1887

Journal of Medical Microbiology logo

Volume 70, Issue 9

Sickle cell disease children’s gut colonization by extended-spectrum β-lactamase (ESBL)-producing : an antibiotic prophylaxis effect? No Access

Abstract

Sickle cell disease (SCD) children have a high susceptibility to pneumococcal infection. For this reason, they are routinely immunized with pneumococcal vaccines and use antibiotic prophylaxis (AP).

Yet, little is known about SCD children’s gut microbiota. If antibiotic-resistant may colonize people on AP, we hypothesized that SCD children on AP are colonized by resistant enterobacteria species.

To evaluate the effect of continuous AP on gut colonization from children with SCD.

We analysed 30 faecal swabs from SCD children on AP and 21 swabs from children without the same condition. was isolated on MacConkey agar plates and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (bioMérieux, Marcy l'Etoile, France). We performed the antibiogram by Vitek 2 system (bioMérieux, Marcy l'Etoile, France), and the resistance genes were identified by multiplex PCR.

We found four different species with resistance to one or more different antibiotic types in the AP-SCD children’s group: , , , and . Colonization by resistant was associated with AP (prevalence ratio 2.69, 95 % confidence interval [CI], 1.98–3.67, <0.001). Strains producing extended-spectrum β-lactamases (ESBL) were identified only in SCD children, , 4/30 (13 %), and , 2/30 (7 %). The ESBL-producing were associated with penicillin G benzathine use (95 % CI, 22.91–86.71, <0.001). CTX-M-1 was the most prevalent among ESBL-producers (3/6, 50 %), followed by CTX-M-9 (2/6, 33 %), and CTX-M-2 (1/6, 17 %).

Resistant enterobacteria colonize SCD children on AP, and this therapy raises the chance of ESBL-producing colonization. Future studies should focus on prophylactic vaccines as exclusive therapy against pneumococcal infections.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antibiotic prophylaxis , Enterobacterales , gut microbiota , multidrug resistance and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and sickle cell disease
Funding
This study was supported by the:
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Award 001)
    • Principle Award Recipient: de Souza Santos MonteiroAdriano
  • Fundação de Amparo à Pesquisa do Estado da Bahia (Award SUS0036/2018)
    • Principle Award Recipient: ApplicableNot
© 2021 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001414
2021-09-03
2024-04-23
Loading full text...

Full text loading...

