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This study investigates the potential bactericidal effects of fosfomycin combinations with clarithromycin, metronidazole, ciprofloxacin, amoxicillin, rifampicin, and doxycycline against thirty-six <jats:italic>H. pylori<\/jats:italic> strains using the checkerboard and time-kill assay methods. The results showed that\u2009\u2265\u200950% of the strains were resistant to the six antibiotics. Remarkably, only six strains exerted resistance to these antibiotics, with the minimum inhibitory concentrations (MICs) ranges of (3.2\u201312.8\u00a0mg\/l), (32\u2013256\u00a0mg\/l), (3.2\u201351.2\u00a0mg\/l), (3.2\u201325.6\u00a0mg\/l), (1.6\u20133.2\u00a0mg\/l), and (25.6\u2009&gt;\u200951.2\u00a0mg\/l), respectively. The seven antibiotics were evaluated through in silico studies for their permeability and ability to bind UDP-N-acetylglucosamine1-carboxyvinyltransferase (MurA) of <jats:italic>H. pylori.<\/jats:italic> The results indicated that fosfomycin exhibited the highest predicted membrane permeability (membrane \u2206G insert\u2009=\u2009\u2212\u00a037.54\u00a0kcal\/mol) and binding affinity (docking score\u2009=\u2009\u2212\u00a05.310\u00a0kcal\/mol) for <jats:italic>H. pylori<\/jats:italic> MurA<jats:italic>,<\/jats:italic> compared to other tested antibiotics. The combinations of fosfomycin with these antibiotics exerted synergistic interactions (Fractional inhibitory concentration, FIC index\u2009&lt;\u20091) against the six strains. Importantly, the combinations of fosfomycin with clarithromycin, doxycycline and rifampicin achieved bactericidal effects (reduction\u2009\u2265\u20093.0 Log<jats:sub>10<\/jats:sub> cfu\/ml) against the most resistant <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic> strain. Notably, these effects increased with presence of metronidazole, which enhanced the activity of the fosfomycin combination with amoxicillin from a weak inhibition to bactericidal effect. This study provides evidence that the combination of fosfomycin with either clarithromycin, amoxicillin, doxycycline, or rifampicin (especially with the presence of metronidazole) could be a promising option for treating MDR <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic> infection.<\/jats:p>","DOI":"10.1007\/s11274-022-03289-2","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T11:10:55Z","timestamp":1651230655000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synergistic activity and molecular modelling of fosfomycin combinations with some antibiotics against multidrug resistant Helicobacter pylori"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8745-8628","authenticated-orcid":false,"given":"Ahmed Megahed","family":"Abouwarda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek Abdelmonem","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-997X","authenticated-orcid":false,"given":"Wael Mohamed","family":"Abu El-Wafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-6059","authenticated-orcid":false,"given":"Ahmed Hassan Ibrahim","family":"Faraag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"3289_CR1","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s00284-019-01871-w","volume":"77","author":"WMA Abu El-Wafa","year":"2020","unstructured":"Abu El-Wafa WMA, Ibrahim YM (2020) In vitro activity of fosfomycin in double and triple combinations with imipenem, ciprofloxacin and tobramycin against multidrug-resistant Escherichia coli. 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