Assessment of Community Pediatric Providers’ Approach to Children With Helicobacter pylori

Supplemental Digital Content is available in the text.

H elicobacter pylori is a gram-negative spiral bacterium that typically causes infection in early childhood around the ages of 5 to 10 (1). The prevalence of H. pylori in children varies in the world from 2.5% to 34.6% and has been fluctuating rapidly (2). The clinical presentation, need for diagnostic testing, and treatment in children is significantly different from adults where often they present with gastroduodenal ulcer or gastric cancer. Also, unlike in adult guidelines, testing for H. pylori is not recommended for children presenting with functional abdominal pain (3,4). The majority of children infected with H. pylori are asymptomatic (5). Recent literature has suggested that H. pylori infection may convey immunologic benefits later in life (6). The accuracy of noninvasive diagnostic testing in pediatrics is also highly variable.
In 2016, the European and North American Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN/NASP-GHAN) updated guidelines for management of H. pylori in children due to the changing epidemiology of H. pylori infection and decreasing efficacy of treatment (1). There has been increasing resistance to antibiotics and decreasing efficacy of H. pylori eradication in young children. The updated guidelines emphasize the importance of diagnostic testing with endoscopy and performance of H. pylori culture to help guide medical therapy. The former "test and treat" strategy has been discouraged. When bacterial culture and sensitivity are not available, empiric therapy with high-dose amoxicillin, metronidazole, and proton pump inhibitor (PPI) is recommended. In addition, the guidelines include a noninvasive test of cure, either a stool antigen or urea breath test, to be performed at least 4 weeks after completion of treatment.
We assessed the knowledge and practice habits of H. pylori management among the community pediatric providers in one state and how they adhered to new guidelines recommendations. We hypothesized that at least 20% of the community pediatricians would not be consistently following guideline recommendations.

METHODS
This study followed a one-time cross-sectional observational study design. Subjects included Connecticut primary care pediatric practitioners affiliated with one tertiary care center and/or affiliated with the Connecticut American Academy of Pediatrics chapter. We developed an electronic survey using an online form through Qualtrics and distributed it through an email list-serve. A questionnaire previously utilized to assess knowledge of celiac guidelines in community pediatricians guided survey development (7). Content was based on recent major changes to the H. pylori guidelines. The survey questions addressed each component of the new guidelines: (1) diagnostic testing,

Demographics
A total of 101 providers completed the questionnaire. Seventy percent of the providers were female. The majority (91%) of responders identified themselves as physicians. Most (83%) had greater than 10 years of experience. Fifty-one percent of the providers reported that they diagnosed H. pylori within the practice (Table 1).

Diagnostic Testing
Of the subset who reported experience diagnosing H. pylori, 56% of the providers used stool antigen testing, 44% used urea breath testing, and 17% used blood serology as a diagnostic test. Providers could choose more than one test. Most providers (62%) reported that they were somewhat confident or very confident in their choice of diagnostic test. About a third (34%) of providers reported performing a H. pylori stool antigen diagnostic test while their patients were on PPIs. If noninvasive testing was positive, 26% of the providers reported that they referred greater than 95% of their patients to a pediatric gastroenterologist for management. Forty-four percent of the providers referred atleast 50% of their patients to a pediatric gastroenterologist for management. The rest were presumably treated by their primary provider, although were not directly asked on the survey ( Table 2).

Treatment and Assessment of Cure
Twenty-eight percent of pediatric providers correctly stated that first-line therapy contained metronidazole and amoxicillin. Out of the providers who selected the correct first-line antibiotic therapy, 20% selected the correct amoxicillin dose. The majority selected incorrect first-line antibiotic dosing responses when antibiotic sensitivities were not known. Sixty percent of providers selected firstline therapy that at least contained clarithromycin: 14% of providers selected clarithromycin and metronidazole, while 46% of the providers selected amoxicillin and clarithromycin as first-line therapy treatment. Thirty-four percent of the providers who chose the correct regimen stated that they were at least somewhat confident on their answers and 67% of the providers who choose the incorrect regimen reported that they were at least somewhat confident on their answers.
In assessing test of cure, 42% selected either urease breath test or stool antigen testing. Approximately 63% of pediatric providers assessed cure by resolution of symptoms ( Table 2). The most commonly used resources reported by pediatric providers were UpTo-Date (45%) and Redbook (31%).

