Children with respiratory tract infections in Swedish primary care; prevalence of antibiotic resistance in common respiratory tract pathogens and relation to antibiotic consumption

Mia Tyrstrup, Eva Melander, Katarina Hedin, Anders Beckman, Sigvard Mölstad, Mia Tyrstrup, Eva Melander, Katarina Hedin, Anders Beckman, Sigvard Mölstad

Abstract

Background: The majority of antibiotics consumed in developed countries are prescribed in primary care. However, little is known about resistance levels in the primary care population.

Method: Nasopharyngeal cultures were obtained from children, 0-10 years of age, seeking care at their Primary Health Care Centre with symptoms of respiratory tract infection. Parental questionnaires were used to retrieve information about the child's previous antibiotic consumption.

Result: Cultures from 340 children were gathered. The level of resistant Haemophilus influenzae was low and the prevalence of penicillin non-susceptible pneumococci (PNSP MIC ≥ 0.125 mg/L) was 6% compared to 10% (p = 0.31) in corresponding cultures from children diagnosed at the local clinical microbiology laboratory. Antibiotic treatment within the previous 4 weeks predisposed for resistant bacteria in the nasopharynx, OR: 3.08, CI 95% (1.13-8.42).

Conclusion: Low prevalence of PNSP supports the use of phenoxymethylpenicillin as empirical treatment for childhood upper respiratory tract infections attending primary care in our setting. It is important that studies on resistance are performed in primary care populations to evaluate data from microbiological laboratories. Recent antibiotic treatment increases risk of bacterial resistance in children and continuous work to reduce unnecessary antibiotic prescribing should be prioritised.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Ethical Review board at Lund University, (Dnr. 2013/ 513). Information about the study and a written invitation was given to the parents at arrival at the clinic and informed parental consent was obtained for each case.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of children in the study. 1 Either Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Group A Streptococci. 2Streptococcus pneumoniae. 3Haemophilus influenzae. 4 penicillin non-susceptible Streptococcus pneumoniae. 5 beta-lactamase producing Haemophilus influenzae. 6 beta-lactamase negative ampicillin resistant Haemophilus influenzae

