigilant monitoring to manage Mollaret's syndrome effectively.

Respiratory Syncytial Virus-Load Kinetics and Clinical Course of Acute Bronchiolitis in Hospitalized Infants: Interim Results and Review of the Literature.

Respiratory Syncytial Virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. The role of RSV load in disease severity is still debated. We present the interim results of a prospective monocentric study enrolling previously healthy infants hospitalized for RSV bronchiolitis, collecting nasopharyngeal aspirates every 48 h from admission to discharge, and evaluating RSV load dynamics in relation to clinical outcome measures of bronchiolitis severity, including: need, type and duration of oxygen therapy, length of hospitalization, and the bronchiolitis clinical score calculated at admission. The results showed that the highest viral replication occurs within the first 48 hours after admission, with a significant decrease at subsequent time points (p < 0.0001). Moreover, higher RSV-RNA values were associated with the need for oxygen therapy (p = 0.03), particularly high-flow nasal cannula type (p = 0.04), and longer duration of respiratory support (p = 0.04). Finally, higher RSV load values were correlated with lower white blood cells, especially lymphocyte counts and C-reactive protein levels (p = 0.03, p = 0.04, and p = 0.01, respectively), as well as with patients of a younger age (p = 0.02). These data suggest that RSV may actively contribute to the clinical severity of bronchiolitis, together with other potential non-viral factors.

Inherited Chromosomally Integrated Human Herpesvirus 6: Laboratory and Clinical Features.

Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the chromosomes of the host germ cell and is vertically transmitted. The aims of this study were to identify iciHHV-6 prevalence in hospitalized patients and clinical features in individuals carrying this integration. HHV-6 PCR on hair follicles was used to confirm iciHHV-6 status when the blood viral load was more than 5 Log10 copies/mL. From January 2012 to June 2022, HHV-6 DNAemia was investigated in 2019 patients. In particular, 49 had a viral load higher than 6 Log10 copies/mL and HHV-6 DNA in hair follicles was positive. A viral load between 5.0 and 5.9 Log10 copies/mL was observed in 10 patients: 6 infants with acute HHV-6 infection and 4 patients with leukopenia and HHV-6 integration. Therefore, the iciHHV-6 prevalence in our population was 2.6% (53/2019). Adult patients with integration presented hematological (24%), autoimmune (11%), autoimmune neurological (19%), not-autoimmune neurological (22%), and other diseases (19%), whereas 5% had no clinically relevant disease. Although in our study population a high percentage of iciHHV-6 adult hospitalized patients presented a specific pathology, it is still unknown whether the integration is responsible for, or contributes to, the disease development.

Efficacy of a new nutraceutical formulation: L-tryptophan, probiotics, charcoal, chamomile, mint, and licorice (COLONIR®) in the improvement of gastrointestinal symptoms in subjects with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. IBS is characterized by recurrent chronic abdominal pain and altered bowel habits in the absence of organic damage. Although there are reviews and guidelines for treating IBS, the complexity and diversity of IBS presentation make treatment difficult. Treatment of IBS focuses on relieving symptoms as mild signs and symptoms can often be controlled by managing stress and by making changes in diet and lifestyle. The use of nutraceutical compounds has been advocated as a possible alternative treatment in patients with IBS. COLONIR® (Omega Pharma Srl, Milan, Italy) may be an alternative or adjuvant treatment in patients with gastrointestinal symptoms. This study aimed to evaluate the effect of this new nutraceutical formulation in inducing symptoms remission and improve gastrointestinal habits. METHODS: An initial cohort of 1004 consecutive patients referred to 25 different Units of Internal Medicine a/o Gastroenterology in Italy to perform colonoscopy for intestinal symptoms was asked to participate. Patients were treated for 2 months with two doses of nutraceuticals/day during meals namely COLONIR®. Patients were assessed at baseline and after 2 months to evaluate the frequency and severity of gastrointestinal symptoms in the past seven days with a questionnaire based on ROMA IV criteria. RESULTS: After 2 months, 899 patients completed the follow-up. COLONIR® achieved a statistically significant reduction of severity of symptoms in the study population without any documented side effects. CONCLUSIONS: These promising results, here reported, need to be confirmed, valuating the efficacy of COLONIR® in relieving gastrointestinal symptoms in IBS patients in further studies.

