Introduction: Helicobacter pylori antibiotic resistance has increased worldwide and multidrug resistance (MDR), which seriously hampers eradication success of the frequent chronic infection, has often been reported. Areas covered: H. pylori MDR rates are discussed, mostly from recent articles published since 2015. Present approaches and future directions to counteract the MDR are outlined. Expert opinion: Alarming presence of triple, quadruple and, in some studies, quintuple and sextuple resistance was detected. Primary MDR rates ranged from <10% in most European countries to >40% in Peru. Post-treatment or overall MDR rates were >23-36% in about half of the studies. MDR prevalence has varied both among and within the countries. Factors linked to the MDR are national antibiotic consumption, antibiotic misuse, treatment failures and bacterial factors such as mutations, efflux pumps, and biofilms. Important directions to counteract the MDR increase can be optimization of present and new eradication regimens, wider use of bismuth-containing regimens, assessment of benefit of vonoprazan, new antibiotics such as newer fluoroquinolones and oxazolidinone analogues, adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipid and development of vaccines and non-invasive tests for resistance detection. However, more efforts and studies are required. Strain susceptibility testing is increasingly important.
Keywords: Helicobacter pylori; antibiotics; biofilm; eradication; multidrug; resistance.