A systematic review and meta-analysis of data from 28 countries shows rising Helicobacter pylori antibiotic resistance in children, an international team of researchers reported last week in BMC Medicine.

The review, led by researchers from Iran's Shahid Beheshti University of Medical Sciences, included 63 studies involving 15,953 children from 28 countries in 5 World Health Organization regions. The European region was the most widely represented area, with 30 studies involving 7,462 children, followed by the Western Pacific region (20 studies, 7,202 children). The average age of study participants was 11.8 years and 59% were female. The studies, published from 2000 to 2023, assessed H pylori resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, and tetracycline. 

H pylori affects over half the global population, with a higher incidence in developing countries. Infection is associated with gastritis, peptic ulcers, and gastric cancer. The global prevalence of H pylori in children, in whom the bacterium can contribute to malnutrition and growth issues, is 32.3%. While treatment involves a combination of antibiotics and antisecretory drugs, such as proton pump inhibitors, rising antibiotic resistance has emerged as a leading reason for treatment failure in some parts of the world. 

Findings warrant 'urgent attention'

The rate of primary resistance to metronidazole was 35.3%, clarithromycin 32.6%, levofloxacin 13.2%, amoxicillin 4.8%, and tetracycline 1.2%. The rates of secondary resistance, based on information from 115 isolates, were 69.3% for clarithromycin, 45.8% for metronidazole, 36.4% for levofloxacin, and 2.9% for tetracycline. Analysis of time trends found significant increases in resistance from 2000-2005 to 2020-2023, escalating from 1.1% to 16.1% for amoxicillin, 20.4% to 49.5% for clarithromycin, 25.0% to 38.5% for metronidazole, and 2.0% to 2.7% for tetracycline.

The escalating trend of H. pylori antibiotic resistance in children warrants urgent attention globally.

The highest rate of metronidazole resistance (61.5%) was found in children ages 5 to 10, while the highest rate of clarithromycin resistance (51%) was in children 0 to 5 years. 

"The escalating trend of H. pylori antibiotic resistance in children warrants urgent attention globally," the study authors wrote. "National and regional surveillance networks are required for antibiotic stewardship in children infected with H. pylori."

An observational study of community-dwelling older adults in Canada found that longer antibiotic courses were not associated with a greater risk of harm than shorter courses, researchers reported today in Clinical Infectious Diseases.

Using province-wide administrative health data, researchers with the University of Toronto evaluated harms in 117,682 outpatients in Ontario aged 66 to 110 years who had received prescriptions amoxicillin, ciprofloxacin, and cephalexin for short (3 to 7 days) or long (8 to 14 days) duration in 2018. The primary outcome was a composite of antibiotic-related harms, including adverse reactions, Clostridioides difficile infection, and antibiotic resistance. The secondary outcome was a composite of safety measures, including repeat antibiotic prescriptions, hospital visits and mortality. 

To reduce the risk of bias, the researchers used an instrumental variable analysis that accounted for prescriber preference to select longer durations.

"Given the high degree of inter-prescriber variability independent of patient population, physician tendency to prescribe prolonged duration may be a key instrumental variable," the study authors wrote.

No increased risk of harms, safety outcomes

The primary and secondary outcomes were similar across patients receiving prescriptions from low, moderate, and high prescribers of long duration across all three antibiotics evaluated. After adjustment for patient- and prescriber-level variables, longer courses were not associated with greater odds of antibiotic-related harms for amoxicillin (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.84 to 1.15), cephalexin (OR, 1.11; 95% CI, 0.90 to 1.38), or ciprofloxacin (OR, 0.94; 95% CI, 0.74 to 1.20). Safety outcomes were similar (amoxicillin OR, 1.01; 95%CI, 0.94 to 1.08; cephalexin OR, 1.06; 95%CI, 0.97 to 1.17; ciprofloxacin OR, 0.99; 95%CI, 0.85 to 1.15).

While several previous studies have found that longer antibiotic courses are associated with greater risk of patient harms, the authors note that those studies were primarily conducted in hospital settings, where patients may be more prone to antibiotic-related harms due to age, acuity of illness, and presence of comorbidities.

"These findings may suggest that in community-dwelling patients who are at lower risk of harms and benefits from antibiotic therapy, the impact of duration may be negligible," they wrote.

The first study measuring antibody response to respiratory syncytial virus (RSV) vaccinations in immunocompromised individuals shows approximately 40% of participants did not seroconvert or achieve a conservative neutralization threshold post-vaccination. 

The study is published in JAMA. 

Previous studies have measured seroconversion in immunocompetent adults, resulting in 13- to 14-fold increases in antibody titers 1 month after vaccination and 82.6% efficacy against confirmed RSV-related lower respiratory tract disease.

Study suggests need for additional vaccine doses 

In the present study, 38 immunocompromised patients from a group of 139 had antibody levels measured at baseline and 4 weeks post-vaccination. Of the 38 patients, 82% were solid organ transplant recipients, and 74% were taking 2 or more immunosuppressive medications. The average age was 66. 

In total, 23 participants (61%) achieved seroconversion at 4 weeks. 

Low antibody titers may indicate a role for additional vaccine doses to enhance immune response among immunocompromised persons.

“Approximately 40% of immunocompromised participants did not seroconvert or achieve a conservative neutralization threshold postvaccination,” the authors wrote. “Low antibody titers may indicate a role for additional vaccine doses to enhance immune response among immunocompromised persons.”