Skeletal Muscle Proteome Modifications following Antibiotic-Induced Microbial Disturbances in Cancer Cachexia.

Cancer cachexia is an involuntary loss of body weight, mostly of skeletal muscle. Previous research favors the existence of a microbiota-muscle crosstalk, so the aim of the study was to evaluate the impact of microbiota alterations induced by antibiotics on skeletal muscle proteins expression. Skeletal muscle proteome changes were investigated in control (CT) or C26 cachectic mice (C26) with or without antibiotic treatment (CT-ATB or C26-ATB, n = 8 per group). Muscle protein extracts were divided into a sarcoplasmic and myofibrillar fraction and then underwent label-free liquid chromatography separation, mass spectrometry analysis, Mascot protein identification, and METASCAPE platform data analysis. In C26 mice, the atrogen mafbx expression was 353% higher than CT mice and 42.3% higher than C26-ATB mice. No effect on the muscle protein synthesis was observed. Proteomic analyses revealed a strong effect of antibiotics on skeletal muscle proteome outside of cachexia, with adaptative processes involved in protein folding, growth, energy metabolism, and muscle contraction. In C26-ATB mice, proteome adaptations observed in CT-ATB mice were blunted. Differentially expressed proteins were involved in other processes like glucose metabolism, oxidative stress response, and proteolysis. This study confirms the existence of a microbiota-muscle axis, with a muscle response after antibiotics that varies depending on whether cachexia is present.

Probiotics and Antibiotic-Induced Microbial Aberrations in Children: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Probiotics are often considered in children to prevent antibiotic-associated diarrhea. However, the underlying mechanistic effects and impact of probiotics on antibiotic-induced microbiota changes are not well understood. Objective: To investigate the effects of a multispecies probiotic on the gut microbiota composition in children receiving antibiotics. Design, Setting, and Participants: This is a secondary analysis of a randomized, quadruple-blind, placebo-controlled clinical trial from February 1, 2018, to May 31, 2021, including 350 children receiving broad-spectrum antibiotics in the inpatient and outpatient settings. Patients were followed up until 1 month after the intervention period. Fecal samples and data were analyzed between September 1, 2022, and February 28, 2023. Eligibility criteria included 3 months to 18 years of age and recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics. In total, 646 eligible patients were approached and 350 participated in the trial. Intervention: Participants were randomly assigned to receive daily placebo or a multispecies probiotic formulation consisting of 8 strains from 5 different genera during antibiotic treatment and for 7 days afterward. Main Outcomes and Measures: Fecal stool samples were collected at 4 predefined times: (1) inclusion, (2) last day of antibiotic use, (3) last day of the study intervention, and (4) 1 month after intervention. Microbiota analysis was performed by 16S ribosomal RNA gene sequencing. Results: A total of 350 children were randomized and collected stool samples from 88 were eligible for the microbiota analysis (54 boys and 34 girls; mean [SD] age, 47.09 [55.64] months). Alpha diversity did not significantly differ between groups at the first 3 times. Shannon diversity (mean [SD], 3.56 [0.75] vs 3.09 [1.00]; P = .02) and inverse Simpson diversity (mean [SD], 3.75 [95% CI, 1.66-5.82] vs -1.31 [95% CI, -3.17 to 0.53]; P = 1 × 10-4) indices were higher in the placebo group compared with the probiotic group 1 month after intervention. Beta diversity was not significantly different at any of the times. Three of 5 supplemented genera had higher relative abundance during probiotic supplementation, but this difference had disappeared after 1 month. Conclusions and Relevance: The studied probiotic mixture had minor and transient effects on the microbiota composition during and after antibiotic treatment. Further research is needed to understand their working mechanisms in manipulating the microbiome and preventing antibiotic-associated dysbiosis and adverse effects such as antibiotic-associated diarrhea. Trial Registration: ClinicalTrials.gov Identifier: NCT03334604.

Risk of emergency hospital admission related to adverse events after antibiotic treatment in adults with a common infection: impact of COVID-19 and derivation and validation of risk prediction models.

