Multidrug resistant bacteremia in hematopoietic stem cell transplant recipients

##plugins.themes.academic_pro.article.main##

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

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.

Keywords:

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

##plugins.themes.academic_pro.article.details##

References

  1. 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