title: Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance.
abstract: OBJECTIVE
  Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy (optimization). We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents.
  
  
  METHODS
  We performed a prospective noninferiority multicenter trial in which 343 consecutive individuals with H pylori infection were assigned randomly to groups given hybrid therapy (40 mg omeprazole and 1 g amoxicillin, twice daily for 14 days; 500 mg clarithromycin and 500 mg nitroimidazole were added, twice daily for the final 7 days) or concomitant therapy (same 4 drugs taken concurrently, twice daily for 14 days). We assessed bacterial resistance to these drugs in a subset of patients using the E-test. Efficacy, side effects, and compliance were determined.
  
  
  RESULTS
  In per-protocol analysis, rates of eradication for hybrid and concomitant therapies were 92% (95% confidence interval [CI], 87%-95%) and 96.1% (95% CI, 93%-99%), respectively (P = .07). In intention-to-treat analysis, rates were 90% (95% CI, 86%-93%) and 91.7% (95% CI, 87%-95%), respectively (P = .35). Almost all patients (95.5%) were fully compliant; 23.5% of patients had H pylori strains that were resistant to clarithromycin (Italy, 26%; Spain, 19.5%), 33% were resistant to metronidazole (Italy, 33%; Spain, 34%), and 8.8% were resistant to both drugs (Italy, 7.1%; Spain, 11.5%). Side effects (only mild) were reported in 51.5% of patients (47% hybrid vs 56% concomitant; P = .06). Compliance greater than 80% was the only significant predictor of eradication (odds ratio, 12.5; 95% CI, 3.1-52; P = .001). Significantly more patients were compliant with hybrid therapy (98.8%) than concomitant therapy (95.2%; P = .05).
  
  
  CONCLUSIONS
  Optimized nonbismuth quadruple hybrid and concomitant therapies cured more than 90% of patients with H pylori infections in areas of high clarithromycin and metronidazole resistance. ClinicalTrials.gov number NCT01464060.
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain. Electronic address: xavi_molina@hotmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: Molina-Infante
authors.affiliation: Department of Gastroenterology, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Romano
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernandez-Bermejo
authors.affiliation: Department of Gastroenterology, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Federico
authors.affiliation: Department of Gastroenterology, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Antonietta G
authors.initials: AG
authors.lastname: Gravina
authors.affiliation: Hospital de Merida, Badajoz, Spain.
authors.forename: Liliana
authors.initials: L
authors.lastname: Pozzati
authors.affiliation: Hospital Virgen del Puerto, Plasencia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Garcia-Abadia
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Vinagre-Rodriguez
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez-Alcala
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Moises
authors.initials: M
authors.lastname: Hernandez-Alonso
authors.affiliation: Department of Gastroenterology, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Miranda
authors.affiliation: Department of Microbiology, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Iovene
authors.affiliation: Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pazos-Pacheco
authors.affiliation: Department of Gastroenterology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D064704:Levofloxacin / Q000008:administration & dosage; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin