Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study.

IMPORTANCE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). EXPOSURE: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. MAIN OUTCOME AND MEASURE: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). CONCLUSION AND RELEVANCE: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.

Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. RESULTS: Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. CONCLUSIONS: The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.

Fluoroquinolones and the risk of severe hypoglycaemia among sulphonylurea users: Population-based cohort study.

AIM: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas. MATERIALS AND METHODS: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020). The study cohort included patients initiating either fluoroquinolones or amoxicillin while on sulphonylureas. Using an intent-to-treat exposure definition, we assessed the 30-day risk of severe hypoglycaemia (hospitalization with or death because of hypoglycaemia) associated with fluoroquinolones compared with amoxicillin. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycaemia after 1:5 matching on previous sulphonylurea use and propensity scores. Secondary analyses were stratified by demographics and glycated haemoglobin. RESULTS: Overall, 143 417 patients initiated fluoroquinolones (n = 13 123) or amoxicillin (n = 130 294) while on sulphonylureas. Compared with amoxicillin, fluoroquinolones were not associated with the risk of severe hypoglycaemia (HR, 1.17; 95% CI, 0.91-1.50). Fluoroquinolones were associated with an increased risk in patients <65 years (HR, 2.90; 95% CI, 1.41-5.97) but not in those ≥65 years (HR, 1.03; 95% CI, 0.79-1.35) in stratified analyses. There was no evidence of effect modification by sex or glycated haemoglobin. CONCLUSIONS: In patients using second-generation sulphonylureas, fluoroquinolones were not associated with an increased risk of severe hypoglycaemia compared with amoxicillin. An increased risk among younger adults is possible.

Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.

OBJECTIVE: To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. METHODS: The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27. RESULTS: Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B. CONCLUSIONS: Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration. Clinical Trial Number: Iranian Registry of Clinical Trials: IRCT20221207056738N1.

Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Antibiomania: A Case Report of a Manic Episode Potentially Induced by the Interaction of Clarithromycin and Amoxicillin during H. Pylori Eradication Therapy.

Antibiomanic episodes, or as the DSM-5 refers to them, drug-induced manic episodes, pose a clinical challenge that is still poorly understood. There is insufficient information on the most common clinical presentation, patient profile, or underlying aetiopathogenic mechanisms. We present the clinical case of a 67-year-old woman who, after starting treatment (clarithromycin and amoxicillin) for the eradication of Helicobacter pylori, bacteria presented with a brief manic episode, which resolved after withdrawal of both drugs and with antipsychotic treatment. The possible interaction of both drugs, as GABA antagonists, in the generation of such episodes is discussed, and the clinical importance of such episodes in psychiatric emergency departments and liaison and interconsultation psychiatry, is highlighted.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial.

BACKGROUND: A cure for Helicobacter pylori (H. pylori) remains a problem of global concern. The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide. Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy, tolerability and cost. The most common sequential therapy consists of a dual therapy [proton-pump inhibitors (PPIs) and amoxicillin] for the first period (5 to 7 d), followed by a triple therapy for the second period (PPI, clarithromycin and metronidazole). PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics, hence the idea of using new generation molecules. AIM: To compare an optimized sequential therapy with the standard non-bismuth quadruple therapies of 10 and 14 d, in terms of efficacy, incidence of adverse effects (AEs) and cost. METHODS: This open-label prospective study randomized 328 patients with confirmed H. pylori infection into three groups (1:1:1): The first group received quadruple therapy consisting of twice-daily (bid) omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg for 10 d (QT-10), the second group received a 14 d quadruple therapy following the same regimen (QT-14), and the third group received an optimized sequential therapy consisting of bid rabeprazole 20 mg plus amoxicillin 1 g for 7 d, followed by bid rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 7 d (OST-14). AEs were recorded throughout the study, and the H. pylori eradication rate was determined 4 to 6 wk after the end of treatment, using the 13C urea breath test. RESULTS: In the intention-to-treat and per-protocol analysis, the eradication rate was higher in the OST-14 group compared to the QT-10 group: (93.5%, 85.5% P = 0.04) and (96.2%, 89.5% P = 0.03) respectively. However, there was no statistically significant difference in eradication rates between the OST-14 and QT-14 groups: (93.5%, 91.8% P = 0.34) and (96.2%, 94.4% P = 0.35), respectively. The overall incidence of AEs was significantly lower in the OST-14 group (P = 0.01). Furthermore, OST-14 was the most cost-effective among the three groups. CONCLUSION: The optimized 14-d sequential therapy is a safe and effective alternative. Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study.

