New Guidance on Cytochrome P450 2C19 Phenotype-based Use of Proton Pump Inhibitors.

ABSTRACT: Since the approval of the first proton pump inhibitor (PPI) in 1989, our knowledge regarding this class of medications has further developed. An increasing amount of data now supports the association between cytochrome P450 2C19 (CYP2C19) phenotype and PPI safety and efficacy. This includes pediatric studies, such as those published here and in other pediatric journals within the past year. Moreover, the most recent pediatric Helicobacter pylori guidelines stated that using the PPIs that are less dependent on CYP2C19 for inactivation may be preferred for H pylori eradication among populations that are more likely to have rapid clearance of CYP2C19-metabolized PPIs. Conversely, pantoprazole package insert recommends a dose reduction in known pediatric CYP2C19 poor metabolizers (PMs), citing a 6-fold increase in serum concentrations compared with normal metabolizers (NMs). The purpose of this communication is to introduce a recently published Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C19 and PPI dosing.

Gut Colonization of Healthy Children and Their Mothers With Pathogenic Ciprofloxacin-Resistant Escherichia coli.

BACKGROUND: The reservoir of pathogenic ciprofloxacin-resistant Escherichia coli remains unknown. METHODS: We conducted a prospective cohort study of 80 healthy twins and their mothers to determine the frequency of excretion of ciprofloxacin-resistant, potentially pathogenic E. coli. Stool specimens were cultured selectively for ciprofloxacin-resistant gram-negative bacteria. Isolates were categorized on the basis of additional resistance and virulence profiles. We also prospectively collected clinical metadata. RESULTS: Fifteen children (19%) and 8 mothers (20%) excreted ciprofloxacin-resistant E. coli at least once. Overall, 33% of 40 families had at least 1 member whose stool specimen yielded ciprofloxacin-resistant E. coli on culture. Fifty-seven submitted stool specimens (2.8%) contained such organisms; clones ST131-H30 and ST405 accounted for 52 and 5 of the positive specimens, respectively. Length of hospital stay after birth (P = .002) and maternal colonization (P = .0001) were associated with subsequent childhood carriage of ciprofloxacin-resistant E. coli; antibiotic use, acid suppression, sex, mode of delivery, and maternal perinatal antibiotic use were not. Ciprofloxacin-resistant E. coli were usually resistant to additional antibiotic classes, and all had virulence genotypes typical of extraintestinal pathogenic E. coli. CONCLUSIONS: Healthy children and their mothers commonly harbor ciprofloxacin-resistant E. coli with pathogenic potential.