Abstract

Objective: Klebsiella spp. is a common and severe pathogen of bloodstream infections (BSI) due to gram-negative bacilli. Carbapenems are commonly used agents for the treatment of serious infections. However, the incidence of carbapenem-resistant (CR) Klebsiella infections has increased significantly in recent years. The aim of this study was to determine the characteristics, risk factors, and outcomes of BSI caused by Klebsiella spp. in a tertiary care pediatric hospital.

Method: A retrospective review of pediatric patients with BSI caused by Klebsiella spp. between August 2019 and September 2021 was conducted. Patients with CR isolates were compared with carbapenem-susceptible (CS) isolates for risk factors, outcome, and mortality.

Results: Among 345 Klebsiella isolates, 95 (27.5%) were CR. Catheter-related bloodstream infections (CRBSI) accounted for 52.4% of infections. There was an underlying disease in all patients, most commonly malignancy (31.3%). Mechanical ventilation, percutaneous endoscopic gastrostomy (PEG) tube feeding, previous antibiotic use, especially carbapenems, aminoglycosides, glycopeptides, fluoroquinolones, and colistin, (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p: 0.033, p<0.001, respectively) were strongly affected the development of BSI due to CR Klebsiella spp. Antibiotic treatment in the previous 14 days increased the risk of developing carbapenem resistance by 14 times. Elevated C-reactive protein (CRP) (p<0.001), thrombocytopenia (p<0.001), CRBSI (p=0.002), use of indwelling devices, previous antibiotic therapy (carbapenems, aminoglycosides, glycopeptides, colistin) (p=0.002), and carbapenem resistance (p=0.001) increased the risk of mortality from Klebsiella-associated BSI. The use of colistin in treatment was higher in the CR group (p<0.001). The 28-day mortality was 15.7%.

Conclusion: CR Klebsiella spp. Infections are important and serious causes of BSI in children. The use of indwelling devices and previous antibiotic therapy are risk factors for mortality and carbapenem resistance. Preventive measures, including targeted antimicrobial therapy, good surveillance networks, and less invasive procedures, are important aspects of infection control management in children.

Keywords: Antibiotic resistance, carbapenem, children, Klebsiella

Copyright and license

How to cite

1.
Yahşi A, Bayhan GI, Arslan E, Gökdöl MY, Atay BN, Karaciğer S, et al. Characteristics of Klebsiella bloodstream infections and risk factors for carbapenem-resistant Klebsiella infections in children. Trends in Pediatrics. 2023;4(2):133-142. https://doi.org/10.59213/TP.2023.18894

