Multidrug resistant bacteremia in hematopoietic stem cell transplant recipients

Authors

  • Ameni Mellouli
  • Yosra Chebbi
  • Rym El Fatmi
  • Anis Raddaoui
  • Amel Lakhal
  • Lamia Torjmane
  • Nour Ben Abdeljelil
  • Dorra Belloumi
  • Salwa Ladeb
  • Tarek Ben Othmen
  • Wafa Achour

Keywords:

Multidrug-resistance; hematopoietic stem cell transplantation; bloodstream infection; associated factors; epidemiology.

Abstract

Background: Bacteremia become fearsome in hematopoietic stem cell transplant (HSCT) recipients with the emergence of multidrug-resistant (MDR) strains.
Aim: Our purpose was to investigate the prevalence of MDR bacteremia in HSCT recipients at the Tunisian National Bone Marrow Transplant Center, associated factors and attributable mortality rate.
Methods: Our retrospective study (January 2010-December 2017) included all MDR bacteremia in the Hematology department. MDR rods were: extended spectrum beta-lactamase producing Enterobacterales (ESBL-E), P. aeruginosa and A. baumannii resistant to at least three families of antibiotics, methicillin-resistant S. aureus (MRSA) and vancomycin resistant E. faecium (VRE).
Results: The prevalence of MDR bacteremia among HSCT recipients was 5.9% (48/816) with a stable trend over time (rs=0.18). Neutropenia, prior hospitalization, prior antibiotherapy and prior colonization with MDR pathogens were observed in 59%, 58%, 48% and 31% of cases, respectively. Imipenem was the most prescribed first-line antibiotic (50%). The attributable mortality rate was 13%. MDR bacteria (n=48) belonged to ESBL-E (60%), P. aeruginosa (19%), A. baumannii (13%), MRSA (4%) and VRE (4%). For ESBL-E and P. aeruginosa, the rates of antibiotic resistance were respectively, 17% and 44% to imipenem, 31% and 56% to amikacin and 15% and 0% to colistin. Strains of A. baumannii were susceptible only to colistin. The MRSA (n=2) were resistant to ciprofloxacin and gentamicin and susceptible to glycopeptides. The VRE (n=2) were susceptible to linezolid and tigecycline.
Conclusion: Low prevalence of MDR bacteremia in HSCT recipients but high attributable mortality rate, requiring reinforcement of hygiene measures.

Downloads

Download data is not yet available.