Effectiveness of first and second-line empirical treatment in Italy: Results of the European registry on Helicobacter pylori management.

BACKGROUND AND AIMS: The optimal management of naïve and not naïve Helicobacter pylori patients remains unclear. Therefore, it is essential to evaluate whether the actual clinical practice mirrors the indications suggested by the guidelines. This study aimed to assess the effectiveness and the safety of the empirical first- and second-line treatments prescribed to patients enroled at Italian centres participating in the European Registry on H. pylori Management (Hp-EuReg). METHODS: The Hp-EuReg is an international multicentre prospective non-interventional registry starting in 2013 aiming to evaluate the management of H. pylori infection by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables assessed included demographics, previous eradication attempts, treatment regimen, effectiveness, and tolerance. RESULTS: Overall, 3723 patients from 2013 to February 2021 were included: 2996 and 727 received an empirical first- and second-line treatment, respectively. According to the modified ITT analysis, among the first-line regimens, only the bismuth quadruple therapy with three-in-one-single capsule (BQT-TSC), the concomitant, and the sequential treatment - all lasting 10 days - achieved an eradication rate >90%. Among the second-line regimens, only the 10-day BQT-TSC reported an effectiveness >90%. High-dose PPI twice daily also significantly increased the effectiveness of some therapies. The BQT-TSC was the regimen with the highest incidence of adverse events. CONCLUSIONS: Only quadruple therapies lasting at least 10 days achieved over 90% eradication rates among the empirical first- and second-line regimens. It remains unclear whether high-dose PPI twice daily can improve the efficacy of quadruple treatment.

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013-2022: Data from the European Registry on H. pylori Management (Hp-EuReg).

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Antifungal Activity of Natural Compounds vs. Candida spp.: A Mixture of Cinnamaldehyde and Eugenol Shows Promising In Vitro Results.

Candida spp. are commensal organisms of the skin, mucous membranes, gastrointestinal tract, blood, and vagina of animals and humans. In recent decades, the incidence of human fungal infections has increased, with Candida spp. (mainly C. albicans) infections being the most frequent, and the treatment of fungal infections is still a clinical challenge. Colonization of the human gastrointestinal tract by Candida spp. is significant because infections (e.g., candidemia and vulvovaginal candidiasis) frequently arise from commensal microorganisms. The aim of this study was to test in vitro the antifungal activity and the eventual synergistic effect of five pure components of essential oils: cinnamaldehyde, α-pinene, limonene, eucalyptol, and eugenol. These compounds were tested on 18 Candida strains (15 C. albicans, 2 C. glabrata, and 1 C. lusitaniae) derived from a culture collection of vaginal clinical strains. METHODS: Fungistatic activity was evaluated using the disk diffusion method. For fungicidal activity, microdilution and time-kill curve protocols were set up. The checkerboard method was chosen to evaluate a possible synergistic effect of these compounds when mixed. RESULTS: Cinnamaldehyde and eugenol gave the best results, inhibiting all the Candida strains and showing a highly additive effect (FICI 0.625). The cinnamaldehyde inhibition zone (IZ), MIC, and MFC means were 69 mm, 50.05 mg/L, and 109.26 mg/L respectively. Cinnamaldehyde led to the total loss of viable Candida cells within 4 h. Eugenol IZ, MIC, and MFC means were 35.2 mm, 455.42 mg/L, and 690.09 mg/L, respectively. Eugenol led to the total loss of viable fungal cells within 1 h. Treatment with α-pinene inhibited 88.9% of Candida strains, with an IZ mean of 21.2 mm, a MIC mean of 195.41 mg/L, and a MFC mean of 251.27 mg/L; this compound led to the total loss of viable fungal cells only after 24 h. Limonene inhibited only 33.3% of the tested strains and eucalyptol did not produce an inhibition halo, so these compounds were not tested further. CONCLUSIONS: These characteristics, together with the well-known safety of cinnamaldehyde and eugenol for human use, make these two natural compounds the perfect candidates for the treatment of candidiasis. This was a pilot study, the purpose of which was to evaluate the best composition of a mixture to be used against intestinal and vulvovaginal candidiasis; in vivo studies are needed to confirm these very encouraging results.

Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review.