References

  1. Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005;41:848-54. https://doi.org/10.1086/432803
  2. Marra AR, Camargo LF, Pignatari AC, et al. Nosocomial bloodstream infections in Brazilian hospitals: analysis of 2,563 cases from a prospective nationwide surveillance study. J Clin Microbiol. 2011;49:1866-71. https://doi.org/10.1128/JCM.00376-11
  3. Kosmidis C, Poulakou G, Markogiannokis A, Daikos GL. Treatment Options for Infections Caused by Carbapenem-resistant Gram-negative bacteria. Eur Infect Dis. 2012;6:23-34.
  4. CDC. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE)-November 2015 update CRE toolkit. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. Available at: http://www.cdc.gov/hai/organisms/cre/cre-toolkit (Accessed on April 15, 2023).
  5. Huttner A, Harbarth S, Carlet J, et al. Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum. Antimicrob Resist Infect Control. 2013;2:31. https://doi.org/10.1186/2047-2994-2-31
  6. Lugo DJ, Fisher RG. Klebsiella. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ editors. Feigin and Cherry's Textbook of Pediatric Infectious Diseases (8th ed). Philadelphia: Elsevier; 2019:1046-49.
  7. Lin YT, Liu CJ, Yeh YC, Chen TJ, Fung CP. Ampicillin and amoxicillin use and the risk of Klebsiella pneumoniae liver abscess in Taiwan. J Infect Dis. 2013;208:211-7. https://doi.org/10.1093/infdis/jit157
  8. Paterson DL, Ko WC, Von Gottberg A, et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections. Ann Intern Med. 2004;140:26-32. https://doi.org/10.7326/0003-4819-140-1-200401060-00008
  9. Tanır Basaranoglu S, Ozsurekci Y, Aykac K, et al. A comparison of blood stream infections with extended spectrum beta-lactamase-producing and non-producing Klebsiella pneumoniae in pediatric patients. Ital J Pediatr. 2017;43:79. https://doi.org/10.1186/s13052-017-0398-0
  10. Ozsurekci Y, Aykac K, Cengiz AB, et al. Bloodstream infections in children caused by carbapenem-resistant versus carbapenem-susceptible gram-negative microorganisms: Risk factors and outcome. Diagn Microbiol Infect Dis. 2017;87:359-64. https://doi.org/10.1016/j.diagmicrobio.2016.12.013
  11. Hugonnet S, Sax H, Eggimann P, Chevrolet JC, Pittet D. Nosocomial bloodstream infection and clinical sepsis. Emerg Infect Dis. 2004;10:76-81. https://doi.org/10.3201/eid1001.030407
  12. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49:1-45. https://doi.org/10.1086/599376
  13. Theodorou VP, Papaioannou VE, Tripsianis GA, et al. Procalcitonin and procalcitonin kinetics for diagnosis and prognosis of intravascular catheter-related bloodstream infections in selected critically ill patients: a prospective observational study. BMC Infect Dis. 2012;12:247. https://doi.org/10.1186/1471-2334-12-247
  14. EUCAST. European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs and zone diameters. Version 13.0, 01.01.2023. Available at: https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_13.0_Breakpoint_Tables.pdf (Accessed on April 15, 2023).
  15. Telli M. Investigetion of Carbapenem Resistance Ratio Changes and Resistange Genes in Clinical Isolates of Klebsiella pneumoniae Between 2012 to 2020. Turk Mikrobiyol Cemiy Derg. 2022;52:95-102. https://doi.org/10.54453/TMCD.2022.05025
  16. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL, European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) working group. Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill. 2015;20:1-18. https://doi.org/10.2807/1560-7917.ES.2015.20.45.30062
  17. Central Asian and European Surveillance of Antimicrobial Resistance. Annual report 2020. Available at: https://www.euro.who.int/en/health-topics/disease-prevention/antimicrobial-resistance/publications/2020/central-asian-and-europeansurveillance-of-antimicrobial-resistance.-annualreport-2020 (Accessed on April 15, 2023).
  18. Büyüktuna SA, Hasbek M, Çelik C, et al. Klebsiella pneumoniae Infections in the Intensive Care Unit: Risk Factors Related to Carbapenem Resistance and Patient Mortality. Mikrobiyol Bul. 2020;54:378-91. https://doi.org/10.5578/mb.69679
  19. Nabarro LEB, Shankar C, Pragasam AK, et al. Clinical and Bacterial Risk Factors for Mortality in Children With Carbapenem-resistant Enterobacteriaceae Bloodstream Infections in India. Pediatr Infect Dis J. 2017;36:e161-6. https://doi.org/10.1097/INF.0000000000001499
  20. Wattal C, Goel N. Pediatric Blood Cultures and Antibiotic Resistance: An Overview. Indian J Pediatr. 2020;87:125-31. https://doi.org/10.1007/s12098-019-03123-y
  21. Lake JG, Weiner LM, Milstone AM, Saiman L, Magill SS, See I. Pathogen Distribution and Antimicrobial Resistance Among Pediatric Healthcare-Associated Infections Reported to the National Healthcare Safety Network, 2011-2014. Infect Control Hosp Epidemiol. 2018;39:1-11. https://doi.org/10.1017/ice.2017.236
  22. Aykac K, Ozsurekci Y, Tanır Basaranoglu S, et al. Current epidemiology of resistance among Gram-negative bacilli in paediatric patients in Turkey. J Glob Antimicrob Resist. 2017;11:140-4. https://doi.org/10.1016/j.jgar.2017.07.018
  23. Liu P, Li X, Luo M, et al. Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection: A Meta-Analysis. Microb Drug Resist. 2018;24:190-8. https://doi.org/10.1089/mdr.2017.0061
  24. Aygun F, Aygun FD, Varol F, et al. Infections with Carbapenem-Resistant Gram-Negative Bacteria are a Serious Problem Among Critically Ill Children: A Single-Centre Retrospective Study. Pathogens. 2019;8:69. https://doi.org/10.3390/pathogens8020069
  25. Zhang Y, Guo LY, Song WQ, Wang Y, Dong F, Liu G. Risk factors for carbapenem-resistant K. pneumoniae bloodstream infection and predictors of mortality in Chinese paediatric patients. BMC Infect Dis. 2018;18:248. https://doi.org/10.1186/s12879-018-3160-3
  26. Deresinski SC, Schirmer P. Management of infections due to KPC-producing Klebsiella pneumoniae. F1000 Med Rep. 2009;1:79. https://doi.org/10.3410/M1-79
  27. Lee CS, Doi Y. Therapy of Infections due to Carbapenem-Resistant Gram-Negative Pathogens. Infect Chemother. 2014;46:149-64. https://doi.org/10.3947/ic.2014.46.3.149
  28. Tumbarello M, Viale P, Viscoli C, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55:943-50. https://doi.org/10.1093/cid/cis588
  29. Kontopidou F, Giamarellou H, Katerelos P, et al. Infections caused by carbapenem-resistant Klebsiella pneumoniae among patients in intensive care units in Greece: a multi-centre study on clinical outcome and therapeutic options. Clin Microbiol Infect. 2014;20:O117-23. https://doi.org/10.1111/1469-0691.12341
  30. Zarkotou O, Pournaras S, Tselioti P, et al. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin Microbiol Infect. 2011;17:1798-803. https://doi.org/10.1111/j.1469-0691.2011.03514.x