BACKGROUND & AIMS: Previous studies confirm vonoprazan-amoxicillin effectiveness for Helicobacter pylori. This study aims to investigate vonoprazan with varying amoxicillin dose and duration. METHODS: This multicenter, prospective, randomized controlled, noninferiority trial enrolled patients with treatment naive H pylori infection from 5 clinical centers. Eligible participants were randomly assigned to H-VA-10 (vonoprazan 20 mg twice a day (b.i.d.) + amoxicillin 750 mg 4 times a day, 10 days), L-VA-10 (vonoprazan 20 mg b.i.d. + amoxicillin 1000 mg b.i.d, 10 days), and H-VA-14 (vonoprazan 20 mg b.i.d + amoxicillin 750 mg 4 times a day, 14 days) in a 1:1:1 ratio. The eradication rate was assessed using the 13C-urea breath test at least 28 days after treatment. RESULTS: Of the 623 eligible patients, 516 patients were randomized. In both the intention-to-treat and per-protocol analyses, eradication rates were comparable between H-VA-10 and H-VA-14 groups (86.6% vs 89.5% and 90.9% vs 94.5%, P = .021 and .013 for noninferiority, respectively). However, eradication rates were significantly lower in the L-VA-10 group than the H-VA-14 group (79.7% vs 89.5% and 82.0% vs 94.5%, P = .488 and .759, respectively). Rates of study withdrawal, loss to follow-up, and adverse events were similar across study groups. CONCLUSIONS: H-VA-10 and H-VA-14 regimens provide satisfactory efficacy for H pylori infection, and the L-VA-10 regimen was inferior. CLINICALTRIALS: gov number: NCT05719831.

Clinical Study on the Eradication of Helicobacter pylori by Vonoprazan Combined with Amoxicillin for 10-Day Dual Therapy.

Vonoprazan holds significant research promise for Helicobacter pylori eradication, with the goal of determining the most effective drug regimen. In this study, H. pylori patients (426) were enrolled and randomized into 3 groups: an EA14 group (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days), a VA14 group (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), and a VA10 group (20 mg of vonoprazan bid and 1000 mg of amoxicillin tid for 10 days). Key outcomes encompassed the H. pylori eradication rate, patient adverse effects, and compliance. In the EA14, VA14, and VA10 groups, H. pylori eradication rates were 89.4%, 90.1%, and 88.7% in intention-to-treat analysis, and 94.2%, 94.4%, and 94.6% in per-protocol analysis, respectively. Adverse events incidences were 14.8%, 12.7%, and 5.6%, while compliance rates were 88.7%, 90.9%, and 95.8%, respectively. Notably, the VA10 regimen demonstrated comparable H. pylori eradication rates, adverse effect incidences, and compliance levels to the EA14 and VA14 regimens.

Vonoprazan-amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Recently, vonoprazan-amoxicillin (VA) dual therapy has been reported as a promising approach for Helicobacter pylori (H. pylori) eradication. However, the effects of VA therapy versus bismuth-containing quadruple therapy (BQT) on H. pylori eradication remains unclear. The objective of this meta-analysis was to compare the effects of VA dual therapy with BQT for H. pylori eradication. METHODS: A comprehensive search of the literature was conducted from the beginning to September 2023, utilizing PubMed, Embase, the Cochrane Library and Web of Science database. A random-effects model was used to perform a meta-analysis to determine the pooled relative risk (RR) with 95% confidence intervals (CIs). Moreover, trial sequential analysis (TSA) was conducted to evaluate the conclusiveness of the H. pylori eradication rate. RESULTS: Six randomized controlled trials (RCTs) with 1233 patients were included. The VA therapy has similar eradication rate (ITT analysis: 87% vs. 85.7%, RR = 1.01, 95% CI: 0.93-1.09, p = 0.84; PP analysis: 92.5% vs. 93.2%, RR = 1.00, 95% CI: 0.94-1.06, p = 0.97) and compliance (RR = 1.01, 95% CI: 0.99-1.03, p = 0.32) compared to BQT. The VA therapy group had a significantly lower incidence of total adverse events than the BQT group (16.3% vs. 40.0%, RR = 0.45, 95% CI: 0.37-0.55, p < 0.00001). The TSA result showed that the effect was conclusive. CONCLUSIONS: Current evidence indicated that VA therapy is just as successful as BQT in eliminating H. pylori, yet it has fewer adverse events and similar compliance.