BACKGROUND: With the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common infections is crucial. This study aims to examines the changes in incidence rates of AEs during the COVID-19 pandemic and predict AE risk following antibiotic prescriptions for common infections, considering their previous antibiotic exposure and other long-term clinical conditions. METHODS: With the approval of NHS England, we used OpenSAFELY platform and analysed electronic health records from patients aged 18-110, prescribed antibiotics for urinary tract infection (UTI), lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), sinusitis, otitis externa, and otitis media between January 2019 and June 2023. We evaluated the temporal trends in the incidence rate of AEs for each infection, analysing monthly changes over time. The survival probability of emergency AE hospitalisation was estimated in each COVID-19 period (period 1: 1 January 2019 to 25 March 2020, period 2: 26 March 2020 to 8 March 2021, period 3: 9 March 2021 to 30 June 2023) using the Kaplan-Meier approach. Prognostic models, using Cox proportional hazards regression, were developed and validated to predict AE risk within 30 days post-prescription using the records in Period 1. RESULTS: Out of 9.4 million patients who received antibiotics, 0.6% of UTI, 0.3% of URTI, and 0.5% of LRTI patients experienced AEs. UTI and LRTI patients demonstrated a higher risk of AEs, with a noted increase in AE incidence during the COVID-19 pandemic. Higher comorbidity and recent antibiotic use emerged as significant AE predictors. The developed models exhibited good calibration and discrimination, especially for UTIs and LRTIs, with a C-statistic above 0.70. CONCLUSIONS: The study reveals a variable incidence of AEs post-antibiotic treatment for common infections, with UTI and LRTI patients facing higher risks. AE risks varied between infections and COVID-19 periods. These findings underscore the necessity for cautious antibiotic prescribing and call for further exploration into the intricate dynamics between antibiotic use, AEs, and the pandemic.

Managing COPD exacerbations in primary care.

Chronic obstructive pulmonary disease (COPD) is a common but underdiagnosed lung condition that is frequently managed inappropriately. It impacts poorest communities most, where health inequalities are greatest. New acute symptoms of breathlessness, cough, sputum production and wheeze should prompt clinical suspicion of underlying COPD in someone who is a current or ex-smoker (or has exposure to other risk factors) and be followed by referral for quality-assured spirometry once recovered. Management of COPD exacerbations in primary care includes use of short-acting bronchodilators if mild, and antibiotics and a short course of oral prednisolone if moderate/severe. Hospital at home schemes are safe and effective and should be considered for some patients exacerbating in the community; these are increasingly supported by remote monitoring ('virtual wards'). New or worsening hypoxia is an indication for hospital admission and therefore oxygen saturation monitoring is an important part of exacerbation management; clinicians should be aware of patient safety alerts around use of pulse oximeters. Exacerbations drive poor health status and lung function decline and therefore asking about exacerbation frequency at planned reviews and taking action to reduce these is an important part of long-term COPD care. An exacerbation is an opportunity to ensure that fundamentals of good care are addressed. Patients should be supported to understand and act on exacerbations through a supported self-management plan; prompt treatment is beneficial but should be balanced by careful antibiotic and corticosteroid stewardship. COPD rescue packs on repeat prescription are not recommended.

An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial-an update to the published protocol.

This article reports an update to the protocol of the IMASOY trial, which was prospectively registered on clinicaltrials.gov (NCT04110340) in October 2019.

Real-world evidence of a novel tetravalent immunoglobulin Y effectiveness and safety in patients with the refractory Helicobacter pylori infection.

BACKGROUND: Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection. METHODS: Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting13. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions. RESULTS: Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of 13C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period. CONCLUSIONS: Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.

Determination of a vancomycin nephrotoxicity threshold and assessment of target attainment in hematology patients.

An area-under-the-curve (AUC24)-based approach is recommended to guide vancomycin therapeutic drug monitoring (TDM), yet trough concentrations are still commonly used despite associated risks. A definitive toxicity target is lacking, which is important for hematology patients who have a higher risk of nephrotoxicity. The aims were to (1) assess the impact of trough-based TDM on acute kidney injury (AKI) incidence, (2) establish a vancomycin nephrotoxicity threshold, and (3) evaluate the proportion of hematology patients achieving vancomycin therapeutic targets. Retrospective data was collected from 100 adult patients with a hematological malignancy or aplastic anemia who received vancomycin between April 2020 and January 2021. AKI occurrence was determined based on serum creatinine concentrations, and individual pharmacokinetic parameters were estimated using a Bayesian approach. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pharmacokinetic indices to predict AKI occurrence. The proportion of patients who achieved target vancomycin exposure was evaluated based on an AUC24/MIC ≥400 and the determined toxicity threshold. The incidence of AKI was 37%. ROC curve analysis indicated a maximum AUC24 of 644 mg.h/L over the treatment period was an important predictor of AKI. By Day 4 of treatment, 29% of treatment courses had supratherapeutic vancomycin exposure, with only 62% of courses achieving AUC24 targets. The identified toxicity threshold supports an AUC24 target range of 400-650 mg.h/L, assuming an MIC of 1 mg/L, to optimize vancomycin efficacy and minimize toxicity. This study highlights high rates of AKI in this population and emphasizes the importance of transitioning from trough-based TDM to an AUC-based approach to improve clinical outcomes.

