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Volume 30, Number 6—June 2024
CME ACTIVITY - Research

Carbapenem-Resistant and Extended-Spectrum β-Lactamase–Producing Enterobacterales in Children, United States, 2016–2020

Heather N. GromeComments to Author , Julian E. Grass, Nadezhda Duffy, Sandra N. Bulens, Uzma Ansari, Davina Campbell, Joseph D. Lutgring, Amy S. Gargis, Thao Masters, Alyssa G. Kent, Susannah L. McKay, Gillian Smith, Lucy E. Wilson, Elisabeth Vaeth, Bailey Evenson, Ghinwa Dumyati, Rebecca Tsay, Erin Phipps, Kristina Flores, Christopher D. Wilson, Christopher A. Czaja, Helen Johnston, Sarah J. Janelle, Ruth Lynfield, Sean O’Malley, Paula Snippes Vagnone, Meghan Maloney, Joelle Nadle, and Alice Y. Guh
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (H.N. Grome, J.E. Grass, N. Duffy, S.N. Bulens, U. Ansari, D. Campbell, J.D. Lutgring, A.S. Gargis, T. Masters, A.G. Kent, S.L. McKay, A.Y. Guh); Foundation for Atlanta Veterans Education and Research, Decatur, Georgia, USA (G. Smith); Atlanta Veterans Affairs Medical Center, Decatur (G. Smith); Maryland Department of Health, Baltimore, Maryland, USA (L.E. Wilson, E. Vaeth, B. Evenson); New York Rochester Emerging Infections Program at the University of Rochester Medical Center, Rochester, New York, USA (G. Dumyati, R. Tsay); University of New Mexico, Albuquerque, New Mexico, USA (E. Phipps, K. Flores); New Mexico Emerging Infections Program, Santa Fe, New Mexico, USA (E. Phipps, K. Flores); Tennessee Department of Health, Nashville, Tennessee, USA (C.D. Wilson); Colorado Department of Public Health and Environment, Denver, Colorado, USA (C.A. Czaja, H. Johnston, S.J. Janelle); Minnesota Department of Health, St. Paul, Minnesota, USA (R. Lynfield, S. O’Malley, P. Snippes Vagnone); Connecticut Department of Public Health, Hartford, Connecticut, USA (M. Maloney); California Emerging Infections Program, Oakland, California, USA (J. Nadle)

Main Article

Table 1

Incident CP and ESBL-E–producing Enterobacterales cases in children, by organism, United States*

Organism Incident CRE cases, 2016–2020
 Incident ESBL-E cases, 2019–2020†
No. (%) cases Isolates submitted for carbapenemase testing, no. No. (%) CP isolates‡ No. (%) carbapenemase genes‡
 No. (%) cases No. isolates submitted for ESBL testing No. (%) ESBL-producing organisms§
blaKPC blaNDM blaOXA-48-like
Escherichia coli 50 (31.5) 26 5 (19.2) 0 2 (7.7) 3 (11.5) 182 (87.9) 16 15 (93.8)
Enterobacter cloacae complex 83 (52.2) 47 1 (2.1) 1 (2.1) 0 0 NA NA NA
Klebsiella aerogenes 5 (3.1) 4 1 (25.5) 0 1 (25.0) 0 NA NA NA
K. oxytoca 4 (2.5) 1 1 (100.0) 1 (100) 0 0 2 (1.0) NA NA
K. pneumoniae
 17 (10.7)
 8
 1 (12.5)
 0
 1 (12.5)
 0
23 (11.1)
 3
 3 (100.0)
Total 159 86 9 (10.5) 2 (2.3) 4 (4.7) 3 (3.5) 207 19 18 (94.7)

*All incident pediatric cases with available case report form data as of November 28, 2022, were included in this analysis. CP, carbapenemase-producing; CRE, carbapenem-resistant Enterobacterales; ESBL-E, extended-spectrum β-lactamase–producing Enterobacterales; NA, not applicable (no organisms tested; ESBL-E surveillance included Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae). †ESBL-E surveillance began in July 2019 at all participating sites. California, Connecticut, Minnesota, and Oregon do not participate in ESBL-E surveillance. ‡Percentages shown are of isolates submitted. Carbapenemases and colistin resistance genes not listed in the table were not detected for any isolates. §Percentages shown are of isolates submitted. Phenotypic screening for ESBL-E production was performed by using ceftazidime and cefotaxime alone and in combination with clavulanate according to Clinical and Laboratory Standards Institute guidelines (24).

