Carbapenem resistant Enterobacteriaceae (CRE) are major human pathogens because, these cause high number of difficult-to-treat infections. Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are highly exposed to these type of bacteria. The aim of our study was to investigate prevalence of CRE colonization in AHSCT patients and to determine genes encoding carbapenem resistance. A retrospective study conducted between January 2015 and December 2019, involved 55 patients colonized with CRE strains. We determined the rate of antibiotic resistance according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the carbapenem resistance genes by PCR assays for genes encoding most frequent β-lactamases namely, blaGES, blaKPC, blaIMI, blaNDM, blaVIM, blaIMP and blaOXA-48. Eighty-one episodes of CRE colonization were recorded in 55 patients, mainly suffering from acute leukaemia (30%) and aplastic anemia (26%). History of hospitalization was noted in 80 episodes. Prior antibiotic treatment, severe neutropenia and corticosteroid therapy were respectively found in 94%, 76% and 58% of cases. Among the 55 patients, six patients (11%) developed a CRE infection. The CRE responsible for colonization were carbapenemase producers in 90% of cases. They belonged mostly to Klebsiella pneumoniae (61/81) and Escherichia coli species (10/81). Antibiotic resistance rates were 100% for ertapenem, 53% for imipenem, 42% for amikacin, 88% for ciprofloxacin and 27% for fosfomycin. Molecular study showed that blaOXA-48 gene was the most frequent (60.5%), followed by blaNDM (58%). Thirty-five (43%) strains were co-producers of carbapenemases. In our study, we report a high rate of CRE intestinal colonization in AHSCT recipients of our center.
Tilahun M, kassa Y, Gedefie A, Ashagire M. Emerging carbapenem-resistant Enterobacteriaceae infection, its epidemiology and novel treatment options: a review. Infect Drug Resist 2021; 14: 4363–74. https://doi.org/10.2147/IDR.S337611.
Bousquet A, Mérens A. Diagnostic bactériologique des bactéries multirésistantes et bactéries hautement résistantes émergentes. Rev Francoph Lab 2021; 2021(537): 37–48. https://doi.org/10.1016/S1773-035X(22)00031-4.
Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Enterobacteriaceae: here is the storm. Trends Mol Med 2012; 18(5): 263–72. https://doi.org/10.1016/j.molmed.2012.03.003.
Tischendorf J, De Avila RA, Safdar N. Risk of infection following colonization with carbapenem-resistant Enterobactericeae: a systematic review. Am J Infect Control 2016; 44(5): 539–43. https://doi.org/10.1016/j.ajic.2015.12.005.
Satlin MJ, Jenkins SG, Walsh TJ. The global challenge of carbapenem-resistant Enterobacteriaceae in transplant recipients and patients with hematologic malignancies. Clin Infect Dis 2014; 58(9): 1274–83. https://doi.org/10.1093/cid/ciu052.
Grall N, Andremont A, Armand Lefèvre L. Résistance aux carbapénèmes : vers une nouvelle impasse? J Infect 2011; 13(2): 87–102. https://doi.org/10.1016/j.antinf.2011.03.005.
Société Française de Microbiologie. REMIC : Référentiel en microbiologie médicale, 5ème édition. Paris: Société Française de Microbiologie; 2015. 961p.
Binet R, Deer DM, Uhlfelder SJ. Rapid detection of Shigella and enteroinvasive Escherichia coli in produce enrichments by a conventional multiplex PCR assay. Food Microbiol 2014; 40: 48–54. https://doi.org/10.1016/j.fm.2013.12.001.
Weill FX, Demartin M, Tandé D, Espié E, Rakotoarivony I, Grimont PD. SHV-12- like extended-spectrum-β-lactamase-producing strains of Salmonella enterica serotypes babelsberg and enteritidis isolated in France among infants adopted from Mali. J Clin Microbiol 2004; 42(6): 2432–7. https://doi.org/10.1128/JCM.42.6.2432-2437.2004.
Weill FX, Lailler R, Praud K, Kérouanton A, Fabre L, Brisabois A, et al. Emergence of extended-spectrum-β-lactamase (CTX-M-9)-producing multiresistant strains of Salmonella enterica serotype virchow in poultry and humans in France. J Clin Microbiol 2004; 42(12): 5767–73. https://doi.org/10.1128%2FJCM.42.12.5767-5773.2004.
