Helicobacter pylori eradication rates using clarithromycin and levofloxacin-based regimens in patients with previous COVID-19 treatment: a randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different gastric maliganacies. It has been also correlated to extraintestinal diseases, including refractory iron deficiency anaemia, vitamin B12 deficiency, and immune thrombocytopenic purpura. The misuse of antibiotics during the coronavirus diseases 2019 (COVID-19) pandemic time can affect H. pylori eradication rates. Our aim was to compare the efficacy of clarithromycin versus levofloxacin-based regimens for H. pylori treatment in naïve patients after the COVID-19 pandemic misuse of antibiotics. METHODS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were recruited. Patients were randomized to receive either clarithromycin, esomeprazole, and amoxicillin, or levofloxacin, esomeprazole, and amoxicillin. RESULTS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were included, 135 in each arm. In total, 19 patients in the clarithromycin group and 18 patients in the levofloxacin group stopped treatment after 2-4 days because of side effects or were lost for follow-up. Finally, 116 subjects in the clarithromycin group and 117 in the levofloxacin group were assessed. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: group I, 55.56% and 64.66%; and Group II, 64.44% and 74.36% respectively (p = 0.11). CONCLUSION: As COVID-19 pandemic has moved forward fast, high resistance rates of H. pylori to both clarithromycin and levofloxacin were developed after less than two years from the start of the pandemic. Molecular & genetic testing is highly recommended to identify antimicrobial resistance patterns. Strategies to prevent antibiotic misuse in the treatment of COVID-19 are needed to prevent more antibiotic resistance. TRIAL REGISTRATION: The trial was registered on Clinicaltrials.gov NCT05035186. Date of registration is 2-09-2021.

Impact of COVID-19 on antibiotic prescriptions for Brazilian children.

The COVID-19 brought a new model of sanitary behavior (social distancing, etc.) that may have reduced the transmissibility of respiratory diseases, reflecting in the number of antibiotic prescriptions. This study evaluated antibiotic prescriptions for children throughout Brazil, between 2014 and 2021. An interrupted time series was conducted to assess variations in antibiotic consumption by the 1-12-year-old children. Joinpoint regression was used to assess the monthly variations. 86 million prescriptions were evaluated. On average, there was a 54% reduction in prescriptions during the pandemic. Amoxicillin showed a reduction of 65%. Joinpoint regression showed that the pandemic altered the prescription growth curve, changing the trend to a 22% drop per month. The new sanitary behavior showed us that it is possible, decreasing the use of antibiotics, to control the children's respiratory health.

Geographic distribution of antibiotic resistance of Helicobacter pylori: A study in Bulgaria.

Prevalence of antibiotic resistant Helicobacter pylori was compared between 50 patients living outside the capital city and 50 matched pairs of capital city residents (CCRs). H. pylori isolates from 2018 to 2022 were included. Resistance rates in CCRs and those living elsewhere were 4.0 and 6.0% to amoxicillin, 48.0 and 42.0% to metronidazole, 30 and 30% to clarithromycin, and 4.0 and 4.0% to tetracycline, respectively. Levofloxacin resistance was higher (38.0%) in the capital city vs 20.0% (P = 0.047) in the country. Odd ratio for levofloxacin resistance between pair-matched groups was 2.45 (95% CI, OR 1.0-6.02, P value = 0.05) and relative risk for fluoroquinolone resistance was 1.90 (95% CI for RR 0.98-3.67) for CCRs vs residents in other regions. Resistance rates to levofloxacin and clarithromycin were worryingly high in our study, most probably due to the high quinolone consumption (2.86 DDD/day in 2017) in Bulgaria and the increase in macrolide, lincosamide and streptogramin consumption, especially of azithromycin, by >42% with the start of COVID-19 pandemic. Briefly, antibiotic resistance of H. pylori has a dynamic change, and it can display different patterns in certain geographic regions. The results imply that antibiotic consumption should be carefully controlled and unjustified use of levofloxacin should be restricted, especially in some large cities. Antibiotic policy should be further strengthened and regular monitoring of resistance in various geographic regions is needed for treatment optimization.

Secondary prevention of rheumatic heart disease in Ethiopia: a multicenter study.

BACKGROUND: Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention. METHODS: A multicenter, prospective study was performed on children aged 5-17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated. RESULTS: A total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence. CONCLUSION: Poor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.

