Eradication Failure Research Articles

High neutrophil-to-lymphocyte ratio at Helicobacter pylori eradication increases the risk of eradication failure and post-eradication gastric cancer

Introduction Vonoprazan has been known to have a high Helicobacter pylori (H. pylori) eradication rate since its launch in 2015. Yet, the risk factors for eradication failure and development of post-eradication gastric cancer (GC) using VPZ regimen remain unclear. Methods This single-center cohort study included 934 consecutive patients who underwent H. pylori eradication using VPZ between February 2015 and June 2017 and were followed up for five years by the end of 2022. We examined several indicators of systemic immune, inflammatory, and nutritional status at the time of eradication to identify those indicators could predict eradication success, risk of post-eradication GC development, and long-term prognosis. Results The successful eradication rates were 92.6% (intention-to-treat) and 98.7% (per-protocol). Multivariate analysis showed that only a high peripheral blood neutrophil-to-lymphocyte ratio (NLR) was significantly associated with eradication failure. The 5-year GC incidence rate was 1.67%, and all GCs were stage IA. The mean (standard deviation [SD]) time from eradication to diagnosis was 40.5 (6.1) months. Multivariate analysis showed that high NLR and history of GC and hypertension were significantly associated with GC development. Patients with elevated NLR post-eradication had a higher risk of newly developed GC. Twelve patients died during the study period, and a high NLR was associated with a significantly higher mortality rate. Conclusions NLR has the potential to be a biomarker that predicts the failure of eradication and development of post-eradication GC. High NLR was also associated with poor long-term prognosis after H. pylori eradication.

TMIC-09. DENDRITIC CELL DYSFUNCTION RESTRICTS TUMOR ANTIGEN SPREADING IN ADOPTIVE CELLULAR TRANSFER THERAPY-ESCAPED GLIOMAS: IMPLICATIONS FOR TUMOR IMMUNE EVASION

Abstract Dendritic cells (DCs) play a pivotal role in initiating anti-tumor immune responses. Our group has developed an adoptive cellular transfer therapy (ACT) that significantly increases the infiltration of DCs and T cells into tumors, markedly enhancing survival in murine brain tumor models. However, tumors develop mechanisms to restrict the immune surveillance and the efficacy of immunotherapy, leading to tumor escape. In this study, we identified a mechanism involving DC dysfunction in ACT-escaped brain tumors. The finding that DCs are enriched after ACT treatment prompts an investigation into whether DC function is impaired in ACT-escaped tumors. Our results showed that DCs from both primary and ACT-escaped tumors were dysfunctional in their ability to activate T cells when co-cultured with tumor-reactive T cells or OT1 T cells. RNA-seq data revealed that, compared to primary tumor DCs, ACT-escaped tumor DCs exhibited a more pronounced reduction in conventional DC markers and antigen-presenting genes, alongside increased tolerance markers. Gene set enrichment analysis indicated that epithelial-mesenchymal transition (EMT) and hypoxia pathways were significantly enriched in ACT-escaped tumor DCs, suggesting divergent DC dysfunction mechanisms in primary versus escaped tumors. The anti-tumor role of DCs is primarily exerted through the activation of tumor-reactive T cells. Therefore, we assessed the cytotoxicity and exhaustion status of T cells in tumors. Surprisingly, we found that T cells from ACT-escaped tumors exhibited significantly higher levels of cytotoxicity and lower levels of T cell exhaustion compared to primary tumors. This suggests a T cell exhaustion-independent mechanism in ACT-escaped tumors. We further demonstrated that T cells in ACT-escaped tumor are mainly sourced from the adoptive transferred T cells, which recognize primary tumor antigens but not escaped tumor antigens. These results suggest that a combined mechanism of tumor antigen shifting and impaired DC function leads to a failure of antigen spreading and tumor eradication.

Real-World Situation of Eradication Regimens and Risk Factors for Helicobacter pylori Treatment in China: A Retrospective Single-Center Study.