Main Article

References
  1. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019 [cited 2024 Apr 22]. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
  2. Centers for Disease Control and Prevention. COVID-19: US impact on antimicrobial resistance [cited 2024 Apr 22]. https://www.cdc.gov/drugresistance/pdf/covid19-impact-report-508.pdf
  3. Logan  LK, Weinstein  RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis. 2017;215(suppl_1):S28–36. DOIPubMedGoogle Scholar
  4. Braykov  NP, Eber  MR, Klein  EY, Morgan  DJ, Laxminarayan  R. Trends in resistance to carbapenems and third-generation cephalosporins among clinical isolates of Klebsiella pneumoniae in the United States, 1999-2010. Infect Control Hosp Epidemiol. 2013;34:259–68. DOIPubMedGoogle Scholar
  5. Guh  AY, Bulens  SN, Mu  Y, Jacob  JT, Reno  J, Scott  J, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae in 7 US communities, 2012–2013. JAMA. 2015;314:1479–87. DOIPubMedGoogle Scholar
  6. Kritsotakis  EI, Tsioutis  C, Roumbelaki  M, Christidou  A, Gikas  A. Antibiotic use and the risk of carbapenem-resistant extended-spectrum-β-lactamase-producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case-control study. J Antimicrob Chemother. 2011;66:1383–91. DOIPubMedGoogle Scholar
  7. Swaminathan  M, Sharma  S, Poliansky Blash  S, Patel  G, Banach  DB, Phillips  M, et al. Prevalence and risk factors for acquisition of carbapenem-resistant Enterobacteriaceae in the setting of endemicity. Infect Control Hosp Epidemiol. 2013;34:809–17. DOIPubMedGoogle Scholar
  8. Marchaim  D, Chopra  T, Bhargava  A, Bogan  C, Dhar  S, Hayakawa  K, et al. Recent exposure to antimicrobials and carbapenem-resistant Enterobacteriaceae: the role of antimicrobial stewardship. Infect Control Hosp Epidemiol. 2012;33:817–30. DOIPubMedGoogle Scholar
  9. Duffy  N, Karlsson  M, Reses  HE, Campbell  D, Daniels  J, Stanton  RA, et al. Epidemiology of extended-spectrum β-lactamase-producing Enterobacterales in five US sites participating in the Emerging Infections Program, 2017. Infect Control Hosp Epidemiol. 2022;43:1586–94. DOIPubMedGoogle Scholar
  10. Tamma  PD, Aitken  SL, Bonomo  RA, Mathers  AJ, van Duin  D, Clancy  CJ. Infectious Diseases Society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections. Clin Infect Dis. 2023;ciad428
  11. Romandini  A, Pani  A, Schenardi  PA, Pattarino  GAC, De Giacomo  C, Scaglione  F. Antibiotic resistance in pediatric infections: global emerging threats, predicting the near future. Antibiotics (Basel). 2021;10:393. DOIPubMedGoogle Scholar
  12. Logan  LK, Bonomo  RA. Metallo-β-lactamase (MBL)-producing Enterobacteriaceae in United States children. Open Forum Infect Dis. 2016;3:ofw090. DOIPubMedGoogle Scholar
  13. Logan  LK, Medernach  RL, Domitrovic  TN, Rispens  JR, Hujer  AM, Qureshi  NK, et al. The clinical and molecular epidemiology of CTX-M-9 group producing Enterobacteriaceae infections in children. Infect Dis Ther. 2019;8:243–54. DOIPubMedGoogle Scholar
  14. Logan  LK, Hujer  AM, Marshall  SH, Domitrovic  TN, Rudin  SD, Zheng  X, et al. Analysis of beta-lactamase resistance determinants in Enterobacteriaceae from Chicago children: a multicenter survey. Antimicrob Agents Chemother. 2016;60:3462–9. DOIPubMedGoogle Scholar
  15. Logan  LK, Rispens  JR, Medernach  RL, Domitrovic  TN, Hujer  AM, Marshall  SH, et al. A multicentered study of the clinical and molecular epidemiology of TEM- and SHV-type extended-spectrum beta-lactamase producing Enterobacterales infections in children. Pediatr Infect Dis J. 2021;40:39–43. DOIPubMedGoogle Scholar
