title: Levofloxacin or Clarithromycin-based quadruple regimens: what is the best alternative as first-line treatment for Helicobacter pylori eradication in a country with high resistance rates for both antibiotics?
abstract: BACKGROUND
  Helicobacter pylori eradication rates in Portugal are declining, due to increased resistance of this bacterium to antimicrobial agents, especially Clarithromycin. Quadruple Levofloxacin-containing regimens could be an option for first-line treatment, but its efficacy should be evaluated as fluoroquinolone resistance is rapidly increasing. Our aim was to compare the efficacy of Clarithromycin and Levofloxacin-based sequential quadruple therapies as first-line treatment options and determine factors associated with treatment failure.
  
  
  METHODS
  A total of 200 Helicobacter pylori infected patients were retrospectively included (female 57.5%; average age: 53.2 ± 15.7) and received either 10-day sequential therapy (Proton-Pump Inhibitor + Amoxicillin 1 g bid for 5 days and Proton-Pump Inhibitor + Clarithromycin 500 mg + Metronidazole/Tinidazole 500 mg bid/tid in the following 5 days; group A) or a 10-day modified sequential therapy with Levofloxacin 500 mg id instead of Clarithromycin (group B). Eradication was confirmed with urea breath test. Variables that could influence success rate were analyzed.
  
  
  RESULTS
  There were no differences between groups in terms of gender, age, smoking habits and indications for treatment. The eradication rate obtained with Clarithromycin-based sequential treatment was significantly higher than with Levofloxacin-based therapy (90%, CI95%: 84-96% vs. 79%, CI95%: 71-87%, p = 0.001). Using full-dose proton-pump inhibitor and high-dose Metronidazole in group A, and full-dose proton-pump inhibitor and prescription from a Gastroenterologist in group B were associated with eradication success.
  
  
  CONCLUSIONS
  Ten-day Levofloxacin-based sequential treatment achieved inadequate efficacy rate (<80%) and should not be adopted as first-line therapy. Standard sequential therapy showed significantly better results in this naïve population. Using full-dose proton-pump inhibitor and higher doses of Metronidazole is essential to achieve such results.
authors.affiliation: Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. diogofbranquinho@yahoo.com.|Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal. diogofbranquinho@yahoo.com.
authors.forename: Diogo
authors.identifier: http://orcid.org/0000-0001-8519-6409
authors.initials: D
authors.lastname: Branquinho
authors.affiliation: Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.|Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Almeida
authors.affiliation: Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gregório
authors.affiliation: Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: José Eduardo Pina
authors.initials: JE
authors.lastname: Cabral
authors.affiliation: Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Adriano
authors.initials: A
authors.lastname: Casela
authors.affiliation: Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal.
authors.forename: Maria Manuel
authors.initials: MM
authors.lastname: Donato
authors.affiliation: Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.|Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Tomé
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D064704:Levofloxacin / Q000627:therapeutic use*; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D011174:Portugal; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D014011:Tinidazole / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D014011:Tinidazole; D008795:Metronidazole; D064704:Levofloxacin; D000658:Amoxicillin; D017291:Clarithromycin
keywords: Eradication; First-line; Helicobacter pylori; Levofloxacin; Sequential therapy