The success rate of Helicobacter pylori (H. pylori) eradication in China is declining. The aim of this study was to evaluate eradication outcomes in clinical practice and identifies factors contributing to treatment failure. A retrospective review was conducted on patients treated for H. pylori infection with 14-day bismuth-containing quadruple therapy at a Beijing medical center from January 2020 to December 2023. We analyzed demographic and clinical data, eradication rates across regimens, and performed multivariate analysis to pinpoint predictors of failure. Out of 3340 participants, 2273 (68.1%) achieved eradication. Amoxicillin-based combinations (69.2%) outperformed other antibiotic regimens (58.9%, p < 0.001), with amoxicillin plus doxycycline reaching a 71.4% success rate. Esomeprazole-based regimens were more effective (73.6%) than other PPI regimens (65.2%, p = 0.001), notably, a rabeprazole, amoxicillin, doxycycline, and bismuth combination had an 80.0% success rate. Age, gender, and smoking and drinking were significant eradication failure predictors. In real-world settings, 14-day amoxicillin and esomeprazole-based quadruple regimens have been demonstrated to be more effective than other regimens. Age, gender, and lifestyle habits are identified as independent risk factors for eradication failure. This study was registered in the Chinese Clinical Trial Registry on 08/01/2024 (clinical trial registration number: ChiCTR2400079647).

Single-Arm, Prospective, Interventional Study of Helicobacter pylori Eradication Rescue Therapy with Rifabutin, Metronidazole, and Vonoprazan.

Background and Objective: Rescue Helicobacter pylori eradication can be challenging. Rifabutin (RBT) demonstrates high activity against Helicobacter pylori and is incorporated into various rescue eradication regimens. This exploratory study was performed to evaluate the efficacy and safety of a rescue regimen comprising RBT, metronidazole (MNZ), and vonoprazan (VPZ). Methods: This prospective, single-center, single-arm, interventional study was performed in Japan. Eligible patients were those who underwent failed primary eradication treatment (7-day treatment with three drugs: VPZ or a proton pump inhibitor [PPI], amoxicillin [AMPC], and clarithromycin) and secondary eradication treatment (7-day treatment with three drugs: VPZ or a PPI, AMPC, and MNZ) and those who were unable to receive first- and second-line therapy because of penicillin allergy. Twenty Helicobacter pylori-positive patients were treated with RBT (150 mg twice daily), MNZ (250 mg twice daily), and VPZ (20 mg twice daily) for 10 days (RBT-MNZ-VPZ therapy). Eradication success was evaluated using the urea breath test. Drug susceptibility test results were available in 16 patients. This study is registered in the Japan Registry of Clinical Trials (jRCT031220504). Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of RBT-MNZ-VPZ therapy were 70% (90% confidence interval [CI]: 49.2%-86.0%) and 72.2% (95% CI: 50.2%-88.4%), respectively. In the MNZ-susceptible subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were 100% (90% CI: 68.8%-100%) and 100% (90% CI: 65.2%-100%). In the MNZ-resistant subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were both 62.5% (90% CI: 28.9%-88.9%). All infections were RBT-susceptible. Conclusions: These findings suggest that RBT-MNZ-VPZ therapy may be a promising rescue regimen, especially in MNZ- and RBT-susceptible infections or patients with penicillin allergy.