Hong SS, Kim K, Huh JY, Jung B, Kang MS, Hong SG. Multiplex PCR for rapid detection of genes encoding class a carbapenemases. Ann Lab Med 2012; 32(5): 359–61. https://doi.org/10.3343/alm.2012.32.5.359.
Ellington MJ, Kistler J, Livermore DM, Woodford N. Multiplex PCR for rapid detection of genes encoding acquired metallo-beta-lactamases. J Antimicrob Chemother 2007; 59(2): 321–2. https://doi.org/10.1093/jac/dkl481.
Ballo O, Tarazzit I, Stratmann J, Reinheimer C, Hogardt M, Wichelhaus TA, et al. Colonization with multidrug resistant organisms determines the clinical course of patients with acute myeloid leukaemia undergoing intensive induction chemotherapy. PLoS One 2019; 14(1): e0210991. https://doi.org/10.1371/journal.pone.0210991.
Girmenia C, Rossolini GM, Piciocchi A, Bertaina A, Pisapia G, Pastore D, et al. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transpl 2015; 50(2): 282–8. https://doi.org/10.1038/bmt.2014.231.
Ben Nasr A, Decré D, Compain F, Genel N, Barguellil F, Arlet G. Emergence of NDM-1 in association with OXA-48 in Klebsiella pneumoniae from Tunisia. Antimicrob Agents Chemother 2013; 57(8): 4089–90. https://doi.org/10.1128/AAC.00536-13.
Guh AY, Limbago BM, Kallen AJ. Epidemiology and prevention of carbapenemresistant Enterobacteriaceae in the United States. Expert Rev Anti Infect Ther 2014; 12(5): 565–80. https://doi.org/10.1586/14787210.2014.902306.
Fritzenwanker M, Imirzalioglu C, Herold S, M. Wagenlehner F, Zimmer KP, Chakraborty T. Treatment options for carbapenem-resistant gram-negative infections. Dtsch Arztebl Int 2018; 115(20–21): 345–52. https://doi.org/10.3238/arztebl.2018.0345.
Sbiti M, Mustapha C, Khalid L, houssain L. Détection phénotypique des carbapenemases chez Klebsiella pneumoniae dans les isolats cliniques au Maroc. Int J Adv Res 2017; 5(5): 1823–30. https://doi.org/10.21474/IJAR01/4315.
Xu L, Sun X, Ma X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 2017; 16(1): 18. https://doi.org/10.1186/s12941-017-0191-3.
Brissot E, Villate A, Alsuliman T, Beauvais D, Bonnin A, Mear JB, et al. Dépistage des bactéries multirésistantes (BMR) et hautement résistantes émergentes (BHRe) aux antibiotiques en allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC). Bull Cancer 2020; 107(1): 7–11. https://www.sciencedirect.com/science/article/pii/S0007455119303492.
Heinz WJ, Buchheidt D, Christopeit M, Von Lilienfeld Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the infectious diseases working party (AGIHO) of the German society of hematology and medical oncology (DGHO). Ann Hematol 2017; 96(11): 1775–92. https://doi.org/10.1007/s00277-017-3098-3.
Wang Y, Lin Q, Chen Z, Hou H, Shen N, Wang Z, et al. Construction of a risk prediction model for subsequent bloodstream infection in intestinal carriers of carbapenem-resistant Enterobacteriaceae: a retrospective study in hematology department and intensive care unit. Infect Drug Resist 2021; 14: 815–24. https://doi.org/10.2147/idr.s286401.
Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli 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 leukaemia. Haematologica 2013; 98(12): 1826–35. https://doi.org/10.3324/haematol.2013.091025.
Ferry T, Richard JC. Traitement systémique des infections à bacilles gram négatif producteurs de carbapénémases [En ligne]; 2013. [cité 27 juin 2022]; [8 pages]. Disponible sur: https://www.edimark.fr/Front/frontpost/getfiles/20034.pdf.