References

    1. Swedres Svarm 2013 - Swedres-Svarm-2013.pdf [Internet]. [cited 2016 Oct 10]. Available from: .
    1. Musher DM. Infections caused by Streptococcus Pneumoniae: clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis Off Publ Infect Dis Soc Am. 1992;14:801–807. doi: 10.1093/clinids/14.4.801.
    1. Jacobs MR, Dagan R, Appelbaum PC, Burch DJ. Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media. Antimicrob Agents Chemother. 1998;42:589–595.
    1. Övervakning av barnvaccinationsprogrammet mot pneumokocker - overvakning-barnvaccinationsprogrammet-pneumokocker.pdf [Internet]. [cited 2016 Feb 10]. Available from: .
    1. Pneumokocker med nedsatt känslighet för penicillin (PNSP) - pneumokocker-med-nedsatt-kanslighet-for-penicillin-pnsp-2012-5-13.pdf [Internet]. [cited 2016 Feb 10]. Available from: .
    1. Gray BM, Converse GM, 3rd, Dillon HC., Jr Epidemiologic studies of Streptococcus Pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis. 1980;142:923–933. doi: 10.1093/infdis/142.6.923.
    1. Pebody RG, Morgan O, Choi Y, George R, Hussain M, Andrews N. Use of antibiotics and risk factors for carriage of Streptococcus Pneumoniae: a longitudinal household study in the United Kingdom. Epidemiol Infect. 2009;137:555–561. doi: 10.1017/S0950268808001143.
    1. van Deursen AMM, van den Bergh MR, Sanders EAM. Carriage pilot study group. Carriage of Streptococcus Pneumoniae in asymptomatic, community-dwelling elderly in the Netherlands. Vaccine. 2016;34:4–6. doi: 10.1016/j.vaccine.2015.11.014.
    1. Hansman D, Bullen MM. A resistant pneumococcus. Lancet. 1967;290:264–265. doi: 10.1016/S0140-6736(67)92346-X.
    1. Antimicrobial-resistance-surveillance-europe-2011.pdf [Internet]. [cited 2013 Jan 24]. Available from: .
    1. Kristinsson KG. Epidemiology of penicillin resistant pneumococci in Iceland. Microb Drug Resist Larchmt N. 1995;1:121–125. doi: 10.1089/mdr.1995.1.121.
    1. Arason VA, Kristinsson KG, Sigurdsson JA, Stefánsdóttir G, Mölstad S, Gudmundsson S. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. BMJ. 1996;313:387–391. doi: 10.1136/bmj.313.7054.387.
    1. Melander E, Ekdahl K, Jönsson G, Mölstad S. Frequency of penicillin-resistant pneumococci in children is correlated to community utilization of antibiotics. Pediatr Infect Dis J. 2000;19:1172–1177. doi: 10.1097/00006454-200012000-00011.
    1. Goossens H, Ferech M, Vander Stichele R, Elseviers M, ESAC Project Group Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet Lond Engl. 2005;365:579–587. doi: 10.1016/S0140-6736(05)70799-6.
    1. Forsgren A, Walder M. Antimicrobial susceptibility of bacterial isolates in south Sweden including a 13-year follow-up study of some respiratory tract pathogens. APMIS Acta Pathol Microbiol Immunol Scand. 1994;102:227–235. doi: 10.1111/j.1699-0463.1994.tb04869.x.
    1. Melander E, Ekdahl K, Hansson HB, Kamme C, Laurell M, Nilsson P, et al. Introduction and clonal spread of penicillin- and trimethoprim/sulfamethoxazole-resistant Streptococcus Pneumoniae, serotype 9V, in southern Sweden. Microb Drug Resist Larchmt N. 1998;4:71–78. doi: 10.1089/mdr.1998.4.71.
    1. Skovbjerg S, Söderström A, Hynsjö L, Normark BH, Ekdahl K, Ahrén C. Low rate of pneumococci non-susceptible to penicillin in healthy Swedish toddlers. Scand J Infect Dis. 2013;45(4):279–84.
    1. Folkhälsomyndigheten - Swedres-Svarm-2015-15099.pdf [Internet]. [cited 2016 Oct 10]. Available from: .
    1. Van Eldere J, Slack MPE, Ladhani S, Cripps AW. Non-typeable Haemophilus influenzae, an under-recognised pathogen. Lancet Infect Dis. 2014;14:1281–1292. doi: 10.1016/S1473-3099(14)70734-0.
    1. Fontanals D, Bou R, Pons I, Sanfeliu I, Domínguez A, Pineda V, et al. Prevalence of Haemophilus influenzae carriers in the Catalan preschool population. Working group on invasive disease caused by Haemophilus influenzae. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2000;19:301–304. doi: 10.1007/s100960050480.
    1. Murphy TF, Faden H, Bakaletz LO, Kyd JM, Forsgren A, Campos J, et al. Nontypeable Haemophilus influenzae as a pathogen in children. Pediatr Infect Dis J. 2009;28:43–48. doi: 10.1097/INF.0b013e318184dba2.
    1. Thomas WJ, McReynolds JW, Mock CR, Bailey DW. Letter: Ampicillin-resistant Haemophilus influenzae meningitis. Lancet Lond Engl. 1974;1:313. doi: 10.1016/S0140-6736(74)92617-8.
    1. Tristram S, Jacobs MR, Appelbaum PC. Antimicrobial resistance in Haemophilus influenzae. Clin Microbiol Rev. 2007;20:368–389. doi: 10.1128/CMR.00040-06.
    1. Beekmann SE, Heilmann KP, Richter SS, García-de-Lomas J, Doern GV, GRASP Study Group Antimicrobial resistance in Streptococcus Pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group a beta-haemolytic streptococci in 2002-2003. Results of the multinational GRASP Surveillance Program. Int J Antimicrob Agents. 2005;25:148–156. doi: 10.1016/j.ijantimicag.2004.09.016.
    1. Startpage [Internet]. Stat. Cent. [cited 2016 Feb 10]. Available from: .
    1. ESwab™ Liquid Amies Collection and Transport System [Internet]. Copan Diagn. Inc. [cited 2017 Jan 16]. Available from: .
