3 bs phạm trường sơn hp đề kháng ks

H pylori resistance to antibiotics and clarithromycin: Results from the study on 193 strains isolated from Vietnamese patients with gastro-duodenal ulcer Camelia Quek, Son Pham, Kieu Tran, Binh Pham, Ngan Luu, Thao Le, Kelly Quek, Van Pham An international collaboration project funded by Nam Khoa Co., Ltd  Prevalence of H pylori  H pylori is a Gram-negative bacteria  Causative role in gastric adenocarcinoma, peptic ulcer and chronic gastritis  H pylori prevalence >80% world population  In Vietnam, H pylori prevalence  ~80% in adult  26% -71.4% in children Antibiotic resistance poses biggest challenge in eradication of H pylori  Current recommended therapy: Amoxicillin, metronidazole, tetracycline, levofloxacin, Clarithromycin and all have the resistance reported  33%-45% H pylori resistant against clarithromycin (primary infection) (Binh 2013; Phan 2015; Nguyen 2012)  74% H pylori resistant against clarithromycin (secondary infection) (Phan 2015; Nguyen 2012) Clarithromycin resistance is believed to reside in common 23S point mutations  A2143G, A2142C/G, T2182C  Association studies only   A2142C/G associated with MIC >256μg/mL T2182C associated with MIC >0.5μg/mL Research questions  What is the current prevalence of clarithromycin resistance in Vietnam?  What is the level of clarithromycin resistance of H pylori in Việt Nam?  Can we use point mutations and MIC association as predictor for clarithromycin resistance? Materials and method  Prospective randomised clinical study across 13 hospitals in HCMC  193 gastric samples confirmed by biopsy were obtained:  136 children (3-15 y.o.)  57 adult (19-69 y.o.)  Biochemical confirmation using Gram-stain, oxidase test, catalase test and urease test  MIC values of clarithromycin were obtained using Etest (EUCAST): MIC ≤ 0.5μg/mL (S), MIC > 0.5μg/mL (R)  Sensitivity testing of other antibiotics were carried out by culture on the agar plate with MIC break-point PCR amplification and sequence detection of 23S rRNA mutation  Amplification using DP1 and ZGE23 primers  308 bp amplicons comprising of 2142, 2143, 2182 positions  Sequences were matched on Genbank reference sequence (KU904824-KU905015)  Sequence analyses using MEGA 5.0 Current prevalence of antibiotic resistance of 193 isolates of H pylori Rising resistance rate of other antibiotics in adult vs in children  Levofloxacin is not used in children?  Which MIC value most clarithoromycin resistant strain fall in? Most clarithromycin resistant (82%) have the MIC range from 2-16 μg/mL 97% Clarithromycin concentration Factors contribute to high antibiotic resistance in Vietnam?  Unregulated or widespread over-the-counter use of antibiotics  Clarithromycin is prescribed frequently for other infection treatment due to its high bactericidal effects  Lack of antibiotic stewardship and antibiotic surveillance  Resistance rate is determined in vitro on MIC value  Much lower from achievable tissue concentration (5.2 – 22.2μg/mL) with the using of clarithromycine specific for H pylori  Resistance rate is NOT eradication rate 23S rRNA point mutations were detected in both resistant and susceptible strains 23S rRNA mutations not correlate with clarithromycin resistance  Both A2143G and T2182C detected in 91.7% (n=177) isolates of both resistant (n=155) and susceptible (n=22)  Only with A2142G are resistant to clarithromycin with MIC 8μg/mL and > 256µg/ml  10 resistant isolates with no 23S rRNAmutations Clinical significance  A rising prevalence rate of antibiotic resistance for both clarithromycin and metronidazole  Active surveillance is needed  Molecular testing for antibiotic resistance is not established  The level of clarithromycin resisntace of H pylori in Việt Nam is lower than the concentration of clarithromycin specific for HP   Treatment guideline revision Susceptibility testing of clarithromycin using MIC is necessary to select optimal antibiotic regimens Acknolwedgement  All patients for sample donation  All contributing authors, especially Camelia Quek, Son Pham, Van Pham and Kelly Quek for valuable input  Hospital staffs involved in sample collection and diagnoses  Nam Khoa Co., Ltd for generous funding ... across 13 hospitals in HCMC  193 gastric samples confirmed by biopsy were obtained:  136 children (3-1 5 y.o.)  57 adult (19-69 y.o.)  Biochemical confirmation using Gram-stain, oxidase test, catalase... resisntace of H pylori in Việt Nam is lower than the concentration of clarithromycin specific for HP   Treatment guideline revision Susceptibility testing of clarithromycin using MIC is necessary