Comprehensive Analysis of Factors Associated With Helicobacter pylori Eradication Therapy

Objectives: Associated factors for the failure of &lt;i&gt;Helicobacter pylori&lt;/i&gt; (HP) eradication have been evaluated in many studies; however, the different study population of previous studies prevents us from understanding the comparative risk between factors. We aimed to comprehensively investigate factors associated with successful HP eradication based on a single study population.Methods: We retrospectively reviewed the medical records of adults diagnosed with HP infection between March 2021 and October 2022 at Hanyang University Guri Hospital. The study categorized eradication treatment methods based on the type of acid blockers (proton pump inhibitor [PPI] or potassium-competitive acid blocker [P-CAB]), antibiotic combination, and treatment duration. Demographics and clarithromycin-resistance mutation status were also considered as potential factors of HP eradication.Results: A total of 554 patients who received first-line HP eradication therapy were included. In the full-analysis set, the eradication rates according to the regimen were as follows: 7-day tegoprazan-based triple, 61.6%; 14-day tegoprazan-based triple, 77.5%; 14-day rabeprazole-based triple, 71.1%; 10-day rabeprazole-based concomitant, 73.1%; 10-day tegoprazan-based concomitant, 80.5%. The 14-day triple and 10-day concomitant therapies showed a superior eradication rate to the 7-day triple therapy regardless of the type of acid blockers (PPI or P-CAB). Additionally, clarithromycin-resistance mutation was the strongest predictor for eradication failure (hazard ratio 9.86 [95% confidence interval, 2.07–46.97]).Conclusions: The 14-day triple and 10-day concomitant therapy was superior to the 7-day triple therapy regardless of PPI or P-CAB use. However, clarithromycin-resistance mutation status was a more powerful predictor for HP eradication than the type of antibiotics and treatment duration.

Improving wasp control by identifying likely causes of eradication failure

AbstractStudying the efficacy of control methods is paramount to successful management of invasive pests and understanding why some colonies survive is important to improve management practices. Here, the bait Vespex® was used to control invasive wasps across 64 ha of forest in an invaded range near Hanmer Springs, New Zealand. Bait was applied across a standard 50 m by 300 m arrangement and made available for 3 days. Nest mortality rates after 19 days were 29.8%, although nearly all nests were affected with a median overall reduction in nest traffic of 96.5%. The results from logistic regression showed that, all else remaining equal, larger wasp nests, nests further from bait stations, and more isolated nests exhibited lower rates of mortality after baiting. Investigating the change in activity at surviving nests, the results from beta regression suggest that declines in nest traffic were less severe with increasing distance to the nearest bait, but more severe with increasing nest size. These results indicate that while smaller nests are at a higher risk of being killed by the bait, they may not encounter bait as regularly as larger nests. Bait uptake varied considerably across bait stations. Wasp nests were not randomly or uniformly distributed in space, and instead were aggregated across our treatment area, likely due to some aspects of environmental conditions. We suggest further research to be focused on developing an understanding of the drivers of wasp nest development and foraging behaviour, to produce a more flexible baiting procedure that will increase both baiting efficiency and efficacy.

Complement receptor 3-dependent engagement by Candida glabrata β-glucan modulates dendritic cells to induce regulatory T-cell expansion.

Candida glabrata is an important pathogen causing invasive infection associated with a high mortality rate. One mechanism that causes the failure of Candida eradication is an increase in regulatory T cells (Treg), which play a major role in immune suppression and promoting Candida pathogenicity. To date, how C. glabrata induces a Treg response remains unclear. Dendritic cells (DCs) recognition of fungi provides the fundamental signal determining the fate of the T-cell response. This study investigated the interplay between C. glabrata and DCs and its effect on Treg induction. We found that C. glabrata β-glucan was a major component that interacted with DCs and consequently mediated the Treg response. Blocking the binding of C. glabrata β-glucan to dectin-1 and complement receptor 3 (CR3) showed that CR3 activation in DCs was crucial for the induction of Treg. Furthermore, a ligand-receptor binding assay showed the preferential binding of C. glabrata β-glucan to CR3. Our data suggest that C. glabrata β-glucan potentially mediates the Treg response, probably through CR3-dependent activation in DCs. This study contributes new insights into immune modulation by C. glabrata that may lead to a better design of novel immunotherapeutic strategies for invasive C. glabrata infection.

Treatment failure is a key factor in the development of Helicobacter pylori resistance.

