Multidrug-resistant organisms in urinary tract infections in children

  • Michelle Mahony
  • Brendan McMullan
  • Jeremy Brown
  • Sean E KennedyEmail author


The global spread of multidrug-resistant organisms has led to an increase in urinary tract infections (UTIs) in children that are difficult to treat. This review explores the current literature regarding multidrug-resistant UTIs in childhood and proposes an approach to management. Multidrug-resistant organisms include a wide range of potential urinary tract pathogens and, while most literature on drug resistance in UTIs during childhood has focused on extended-spectrum beta-lactamase producing organisms, in this review, we have included a discussion of multidrug resistance including and beyond beta-lactamase production. We provide definitions for multidrug-resistant organisms in line with current consensus guidelines and summarise clinically relevant mechanisms of resistance. Additionally, in this review, we outline the global epidemiology of multidrug-resistant UTIs in children, summarising published prevalence rates, which range from 5 to 90% in different settings. Finally, we also critically review the evidence on risk factors for colonisation and infection of the urinary tract with multidrug-resistant organisms, including prior antibiotic use, hospitalisation and underlying urological malformations. We also highlight multidrug-resistant UTI occurring in children without any identifiable risk factors, reflecting an increasing prevalence of colonisation with these organisms in the general community. Taken as a whole, this emphasises a need for careful and evidence-based use of antibiotics when treating UTIs in children and, to aide clinicians, we have outlined here potential management strategies for when infection with a multidrug-resistant organism is suspected or confirmed.


Urinary tract infection Children Multidrug resistance Extended-spectrum beta-lactamases 



  1. 1.
    Delbet JD, Lorrot M, Ulinski T (2017) An update on new antibiotic prophylaxis and treatment for urinary tract infections in children. Expert Opin Pharmacother 18:1619–1625CrossRefGoogle Scholar
  2. 2.
    Edlin RS, Shapiro DJ, Hersh AL, Copp HL (2013) Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol 190:222–227CrossRefGoogle Scholar
  3. 3.
    Khoshnood S, Heidary M, Mirnejad R, Bahramian A, Sedighi M, Mirzaei H (2017) Drug-resistant gram-negative uropathogens: a review. Biomed Pharmacother 94:982–994CrossRefGoogle Scholar
  4. 4.
    Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281CrossRefGoogle Scholar
  5. 5.
    Moxon CA, Paulus S (2016) Beta-lactamases in Enterobacteriaceae infections in children. J Inf Secur 72(Suppl):S41–S49Google Scholar
  6. 6.
    Dayan N, Dabbah H, Weissman I, Aga I, Even L, Glikman D (2013) Urinary tract infections caused by community-acquired extended-spectrum beta-lactamase-producing and nonproducing bacteria: a comparative study. J Pediatr 163:1417–1421CrossRefGoogle Scholar
  7. 7.
    Birgy A, Levy C, Bidet P, Thollot F, Derkx V, Bechet S, Mariani-Kurkdjian P, Cohen R, Bonacorsi S (2016) ESBL-producing Escherichia coli ST131 versus non-ST131: evolution and risk factors of carriage among French children in the community between 2010 and 2015. J Antimicrob Chemother 71:2949–2956CrossRefGoogle Scholar
  8. 8.
    Cheng MF, Chen WL, Hung WY, Huang IF, Chiou YH, Chen YS, Lee SS, Hung CH, Wang JL (2015) Emergence of extended spectrum-beta-lactamase-producing Escherichia coli O25b-ST131: a major community-acquired uropathogen in infants. Pediatr Infect Dis J 34:469–475CrossRefGoogle Scholar
  9. 9.
    Bush K (2018) Past and present perspectives on beta-lactamases. Antimicrob Agents Chemother 24;62(10)Google Scholar
  10. 10.
    Hsu AJ, Tamma PD (2014) Treatment of multidrug-resistant Gram-negative infections in children. Clin Infect Dis 58:1439–1448CrossRefGoogle Scholar
  11. 11.
