Antibiotikaresistente mikrober og barn

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1 Antibiotikaresistente mikrober og barn Truls Leegaard avdelingsoverlege/førsteamanuensis Avdeling for mikrobiologi og smittevern Akershus Universitetssykehus

2 Disposisjon Problemet? Antibiotikaforbruk til barn Kan vi ha innflytelse på antibiotikaresistens Hvor lenge er man bærer? Andre innflytelser av antibiotika!

3 Antibiotikaresistente mikrober Multiresistente Gram negative staver: ESBL, KPC, MBL, oxa, etc. Andre Gram negative staver med multiresistens: Acinetobacter og Pseudomonas MRSA Enterokokker: Ampicillinresistente E. faecium & VRE Penicillinresistente pneumokokker (PRSP) Gonokokker TBC: MDR (isoniazid + annet middel)

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5 Routine data NORM surveys MSIS - notification Reference labs Surveillance of AMR in Norway

6 % of isolates E. coli and K. pneumoniae ESBL in blood cultures and urine E. coli, blod Klebsiella spp., blod E. coli, urin Klebsiella spp., urin 0 NORM/NORM-VET 2015

7 Gentamicin resistant E. coli in blood cultures Resistance to gentamicin Intermediate susceptibility to gentamicin 1 0 NORM/NORM-VET 2015

8 DDD/1,000 inhabitants/day % non-susceptibility to ciprofloxacin Ciprofloxacin resistant E. coli and total ciprofloxacin use 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0, NORM/NORM-VET 2015

9 No. of isolates Carbapenemase producing Enterobacteriaceae K. pneumoniae E. coli Enterobacter spp. Citrobacter sp. P. mirabilis P. stuartii S. marcescens M. morganii NORM/NORM-VET 2015

10 No. of isolates Carbapenemase producing Enterobacteriaceae KPC IMI VIM IMP NDM NDM+OXA-48-like OXA-48-like 0 NORM/NORM-VET 2015

11 Carbapenem resistant K. pneumoniae

12 MRSA in blood cultures EARS-Net Report 2014

13 Vancomycin resistant Enterococcus faecium EARS-Net Report 2014

14 Antibiotikaresistens hos barn Antibiotics leave children more likely to contract drug-resistant infections!

15 Antibiotikaresistens hos barn

16 Antibiotikaresistens hos barn

17 MRSA Reported cases by origin of acquisition MRSA ervervet i helsetjenesten MRSA ervervet i samfunnet MRSA ervervet utenlands NORM/NORM-VET 2015

18 Konsekvenser Kan pasienten være bærer av multiresistent bakterie? Når må vi mistenkte det? Når behøver vi ikke tenke på det? Dyrkning og resistensbestemmelse er viktig Behandling og smitteverntiltak på bakgrunn av resistensbestemmelse Persontilpasset medisin!

19 Er det noe som er spesielt for barn i forhold til antibiotikaresistens?

20 «As soon as we use it, we loose it» Clatworthy et al. Nature Chemical Biology 2007;3:541-48

21 Aldersfordeling for brukere av antibiotika (ATC-gruppe J01) i perioden , fordelt på kvinner og menn Irene Litleskare et al. Antibiotikaforbruk i Norge. Tidsskr Nor Legeforen 2008; 128:2324-9

22 High antibiotic consumption: a characterization of heavy users in Spain Heavy antibiotic users (5% of individuals with highest consumption) were responsible for 21% of the total DDD consumed and received 6 packages per year. Elderly adults ( 60 years) and small children (0-9 years) were those exposed to the highest volume of antibiotics and with the most frequent exposure, respectively. Heavy users received a high proportion of antibiotics not recommended as first choice in primary health care. In conclusion, heavy antibiotic users consisted mainly of children and old adults. Inappropriate overuse of antibiotics (high quantity, high frequency, and inappropriate antibiotic choice) leads to a substantial risk of the emergence and spread of resistant bacteria, and interventions to reduce overuse of antibiotics should therefore primarily be targeted children and elderly people. Malo S et al. High antibiotic consumption: a characterization of heavy users in Spain. Basic Clin Pharmacol Toxicol 2014; 115: 231-6

23 Akuttveilederen i pediatri ediatri/infeksjoner-vaksiner/mrsa MRSA behandles som hos voksne Omtaler ikke andre MDR mikrober spesielt Behandling av MDR som hos voksne