References

References 1. Gustinetti G, Mikulska M. Bloodstream infections in neutropenic cancer patients: A practical update. Virulence 2016; 7(3): 280-297. DOI: 10.1080/21505594.2016.1156821. 2. Kim HS, Park BK, Kim SK, et al. Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study. BMC Infect Dis 2017; 17(1): 500. DOI: 10.1186/s12879-017-2597-0. 3. Société Française de Microbiologie. REMIC : Référentiel en microbiologie médicale. 5ème édition. Paris: Société Française de Microbiologie ;2015. 4. Société Française de Microbiologie. Recommandations 2017. Paris: SFM;2017. 5. 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): 1-45. DOI: 10.1086/599376. 6. Almyroudis NG, Fuller A, Jakubowski A, et al. Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2005; 7(1): 11-17. DOI: 10.1111/j.1399-3062.2005.00088.x. 7. Oliveira AL, de Souza M, Carvalho-Dias VMH, et al. Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2007; 39(12): 775-781. DOI: 10.1038/sj.bmt.1705677. 8. Ruhnke M, Arnold R, Gastmeier P. Infection control issues in patients with haematological malignancies in the era of multidrug-resistant bacteria. Lancet Oncol 2014; 15(13): 606-619. DOI: 10.1016/S1470-2045(14)70344-4. 9. Balletto E, Mikulska M. Bacterial infections in hematopoietic stem cell transplant recipients. Mediterr J Hematol Infect Dis 2015 ; 7(1) : e2015045. DOI : 10.4084/MJHID.2015.045. 10. Ferreira AM, Moreira F, Guimaraes T, et al. Epidemiology, risk factors and outcomes of multi-drug-resistant bloodstream infections in haematopoietic stem cell transplant recipients: importance of previous gut colonization. J Hosp Infect 2018; 100(1): 83-91. DOI : 10.1016/j.jhin.2018.03.004. 11. Garnica M, Maiolino A, Nucci M. Factors associated with bacteremia due to multidrug-resistant Gram-negative bacilli in hematopoietic stem cell transplant recipients. Braz J Med Biol Res 2009 ; 42(3) : 289-293. DOI : 10.1590/S0100-879X2009000300010. 12. Patriarca F, Cigana C, Massimo D, et al. Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2017; 23(2): 333-339. DOI : 10.1016/j.bbmt.2016.11.005. 13. Satlin MJ, Calfee DP, Chen L, et al. Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies. Leuk Lymphoma 2013; 54(4): 799-806. DOI : 10.3109/10428194.2012.723210. 14. Giannella M, Trecarichi EM, De Rosa FG, et al. Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study. Clin Microbiol Infect 2014; 20(12): 1357-1362. DOI : 10.1111/1469-0691.12747. 15. Martinho GH, Romanelli RM, Teixeira GM, et al. Infectious complications associated with the use of central venous catheters in patients undergoing hematopoietic stem cell transplantation. Am J Infect Control 2013; 41(7): 642-644. DOI : 10.1016/j.ajic.2012.10.005. 16. Bustarret Colombier M. Bactériémies chez l'allogreffé de moelle sous corticoïdes. Intérêt des hémocultures systématiques [Thèse]. Microbiologie médicale:Paris; 2014. 86 p. 17. Gudiol C, Royo-Cebrecos C, Abdala E, et al. Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia. Antimicrob Agents Chemother 2017; 61(8): 1-8. DOI : 10.1128/AAC.00164-17. 18. Averbuch D, Orasch C, Cordonnier C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 2013; 98(12): 1826-1835. DOI : 10.3324/haematol.2013.091025. 19. Trecarichi EM, Pagano L, Martino B, et al. Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological patients : clinical impact of carbapenem resistance in a multicentre prospective survey: BSIs caused by KP in HM Patients. Am J Hematol 2016; 91(11): 1076-1081. DOI : 10.1002/ajh.24489. 20. Moghnieh RA, Abdallah DI, Fawaz IA, et al. Prescription Patterns for Tigecycline in Severely Ill Patients for Non-FDA Approved Indications in a Developing Country : A Compromised Outcome. Front Microbiol 2017; 8: 1-13. DOI : 10.3389/fmicb.2017.00497. 21. Tamma PD, Newland JG, Pannaraj PS, et al. The use of intravenous colistin among children in the United States: results from a multicenter, case series. Pediatr Infect Dis J 2013; 32(1): 17-22. DOI : 10.1097/INF.0b013e3182703790. 22. Mérens A, Delacour H, Plésiat P, Cavallo J-D, Jeannot K. Pseudomonas aeruginosa et résistance aux antibiotiques. Rev Franc Lab 2011; 2011(435): 49-62. 