Kotb S, Lyman M, Ismail G, Abd El Fattah M, Girgis SA, Etman A, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae in egyptian intensive care units using national healthcare–associated infections surveillance data, 2011–2017. Antimicrob Resist Infect Control 2020; 9(1): 2. https://doi.org/10.1186/s13756-019-0639-7.
Ben Boubaker IB, Saidani M, Ferjani A, Kanzari L, Kechrid A, Smaoui H, et al. L’antibio-résistance en Tunisie LART données 2015- 2016 -2017 [En ligne]; 2018. [cité 27 juin 2022]. Disponible sur: https://docplayer.fr/229149132-Lantibio-resistance-en-tunisie-lart-donnees.html.
Hamzaoui Z, Ocampo Sosa A, Fernandez Martinez M, Landolsi S, Ferjani S, Maamar E, et al. Role of association of OmpK35 and OmpK36 alteration and blaESBL and/or blaAmpC genes in conferring carbapenem resistance among non-carbapenemase-producing Klebsiella pneumoniae. Int J Antimicrob Agents 2018; 52(6): 898–905. https://doi.org/10.1016/j.ijantimicag.2018.03.020.
Ben Helal R, Dziri R, Chedly M, Klibi N, Barguellil F, El Asli MS, et al. Occurrence and characterization of carbapenemase-producing Enterobacteriaceae in a tunisian hospital. Microb Drug Resist 2018; 24(9): 1361–7. https://doi.org/10.1089/mdr.2018.0013.
Mellouli A, Jaoua MA, Dhraief S, Messadi AA, Thabet L. Molecular profile of carbapenemase-producing Enterobacterales in burn patients. Tunis Med 2020; 98(11): 855–60: PMID: 33479984.
Bakthavatchalam YD, Anandan S, Veeraraghavan B. Laboratory detection and clinical implication of oxacillinase-48 like carbapenemase: the hidden threat. J Glob Infect Dis 2016; 8(1): 41–50. https://doi.org/10.4103/0974-777x.176149.
Carrër A, Poirel L, Yilmaz M, Akan ÖA, Feriha C, Cuzon G, et al. Spread of OXA48-encoding plasmid in Turkey and beyond. Antimicrob Agents Chemother 2010; 54(3): 1369–73. https://doi.org/10.1128/aac.01312-09.
Cuzon G, Naas T, Lesenne A, Benhamou M, Nordmann P. Plasmid-mediated carbapenem-hydrolysing OXA-48 β-lactamase in Klebsiella pneumoniae from Tunisia. Int J Antimicrob Agents 2010; 36(1): 91–3. https://doi.org/10.1016/j.ijantimicag.2010.02.014.
Mathlouthi N, El Salabi AA, Ben Jomàa Jemili M, Bakour S, Al Bayssari C, Zorgani AA, et al. Early detection of metallo-β-lactamase NDM-1- and OXA-23 carbapenemase-producing Acinetobacter baumannii in libyan hospitals. Int J Antimicrob Agents 2016; 48(1): 46–50. https://doi.org/10.1016/j.ijantimicag.2016.03.007.
Messaoudi A, Haenni M, Mansour W, Saras E, Bel Haj Khalifa A, Chaouch C, et al. ST147 NDM-1-producing Klebsiella pneumoniae spread in two tunisian hospitals. J Antimicrob Chemother 2017; 72(1): 315–6. https://doi.org/10.1093/jac/dkw401.
Dziri O, Dziri R, Ali El Salabi A, Chouchani C. Carbapenemase producing gramnegative bacteria in Tunisia: history of thirteen years of challenge. Infect Drug Resist 2020; 13: 4177–91. https://doi.org/10.2147/idr.s259562.
Nordmann P. Résistance aux carbapénèmes chez les bacilles à gram négatif. Med Sci 2010; 26(11): 950–9. https://doi.org/10.1051/medsci/20102611950.
Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011; 17(10): 1791–8. https://doi.org/10.3201/eid1710.110655.
Yigit H, Queenan AM, Anderson GJ, Domenech Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001; 45(4): 1151–61. https://doi.org/10.1128/aac.45.4.1151-1161.2001.
Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother 2012; 67(7): 1597–606. https://doi.org/10.1093/jac/dks121.