Helicobacter pylori eradication failure influences its antibiotic resistance. This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns. This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected. The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased. The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.

Fourteen-Day Tegoprazan-Amoxicillin Dual Therapy as the First-Line Treatment of Helicobacter pylori Infection (SHARE2301): A Multicenter, Noninferiority, Randomized Clinical Trial.

Potassium-competitive acid blockers have demonstrated enormous potential in the eradication treatment of Helicobacter pylori infection, with tegoprazan being one of the representatives. The available data on the safety and efficacy of tegoprazan in dual therapy are limited. The multicenter, noninferiority, randomized-controlled trial was conducted from May 2023 to March 2024. Treatment-naive subjects were randomly assigned (1:1) to enter either the tegoprazan-amoxicillin (TA) group (tegoprazan 50 mg twice daily and amoxicillin 750 mg four times daily) or the esomeprazole-amoxicillin (EA) group (esomeprazole 20 mg and amoxicillin 750 mg all four times daily), with a duration for 14 days. The primary outcome was eradication rate as determined by 13C-urea breath test, including per-protocol (PP) analysis and intention-to-treat (ITT) analysis. Secondary outcomes were adverse events and compliance. A total of 368 individuals were included in the randomization. The eradication rates in the EA group and the TA group were 84.2% and 85.8%, respectively, according to an ITT analysis (p = 0.77), and 88.5% and 88.2%, respectively, according to PP analysis (p = 1.00). The eradication rates for the TA group were not inferior to those of the EA group in both PP (p = 0.0023) and ITT analyses (p = 0.0009). There were no significant statistical differences in the incidence of adverse events and compliance between the two groups. The multivariate logistic regression analysis revealed that poor compliance increased the risk of eradication failure (p < 0.001). Dual therapy containing tegoprazan is safe and effective to be considered as a clinical first-line treatment option, but further optimization involving antimicrobial susceptibility testing and adjustments in dosage and frequency is warranted. ClinicalTrials.gov ID: NCT05870683.

Rapid eradication of vancomycin and methicillin-resistant Staphylococcus aureus by MDP1 antimicrobial peptide coated on photocrosslinkable chitosan hydrogel: in vitro antibacterial and in silico molecular docking studies.

Antibiotic resistance and weak bioavailability of antibiotics in the skin due to systemic administration leads to failure in eradication of vancomycin- and methicillin-resistant Staphylococcus aureus (VRSA and MRSA)-associated wound infections and subsequent septicemia and even death. Accordingly, this study aimed at designing a photocrosslinkable methacrylated chitosan (MECs) hydrogel coated by melittin-derived peptide 1 (MDP1) that integrated the antibacterial activity with the promising skin regenerative capacity of the hydrogel to eradicate bacteria by burst release strategy. The MECs was coated with MDP1 (MECs-MDP1), characterized, and the hydrogel-peptide interaction was evaluated by molecular docking. Antibacterial activities of MECs-MDP1 were evaluated against VRSA and MRSA bacteria and compared to MECs-vancomycin (MECs-vanco). Antibiofilm activity of MECs-MDP1 was studied by our novel 'in situ biofilm inhibition zone (IBIZ)' assay, and SEM. Biocompatibility with human dermal fibroblast cells (HDFs) was also evaluated. Molecular docking showed hydrogen bonds as the most interactions between MDP1 and MECs at a reasonable affinity. MECs-MDP1 eradicated the bacteria rapidly by burst release strategy whereas MECs-vanco failed to eradicate them at the same time intervals. Antibiofilm activity of MECs-MDP1 were also proved successfully. As a novel report, molecular docking analysis has demonstrated that MDP1 covers the structure of MECs and also binds to lysozyme with a reasonable affinity, which may explain the inhibition of lysozyme. MECs-MDP1 was also biocompatible with human dermal fibroblast skin cells, which indicates its safe future application. The antibacterial properties of a photocrosslinkable methacrylated chitosan-based hydrogel coated with MDP1 antimicrobial peptide were successfully proved against the most challenging antibiotic-resistant bacteria causing nosocomial wound infections; VRSA and MRSA. Molecular docking analysis revealed that MDP1 interacts with MECs mainly through hydrogen bonds with reasonable binding affinity. MECs-MDP1 hydrogels eradicated the planktonic state of bacteria by burst release of MDP1 in just a few hours whereas MECs-vanco failed to eradicate them. inhibition zone assay showed the anti-biofilm activity of the MECs-MDP1 hydrogel too. These findings emphasize that MECs-MDP1 hydrogel would be suggested as a biocompatible wound-dressing candidate with considerable and rapid antibacterial activities to prevent/eradicate VRSA/MRSA bacterial wound infections.