Background: Primary antibiotic resistance in Helicobacter pylori (H. pylori) strains is increasing worldwide, affecting therapy success. The use of therapies tailored on susceptibility pre-testing at culture has been proposed, but data are still conflicting. Method: We performed a systematic review to evaluate the role of a culture-based therapeutic approach for H. pylori treatment, taking into account the sensitivity of culture and the success rates achieved with tailored therapies in different therapeutic steps. Results: We analyzed data from 51 studies. Overall, H. pylori strains were isolated in 80.7% of 7889 patients, the success rates being 78.1%, 77.5%, 86.3% and 86.6%, before first-, second-, third-line or more therapies, respectively. In comparative studies, the infection was cured in 89.9% of 2052 patients treated with tailored therapies, and in 77.6% of 2516 patients receiving empiric therapy (P<0.001). However, in the subanalysis, the tailored approach achieved optimal eradication rates (>90%) only when it was applied before first- and second-line therapies, but not before third-line or more attempts (<80%). Moreover, no significant difference emerged between the 2 approaches when data from only the most recent (last 5 years) studies were considered, as well as in those performed in Western populations. Conclusions: The attempt to achieve antibiotic susceptibility testing before treatment failed in 20% of infected patients managed in dedicated laboratories. Culture-tailored therapies administered after 2 or more therapies achieved suboptimal eradication rates. The role of bacterial culture in patients whose therapeutic management failed to eradicate H. pylori probably needs to be corroborated by further data.

Next Generation Sequencing for the Prediction of the Antibiotic Resistance in Helicobacter pylori: A Literature Review.

Background and aims: Only a few antimicrobials are effective against H. pylori, and antibiotic resistance is an increasing problem for eradication therapies. In 2017, the World Health Organization categorized clarithromycin resistant H. pylori as a "high-priority" bacterium. Standard antimicrobial susceptibility testing can be used to prescribe appropriate therapies but is currently recommended only after the second therapeutic failure. H. pylori is, in fact, a "fastidious" microorganism; culture methods are time-consuming and technically challenging. The advent of molecular biology techniques has enabled the identification of molecular mechanisms underlying the observed phenotypic resistance to antibiotics in H. pylori. The aim of this literature review is to summarize the results of original articles published in the last ten years, regarding the use of Next Generation Sequencing, in particular of the whole genome, to predict the antibiotic resistance in H. pylori.Methods: a literature research was made on PubMed. The research was focused on II and III generation sequencing of the whole H. pylori genome. Results: Next Generation Sequencing enabled the detection of novel, rare and complex resistance mechanisms. The prediction of resistance to clarithromycin, levofloxacin and amoxicillin is accurate; for other antimicrobials, such as metronidazole, rifabutin and tetracycline, potential genetic determinants of the resistant status need further investigation.

Rescue Therapies for H. pylori Infection in Italy.

Background/Aims: Curing Helicobacter pylori infection remains challenging for clinicians, as no proposed first-line therapy achieves bacterial eradication in all treated patients so that several patients need two or more consecutive treatments. Bacterial culture with antibiotics susceptibility testing is largely unachievable in Italy, and empiric second-line and rescue therapies are generally used. This study aimed to identify what eradication regimens perform better in Italy, following first-line therapy failure. Methods: We performed a literature search on PubMed for studies on standard therapy regimens used as second-line or rescue treatments performed in adult patients. Studies including modified drug combinations were not considered. Both intention-to-treat and per- protocol analyses were computed for each therapy subgroup. Results: Data from 35 studies with a total of 4830 patients were eventually considered. As a second-line therapy, Pylera® (90.6%) and a sequential regimen (89.8%) achieved eradication rates significantly higher than other therapies. For third-line therapy, a levofloxacin-based regimen and Pylera® achieved comparable eradication rates (88.2% vs. 84.7%; p = 0.2). Among therapies used as fourth (or more) attempts, Pylera® and a rifabutin-based therapy achieved 77.4% and 66.4% cure rates, respectively (p = 0.013). A therapy sequence based on the type of first-line therapy used was proposed. Conclusions: Data obtained through our review indicate that standard therapies for H. pylori eradication can be used when following an appropriate sequence, allowing clinicians to improve the cure rate without resorting to bacterial culture.