    Lukac PJ, Bonomo RA, Logan LK (2015) Extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: old foe, emerging threat. Clin Infect Dis 60:1389–1397Google Scholar
  12. 12.
    Wragg R, Harris A, Patel M, Robb A, Chandran H, McCarthy L (2017) Extended spectrum beta lactamase (ESBL) producing bacteria urinary tract infections and complex pediatric urology. J Pediatr Surg 52:286–288CrossRefGoogle Scholar
  13. 13.
    Sedighi I, Arabestani MR, Rahimbakhsh A, Karimitabar Z, Alikhani MY (2015) Dissemination of extended-spectrum beta-lactamases and quinolone resistance genes among clinical isolates of uropathogenic Escherichia coli in children. Jundishapur J Microbiol 8:e19184CrossRefGoogle Scholar
  14. 14.
    Logan LK, Braykov NP, Weinstein RA, Laxminarayan R (2014) Extended-spectrum beta-lactamase-producing and third-generation cephalosporin-resistant Enterobacteriaceae in children: trends in the United States, 1999-2011. J Pediatric Infect Dis Soc 3:320–328CrossRefGoogle Scholar
  15. 15.
    Diaz A, Ortiz DC, Trujillo M, Garces C, Jaimes F, Restrepo AV (2016) Clinical characteristics of Carbapenem-resistant Klebsiella pneumoniae infections in ill and colonized children in Colombia. Pediatr Infect Dis J 35:237–241CrossRefGoogle Scholar
  16. 16.
    Logan LK, Hujer AM, Marshall SH, Domitrovic TN, Rudin SD, Zheng X, Qureshi NK, Hayden MK, Scaggs FA, Karadkhele A, Bonomo RA (2016) Analysis of beta-lactamase resistance determinants in Enterobacteriaceae from Chicago children: a multicenter survey. Antimicrob Agents Chemother 60:3462–3469CrossRefGoogle Scholar
  17. 17.
    Hawkey PM, Warren RE, Livermore DM, McNulty CAM, Enoch DA, Otter JA, Wilson APR (2018) Treatment of infections caused by multidrug-resistant gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party. J Antimicrob Chemother 73:iii2–iii78CrossRefGoogle Scholar
  18. 18.
    Ramirez-Castillo FY, Moreno-Flores AC, Avelar-Gonzalez FJ, Marquez-Diaz F, Harel J, Guerrero-Barrera AL (2018) An evaluation of multidrug-resistant Escherichia coli isolates in urinary tract infections from Aguascalientes, Mexico: cross-sectional study. Ann Clin Microbiol Antimicrob 17:34CrossRefGoogle Scholar
  19. 19.
    Mishra MP, Sarangi R, Padhy RN (2016) Prevalence of multidrug resistant uropathogenic bacteria in pediatric patients of a tertiary care hospital in eastern India. J Infect Public Health 9:308–314CrossRefGoogle Scholar
  20. 20.
    Strysko JP, Mony V, Cleveland J, Siddiqui H, Homel P, Gagliardo C (2016) International travel is a risk factor for extended-spectrum beta-lactamase-producing Enterobacteriaceae acquisition in children: a case-case-control study in an urban U.S. hospital. Travel Med Infect Dis 14:568–571CrossRefGoogle Scholar
  21. 21.
    Crivaro V, Bagattini M, Salza MF, Raimondi F, Rossano F, Triassi M, Zarrilli R (2007) Risk factors for extended-spectrum beta-lactamase-producing Serratia marcescens and Klebsiella pneumoniae acquisition in a neonatal intensive care unit. J Hosp Infect 67:135–114CrossRefGoogle Scholar
  22. 22.
    Denkel LA, Schwab F, Kola A, Leistner R, Garten L, von Weizsacker K, Geffers C, Gastmeier P, Piening B (2014) The mother as most important risk factor for colonization of very low birth weight (VLBW) infants with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). J Antimicrob Chemother 69:2230–2237CrossRefGoogle Scholar
  23. 23.