Maternal sepsis caused by Listeria monocytogenes with a fatal fetal outcome.

Improving maternal and child health is a global priority. Although infection with Listeria monocytogenes (LM), a small facultative anaerobic, gram-positive motile bacillus is rare, when it infects the maternal-fetoplacental unit, it can result in adverse fetal sequelae such as chorioamnionitis, preterm labour, neonatal sepsis, meningitis and neonatal death. Pregnancy-associated listeriosis may present with a plethora of diverse, non-specific symptoms such as fever, influenza-like or gastrointestinal symptoms, premature contractions and preterm labour. It has a predilection for the second and third trimester of pregnancy, occurring sporadically or as part of an outbreak, most of which have involved unpasteurised dairy products, long shelf life products, contaminated ready-to-eat food, deli meats and soft cheeses. Strains belonging to the clonal complexes 1, 4 and 6 are hypervigilant and are commonly associated with maternal-neonatal infections. Maternal listeriosis occurs as a direct consequence of LM-specific placental tropism, which is mediated by the conjugated action of internalin A and internalin B at the placental barrier. The diagnosis is established from placental culture. Penicillin, ampicillin and amoxicillin are the antimicrobials of choice. It has a high fetal morbidity of up to 30%. The authors present the case of a multiparous woman in her early 20s presenting with sepsis and preterm premature rupture of her membranes at 21 weeks gestation. A live baby was delivered spontaneously and died shortly after birth. Placental cultures and postmortem examination were consistent with the diagnosis of disseminated Listeria infection. Due to the increased susceptibility of pregnant women for LM, a high index of clinical suspicion is required to establish the diagnosis and initiate appropriate antimicrobial therapy to reduce adverse fetal outcomes.

Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial.

BACKGROUND & AIMS: Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs standard treatment on H pylori eradication in the United States and Europe. METHODS: In a randomized, controlled, phase 3 trial, treatment-naïve adults with H pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin 3 times daily), or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary outcome was noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (noninferiority margin = 10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients. RESULTS: A total of 1046 patients were randomized. Primary outcome eradication rates (nonresistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, vs lansoprazole triple therapy 78.8% (both noninferior; difference 5.9%; 95% confidence interval [CI], -0.8 to 12.6; P < .001; difference -0.3%; 95% CI, -7.4 to 6.8; P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, vs lansoprazole triple therapy 31.9% (both superior; difference 33.9%; 95% CI, 17.7-48.1; P < .001; difference 37.7%; 95% CI, 20.5-52.6; P < .001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5%, difference 12.3%; 95% CI, 5.7-18.8; P < .001; difference 8.7%; 95% CI, 1.9-15.4; P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P > .05). CONCLUSION: Both vonoprazan-based regimens were superior to proton pump inhibitor-based triple therapy in clarithromycin-resistant strains and in the overall study population. CLINICALTRIALS: gov; NCT04167670.

Drug delivery of amoxicillin molecule as a suggested treatment for covid-19 implementing functionalized mesoporous SBA-15 with aminopropyl groups.

SARS-CoV-2 is a novel coronavirus that was isolated and identified for the first time in Wuhan, China in 2019. Nowadays, it is a worldwide danger and the WHO named it a pandemic. In this investigation, a functionalization post-synthesis method was used to assess the ability of an adapted SBA-15 surface as a sorbent to load the drug from an aqueous medium. Different characterization approaches were used to determine the characterization of the substance before and after functionalization such as X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), nitrogen adsorption-desorption porosimetry (Brunauer-Emmett-Teller) BET surface area analysis, and thermal gravimetric analysis (TGA). Batch adsorption testing was carried out in a single adsorption device to find the impact of multiple variables on the drug amoxicillin charge output. The following parameters were studied: 0-72 hr. contact time, 20-120 mg/l initial concentration, and 20-250 mg of NH2-SBA-15 dose. The outcomes from such experiments revealed the strong influence and behavior of the amino-functional group to increase the drug's load. Drug delivery outcomes studies found that amoxicillin loading was directly related to NH2-SBA-15 contact time and dose, but indirectly related to primary concentration. It was observed that 80% of amoxicillin was loaded while the best release test results were 1 hour and 51%.

Concurrent coronavirus disease 2019 and primary syphilis in a young man: A rare case report.