Adverse events during intravenous fosfomycin therapy in a real-life scenario. Risk factors and the potential role of therapeutic drug monitoring.

BACKGROUND: Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting. PATIENTS AND METHODS: Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated. RESULTS: Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0-7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RRadjusted 1.59 (95%CI:1.09-2.31), 1.46 (95%CI:1.03-2.07) and 1.73 (95%CI:1.27-2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44-0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39-0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css. CONCLUSIONS: We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs. KEY POINTS: Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.

Bile acids and the gut microbiome are involved in the hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA).

Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia.

Low-dose or high-dose amoxicillin in vonoprazan-based dual therapy for Helicobacter pylori eradication? A systematic review and meta-analysis.

BACKGROUND: The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low- and high-dose amoxicillin in vonoprazan-amoxicillin dual therapy. MATERIALS AND METHODS: A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan-amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented. RESULTS: Eighteen studies with 12 low-dose amoxicillin (VLA) and 13 high-dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention-to-treat and per-protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention-to-treat (76.9% vs 81.4%, p = 0.337) and per-protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups. CONCLUSION: VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan-amoxicillin treatment.

[Penicillin allergy-Truth or duty?] / Penicillinallergie ­ Wahrheit oder Pflicht?

The beta-lactam antibiotics are some of the safest and best-tolerated antibiotic agents; however, many patients have reported allergies against penicillin. All beta-lactam antibiotics are only restrictively prescribed for these patients and alternative antibiotics are increasingly given, which carries the risk of negative clinical results and socioeconomic sequelae; however, over 95% of patients who reported an allergy to penicillin show a negative result in the allergy tests for penicillin and this antibiotic can safely be prescribed. The use of sensitive and specific instruments for identification of false penicillin allergies should be an important topic within the framework of antibiotic stewardship. Anesthesists can play a central role in the reduction of the enormous individual and public health burden associated with the classification of penicillin allergy by taking an appropriate medical history and a risk stratification for the identification of patients with a penicillin allergy. This overview article presents a possible delabelling algorithm within the framework of the clarification of a beta-lactam antibiotic allergy. The focus is on a structured allergy anamnesis using the penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR) and treatment required for allergy episode (PEN-FAST) score.

Peptic ulcer disease.

Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic. The clinical presentation is usually uncomplicated, with peptic ulcer disease management based on eradicating H pylori if present, the use of acid-suppressing medications-most often proton pump inhibitors (PPIs)-or addressing complications, such as with early endoscopy and high-dose PPIs for peptic ulcer bleeding. Special considerations apply to patients on antiplatelet and antithrombotic agents. H pylori treatment has evolved, with the choice of regimen dictated by local antibiotic resistance patterns. Indications for primary and secondary prophylaxis vary across societies; most suggest PPIs for patients at highest risk of developing a peptic ulcer, its complications, or its recurrence. Additional research areas include the use of potassium-competitive acid blockers and H pylori vaccination; the optimal approach for patients at risk of stress ulcer bleeding requires more robust determinations of optimal patient selection and treatment selection, if any. Appropriate continuation of PPI use outweighs most possible side-effects if given for approved indications, while de-prescribing should be trialled when a definitive indication is no longer present.

Severe hepatic cholestasis after treatment with amoxicillin/clavulanic acid.

Amoxicillin/clavulanate is a commonly used antibiotic. Though relatively rare, amoxicillin/clavulanate carries the highest incidence of idiosyncratic drug-induced liver disease. This case report presents an 80-year-old woman treated for simple respiratory tract infection with amoxicillin/clavulanate who was subsequently hospitalized with malaise and icterus and a biochemical cholestatic pattern with high alkaline phosphatase and bilirubin. Diagnostically challenging, ultimately, liver biopsy revealed drug-induced liver injury with a fatal course after attempt of supportive, symptomatic treatment.

Antibiotic treatment to prevent pediatric acute otitis media infectious complications: A meta-analysis.