    Madigan T, Johnson JR, Clabots C, Johnston BD, Porter SB, Slater BS, Banerjee R (2015) Extensive household outbreak of urinary tract infection and intestinal colonization due to extended-spectrum beta-lactamase-producing Escherichia coli sequence type 131. Clin Infect Dis 61:e5–e12Google Scholar
  24. 24.
    Fan NC, Chen HH, Chen CL, Ou LS, Lin TY, Tsai MH, Chiu CH (2014) Rise of community-onset urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli in children. J Microbiol Immunol Infect 47:399–405CrossRefGoogle Scholar
  25. 25.
    Topaloglu R, Er I, Dogan BG, Bilginer Y, Ozaltin F, Besbas N, Ozen S, Bakkaloglu A, Gur D (2010) Risk factors in community-acquired urinary tract infections caused by ESBL-producing bacteria in children. Pediatr Nephrol 25:919–925CrossRefGoogle Scholar
  26. 26.
    Raman G, McMullan B, Taylor P, Mallitt KA, Kennedy SE (2018) Multiresistant E. coli urine infections in children: a case-control study. Arch Dis Child 103:336–340CrossRefGoogle Scholar
  27. 27.
    Kim YH, Yang EM, Kim CJ (2017) Urinary tract infection caused by community-acquired extended-spectrum beta-lactamase-producing bacteria in infants. J Pediatr 93:260–266CrossRefGoogle Scholar
  28. 28.
    Zerr DM, Miles-Jay A, Kronman MP, Zhou C, Adler AL, Haaland W, Weissman SJ, Elward A, Newland JG, Zaoutis T, Qin X (2016) Previous antibiotic exposure increases risk of infection with extended-spectrum-beta-lactamase- and AmpC-producing Escherichia coli and Klebsiella pneumoniae in pediatric patients. Antimicrob Agents Chemother 60:4237–4243CrossRefGoogle Scholar
  29. 29.
    Selekman RE, Shapiro DJ, Boscardin J, Williams G, Craig JC, Brandstrom P, Pennesi M, Roussey-Kesler G, Hari P, Copp HL (2018) Uropathogen resistance and antibiotic prophylaxis: a meta-analysis. Pediatrics 142(1).
  30. 30.
    Cheng CH, Tsai MH, Huang YC, Su LH, Tsau YK, Lin CJ, Chiu CH, Lin TY (2008) Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy. Pediatrics 122:1212–1217CrossRefGoogle Scholar
  31. 31.
    Sakran W, Smolkin V, Odetalla A, Halevy R, Koren A (2015) Community-acquired urinary tract infection in hospitalized children: etiology and antimicrobial resistance. A comparison between first episode and recurrent infection. Clin Pediatr (Phila) 54:479–483CrossRefGoogle Scholar
  32. 32.
    Forster CS, Courter J, Jackson EC, Mortensen JE, Haslam DB (2017) Frequency of multidrug-resistant organisms cultured from urine of children undergoing clean intermittent catheterization. J Pediatric Infect Dis Soc 6:332–338Google Scholar
  33. 33.
    Clarke SA, Samuel M, Boddy SA (2005) Are prophylactic antibiotics necessary with clean intermittent catheterization? A randomized controlled trial. J Pediatr Surg 40:568–571CrossRefGoogle Scholar
  34. 34.
    Lorenzo AJ, Rickard M, Santos JD (2019) The role of bladder function in the pathogenesis and treatment of urinary tract infections in toilet-trained children. Pediatr Nephrol.
  35. 35.
    Shaikh N, Hoberman A, Keren R, Ivanova A, Gotman N, Chesney RW, Carpenter MA, Moxey-Mims M, Wald ER (2016) Predictors of antimicrobial resistance among pathogens causing urinary tract infection in children. J Pediatr 171:116–121CrossRefGoogle Scholar
  36. 36.
    Perez Heras I, Sanchez-Gomez JC, Beneyto-Martin P, Ruano-de-Pablo L, Losada-Pinedo B (2017) Community-onset extended-spectrum beta-lactamase producing Escherichia coli in urinary tract infections in children from 2015 to 2016: prevalence, risk factors, and resistances. Medicine 96:e8571CrossRefGoogle Scholar
  37. 37.
