‘Significant concerns’ about H. pylori resistance spark calls for updated treatment guidelines

GI tract

By Sunalie Silva

20 May 2021

Evidence suggesting an ‘insidious’ rise in H.pylori antimicrobial resistance (AMR) has led to calls for re-evaluation of the decades-old data informing Australia’s therapeutic guidelines.

Concerns about resistance – and availability of appropriate antibiotics – were raised by researchers led by Dr Sadid Khan from the Department of Microbiology at Melbourne Pathology and the Department of Gastroenterology at St Vincent‟s Hospital in Melbourne based on their analysis of over 380 H. pylori isolates from their laboratory between 2015 and 2020.

They said outdated AMR surveillance data informing the now 20-year old treatment guidelines would lead to “uninformed prescribing that is possibly both increasingly ineffective as well as harmful, through either drug or microbiome adverse effects, or through the potential morbidity and mortality associated with ineffective H. pylori treatment.”

Their microbiology results for gastric biopsy samples from patients attending private hospitals, gastroenterology clinics, and endoscopy suites in Melbourne revealed the overall resistance rate to clarithromycin was 89%.

For amoxicillin the rate was 23.5%, significantly higher than previously reported both in Australia and overseas. High rates of amoxicillin resistance -13% – were also reported in a Queensland cohort, the investigators noted. Together the findings contradicted previous statements that amoxicillin resistance was “very rare and does not develop after treatment failure”.

The high rates of amoxicillin prescribing and resistance in Australian – a pattern less common in other parts of the world –  could be due to the unappreciated high rates of primary clarithromycin resistance, the researchers suggested, which could result to inadvertent amoxicillin monotherapy in primary treatment of H. pylori.

Documentation of clinical history, in particular prior H. pylori treatment, was often incomplete and not able to be accurately captured in the observational study, they acknowledged. But, given local practices, they speculated that the cohort likely represented a treatment experienced population with a bias towards resistant isolates and, in particular, patients who had failed first line macrolide and amoxicillin-based therapy. 

While no definitive conclusions could be drawn from the current study, investigators noted that this frequency of high-level amoxicillin resistance had not been previously been reported and may represent an important shift in epidemiological patterns.

Meanwhile, rates of resistance to metronidazole in the cohort came in at 66.1% and for tetracycline the rate was 4.4% – all suggesting an increase compared to historical data.

Routine levofloxacin or rifabutin susceptibility testing for H. pylori was not carried out by the researchers’ lab, but other studies had shown rising rates of levofloxacin resistance in Australia and surrounding regions.

Unappreciated community levofloxacin resistance from lack of surveillance would likely impact the efficacy of the levofloxacin-based regimen, which was recommended as part of 2nd line treatment. However, this concern was not currently reflected in national therapeutic guidelines for H.pylori, which have not been updated for 20 years, they noted. 

Describing the current state of  H.pylori AMR surveillance as ‘a poor testament to the Australian legacy of the Nobel Prize for its discovery’ the group said the overall ‘insidious trends raise significant concerns’ for unappreciated increases in primary treatment resistance. These were probably already at a threshold that should prompt re-evaluation of current H.pylori treatment guidelines, they believed.

New recommendations

Among several recommendations for improving management of the infection, the group suggested establishing a centralised prospective data collection of laboratory H. pylori antimicrobial resistance rates, similar to reporting of other drug resistant organisms of high importance. They also recommended data collection for positive culture results – similar to processes already established in most states for non-urgent notifiable diseases like syphilis.

Other recommendations include a standardised antimicrobial susceptibility panel with testing for levofloxacin and rifabutin, and improved access to tetracycline, levofloxacin and bismuth.

The study authors noted that despite being recommended as part of 2nd line treatment, levofloxacin was currently not available in Australia outside of a TGA Special Access Scheme. Likewise tetracycline usage in Australia continued to remain low because it was also difficult to access.

The availability of these medications on the PBS – with PBS requirement for reporting of treatment failure or intolerance prior to accessing second line medication – along with improved access to combination or compounded drug formulations to improve tolerability of regimens and re-evaluation of existing treatment guidelines could be a fix for the likely underappreciated concerns.

The study in published in the Internal Medicine Journal here.

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