Antibiomania: A Case Report of a Manic Episode Potentially Induced by the Interaction of Clarithromycin and Amoxicillin during H. Pylori Eradication Therapy

Antibiomanic episodes, or as the DSM-5 refers to them, drug-induced manic episodes, pose a clinical challenge that is still poorly understood. There is insufficient information on the most common clinical presentation, patient profile, or underlying aetiopathogenic mechanisms. We present the clinical case of a 67-year-old woman who, after starting treatment (clarithromycin and amoxicillin) for the eradication of Helicobacter pylori, bacteria presented with a brief manic episode, which resolved after withdrawal of both drugs and with antipsychotic treatment. The possible interaction of both drugs, as GABA antagonists, in the generation of such episodes is discussed, and the clinical importance of such episodes in psychiatric emergency departments and liaison and interconsultation psychiatry, is highlighted. (AU)

The Efficacy and Safety of Regimens for Helicobacter pylori Eradication Treatment in China: A Systemic Review and Network Meta-Analysis.

BACKGROUND: With Helicobacter pylori's increasing antibiotic resistance, evidence of more effective treatments is lacking in China, where H. pylori prevalence is nearly 50%. Thus, we performed a network meta-analysis to compare therapeutic regimens. METHODS: Data extracted from eligible randomized controlled trials from January 2000 to September 2021 were entered into a Bayesian hierarchical random-effects model to evaluate the efficacy and safety of H. pylori eradication regimens. RESULTS: This study included 101 trials involving 21,745 patients. Vonoprazan-bismuth-containing quadruple therapy (VBQT) ranked the highest [surfaces under cumulative ranking curve (SUCRA), 83.64%], followed by high-dose amoxicillin dual therapy (HDDT) [SUCRA, 79.70%, odds ratio (OR)=1.31, 95% credible interval (CrI) (0.36, 4.72)] and proton pump inhibitor-based bismuth-containing quadruple therapy (BQT) [SUCRA, 63.59%, OR=1.59, 95% CrI (0.48, 5.24)]. HDDT [OR=2.47, 95% CrI (1.51, 4.06)], BQT [OR=2.04, 95% CrI (1.69, 2.47)], concomitant quadruple nonbismuth therapy (CT) [OR=1.93, 95% CrI (1.19, 3.15)], and sequential therapy (ST) [OR=1.86, 95% CrI (1.50, 2.32)] had higher eradication rates than standard triple therapy (TT). ST (SUCRA, 82.52%) and VBQT (SUCRA, 83.89%) had the highest eradication rate before and after 2010 in the effectiveness ranking, respectively. Furthermore, the H. pylori eradication rate of patients receiving 14-day BQT treatment was higher than that of 10-day BQT regimen [OR=2.55, 95% CI (1.84, 3.53)] and 7-day BQT regimen [OR=3.64, 95% CI (2.64, 5.01)]. CONCLUSIONS: The TT regimen was not an optimal choice in China for H. pylori eradication; VBQT, HDDT, and BQT showed better efficacy. After 2010, there is a trend toward significance that VBQT provided a higher H. pylori eradication rate in China, but with only 1 randomized controlled trial. Thus, more supportive real-world data are needed to confirm its effectiveness.