References

  1. El Hoss S, Brousse V. Considering the spleen in sickle cell disease. Expert Rev Hematol 2019; 12:563–573 [View Article] [PubMed]
     [Google Scholar]
  2. Telfer P, Coen P, Chakravorty S, Wilkey O, Evans J et al. Clinical outcomes in children with sickle cell disease living in England: A neonatal cohort in East London. Haematologica 2007; 92:905–912 [View Article] [PubMed]
     [Google Scholar]
  3. Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood 2010; 115:3447–3452 [View Article] [PubMed]
     [Google Scholar]
  4. Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med 1986; 314:1593–1599 [View Article] [PubMed]
     [Google Scholar]
  5. Halasa NB, Shankar SM, Talbot TR, Arbogast PG, Mitchel EF et al. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2007; 44:1428–1433 [View Article] [PubMed]
     [Google Scholar]
  6. Hirst C, Owusu-Ofori S. Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease. Cochrane Database Syst Rev 2014CD003427 [View Article] [PubMed]
     [Google Scholar]
  7. Magnus SA, Hambleton IR, Moosdeen F, Serjeant GR. Recurrent infections in homozygous sickle cell disease. Arch Dis Child 1999; 80:537–541 [View Article] [PubMed]
     [Google Scholar]
  8. Williams TN, Uyoga S, Macharia A, Ndila C, McAuley CF et al. Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case-control study. Lancet 2009; 374:1364–1370 [View Article] [PubMed]
     [Google Scholar]
  9. Guentzel MN. Escherichia, Klebsiella, Enterobacter, Serratia, Citrobacter and Proteus. Baron S. eds In Medical Microbiology, 4th. edn Galveston (TX: University of Texas Medical Branch at Galveston; 1996
     [Google Scholar]
  10. Talebi Bezmin Abadi A, Rizvanov AA, Haertlé T, Blatt NL. World Health Organization Report: Current crisis of antibiotic resistance. BioNanoSci 2019; 9:778–788 [View Article]
     [Google Scholar]
  11. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 201818318–327 [View Article] [PubMed]
     [Google Scholar]
  12. De Angelis G, Del Giacomo P, Posteraro B, Sanguinetti M, Tumbarello M. Molecular mechanisms, epidemiology, and clinical importance of β-lactam resistance in enterobacteriaceae. Int J Mol Sci 2020; 21:5090 [View Article] [PubMed]
     [Google Scholar]
  13. Chow JW, Fine MJ, Shlaes DM, Quinn JP, Hooper DC et al. Enterobacter bacteremia: Clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med 1991; 115:585–590 [View Article] [PubMed]
     [Google Scholar]
  14. Zhang L, Huang Y, Zhou Y, Buckley T, Wang HH. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota. Antimicrob Agents Chemother 2013; 57:3659–3666 [View Article] [PubMed]
     [Google Scholar]
  15. CLSI Performance Standards for Antimicrobial Susceptibility Testing, 29th ed. CLSI M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019
     [Google Scholar]
  16. ANVISA Technical Note no 01/2013: Measures for the Prevention and Control of Infections by Multidrug-resistant Enterobacteria Brasília: DF: Brazilian Health Regulatory Agency; 2013 pp 1–22
     [Google Scholar]
  17. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268–281 [View Article] [PubMed]
     [Google Scholar]
  18. Dallenne C, da Costa A, Decré D, Favier C, Arlet G. Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae. J Antimicrob Chemother 2010; 65:490–495 [View Article] [PubMed]
     [Google Scholar]
  19. Falletta JM, Woods GM, Verter JI, Buchanan GR, Pegelow CH et al. Discontinuing penicillin prophylaxis in children with sickle cell anemia. J Pediatr 1995; 127:685–690 [View Article] [PubMed]
     [Google Scholar]
  20. Rocha LC, Carvalho MOS, Nascimento VML, dos Santos MS, Barros TF et al. Nasopharyngeal and oropharyngeal colonization by Staphylococcus aureus and Streptococcus pneumoniae and prognostic markers in children with sickle cell disease from the Northeast of Brazil. Front Microbiol 2017; 8:217 [View Article] [PubMed]
     [Google Scholar]
  21. Roger LC, McCartney AL. Longitudinal investigation of the faecal microbiota of healthy full-term infants using fluorescence in situ hybridization and denaturing gradient gel electrophoresis. Microbiology (Reading) 2010; 156:3317–3328 [View Article] [PubMed]
     [Google Scholar]
  22. Bitarães EL, de OB, Viana MB. Compliance with antibiotic prophylaxis in children with sickle cell anemia: a prospective study. J Pediatr (Rio J) 2008; 84:316–322 [View Article] [PubMed]
     [Google Scholar]
  23. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16s rRNA sequencing. PLoS Biol 2008; 6:e280 [View Article] [PubMed]
     [Google Scholar]
  24. Panda S, Khader E, Casellas F, López Vivancos J, García Cors M et al. Short-term effect of antibiotics on human gut microbiota. PLoS One 2014; 9:e95476 [View Article] [PubMed]
     [Google Scholar]
  25. Hanna-Wakim RH, Ghanem ST, El Helou MW, Khafaja SA, Shaker RA et al. Epidemiology and characteristics of urinary tract infections in children and adolescents. Front Cell Infect Microbiol 2015; 5:45 [View Article] [PubMed]
     [Google Scholar]
  26. Henderson JP, Crowley JR, Pinkner JS, Walker JN, Tsukayama P et al. Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli. PLoS Pathog 2009; 5:e1000305 [View Article] [PubMed]
     [Google Scholar]