Independent risk factors predicting eradication failure of standard bismuth quadruple therapy for the first‐line treatment of Helicobacter pylori infection in Taiwan

AbstractBismuth quadruple therapy is recommended as the choice treatment for Helicobacter pylori (H. pylori) infection in areas of either low or high clarithromycin resistance in the Maastricht VI/Florence Consensus Report. However, the optimal treatment duration and drug dosages of bismuth quadruple therapy remain unclear. The study aimed to search the independent risk factors predicting eradication failure of standard bismuth quadruple therapy in the first‐line treatment of H. pylori infection. From July 2014 to June 2022, 274 H. pylori‐infected patients who received 10‐day or 14‐day bismuth quadruple therapy containing a proton pump inhibitor, bismuth, tetracycline and metronidazole were included for the study. Post‐treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 clinical parameters were analyzed by univariate and multivariate analyses. The eradication rates of standard bismuth quadruple therapy were 93.8% and 94.2% by intention‐to‐treat and per‐protocol analyses, respectively. Univariate analysis revealed that patients harboring metronidazole‐resistant strains had a lower eradication rate than those harboring metronidazole‐susceptible strains (88.7% [55/62] vs. 96.7% [148/153]). The other factors including smoking, treatment duration and drug adherence were not significantly associated with cure rate. Multivariate analysis revealed that metronidazole resistance of H. pylori was the only independent risk factors related to eradication failure of standard bismuth quadruple therapy with an odds ratio of 3.8 (95% CI: 1.2–12.4). In conclusion, metronidazole resistance is an independent risk factor predicting eradication failure of standard bismuth quadruple therapy in the first‐line treatment of H. pylori infection. There is no difference in eradication efficacy between 10‐day and 14‐day bismuth quadruple therapies in Taiwan.

Helicobacter pylori Secondary Antibiotic Resistance after One or More Eradication Failure: A Genotypic Stool Analysis Study.

Helicobacter pylori (H. pylori) antibiotic resistance is the leading cause for unsuccessful eradication therapy. After one or more failures, the chance of encountering secondary antibiotic resistance increases. The aim of this study was to characterize genotypic secondary resistance in a cohort of southern Italian H. pylori patients with at least one previous failure. Such patients collected stool samples using a dedicated kit (THD fecal testTM), and bacterial DNA was extracted and amplified using RT-PCR. Resistance to clarithromycin, amoxicillin, metronidazole, levofloxacin, and tetracycline was assessed using a high-resolution melting curve. We enrolled 50 patients. A total of 72% of patients failed one previous antibiotic course, 16% failed two, 10% failed three, and 2% failed four. The rate of secondary antibiotic resistance was 16% for clarithromycin, 18% for metronidazole, 14% for amoxicillin, 14% for levofloxacin, and 2% for tetracycline. Among the eight clarithromycin-resistant patients, five (62.5%) previously received a clarithromycin-based regimen. The same rate was 33.3% (3/9) for metronidazole. The only tetracycline-resistant patient had received Pylera. In conclusion, our data seem to show that, even though secondary resistance is not very high, resistance to clarithromycin could be very likely related to previous exposure to this antibiotic.