BACKGROUND: Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of antibiotics versus watchful waiting have focused on symptom resolution and RCTs, limiting the assessment of serious, rare complications. We sought to evaluate these complications by including observational studies. METHODS: RCTs and observational studies that compared antibiotics to placebo or watchful waiting for pediatric clinician diagnosed AOM were identified [PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, and Web of Science] and reviewed for meta-analysis. Two reviewers independently extracted study characteristics, patient characteristics, and outcomes. We assessed publication bias, study bias with ROBINS-1 and RoB-2 and used random-effects models to assess treatment effects. RESULTS: 24 studies were included. Antibiotics decreased the risk of acute mastoiditis [incidence 0.02%, RR 0.48, 95% CI 0.40-0.59; NNT 5,368]. This protective effect may be underestimated because of misclassification of non-suppurative conditions as AOM. Intracranial complications remained too rare to assess. Antibiotics markedly increased the risk of adverse effects [incidence 10.5%, RR 1.49, 1.27-1.73; NNH 23]. Studies used non-specific criteria for acute mastoiditis, potentially underestimating treatment effects. CONCLUSIONS: Prompt antibiotic therapy reduces the risk for some AOM complications. The NNT to prevent serious, rare complications is high, while the NNH is relatively low. Large-scale population-based observational studies using real-world datasets with validated measures of severe complications are needed to improve understanding of risk factors for serious AOM complications, facilitate more selective antibiotic therapy, and optimize individual outcomes and public health.

Evaluating a Modified Use of the Kaiser Permanente Early-onset Sepsis Risk Calculator to Reduce Antibiotic Exposure: a Retrospective Study.

BACKGROUND: Early-onset neonatal sepsis (EONS) remains an important disease entity due to very serious adverse outcomes if left untreated. Lack of diagnostic tools in identifying healthy from diseased neonates, and clinicians' fear of the missing positive-culture sepsis babies, or babies with clinical sepsis have led to overtreating and unnecessary antibiotic exposure. Kaiser Permanente EONS risk calculator is an internally validated tool that can predict EONS. This sepsis risk calculator (SRC) classifies neonates into three subgroups: (1) ill-appearing, (2) equivocal and (3) well-appearing. We propose a modification to this tool that aims to use it solely for well-appearing babies. This modification represents a more conservative approach to decrease antibiotic exposure and offers an alternative for those hesitant to fully implement this tool. METHODS: This is a dual-centre retrospective study where data were extracted from the electronic medical records. Our primary outcome was to validate the modified use of the SRC with a two-by-two table. Specificity, negative predictive value and expected antibiotic reduction were used to evaluate the tool's feasibility. RESULT: Among 770 babies suspected of EONS, the feasibility of the modified use was tested. The expected antibiotic exposure reduction rate on the modification was 40.4% overall. The proposed modification resulted in a specificity and negative predictive value of 99.28% (95% CI: 97.92% to 99.85%) and 99.5% (95% CI: 99% to 99.8%), respectively. CONCLUSION: The modified use of the sepsis risk calculator has shown that it can safely reduce antibiotic exposure in well-appearing babies. The modified use is used as a 'rule out' test that can identify very low risk of EONS babies, and safely minimise antibiotic exposure. Further prospective studies are needed to examine the efficacy of this use, and quality improvement projects are required to evaluate its applicability in different clinical settings.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05870683.

When Should Patients at the End of Life Get Antimicrobials?

Although antimicrobial medications are commonly prescribed to patients at the end of life (EOL), clinicians might not discuss the benefits and harms of antimicrobials with their patients in the advance care planning process. This commentary on a case discusses challenges and strategies in antimicrobial decision making for patients at the EOL. As antimicrobial use can harm some patients, and as antimicrobial resistance remains an urgent public health issue, this article advocates for ethical reasoning to guide antimicrobial decision making for patients at the EOL.

[Supposed allergy to beta-lactam antibiotics: is it time for reflections and actions?] / Presunta allergia agli antibiotici beta-lattamici: è tempo di riflessioni e azioni?

The excessive, often unconfirmed suspicions of beta-lactam allergy affect up to 10% of the general population, improperly denying a significant percentage of individuals the opportunity to be treated with first-line antibiotics, forcing clinicians to resort to second-line choices that are not always equally effective, safe, and contribute to the increase in antibiotic resistance. Pediatricians and general practitioners can play a crucial role in recognizing and addressing weak suspicions of beta-lactam allergy, actively participating in removing the "label" of being allergic. The article, based on Who AWaRe Manual recommendations, presents current evidence on the issue with practical guidance to promote accurate interpretation and management of an overestimated problem that does not encourage a culture of optimal and prudent antibiotic use.