    1. Referensmetodik: Övre luftvägsinfektioner (ÖLI) - Referensmetodik för laboratoriediagnostik [Internet]. [cited 2017 Jan 16]. Available from: .
    1. EUCAST: EUCAST [Internet]. [cited 2017 Jul 15]. Available from: .
    1. Sánchez-Tatay D, Arroyo LA, Tarragó D, Lirola MJ, Porras A, Fenoll A, et al. Antibiotic susceptibility and molecular epidemiology of nasopharyngeal pneumococci from Spanish children. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2008;14:797–801.
    1. Stacevičienė I, Petraitienė S, Vaičiūnienė D, Alasevičius T, Kirslienė J, Usonis V. Antibiotic resistance of Streptococcus Pneumoniae, isolated from nasopharynx of preschool children with acute respiratory tract infection in Lithuania. BMC Infect Dis. 2016;16:216. doi: 10.1186/s12879-016-1544-9.
    1. Angoulvant F, Cohen R, Doit C, Elbez A, Werner A, Béchet S, et al. Trends in antibiotic resistance of Streptococcus Pneumoniae and Haemophilus influenzae isolated from nasopharyngeal flora in children with acute otitis media in France before and after 13 valent pneumococcal conjugate vaccine introduction. BMC Infect Dis. 2015;15:236. doi: 10.1186/s12879-015-0978-9.
    1. Finkelstein JA, Huang SS, Daniel J, Rifas-Shiman SL, Kleinman K, Goldmann D, et al. Antibiotic-resistant Streptococcus Pneumoniae in the heptavalent pneumococcal conjugate vaccine era: predictors of carriage in a multicommunity sample. Pediatrics. 2003;112:862–869. doi: 10.1542/peds.112.4.862.
    1. Felmingham D, Grüneberg RN, Group >the Alexander Project The Alexander project 1996–1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections. J Antimicrob Chemother. 2000;45:191–203. doi: 10.1093/jac/45.2.191.
    1. Mölstad S, Erntell M, Hanberger H, Melander E, Norman C, Skoog G, et al. Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish Strama programme. Lancet Infect Dis. 2008;8:125–132. doi: 10.1016/S1473-3099(08)70017-3.
    1. Ghaffar F, Muniz LS, Kathy K, Smith JL, Shouse T, Davis P, et al. Effects of large dosages of amoxicillin/Clavulanate or Azithromycin on nasopharyngeal carriage of Streptococcus Pneumoniae, Haemophilus influenzae, nonpneumococcal α-hemolytic streptococci, and Staphylococcus Aureus in children with acute Otitis media. Clin Infect Dis. 2002;34:1301–1309. doi: 10.1086/340054.
    1. Melander E, Mölstad S, Persson K, Hansson HB, Söderström M, Ekdahl K. Previous antibiotic consumption and other risk factors for carriage of penicillin-resistant Streptococcus Pneumoniae in children. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 1998;17:834–838. doi: 10.1007/s100960050202.
    1. Arason VA, Sigurdsson JA, Erlendsdottir H, Gudmundsson S, Kristinsson KG. The role of antimicrobial use in the epidemiology of resistant pneumococci: a 10-year follow up. Microb Drug Resist Larchmt N. 2006;12:169–176. doi: 10.1089/mdr.2006.12.169.
    1. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010;340:c2096. doi: 10.1136/bmj.c2096.
    1. Gisselsson-Solen M, Hermansson A, Melhus Å. Individual-level effects of antibiotics on colonizing otitis pathogens in the nasopharynx. Int J Pediatr Otorhinolaryngol. 2016;88:17–21. doi: 10.1016/j.ijporl.2016.06.036.
    1. Eliasson I, Holst E, Mölstad S, Kamme C. Emergence and persistence of beta-lactamase-producing bacteria in the upper respiratory tract in children treated with beta-lactam antibiotics. Am J Med. 1990;88:51S–55S. doi: 10.1016/0002-9343(90)90263-D.
    1. Chung A, Perera R, Brueggemann AB, Elamin AE, Harnden A, Mayon-White R, et al. Effect of antibiotic prescribing on antibiotic resistance in individual children in primary care: prospective cohort study. BMJ. 2007;335:429. doi: 10.1136/.
    1. Seaton RA, Steinke DT, Phillips G, MacDonald T, Davey PG. Community antibiotic therapy, hospitalization and subsequent respiratory tract isolation of Haemophilus influenzae resistant to amoxycillin: a nested case–control study. J Antimicrob Chemother. 2000;46:307–309. doi: 10.1093/jac/46.2.307.
    1. Varon E, Levy C, De La Rocque F, Boucherat M, Deforche D, Podglajen I, et al. Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus Pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections. Clin Infect Dis Off Publ Infect Dis Soc Am. 2000;31:477–481. doi: 10.1086/313981.
    1. Dabernat H, Geslin P, Megraud F, Bégué P, Boulesteix J, Dubreuil C, et al. Effects of cefixime or co-amoxiclav treatment on nasopharyngeal carriage of Streptococcus Pneumoniae and Haemophilus influenzae in children with acute otitis media. J Antimicrob Chemother. 1998;41:253–258. doi: 10.1093/jac/41.2.253.
    1. Jensen-Fangel S, Mohey R, Johnsen SP, Andersen PL, Sørensen HT, Ostergaard L. Gender differences in hospitalization rates for respiratory tract infections in Danish youth. Scand J Infect Dis 2004;36:31–6.
    1. Monto AS, Ullman BM. Acute respiratory illness in an American community. The Tecumseh study. JAMA. 1974;227:164–169. doi: 10.1001/jama.1974.03230150016004.
    1. Falagas ME, Mourtzoukou EG, Vardakas KZ. Sex differences in the incidence and severity of respiratory tract infections. Respir Med. 2007;101:1845–1863. doi: 10.1016/j.rmed.2007.04.011.

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