Bismuth add-on improves the efficacy of 2-week tegoprazan-based triple therapy for first-line Helicobacter pylori eradication: a real-world evidence study

ABSTRACT Background This study aimed to investigate the efficacy of bismuth added to a 2-week triple therapy consisting of tegoprazan (TPZ), amoxicillin, and clarithromycin for first-line Helicobacter pylori eradication. Research design and methods We reviewed the retrospective data of patients who received a 2-week TPZ-based triple therapy with or without 300 mg bismuth twice daily. The primary endpoint was the H. pylori eradication rate of adding bismuth to the TPZ-based triple regimen (TAC-B group), compared to no bismuth added (TAC group). Results In total, 306 and 256 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. The eradication success rates were significantly higher in the TAC-B group than in the TAC group (ITT, 82.9% vs. 71.8%, p = 0.029; PP, 95.8% vs. 87.5%, p = 0.027, respectively). The adherence rate to the eradication regimen was 100% in the TAC-B group and 97.0% in the TAC group. The adverse drug event rate in the TAC-B group was comparable to that in the TAC group (29.2% vs. 27.3%, p = 0.742). No use of bismuth was significantly associated with eradication failure (p = 0.038). Conclusions The bismuth add-on increased the first-line H. pylori eradication rate of 2-week TPZ-based triple therapy. Clinical trial registration www.clinicaltrials.gov identifier is NCT05453994.

The multicenter real-world report of the efficacies of 14-day esomeprazole-based and rabeprazole-based high-dose dual therapy in first-line Helicobacter pylori eradication in Taiwan

BackgroundHigh-dose dual therapy (HDDT) using proton-pump inhibitors (PPI) and amoxicillin attracted attention for its simplicity and lower adverse event profile. Besides, vonoprazan is not available worldwide. This real-world study aims to compare the efficacy of esomeprazole-based and rabeprazole-based HDDT regimens and to identify clinical factors influencing outcomes. MethodsA retrospective study enrolled 346 Helicobacter pylori-infected naïve patients from January 2016 to August 2023. Patients were assigned to either a 14-day esomeprazole-based HDDT (EA-14; esomeprazole 40 mg t.i.d. and amoxicillin 750 mg q.i.d. for 14 days, n = 173) or a 14-day rabeprazole-based HDDT (RA-14; rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days, n = 173). ResultsFive patients from the EA-14 group and 10 from the RA-14 group were lost to follow-up, resulting in 168 and 163 patients for the per-protocol (PP) analysis, respectively. Eradication rates for the EA-14 and RA-14 groups were 90.2% and 80.9% (P = 0.014) in intention-to-treat (ITT) analysis; and 92.9% and 85.9% (P = 0.039) in PP analysis. Adverse event rates were similar between the two groups (11.9% vs 11.7%, P = 0.944). In multiple logistic regression analysis, age≧60 was associated with eradication failure (P = 0.046) and a trend of significance for smoking (P = 0.060) in the EA-14 group but not in the RA-14 group. A trend of significance was also observed for eradication regimens (EA-14 vs RA-14) (P = 0.071).The antibiotic resistance rates were amoxicillin (2.3%), clarithromycin (14.7%), metronidazole (40.3%), and dual resistance to clarithromycin and metronidazole (7.0%). ConclusionsEsomeprazole-based HDDT achieved over 90% eradication rates but rabeprazole-based HDDT, which failed.

Analysis of Helicobacter pylori resistance in patients with different gastric diseases

Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.