23. Gelfand MS, Cleveland KO. Ceftolozane/Tazobactam Therapy of Respiratory Infections due to Multidrug-Resistant Pseudomonas aeruginosa. Clin Infect Dis 2015; 61(5): 853-855. DOI : 10.1093/cid/civ411. 24. Karageorgopoulos DE, Falagas ME. Current control and treatment of multidrug-resistant Acinetobacter baumannii infections. Lancet Infect Dis 2008; 8(12): 751-762. DOI : 10.1016/S1473-3099(08)70279-2. 25. Al-Anazi KA, Al-Jasser AM. Infections Caused by Acinetobacter baumannii in Recipients of Hematopoietic Stem Cell Transplantation. Front Oncol 2014; 4: 1-10. DOI : 10.3389/fonc.2014.00186. 26. Bastug A, Kayaaslan B, Kazancioglu S, et al. Emergence of multidrug resistant isolates and mortality predictors in patients with solid tumors or hematological malignancies. J Infect Dev Ctries 2015; 9(10): 1100. DOI : 10.3855/jidc.6805. 27. Nørgaard M, Larsson H, Pedersen G, Schønheyder HC, Sørensen HT. Haematological malignancies - A predictor of a poor outcome in patients with bacteraemia. J Infect 2006; 53(3): 190-198. DOI: 10.1016/j.jinf.2005.10.024. 28. Tofas P, Samarkos M, Piperaki E-T, et al. Pseudomonas aeruginosa bacteraemia in patients with hematologic malignancies : risk factors, treatment and outcome. Diagn Microbiol Infect Dis 2017; 88(4): 335-341. DOI : 10.1016/j.diagmicrobio.2017.05.003. 29. Moghnieh R, Estaitieh N, Mugharbil A, et al. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis. Front Cell Infect Microbiol 2015; 5: 1-9. DOI : 10.3389/fcimb.2015.00011. 30. Picot-Guéraud R, Batailler P, Caspar Y, Hennebique A, Mallaret M-R. Bacteremia caused by multidrug-resistant bacteria in a French university hospital center: 3 years of collection. Am J Infect Control 2015; 43(9): 960-964. DOI : 10.1016/j.ajic.2015.05.004. 31. Pfaller MA, Segreti J. Overview of the epidemiological profile and laboratory detection of extended-spectrum beta-lactamases. Clin Infect Dis 2006; 42(2): 153-163. DOI : 10.1086/500662. 32. Macesic N, Morrissey CO, Cheng AC, Spencer A, Peleg AY. Changing microbial epidemiology in hematopoietic stem cell transplant recipients: increasing resistance over a 9-year period. Transpl Infect Dis 2014; 16(6): 887-896. DOI : 10.1111/tid.12298. 33. Surgers L, Boyd A, Boelle PY, et al. Clinical and microbiological determinants of severe and fatal outcomes in patients infected with Enterobacteriaceae producing extended-spectrum beta-lactamase. Eur J Clin Microbiol Infect Dis 2017; 36(7): 1261-1268. DOI : 10.1007/s10096-017-2932-9. 34. Ha YE, Kang C-I, Cha MK, et al. Epidemiology and clinical outcomes of bloodstream infections caused by extended-spectrum β-lactamase-producing Escherichia coli in patients with cancer. Int J Antimicrob Agents 2013; 42(5): 403-409. DOI : 10.1016/j.ijantimicag.2013.07.018. 35. Tam VH, Chang KT, Abdelraouf K, et al. Prevalence, Resistance Mechanisms, and Susceptibility of Multidrug-Resistant Bloodstream Isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2010; 54(3): 1160-1164. DOI : 10.1128/AAC.01446-09. 36. Averbuch D, Tridello G, Hoek J, et al. Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group. Clin Infect Dis 2017; 65(11): 1819-1828. DOI : 10.1093/cid/cix646. 37. Decré D. Acinetobacter baumannii et résistance aux antibiotiques: Un modèle d'adaptation. Rev Franc Lab 2012; 2012(441): 43-52. DOI : 10.1016/S1773-035X(12)71412-0. 38. Desroches M, Jehl F, Leclercq R, et al. Résistance aux antibiotiques des Staphylococcus aureus résistants à la méticilline et staphylocoques à coagulase négative isolées d'infections ostéo-articulaires : étude prospective multicentrique française. Med Mal Infect 2013; 43: 52. 39. Balode A, Punda-Polic V, Dowzicky MJ. Antimicrobial susceptibility of gram-negative and gram-positive bacteria collected from countries in Eastern Europe : results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) 2004-2010. Int J Antimicrob Agents 2013; 41(6): 527-535.DOI : 10.1016/j.ijantimicag.2013.02.022

Downloads

Published

2021-02-12

Issue

Section

Original articles