24 Hva får barn antibiotika for? Luftveisinfeksjoner Øreinfeksjoner Fordi andre ikke vil vente: f.eks. barnehager

25 Hvis vi kan redusere forbruket vil etter hvert antibiotikaresistensen gå ned! Handlingsplanen De fleste luftveisinfeksjoner (inkl. pneumonier) er virale (1) Kan vi bruke «vent-og-se»- resepter? Ny konsultasjon istedenfor resept? 1 Berg AS et al. Pediatr Infect Dis J 2016;35:e69-75

26 Hvor lenge er man så bærer? MRSA ESBL VRE Andre

27 MRSA Robicsek et al. Clin Infect Dis 2009; 48: admissions after a clinical culture or surveillance test positive for methicillin-resistant Staphylococcus aureus. Retested patients for methicillin-resistant Staphylococcus aureus colonization. During the first year after the positive culture result was obtained, 48.8% of the patients (95% confidence interval, 45.8% 51.7%) remained colonized; at 4 years, 21.2% of the patients (95% confidence interval, 13.1% 31.4%) remained colonized. Chen et al. J Clin Microbiol 2013; 51: Longitudinal analysis of methicillin-resistant and methicillinsusceptible Staphylococcus aureus carriage in healthy adolescents: the long-term carriage patterns for MRSA and MSSA in healthy individuals were similar. MRSA carriers were more likely to carry a single strain, with a trend toward a higher chance of developing cellulitis than for MSSA carriers.

28 ESBL Faecal Carriage of Extended Spectrum β-lactamase Producing Escherichia coli and Klebsiella pneumoniae After Urinary Tract Infection - A Three Year Prospective Cohort Study We observed an overall ESBL-E fecal clearance rate of 56% one year after a UTI caused by an ESBL-producing E. coli or K. pneumoniae. The ESBL point prevalence of fecal carriage were 61% at 4 months, 56% at 7 months, 48% at 10 months, 39% at 13 months, 19% after two years, and 15% after three years or more. A single negative sample is not sufficient to assume ESBL-clearance. ESBL production can be detected in several fecal Enterobacteriaceae species, and in diverse E. coli genotypes within the same host. When investigating cross-transmission of ESBL producing bacteria in health care institutions, this should be taken into account. SB Jørgensen et al. PlosOne 2017; 12: e

29 UTI caused by E. coli phylogroup B2 or D strains are associated with prolonged fecal ESBL-E carriage SB Jørgensen et al. PlosOne 2017; 12: e

30 VRE Sør Korea 1 : After hospitalisation the median duration of culture positivity of VRE was 5.57 weeks (range weeks) Australia 2 : Of the 345 eligible patients, 103 participated, 13 were found to have current VRE fecal carriage. The proportion of colonized patients fell from 40% (2/5) in the first year to 23.3% (7/30) in year 4. None of the 40 patients who had VRE detected >4 years prior were found to be colonized at the time of the study. The longest duration of detected VRE positivity was 46.5 months. France 3 : 2 patients with at least two positive RS results (mean, 4 positive RS results per patient) followed by at least one negative RS result. The median duration of carriage was 42 days (75th percentile, 101 days; 90th percentile, 221 days), and the maximum was 708 days (23,8 months). 1 Sohn et al. Int J Infect Dis 2013; 17: e Karki et al. J Clin Microbiol 2013; 51: Henard et al. Am J Infect Control 2011; 39:

31 Konsekvenser Vi vet for lite om bæreskap hos barn ift hos voksne Men mye tyder på at barn ikke er bærere lengre enn voksne Hvis en nyfødt er en del av en utbrudd med en resistente bakterie burde vi flagge journalen for resten av livet? sannsynligvis ikke!

32 Andre innflytelser av antibiotika Turta & Rautava. BMC Medicine 2016 Antibiotics, obesity and the link to microbes - what are we doing to our children? Antibiotika leder til mikrobiomforandringer uante konsekvenser Cotten. Curr Opin Pediatr 2016 The clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. Metsälä et al. Clin Exp Allergy 2015; 45: Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood: Both prenatal and post-natal exposure to antibiotics was associated with an increased risk of asthma. The potential role of adverse effects of antibiotics on the gut microbiota and the development of asthma should be further explored.

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