High failure rate of 2-stage revision for the infected total elbow arthroplasty: a single institution’s experience

Despite 2 stage revision being a common treatment for elbow prosthetic joint infection (PJI), failure rates are high. The purpose of this study was to report on a single institution's experience with two stage revisions for elbow PJI and determine risk factors for failed eradication of infection. The secondary purpose was to determine risk factors for needing allograft bone at the second stage of revision in the setting of compromised bone stock. We retrospectively analyzed all two stage revision TEAs performed for infection at a single institution between 2006 and 2020. Data collected included demographics, and treatment course prior to, during and after 2 stage revision. Radiographs obtained after explantation and operative reports were reviewed to evaluate for partial component retention and incomplete cement removal. The primary outcome was failed eradication of infection, defined as the need for repeat surgery to treat infection after the second stage revision. The secondary outcome was the use of allograft for compromised bone stock during the second stage revision. Risk factors for both outcomes were determined. Nineteen patients were included. Seven (37%) patients had either the humeral or ulnar component retained during the 1st stage and ten (53%) had incomplete removal of cement in either the humerus or ulna. Nine (47%) patients had allograft strut used during reimplantation and reconstruction. Nine (47%) patients failed to eradicate the infection after 2 stage revision. Demographic data was similar between the repeat infection and non-repeat infection groups. Six patients (60%) with retained cement failed compared to three patients (33%) with full cement removal (p=0.370). Two patients (29%) with a retained component failed compared to seven patients (58%) with full component removal (p=0.350). Allograft was used less frequently when a well-fixed component or cement was retained, with no patients with a retained component needing allograft compared to nine with complete component removal (p=0.003). Three (30%) patients with retained cement needed allograft, compared to six (67%) patients who had complete cement removal (p=0.179). Nearly half of the patients failed to eradicate infection after 2 stage revision. The data did not demonstrate a clear association between retained cement or implants and risk of recurrent infection. Allograft was used less frequently when a component and cement were retained, possibly serving as a proxy for decreased bone loss during the first stage of revision. Therefore, the unclear benefit of removing well-fixed components and cement need to be carefully considered as it likely leads to compromised bone stock that complicates the second stage of revision.

Association between failed eradication of 7-day triple therapy for Helicobacter pylori and untreated dental caries in Japanese adults

Helicobacter pylori (H. pylori) infection is a cause of gastric disorders and is treated mainly by pharmacotherapy with antimicrobial agents. An association has been reported between dental caries and H. pylori infection. As antimicrobial agents are less effective inside dental caries because of impaired blood circulation, the presence of untreated dental caries (decayed teeth) may influence the success of H. pylori eradication treatment. In this cross-sectional study, we examined whether failed eradication of H. pylori was associated with decayed teeth in Japanese adults. Enrolled were 226 participants who received dental checkups among those treated for eradication of H. pylori at Asahi University Hospital between April 2019 and March 2021. Treatment efficacy was assessed by urea breath test. Eradication failed in 38 participants (17%), decayed teeth in 32 participants (14%), and number of 0.34 teeth per participants. Multivariate logistic regression analyses showed that failed eradication of H. pylori was associated with decayed teeth (presence: odds ratio, 2.672; 95% confidence interval, 1.093–6.531) after adjusting for gender, age, and brushing frequency. These results indicate that failed eradication of H. pylori was associated with decayed teeth and suggest that untreated dental caries may impact treatment for eradication of H. pylori.

A Systematic Review of the Pulmonary Microbiome in Patients with Acute Exacerbation COPD Requiring ICU Admission.