Development of a Pipeline for Removing Allergy Labels in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Penicillin allergy is reported by 10% to 20 % of patients, but when evaluated only 1% to 2% may have a true allergy. Patients undergoing hematopoietic stem cell transplantation (HSCT) have a high likelihood of requiring beta-lactam antibiotics due to increased infection risk, which can be limited by a penicillin allergy label. When a penicillin allergy is recorded, alternatives are needed, including more expensive broader-spectrum antibiotics, with increases in drug-resistant bacteria, longer hospital stays, higher expenditures, and increases in nosocomial infections, such as Clostridium difficile colitis. This group of patients already undergoes extensive pretreatment testing and would especially benefit from allergy delabeling. This study aimed to develop a self-sustaining, low-cost pipeline between an HSCT clinic and an allergy clinic to identify and successfully delabel low-risk patients who endorse an allergy to penicillin, amoxicillin, amoxicillin-clavulanate, piperacillin-tazobactam, or ampicillin before admission to the hospital. We developed a survey to triage allergy risk, identified key stakeholders in building the pipeline, and underwent 4 plan, do, study, act (PDSA) cycles. Changes were made in each of the PDSA cycles to minimize cost and uncompensated provider time, as well as to increase patient retention throughout the pipeline by increasing appointment availability and decreasing reliance on patients to independently progress through the pathway. Of the 410 patients with planned HSCT who were screened over 11 months, 89 (21.7%) were listed as having a penicillin and/or beta lactam allergy. All but 1 (66 of 67; 98.5%) of the participants completed the survey accurately when confirmed by an allergist, and the survey was 100% accurate in predicting delabeling success in low-risk patients. Of eligible patients, 43.8% (n = 39) were successfully delabeled before their transplant date, and 97.4% of these (n = 38) have undergone HSCT to date. This pipeline is maintained by approximately 5 hours of work per week (1 hour of allergy physician time, 4 hours of nurse and/or clinical coordinator time), with no other direct costs. There is an estimated direct savings of at least $1914.93 per patient delabeled. We successfully designed and implemented a pipeline between the HSCT clinic and the allergy clinic as a quality improvement initiative to identify and address high rates of reported beta-lactam allergies. We identified and addressed patient-based factors, logistical, temporal, and financial barriers that impacted patient retention and sustainability. This model is expected to yield significant and sustained cost savings for the healthcare system as well as to improve patient outcomes, and this hypothesis is currently undergoing formal analysis. We anticipate that this model can be used to create a similar pipeline in other healthcare systems for HSCT recipients, as well as patients in other clinical settings, such as oncology and chimeric antigen receptor T cell therapy.

Inpatient allergy delabeling of pediatric patients with low-risk penicillin allergy status through direct oral amoxicillin challenge.

Background: Less than 5% of children who report penicillin allergy have clinically pertinent type 1 immunoglobulin E mediated hypersensitivity reaction by using direct oral amoxicillin challenge. Several pathways have been developed to delabel penicillin allergy by using direct oral amoxicillin challenge, mostly in the outpatient settings, but there is relative scarcity on published outcomes of these pathways, especially in the inpatient pediatric settings. Objective: This study aimed to evaluate the performance of an institutionally derived inpatient penicillin allergy screening tool. Methods: Patients were stratified into three penicillin allergy risk categories by using an institutional screening questionnaire. Patients with a no-risk status were delabeled without challenge testing. Patients with low-risk status underwent direct graded oral amoxicillin challenge and delabeled based on their response. Patients with high-risk status were referred to allergy service. Results: Ninety-two patients were identified with penicillin allergy. Forty of the 92 patients (43%) were screened. Of the 40 patients screened, 6 (15%) were identified as no risk, 28 (70%) were identified as low risk, and 6 (15%) were identified as high risk. Twenty-four of the 28 patients at low risk (86%) were eligible for direct amoxicillin oral challenge. Seventeen of the 24 (71%) consented to oral challenge but only 12 (71%) underwent direct amoxicillin oral challenge. Eleven of the 12 who underwent oral challenge (92%) were successfully delabeled. Five of the six patients at no risk (83%) were successfully delabeled. Three of the six patients at high risk (50%) were referred for further allergy evaluation. Overall, 16 of the 40 patients screened (40%) were successfully delabeled. Conclusion: In this small pediatric inpatient study, our institutional risk stratification screening tool identified patients at low risk for penicillin allergy and direct graded oral amoxicillin challenge was safely administered to delabel penicillin allergy in these patients.Clinical trial NCT05020327, www.clinicaltrials.gov.

Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori infection: rationale and design of an open-label, multicenter, randomized controlled trial.

BACKGROUND: Owing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance. METHODS: This randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses. DISCUSSION: This study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do .

Different antibiotic treatments for group A streptococcal pharyngitis.

BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2021. OBJECTIVES: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures recommended by Cochrane. We assessed the risk of bias in the included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results. MAIN RESULTS: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both, heterogeneity, and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials, 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials, 1660 participants; very low-certainty evidence). Based on an analysis of evaluable participants, we are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials, 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials, 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79 (95% CI 0.57 to 1.09; 6 trials, 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials, 802 participants; low-certainty evidence). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial, 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29 (95% CI 0.11 to 0.73; 1 trial, 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial, 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial, 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials, 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better at preventing serious but rare complications. AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high.