INTRODUCTION: The global rise of syphilis infections and the ongoing coronavirus disease 2019 (COVID-19) pandemic are causes for concern. We herein report a rare case of concurrent primary syphilis and COVID-19. CASE REPORT: A 29-year-old man was admitted with a diagnosis of COVID-19. Although COVID-19 pneumonia appeared during ciclesonide and favipiravir treatment, his symptoms improved without developing severe hypoxemia. A small, red ulcer on the left-side of his glans penis was noted and left inguinal lymph node swellings were detected on computed tomography (CT). He reported that his last engagement in sexual intercourse had been 3 months previously, and that his partner had subsequently been diagnosed with syphilis. Although both serum Treponema pallidum (TP) antibody and rapid plasma reagin (RPR) quantitative tests were negative on the day of admission, we clinically diagnosed a suspected case of primary syphilis and started treatment with amoxicillin (1500 mg/day). We subsequently learned that the TP antibody and RPR quantitative tests had been positive 4 days before starting syphilis treatment. Amoxicillin treatment was continued for 61 days, and the ulcer gradually improved. One year later, the RPR quantitative test was negative, and CT revealed a reduction in size of the inguinal lymph nodes and no residual signs of COVID-19 pneumonia. CONCLUSION: The prevalence of syphilis has been increasing even during the COVID-19 pandemic, and the incidence of concurrent syphilis and COVID-19 might be higher than is recognized. Asking patients with COVID-19 about high-risk sexual behavior and genital lesions could help with early diagnosis of syphilis.

Simplifying the drug provocation test in non-immediate hypersensitivity reactions to amoxicillin in children: The experience of a tertiary care allergy unit.

BACKGROUND: Mild non-immediate reactions (NIR) to beta-lactams (ßLs) are the most common manifestation of adverse drug reactions in children, and the drug provocation test (DPT) remains the gold standard for diagnosis. However, there are still controversies about the protocol that should be used, especially regarding the administration of doses and the DPT length. OBJECTIVE: This study aimed to evaluate a pediatric population with a history of mild NIR to amoxicillin (AMX) or to amoxicillin-clavulanic acid (AMX/CL) who underwent a diagnostic workup including a DPT with the culprit drug, to understand if a graded DPT or, instead, a single full dose could be the most appropriate way of administration in clinical practice. METHODS: The data of children were retrospectively analyzed for a 5-year period, with demographic and clinical characteristics collected. We reported the allergy workup and the results of the DPT performed with the administration of incremental doses and a prolonged DPT at home for a total of 5 days. RESULTS: Three hundred fifty-four patients were included. Overall, 23/354 (6.5%) DPTs were positive: 11/23 patients showed a reaction after 2-8 h after the last dose on the 1st or 2nd day (1 reacted 30 min after the last dose), 1/23 reacted with urticaria 30 min after the first dose, 11/23 reacted at home on the 5th day of the DPT. CONCLUSION: This paper indirectly suggests that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild NIR to AMX/CL. Moreover, this could be less time-consuming as patients would spend less time in the hospital, also considering the public health restrictions imposed during the COVID-19 pandemic.

Beneficial ex vivo immunomodulatory and clinical effects of clarithromycin in COVID-19.

INTRODUCTION: Macrolide antibiotics have immunomodulatory properties which may be beneficial in viral infections. However, the precise effects of macrolides on T cell responses to COVID, differences between different macrolides, and synergistic effects with other antibiotics have not been explored. METHODS: We investigated the effect of antibiotics (amoxicillin, azithromycin, clarithromycin, and combined amoxicillin with clarithromycin) on lymphocyte intracellular cytokine levels and monocyte phagocytosis in healthy volunteer PBMCs stimulated ex vivo with SARS-CoV-2 S1+2 spike protein. A retrospective cohort study was performed on intensive care COVID-19 patients. RESULTS: Co-incubation of clarithromycin with spike protein-stimulated healthy volunteer PBMCs ex vivo resulted in an increase in CD8+ (p = 0.004) and CD4+ (p = 0.007) IL-2, with a decrease in CD8+ (p = 0.032) and CD4+ (p = 0.007) IL-10. The addition of amoxicillin to clarithromycin resulted in an increase in CD8+ IL-6 (p = 0.010), decrease in CD8+ (p = 0.014) and CD4+ (p = 0.022) TNF-alpha, and decrease in CD8+ IFN-alpha (p = 0.038). Amoxicillin alone had no effect on CD4+ or CD8+ cytokines. Co-incubation of azithromycin resulted in increased CD8+ (p = 0.007) and CD4+ (p = 0.011) IL-2. There were no effects on monocyte phagocytosis. 102 COVID-19 ICU patients received antibiotics on hospital admission; 62 (61%) received clarithromycin. Clarithromycin use was associated with reduction in mortality on univariate analysis (p = 0.023), but not following adjustment for confounders (HR = 0.540; p = 0.076). CONCLUSIONS: Clarithromycin has immunomodulatory properties over and above azithromycin. Amoxicillin in addition to clarithromycin is associated with synergistic ex vivo immunomodulatory properties. The potential benefit of clarithromycin in critically ill patients with COVID-19 and other viral pneumonitis merits further exploration.

Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups. METHODS: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298). FINDINGS: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis. INTERPRETATION: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections. FUNDING: National Institute for Health Research.

High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults With Acute Sinusitis: A Randomized Clinical Trial.

Importance: Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit. Objective: To confirm the previous finding that high-dose amoxicillin plus clavulanate (with double the amount of amoxicillin) may be superior to standard-dose amoxicillin plus clavulanate in adults. Design, Setting, and Participants: This double-blind, comparative-effectiveness randomized clinical trial was conducted from February 26, 2018, through May 10, 2020, at the academic primary care internal medicine and pediatrics practice of Albany Medical Center, located in Cohoes, New York. Participants included adults aged 18 years or older who were prescribed amoxicillin plus clavulanate for acute bacterial sinusitis diagnosed in accordance with the Infectious Diseases Society of America guidelines. Interventions: Amoxicillin 875 mg with clavulanate 125 mg plus either placebo (standard dose) or amoxicillin 875 mg (high dose) twice a day for 7 days. Main Outcomes and Measures: The primary efficacy outcome was a global rating of "a lot better" or "no symptoms" at the end of 3 days of treatment using a Global Rating of Improvement scale, with outcomes ranging from 1 (a lot worse) to 6 (no symptoms). The primary adverse effect outcome was severe diarrhea at 3 or 10 days after the start of treatment. Results: At an unplanned interim analysis prompted by COVID-19 restrictions, 157 of a projected 240 participants had been enrolled (mean age, 48.5 [range, 18.7-84.0] years; 117 women [74.5%]), with 79 randomized to the standard dose and 78 to the high dose; 9 and 12, respectively, withdrew or were lost to follow-up before the assessment of the primary outcome. At day 3, 31 of 70 participants (44.3%) in the standard-dose group reported a global rating of "a lot better" or "no symptoms," as did 24 of 66 (36.4%) in the high-dose group, for a difference of -7.9% (95% CI, -24.4% to 8.5%; P = .35). The study was, therefore, stopped for futility. Diarrhea was common in both groups by day 3, with any diarrhea reported in 29 of 71 participants (40.8%) receiving the standard dose and 28 of 65 (43.1%) receiving the high dose and severe diarrhea reported in 5 of 71 (7.0%) and 5 of 65 (7.7%), respectively. Conclusions and Relevance: The results of this randomized clinical trial suggest that adults treated for clinically diagnosed acute sinusitis did not appear to benefit from taking high-dose compared with standard-dose amoxicillin plus clavulanate. Trial Registration: ClinicalTrials.gov Identifier: NCT03431337.

Bacterial meningitis and COVID-19: a complex patient journey.

A woman in her 70s presented to the emergency department with fever, fluctuating cognition and headache. A detailed examination revealed neurological weakness to the lower limbs with atonia and areflexia, leading to a diagnosis of bacterial meningitis, alongside a concurrent COVID-19 infection. The patient required critical care escalation for respiratory support. After stepdown to a rehabilitation ward, she had difficulties communicating due to new aphonia, hearing loss and left third nerve palsy. The team used written communication with the patient, and with this the patient was able to signal neurological deterioration. Another neurological examination noted a different pattern of weakness to the lower limbs, along with new urinary retention, and spinal arachnoiditis was identified. After more than 10 weeks in the hospital, the patient was discharged. Throughout this case, there were multiple handovers between teams and specialties, all of which were underpinned by good communication and examination to achieve the best care.