  27. Peña C, Pujol M, Ardanuy C, Ricart A, Pallares R et al. Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended spectrum β-lactamases. Antimicrob Agents Chemother 1998; 42:53–58 [View Article] [PubMed]
     [Google Scholar]
  28. Richard P, Delangle MH, Raffi F, Espaze E, Richet H. Impact of fluoroquinolone administration on the emergence of fluoroquinolone-resistant gram-negative bacilli from gastrointestinal flora. Clin Infect Dis 2001; 32:162–166 [View Article] [PubMed]
     [Google Scholar]
  29. Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: A major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev 2017; 41:252–275 [View Article] [PubMed]
     [Google Scholar]
  30. Kang CI, Kim SH, Bang JW, Bin KH, Kim NJ et al. Community-acquired versus nosocomial Klebsiella pneumoniae bacteremia: Clinical features, treatment outcomes, and clinical implication of antimicrobial resistance. J Korean Med Sci 2006; 21:816–822 [View Article] [PubMed]
     [Google Scholar]
  31. Ko W-C, Paterson DL, Sagnimeni AJ, Hansen DS, Von Gottberg A et al. Community-acquired Klebsiella pneumoniae bacteremia: Global differences in clinical patterns. Emerg Infect Dis 2002; 8:160–166 [View Article] [PubMed]
     [Google Scholar]
  32. Martin RM, Cao J, Brisse S, Passet V, Wu W et al. Molecular epidemiology of colonizing and infecting isolates of Klebsiella pneumoniae. mSphere 2016; 1:e00261-16 [View Article] [PubMed]
     [Google Scholar]
  33. Kizilca O, Siraneci R, Yilmaz A, Hatipoglu N, Ozturk E et al. Risk factors for community-acquired urinary tract infection caused by ESBL-producing bacteria in children. Pediatr Int 2012; 54:858–862 [View Article] [PubMed]
     [Google Scholar]
  34. Pitout JD, Laupland KB. Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis 2008; 8:159–166 [View Article] [PubMed]
     [Google Scholar]
  35. Khanfar HS, Bindayna KM, Senok AC, Botta GA. Extended spectrum beta-lactamases (ESBL) in Escherichia coli and Klebsiella pneumoniae: trends in the hospital and community settings. J Infect Dev Ctries 2009; 3:295–299 [View Article] [PubMed]
     [Google Scholar]
  36. Pitout JDD. Enterobacteriaceae that produce extended-spectrum β-lactamases and AmpC β-lactamases in the community: the tip of the iceberg?. Curr Pharm Des 2013; 19:257–263 [View Article] [PubMed]
     [Google Scholar]
  37. Shah AA, Hasan F, Ahmed S, Hameed A. Characteristics, epidemiology and clinical importance of emerging strains of Gram-negative bacilli producing extended-spectrum β-lactamases. Res Microbiol 2004; 155:409–421 [View Article] [PubMed]
     [Google Scholar]
  38. Blazquez J, Baquero MR, Canton R, Alos I, Baquero F. Characterization of a new TEM-type β-lactamase resistant to clavulanate, sulbactam, and tazobactam in a clinical isolate of Escherichia coli. Antimicrob Agents Chemother 1993; 37:2059–2063 [View Article] [PubMed]
     [Google Scholar]
  39. Zhou K, Tao Y, Han L, Ni Y, Sun J. Piperacillin-tazobactam (TZP) resistance in Escherichia coli due to hyperproduction of tem-1 β-lactamase mediated by the promoter PA/PB. Front Microbiol 2019; 10:833 [View Article]
     [Google Scholar]
  40. Luvsansharav UO, Hirai I, Nakata A, Imura K, Yamauchi K et al. Prevalence of and risk factors associated with faecal carriage of CTX-M β-lactamase-producing Enterobacteriaceae in rural Thai communities. J Antimicrob Chemother 2012; 67:1769–1774 [View Article] [PubMed]
     [Google Scholar]
  41. Leal HF, Azevedo J, Silva GEO, Amorim AML, de Roma LRC et al. Bloodstream infections caused by multidrug-resistant gram-negative bacteria: epidemiological, clinical and microbiological features. BMC Infect Dis 2019; 19:609 [View Article] [PubMed]
     [Google Scholar]
  42. Villegas M, Kattan JN, Quinteros MG, Casellas JM. Prevalence of extended-spectrum β-lactamases in South America. Clin Microbiol Infect 2008; 14:154–158 [View Article] [PubMed]
     [Google Scholar]
  43. Rocha FR, Pinto VPT, Barbosa FCB. The spread of ctx-m-type extended-spectrum β-lactamases in Brazil: A systematic review. Microb Drug Resist 2016; 22:301–311 [View Article] [PubMed]
     [Google Scholar]
  44. Bonnet R. Growing group of extended-spectrum beta-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 2004; 48:1–14 [View Article] [PubMed]
     [Google Scholar]
  45. Sedman PC, Macfle J, Sagar P, Mitchell CJ, May J et al. The prevalence of gut translocation in humans. Gastroenterology 1994; 107:643–649 [View Article] [PubMed]
     [Google Scholar]
  46. O’Boyle CJ, MacFie J, Mitchell CJ, Johnstone D, Sagar PM et al. Microbiology of bacterial translocation in humans. Gut 1998; 42:29–35 [View Article] [PubMed]
     [Google Scholar]
  47. Donskey CJ. The role of the intestinal tract as a source for transmission of nosocomial pathogens. Curr Infect Dis Rep 2004; 39:219–226 [View Article]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001414
Loading
Sickle cell disease children’s gut colonization by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales: an antibiotic prophylaxis effect?
J. Med. Microbiol. 70, 001414 (2021); https://doi.org/10.1099/jmm.0.001414
/content/journal/jmm/10.1099/jmm.0.001414
/content/journal/jmm/10.1099/jmm.0.001414
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error