Phenotypic and genotypic Helicobacter pylori clarithromycin resistance and therapeutic outcome: benefits and limits.
BACKGROUND
Primary clarithromycin resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. However, the clinical consequence of either phenotypic or genotypic resistance still remains unclear. This study aimed to evaluate: (i) the concordance between phenotypic (culture) and genotypic (real-time PCR) tests in assessing primary clarithromycin resistance; and (ii) the role of both in therapeutic outcome.


METHODS
A post hoc subgroup study was selected from a double-blind, placebo-controlled trial, enrolling 146 patients with dyspepsia or peptic ulcers never previously treated. Real-time PCR and Etest on bacterial culture for assessing clarithromycin resistance were performed. [(13)C]urea breath test (UBT), histology and rapid urease tests at entry and UBT after 4-8 weeks were used to assess infection and eradication. All patients received a 10 day therapy.


RESULTS
Prevalence of clarithromycin phenotypic resistance was significantly lower as compared with genotypic resistance (18.4% versus 37.6%, P < 0.001). A concordance between the two methods was present in 71.2% of cases. A significant difference in the eradication rate was seen between clarithromycin-susceptible and -resistant strains, when assessed with either Etest (92.4% versus 55.5%, P < 0.001) or a PCR-based method (94.5% versus 70.9%; P < 0.001). Of note, the eradication rate showed the lowest value (30.7%) when phenotypic bacterial resistance was genetically linked to the A2143G point mutation.


CONCLUSIONS
This study showed that: (i) there is a relevant discordance between the two methods; and (ii) phenotypic clarithromycin resistance markedly reduces H. pylori eradication when it is linked to a specific point mutation.
De Francesco
Vincenzo
V
Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Foggia, Italy.
Zullo
Angelo
A
Ierardi
Enzo
E
Giorgio
Floriana
F
Perna
Federico
F
Hassan
Cesare
C
Morini
Sergio
S
Panella
Carmine
C
Vaira
Dino
D
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001944:Breath Tests; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D004269:DNA, Bacterial / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D016896:Treatment Outcome; D014510:Urease / Q000032:analysis
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012338:RNA, Ribosomal, 23S; D014510:Urease; D017291:Clarithromycin