  16. Logan  LK, Medernach  RL, Rispens  JR, Marshall  SH, Hujer  AM, Domitrovic  TN, et al. Community origins and regional differences highlight risk of plasmid-mediated fluoroquinolone resistant Enterobacteriaceae infections in children. Pediatr Infect Dis J. 2019;38:595–9. DOIPubMedGoogle Scholar
  17. Zerr  DM, Weissman  SJ, Zhou  C, Kronman  MP, Adler  AL, Berry  JE, et al. The molecular and clinical epidemiology of extended-spectrum cephalosporin- and carbapenem-resistant Enterobacteriaceae at 4 US pediatric hospitals. J Pediatric Infect Dis Soc. 2017;6:366–75. DOIPubMedGoogle Scholar
  18. Chiotos  K, Tamma  PD, Flett  KB, Naumann  M, Karandikar  MV, Bilker  WB, et al. Multicenter study of the risk factors for colonization or infection with carbapenem-resistant Enterobacteriaceae in children. Antimicrob Agents Chemother. 2017;61:e01440–17. DOIPubMedGoogle Scholar
  19. Meropol  SB, Haupt  AA, Debanne  SM. Incidence and outcomes of infections caused by multidrug-resistant Enterobacteriaceae in children, 2007–2015. J Pediatric Infect Dis Soc. 2018;7:36–45. DOIPubMedGoogle Scholar
  20. Centers for Disease Control and Prevention. Multi-site Gram-negative Surveillance Initiative [cited 2023 Apr 24]. https://www.cdc.gov/hai/eip/mugsi.html#anchor_46658
  21. US Census Bureau. 2020 Population estimates 2020 [cited 2023 Jan 19]. https://www.census.gov/quickfacts/fact/faq/US/PST045221
  22. Migliavacca  R, Docquier  JD, Mugnaioli  C, Amicosante  G, Daturi  R, Lee  K, et al. Simple microdilution test for detection of metallo-β-lactamase production in Pseudomonas aeruginosa. J Clin Microbiol. 2002;40:4388–90. DOIPubMedGoogle Scholar
  23. Karlsson  M, Lutgring  JD, Ansari  U, Lawsin  A, Albrecht  V, McAllister  G, et al. Molecular characterization of carbapenem-resistant Enterobacterales collected in the United States. Microb Drug Resist. 2022;28:389–97. DOIPubMedGoogle Scholar
  24. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; 33rd edition. Supplement M100. Wayne (PA): The Institute; 2023.
  25. Rasheed  JK, Kitchel  B, Zhu  W, Anderson  KF, Clark  NC, Ferraro  MJ, et al. New Delhi metallo-β-lactamase-producing Enterobacteriaceae, United States. Emerg Infect Dis. 2013;19:870–8. DOIPubMedGoogle Scholar
  26. Lutgring  JD, Zhu  W, de Man  TJB, Avillan  JJ, Anderson  KF, Lonsway  DR, et al. Phenotypic and genotypic characterization of Enterobacteriaceae producing oxacillinase-48-like carbapenemases, United States. Emerg Infect Dis. 2018;24:700–9. DOIPubMedGoogle Scholar
  27. Campbell  D, Daniels  J, Rasheed  JK, Karlsson  M. Development of a multiplex TaqMan probe-based real-time PCR assay for detection of blaIMP variants. Poster presented at: ASM Microbe 2017; New Orleans, LA, USA; 2017 June 1–5.
  28. Prussing  C, Canulla  T, Singh  N, McAuley  P, Gosciminski  M, King  E, et al. Characterization of the first carbapenem-resistant Pseudomonas aeruginosa clinical isolate harboring blaSIM-1 from the United States. Antimicrob Agents Chemother. 2021;65:e0106621. DOIPubMedGoogle Scholar
  29. Daniels  JB, Campbell  D, Boyd  S, Ansari  U, Lutgring  J, Rasheed  JK, et al. Development and validation of a Clinical Laboratory Improvement Amendments-compliant multiplex real-time PCR assay for detection of mcr genes. Microb Drug Resist. 2019;25:991–6. DOIPubMedGoogle Scholar
  30. Logan  LK, Renschler  JP, Gandra  S, Weinstein  RA, Laxminarayan  R; Centers for Disease Control; Prevention Epicenters Program. Carbapenem-Resistant Enterobacteriaceae in Children, United States, 1999-2012. Emerg Infect Dis. 2015;21:2014–21. DOIPubMedGoogle Scholar
  31. Chea  N, Bulens  SN, Kongphet-Tran  T, Lynfield  R, Shaw  KM, Vagnone  PS, et al. Improved phenotype-based definition for identifying carbapenemase producers among carbapenem-resistant Enterobacteriaceae. Emerg Infect Dis. 2015;21:1611–6. DOIPubMedGoogle Scholar
  32. Thaden  JT, Fowler  VG Jr, Sexton  DJ, Anderson  DJ. Increasing incidence of extended-spectrum beta-lactamase-producing Escherichia coli in community hospitals throughout the southeastern United States. Infect Control Hosp Epidemiol. 2016;37:49–54. DOIPubMedGoogle Scholar
  33. Horie  A, Nariai  A, Katou  F, Abe  Y, Saito  Y, Koike  D, et al. Increased community-acquired upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in children and the efficacy of flomoxef and cefmetazole. Clin Exp Nephrol. 2019;23:1306–14. DOIPubMedGoogle Scholar
  34. Collingwood  JD, Yarbrough  AH, Boppana  SB, Dangle  PP. Increasing prevalence of pediatric community-acquired UTI by extended spectrum β-lactamase-producing E. coli: cause for concern. Pediatr Infect Dis J. 2023;42:106–9. DOIPubMedGoogle Scholar
  35. Yin  L, He  L, Miao  J, Yang  W, Wang  X, Ma  J, et al. Carbapenem-resistant Enterobacterales colonization and subsequent infection in a neonatal intensive care unit in Shanghai, China. Infect Prev Pract. 2021;3:100147. DOIPubMedGoogle Scholar
  36. Flannery  DD, Chiotos  K, Gerber  JS, Puopolo  KM. Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management. Pediatr Res. 2022;91:380–91. DOIPubMedGoogle Scholar
  37. Yaffee  AQ, Roser  L, Daniels  K, Humbaugh  K, Brawley  R, Thoroughman  D, et al. Notes from the field: Verona integron-encoded metallo-beta-lactamase-producing carbapenem-resistant Enterobacteriaceae in a neonatal and adult intensive care unit—Kentucky, 2015. MMWR Morb Mortal Wkly Rep. 2016;65:190. DOIPubMedGoogle Scholar
  38. Principe  L, Meroni  E, Conte  V, Mauri  C, Di Pilato  V, Giani  T, et al. Mother-to-child transmission of KPC-producing Klebsiella pneumoniae: potential relevance of a low microbial urinary load for screening purposes. J Hosp Infect. 2018;98:314–6. DOIPubMedGoogle Scholar
  39. Sotgiu  G, Are  BM, Pesapane  L, Palmieri  A, Muresu  N, Cossu  A, et al. Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae in an Italian university hospital: a molecular epidemiological study. J Hosp Infect. 2018;99:413–8. DOIPubMedGoogle Scholar
  40. Islam  S, Selvarangan  R, Kanwar  N, McHenry  R, Chappell  JD, Halasa  N, et al. Intestinal carriage of third-generation cephalosporin-resistant and extended-spectrum β-lactamase-producing Enterobacteriaceae in healthy US children. J Pediatric Infect Dis Soc. 2018;7:234–40. DOIPubMedGoogle Scholar
  41. Wernroth  ML, Peura  S, Hedman  AM, Hetty  S, Vicenzi  S, Kennedy  B, et al. Development of gut microbiota during the first 2 years of life. Sci Rep. 2022;12:9080. DOIPubMedGoogle Scholar
  42. Darda  VM, Iosifidis  E, Antachopoulos  C, Kirvasilis  F, Zarras  C, Simitsopoulou  M, et al. A longitudinal study of spontaneous gut decolonization of carbapenem-resistant gram-negative bacteria in neonatal and pediatric patients. Pediatr Infect Dis J. 2022;41:648–53. DOIPubMedGoogle Scholar
  43. Dierikx  TH, Visser  DH, Benninga  MA, van Kaam  AHLC, de Boer  NKH, de Vries  R, et al. The influence of prenatal and intrapartum antibiotics on intestinal microbiota colonisation in infants: A systematic review. J Infect. 2020;81:190–204. DOIPubMedGoogle Scholar

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