DISCUSSION
H. pylori diagnosis, management, and eradication in children continue to remain a challenge as evident by variation in provider answers. The 2016 ESPGHAN/NASPGHAN recommendations

Diagnosis
In our study, a majority of the providers were incorrectly utilizing the now disproven "test and treat" strategy for H. pylori infection in children and doing so through nonguideline concordant noninvasive testing. Noninvasive testing is inappropriate given the low prevalence of primary infection among children born and raised in North America (8,9). Diagnostic testing for H. pylori with noninvasive test for children experiencing pain or nausea and treating in case of positive result is not recommended as it can be found incidentally (6,10). H. pylori infection typically does not play a role in functional abdominal pain disorders and treatment will unlikely provide symptom relief or benefit (10). Furthermore, infection with H. pylori in an otherwise asymptomatic patient has also been associated with potentially immunologic benefits later in life including decrease risk of Barrett's esophagus, celiac disease, and inflammatory bowel disease (11)(12)(13). H. pylori treatment should only be started if a patient is symptomatic with presence of ulceration on endoscopy. In those using noninvasive diagnostic testing, a third of the providers did not have their patients off of a PPI at time of testing for H. pylori. Calvet (14) showed that PPI therapy can suppress H. pylori replication and hence can give false negative diagnostic test results. Patients should be off PPI for at least 2 weeks to reduce the chance of false negative testing (15). It is important for pediatric providers to understand that H. pylori serology is no longer a viable diagnostic test and can lead to unnecessary treatment.

Treatment
Beyond the deviation from guidelines with the persistence of noninvasive testing among community pediatric practices, we found only one in 5 pediatric providers were treating their patients with the evidence-based guideline recommended type and dosing of antibiotics. Similar to a study of pediatricians in Israel, we found that most participants prescribed clarithromycin, even though there is rising clarithromycin resistance to H. pylori in community (16). Clarithromycin resistance to H. pylori in the United States is estimated between 23% and 46% (17). This is a major inconsistency with the new guidelines and could continue to perpetuate the local antibiotic resistance to H. pylori strains. Dosing of antibiotics is also important as almost a fifth of the providers who chose the correct antibiotic of amoxicillin selected incorrect dosing. Electronic order sets with weight-based dosing already preassigned may assist in decreasing future errors (18). Providers should be aware that when ordering combination medications such as Prevpac (Lansoprazole, Amoxicillin, and Clarithromycin) for older children that their patients may get inadequate dosing of the medication.
Only about half of the providers reported referring patients to pediatric gastroenterology for testing and treatment, which may increase risk of treatment failure as the majority of providers only assessed cure of H. pylori by resolution of symptoms. These patients should be referred and receive an endoscopy before starting treatment. In settings where endoscopy and pediatric gastroenterology are not readily available, such as during the coronavirus disease pandemic, it is imperative that pediatricians be aware of appropriate dosing for antibiotics.

Test of Cure
A majority of our surveyed pediatric providers incorrectly assessed cure by resolution of symptoms. Even when children are asymptomatic after treatment, it is imperative that test of cure be performed. For those that performed test of cure, the majority of providers appropriately chose the evidence-based guideline indicated tests, either stool antigen or urease breath test. Test of cure should be performed to not only confirm H. pylori eradication in patients but can also potentially inform on community antibiotic resistance patterns (19). Test of cures should be performed at least 2 weeks after stopping the PPI and at least 4 weeks after completion of the antibiotic treatment (1).
Overall, we have shown that community pediatricians have poor adherence to the recent H. pylori 2016 guidelines. The most commonly used resource for our pediatricians was UpToDate. We hypothesize that one future intervention would be to create a pediatric-focused H. pylori treatment page on UpToDate. Currently, while searching for "H. pylori in children/pediatrics" on UpToDate, the search results were limited to solely link to guidelines. While the recent JPGN guidelines were linked, many of the other links were composed of adult management guidelines, which are vastly different from pediatric guidelines. There are many other potential reasons for the evidence-practice gap, and understanding barriers to unlearning and implementing new knowledge is a novel research area alone (20).
There are several limitations to our study. Our study is an observational study from a single state. Although it includes greater than 100 pediatric providers in one region, it may not reflect the national clinical practice and knowledge of all providers practicing in North America. We did not compare with other types of providers, including pediatric gastroenterologists. In addition, we do not have knowledge of the exact percentage of respondents. The survey did not have any mechanisms to prevent respondents from consulting outside sources, and responses may not be reflective of clinical practice. Furthermore, the survey also relied on self-respondent questionnaires that may have recall and response biases.
Future work will focus on improvement of systems, including dissemination of new guidelines, educational outreach, and integration of practice protocols to address barriers to learning and implementing new knowledge and to ensure official adherence to H. pylori guidelines. As pediatric gastroenterologists, we can contribute to closing this gap by providing educational outreach and work with our primary care colleagues to identify impactful informative interventions. We provided survey respondents an informative PowerPoint (Appendix C, Supplemental Digital Content 3, http://links.lww.com/ PG9/A9) after completion of survey and provided community outreach to the providers.

CONCLUSIONS
Although new guidelines for H. pylori diagnosis and management have been in place since 2016, the majority of surveyed community providers have not yet adopted them in full. An evidence-practice gap for use of noninvasive testing for diagnosis of H. pylori disease can lead to poor resource utilization, inadequate antibiotic prescriptions, worsening antibiotic resistance, and prolonged symptoms in patients. Opportunities exist for improved education interventions and communication with providers on appropriate antibiotic dosing as well as appropriate follow-up of patients with H. pylori. As pediatric gastroenterologists, we have a role to play in ensuring our primary care colleagues are informed on new guidelines modifications.