    Poey N, Madhi F, Biscardi S, Bechet S, Cohen R (2017) Aminoglycosides monotherapy as first-line treatment for febrile urinary tract infection in children. Pediatr Infect Dis J 36:1104–1107CrossRefGoogle Scholar
  38. 38.
    Edwards SJ, Emmas CE, Campbell HE (2005) Systematic review comparing meropenem with imipenem plus cilastatin in the treatment of severe infections. Curr Med Res Opin 21:785–794CrossRefGoogle Scholar
  39. 39.
    Karaaslan A, Kadayifci EK, Atici S, Akkoc G, Yakut N, Ocal Demir S, Soysal A, Bakir M (2015) The clinical efficacy and safety of Ertapenem for the treatment of complicated urinary tract infections caused by ESBL-producing bacteria in children. Int J Nephrol 2015:595840CrossRefGoogle Scholar
  40. 40.
    Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, Alenazi TH, Arabi Y, Falcone M, Bassetti M, Righi E, Rogers BA, Kanj S, Bhally H, Iredell J, Mendelson M, Boyles TH, Looke D, Miyakis S, Walls G, Al Khamis M, Zikri A, Crowe A, Ingram P, Daneman N, Griffin P, Athan E, Lorenc P, Baker P, Roberts L, Beatson SA, Peleg AY, Harris-Brown T, Paterson DL (2018) Effect of piperacillin-Tazobactam vs Meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA 320:984–994CrossRefGoogle Scholar
  41. 41.
    Kaye KS, Bhowmick T, Metallidis S, Bleasdale SC, Sagan OS, Stus V, Vazquez J, Zaitsev V, Bidair M, Chorvat E, Dragoescu PO, Fedosiuk E, Horcajada JP, Murta C, Sarychev Y, Stoev V, Morgan E, Fusaro K, Griffith D, Lomovskaya O, Alexander EL, Loutit J, Dudley MN, Giamarellos-Bourboulis EJ (2018) Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial. JAMA 319:788–799CrossRefGoogle Scholar
  42. 42.
    Wright H, Bonomo RA, Paterson DL (2017) New agents for the treatment of infections with gram-negative bacteria: restoring the miracle or false dawn? Clin Microbiol Infect 23:704–712CrossRefGoogle Scholar
  43. 43.
    Polat M, Tapisiz A (2018) Amikacin monotherapy for treatment of febrile urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli in children. Pediatr Infect Dis J 37:378–379CrossRefGoogle Scholar
  44. 44.
    Bacci C, Galli L, de Martino M, Chiappini E (2015) Fluoroquinolones in children: update of the literature. J Chemother 27:257–265CrossRefGoogle Scholar
  45. 45.
    Sahbudak Bal Z, Kamit Can F, Yazici P, Berna Anil A, Duyu M, Yilmaz Ciftdogan D, Nisel Yilmaz O, Cilli F, Karapinar B (2018) The evaluation of safety and efficacy of colistin use in pediatric intensive care unit: results from two reference hospitals and review of literature. J Infect Chemother 24:370–375CrossRefGoogle Scholar
  46. 46.
    Iosifidis E, Violaki A, Michalopoulou E, Volakli E, Diamanti E, Koliouskas D, Antachopoulos C, Drossou-Agakidou V, Sdougka M, Roilides E (2017) Use of tigecycline in pediatric patients with infections predominantly due to extensively drug-resistant gram-negative bacteria. J Pediatric Infect Dis Soc 6:123–128CrossRefGoogle Scholar
  47. 47.
    Green DA, Srinivas N, Watz N, Tenover FC, Amieva M, Banaei N (2013) A pediatric case of New Delhi metallo-beta-lactamase-1-producing Enterobacteriaceae in the United States. Pediatr Infect Dis J 32:1291–1294CrossRefGoogle Scholar
  48. 48.
