CYP2C19 Phenotype and Risk of Proton Pump Inhibitor-Associated Infections

被引:34
作者
Bernal, Christiana J. [1 ]
Aka, Ida [1 ]
Carroll, Robert J. [2 ]
Coco, Joseph R. [2 ]
Lima, John J. [4 ]
Acra, Sari A. [1 ]
Roden, Dan M. [2 ,3 ]
Van Driest, Sara L. [1 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Pediat, 2200 Childrens Way, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Dept Med & Pharmacol, Nashville, TN 37232 USA
[4] Nemours Childrens Hlth Syst, Ctr Pharmacogen & Translat Res, Jacksonville, FL USA
基金
美国国家卫生研究院;
关键词
SINGLE-DOSE PHARMACOKINETICS; OPT-OUT; CHILDREN; PANTOPRAZOLE; PHARMACOGENETICS; LANSOPRAZOLE; POLYMORPHISM; METABOLISM; OMEPRAZOLE; GENOTYPE;
D O I
10.1542/peds.2019-0857
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
OBJECTIVES: Proton pump inhibitors (PPIs) are often used in pediatrics to treat common gastrointestinal disorders, and there are growing concerns for infectious adverse events. Because CYP2C19 inactivates PPIs, genetic variants that increase CYP2C19 function may decrease PPI exposure and infections. We tested the hypothesis that CYP2C19 metabolizer phenotypes are associated with infection event rates in children exposed to PPIs. METHODS: This retrospective biorepository cohort study included individuals aged 0 to 36 months at the time of PPI exposure. Respiratory tract and gastrointestinal tract infection events were identified by using International Classification of Diseases codes in the year after the first PPI mention. Variants defining CYP2C19 *2, *3, *4, *8, *9, and *17 were genotyped, and all individuals were classified as CYP2C19 poor or intermediate, normal metabolizers (NMs), or rapid or ultrarapid metabolizers (RM/UMs). Infection rates were compared by using univariate and multivariate analyses. RESULTS: In all, 670 individuals were included (median age 7 months; 44% girls). CYP2C19 NMs (n = 267; 40%) had a higher infection rate than RM/UMs (n = 220; 33%; median 2 vs 1 infections per person per year; P = .03). There was no difference between poor or intermediate (n = 183; 27%) and NMs. In multivariable analysis of NMs and RM/UMs adjusting for age, sex, PPI dose, and comorbidities, CYP2C19 metabolizer status remained a significant risk factor for infection events (odds ratio 0.70 [95% confidence interval 0.50-0.97] for RM/UMs versus NMs). CONCLUSIONS: PPI therapy is associated with higher infection rates in children with normal CYP2C19 function than in those with increased CYP2C19 function, highlighting this adverse effect of PPI therapy and the relevance of CYP2C19 genotypes to PPI therapeutic decision-making.
引用
收藏
页数:8
相关论文
共 47 条
[1]  
Agency for Healthcare Research and Quality, 2019, PRESCR DRUGS NUMB PE
[2]   Increased omeprazole metabolism in carriers of the CYP2C19*17 allele;: a pharmacokinetic study in healthy volunteers [J].
Baldwin, R. Michael ;
Ohlsson, Staffan ;
Pedersen, Rasmus Steen ;
Mwinyi, Jessica ;
Ingelman-Sundberg, Magnus ;
Eliasson, Erik ;
Bertilsson, Leif .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2008, 65 (05) :767-774
[3]   Proton pump inhibitor utilization patterns in infants [J].
Barron, John J. ;
Tan, Hiangkiat ;
Spalding, James ;
Bakst, Wan W. ;
Singer, Joseph .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2007, 45 (04) :421-427
[4]   Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection [J].
Bavishi, C. ;
DuPont, H. L. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2011, 34 (11-12) :1269-1281
[5]   National Study of Off-label Proton Pump Inhibitor Use Among New Zealand Infants in the First Year of Life (2005-2012) [J].
Blank, Mei-Ling ;
Parkin, Lianne .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2017, 65 (02) :179-184
[6]   Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children [J].
Canani, RB ;
Cirillo, P ;
Roggero, P ;
Romano, C ;
Malamisura, B ;
Terrin, G ;
Passariello, A ;
Manguso, F ;
Morelli, L ;
Guarino, A .
PEDIATRICS, 2006, 117 (05) :E817-E820
[7]   Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC) [J].
Caudle, Kelly E. ;
Dunnenberger, Henry M. ;
Freimuth, Robert R. ;
Peterson, Josh F. ;
Burlison, Jonathan D. ;
Whirl-Carrillo, Michelle ;
Scott, Stuart A. ;
Rehm, Heidi L. ;
Williams, Marc S. ;
Klein, Teri E. ;
Relling, Mary V. ;
Hoffman, James M. .
GENETICS IN MEDICINE, 2017, 19 (02) :215-223
[8]   Novel Implementation of Genotype-Guided Proton Pump Inhibitor Medication Therapy in Children: A Pilot, Randomized, Multisite Pragmatic Trial [J].
Cicali, Emily J. ;
Blake, Kathryn ;
Gong, Yan ;
Mougey, Edward B. ;
Al-Atrash, Hadeel ;
Chambers, Nancy ;
Denham, Jolanda ;
Evans, Jonathan ;
George, Donald E. ;
Gomez, Roberto ;
Palomo, Pablo ;
Taufiq, Salik ;
Johnson, Julie A. ;
Lima, John J. ;
Franciosi, James P. .
CTS-CLINICAL AND TRANSLATIONAL SCIENCE, 2019, 12 (02) :172-179
[9]  
CPIC, 2018, CPIC GUID CLOP CYP2C
[10]   Toxicity of long-term use of proton pump inhibitors in children [J].
De Bruyne, Pauline ;
Ito, Shinya .
ARCHIVES OF DISEASE IN CHILDHOOD, 2018, 103 (01) :78-82