Background: Chronic obstructive pulmonary disease (COPD) is a major health concern. Acute exacerbations (AECOPD) may require intensive care unit (ICU) admission and mechanical ventilation. Acute infections and chronic colonization of the respiratory system are known to precipitate AECOPD. Detailed knowledge of the respiratory microbiome could lead to effective treatment and prevention of exacerbations. Objective: The aim of this review is to summarize the available evidence on the respiratory microbiome of patients with a severe AECOPD requiring mechanical ventilation and intensive care admission. Methods: A systematic literature search was conducted to identify the published papers until January 2023. The collected data were then subjected to qualitative analysis. After the first analysis, a secondary focused review of the most recent publications studying the relationship between microbiome and mortality in AECOPD was performed. Results: Out of 120 screened articles six articles were included in this review. Potentially pathogenic microorganisms (PPMs) were identified in 30% to 72% of the patients with community-acquired bacteria, gram-negative enteric bacilli, Stenotrophomonas and Pseudomonas being the most frequently isolated. During hospitalization, 21% of patients experienced colonization by PPMs. Adequate antimicrobial therapy resulted in the eradication of 77% of the identified PPMs. However, 24% of the bacteria displayed multi-drug resistance leading to prolonged or failure of eradication. Conclusion: PPMs are prevalent in a significant proportion of patients experiencing an AECOPD. The most identified PPMs include community-acquired pathogens and gram-negative enteric bacilli. Notably, no differences in mortality or duration of ventilation were observed between patients with and without isolated PPMs. However, the included studies did not investigate the virome of the patients, which may influence the microbiome and the outcome of infection. Therefore, further research is essential to comprehensively investigate the complete microbial and viral composition of the lower respiratory system in COPD patients admitted to the ICU.

Genetic Determinants in MRSA Carriage and Their Association with Decolonization Outcome

Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. The aim of this study was to explore genetic characteristics that are associated with MRSA decolonization failure. This cohort study was performed in a tertiary care hospital in the Netherlands. Patients with ≥ 1 positive MRSA culture from any site and with available whole -genome sequencing data of the MRSA isolate between 2017 and 2022 were included. Lineages, resistance, and virulence factors were stratified by MRSA decolonization outcome. In total, 56 patients were included: 12/56 (21%) with treatment failure and 44/56 (79%) with successful decolonization (with or without preceding treatment). A significant association was found between ciprofloxacin-resistant lineages and failure of eradication (OR 4.20, 95%CI 1.11–15.96, P = 0.04). Furthermore, livestock-associated MRSA and the major community-associated MRSA lineages ST6-t304 and ST8-t008 were associated with successful eradication treatment or spontaneous clearance. In conclusion, this explorative study showed a higher eradication failure rate in complicated MRSA carriers with ciprofloxacin-resistant MRSA lineages, which are predominantly healthcare-associated. Further studies are warranted to confirm the higher eradication failure risk of ciprofloxacin-resistant lineages, and identify the underlying mechanisms.

The efficacy and safety of vonoprazan in quadruple therapy for Helicobacter pylori eradication: a comparative study.

The efficacy and optimal dose of the new acid-suppressant vonoprazan (VPZ) for quadruple therapy remain uncertain. This study aimed to compare the efficacy and safety of 20 mg VPZ daily (VOD) and 20 mg VPZ twice daily (VTD) with a proton pump inhibitor (PPI) twice daily in quadruple therapy. We retrospectively analyzed the data of 954 patients treated with quadruple therapy to eradicate Helicobacter pylori. Eradication rates and adverse events were compared between the VOD and VTD groups, and between the VOD and PPI groups. Multivariate analysis was conducted to identify the predictors of eradication failure. Eradication was successful in 875 (91.7%) of the 954 patients. The total, initial, and rescue eradication rates in the VOD group were 92.1%, 93.3%, and 77.8%, respectively. In both the crude and multivariate analyses, the VOD group showed eradication rates comparable to those of the VTD and PPI groups (all P > 0.05). Age > 60 years (odds ratio [OR] = 2.165, P = 0.012) and use of rescue therapy (OR = 3.496, P < 0.001) were independent risk factors for eradication failure, whereas VPZ at a low dosing frequency of 20 mg daily was not. A total of 787 patients (82.5%) were followed up (mean follow-up time, 6.7 ± 2.0 months). Compared with the VOD group, the VTD group was more likely to experience adverse events (OR = 2.073, P = 0.035). VPZ at a low dose of 20 mg daily is an effective and safe component of the quadruple therapy for H.pylori eradication.