    Kresken M, Pfeifer Y, Hafner D, Wresch R, Korber-Irrgang B, Working Party 'Antimicrobial Resistance' of the Paul-Ehrlich-Society for Chemotherapy (2014) Occurrence of multidrug resistance to oral antibiotics among Escherichia coli urine isolates from outpatient departments in Germany: extended-spectrum beta-lactamases and the role of fosfomycin. Int J Antimicrob Agents 44:295–300CrossRefGoogle Scholar
  49. 49.
    Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE (2010) Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis 10:43–50CrossRefGoogle Scholar
  50. 50.
    Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ (2016) Fosfomycin. Clin Microbiol Rev 29:321–347CrossRefGoogle Scholar
  51. 51.
    Falagas ME, Vouloumanou EK, Togias AG, Karadima M, Kapaskelis AM, Rafailidis PI, Athanasiou S (2010) Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother 65:1862–1877CrossRefGoogle Scholar
  52. 52.
    Traunmuller F, Popovic M, Konz KH, Vavken P, Leithner A, Joukhadar C (2011) A reappraisal of current dosing strategies for intravenous fosfomycin in children and neonates. Clin Pharmacokinet 50:493–503CrossRefGoogle Scholar
  53. 53.
    Salomonsson P, von Linstow ML, Knudsen JD, Heiberg I, Mola G, Wenger TR, Cortes D, Nygaard U (2016) Best oral empirical treatment for pyelonephritis in children: do we need to differentiate between age and gender? Infect Dis Ther 48:721–725CrossRefGoogle Scholar
  54. 54.
    Thomas K, Weinbren MJ, Warner M, Woodford N, Livermore D (2006) Activity of mecillinam against ESBL producers in vitro. J Antimicrob Chemother 57:367–368CrossRefGoogle Scholar
  55. 55.
    Salam MA, Dhar U, Khan WA, Bennish ML (1998) Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis. Lancet 352:522–527CrossRefGoogle Scholar
  56. 56.
    (1991) Short-term treatment of acute urinary tract infection in girls. Copenhagen Study Group of Urinary Tract Infections in Children. Scand J Infect Dis 23:213–220Google Scholar
  57. 57.
    Concia E, Bragantini D, Mazzaferri F (2017) Clinical evaluation of guidelines and therapeutic approaches in multi drug-resistant urinary tract infections. J Chemother 29:19–28CrossRefGoogle Scholar
  58. 58.
    Strohmeier Y, Hodson EM, Willis NS, Webster AC, Craig JC (2014) Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev 7:CD003772Google Scholar
  59. 59.
    Glasser JS, Markelz AE, Zera WC, Beckius ML, Mende K, Murray CK (2011) Oral antibiotics for infections due to multidrug-resistant gram-negative organisms. Scand J Infect Dis 43:649–651CrossRefGoogle Scholar
  60. 60.
    Meropol SB, Haupt AA, Debanne SM (2018) Incidence and outcomes of infections caused by multidrug-resistant Enterobacteriaceae in children, 2007-2015. J Pediatric Infect Dis Soc 7:36–45CrossRefGoogle Scholar
  61. 61.
    Kim JY, Sohn JW, Park DW, Yoon YK, Kim YM, Kim MJ (2008) Control of extended-spectrum {beta}-lactamase-producing Klebsiella pneumoniae using a computer-assisted management program to restrict third-generation cephalosporin use. J Antimicrob Chemother 62:416–421CrossRefGoogle Scholar
  62. 62.
    Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, Chesney RW, Carpenter MA (2014) Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 370:2367–2376CrossRefGoogle Scholar

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© IPNA 2019

Authors and Affiliations

  1. 1.School of Women’s & Children’s Health, UNSW MedicineUniversity of New South WalesSydneyAustralia
  2. 2.Department of Immunology and Infectious DiseasesSydney Children’s HospitalRandwickAustralia
  3. 3.National Centre for Infections in Cancer, Peter MacCallum Cancer CentreMelbourneAustralia
  4. 4.Department of Infectious DiseasesBlacktown HospitalSydneyAustralia
  5. 5.Department of Infectious DiseasesNepean HospitalSydneyAustralia
  6. 6.Department of NephrologySydney Children’s HospitalRandwickAustralia

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