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Journal Pre-proofImpact of narrow spectrum Penicillin V on the oral and fecal resistome ina young child treated for otitis mediaKjersti Sturød, Achal Dhariwal, Ulf R. Dahle, Didrik F. Vestrheim,Fernanda C. PetersenPII:S2213-7165(19)30202-4DOI: 1014To appear in:Received Date:16 May 2019Revised Date:2 August 2019Accepted Date:6 August 2019Please cite this article as: Sturød K, Dhariwal A, Dahle UR, Vestrheim DF, Petersen FC,Impact of narrow spectrum Penicillin V on the oral and fecal resistome in a young child treatedfor otitis media,Journal of Global Antimicrobial Resistance(2019),doi: is a PDF file of an article that has undergone enhancements after acceptance, such asthe addition of a cover page and metadata, and formatting for readability, but it is not yet thedefinitive version of record. This version will undergo additional copyediting, typesetting andreview before it is published in its final form, but we are providing this version to give earlyvisibility of the article. Please note that, during the production process, errors may bediscovered which could affect the content, and all legal disclaimers that apply to the journalpertain.© 2019 Published by Elsevier.
Journal Pre-proof1Impact of narrow spectrum Penicillin V on the oral and fecal resistome in a young child treated for otitis mediaKjersti Sturød1, Achal Dhariwal1,Ulf R Dahle2, Didrik F Vestrheim2,FernandaCPetersen1,*1 Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway2 Norwegian Institute of Public Health, Oslo, Norway*corresponding authorHighlights:Anotableincrease in the fecal resistome wasobserved 25 days after Penicillin V treatment Penicillin V contributes to an extensive taxonomic shift in the fecal microbiomeby end of treatmentNo major shifts were observed in the oral microbiome orresistome after antibiotic treatmentAbstractBackground:Antibiotic overuse has led to a global emergence of resistant bacteria, and children are among the frequent users. Most studies with broad-spectrum antibiotics show severe impact on the resistome development of patients. Although narrow-spectrum antibiotics are believed to have less side-effects, their impact on the microbiome and resistome is mostly unknown. The aim of this study was to investigate the impact of the narrow-spectrum antibiotic
Journal Pre-proof2phenoxymethylpenicillin (Penicillin V) on the microbiome and resistome of a child treated for acute otitis media (OM).Methods:Oral and fecal samples were collected from a one-year child before (day 0) and after (day 5 and 30) receiving Penicillin V against OM. Metagenomic sequencing data was analysed to determine taxonomic profiling, using Kraken and Bracken software, and resistance profiling, using KMA in combination with the ResFinder database.Results:In the oral samples, antimicrobial resistance genes (ARGs) belonging to four classes were identified at baseline. At day 5, the abundance of some ARGs was increased;some remained unchanged, while others disappeared. At day 30, most ARGs had returned to baseline levels, or lower. In the fecal samples,we observed seven ARGs at baseline and five at day 5.At day 30,the number increased to 21 ARGs from sevendifferent classes. Conclusions: Penicillin V had a remarkable impact on the fecal resistome indicating that even narrow-spectrumantibiotics may have important consequences in selecting for a more resistant microbiome. Keywords:resistome, microbiome, antibiotic, narrow-spectrum, otitis media, antibiotic resistance genes IntroductionIncreasing prevalence of antibiotic resistant bacteria is now threatening what have been modern medicines’ security blanket for over 70 years, namely effective antibiotics1.Antibiotics are among the most essential and prescribed drugs in the world, butthe extensiveuse of antibiotics
Journal Pre-proof3has led toa global emergence of resistant bacteria makingbacterialinfections once again difficult to treat.Antibiotic use is particularly high in children less than fouryears of age2,3.The leading cause for prescriptionsin these childrenisupper airway infections, includingotitis media(OM)3,4. In Scandinavia,the treatment-guidelines for OMaremuch more restrictive than they were some years ago3,5, and doctors are encouraged to use as little antibiotics as possible in these cases. However, when recommended, the first-line antibiotic is phenoxymethylpenicillin, also known as Penicillin V6,7. Penicillin V has antibiotic activity against gram-positive bacteria, but is less active against gram-negative bacteria. This drug isamong the narrowestspectrum antibiotics in use. Use of broad spectrum antibiotics isassociated witha reduction in gut microbiome diversity, as demonstrated in several studies8,9.The impacton the microbiotain other body sites isless known, but the microbiome in saliva seems to be more resilient to antibiotics than the gut microbiome, at least in healthy volunteers exposed to broad-spectrum antibiotics 10.In children, loss in diversityis of particular importance, given the relevance of the microbiome on immune system maturation 11. While such antibiotic effects on microbial compositionhave been the focus of several investigations, less is known about the effectson the overall antibiotic resistance gene load in the human microbiome, known as the resistome12. The resistome constitutes an importantreservoir of antibiotic resistancegenesthat can be transferred to pathogens 13. Emerging data indicates that broad-spectrumantibiotics can lead not only to a general increase in resistance genes related to the antibiotic target, but also to other groups of antibiotics 14.Such resistance genes can in some cases persist for longperiods, and increaseupon cumulative exposure to antibiotics 15. For narrow-spectrum antibiotics like Penicillin V, the impact on the resistome remains largely unknown.