Evaluating the use of meropenem in hematologic patients with febrile neutropenia A retrospective observational single-cohort study

Main Article Content

R.A. Stuurman
E. Jong
P.C.R. Godschalk
M.F. Corsten
J.E. Nagtegaal


antibiotic stewardship, antibiotic resistance, meropenem, hematologic disease, febrile neutropenia




The Antibiotic Stewardship Team of Meander Medical Centre (Meander MC) instigated a revaluation of its treatment protocol for hematologic patients admitted with febrile neutropenia. The current hospital protocol advises administering meropenem for 72 hours, followed by antibiotic therapy guided by microbiological cultures. In order to responsibly adjust the current empiric regimen, this study aimed to determine the frequency of bacteria resistant to alternative antibiotics, namely ceftazidime and piperacillin/tazobactam, in both surveillance and diagnostic cultures.


This retrospective, observational, single-centre study included adult patients with a hematologic malignancy and febrile neutropenia admitted between October 2018 and June 2021. Collected metadata included patient characteristics, surveillance and diagnostic culture results, and antibiotic use.


A total of 100 patients were included. One or more bacteria resistant to ceftazidime or piperacillin/tazobactam were identified in blood and urine cultures in seven (7%) and one (1%) patients respectively.


Our results support the safe reduction of the use of meropenem by changing the empiric treatment protocol for patients with hematologic malignancy and febrile neutropenia. As this study showed a lower resistance frequency to piperacillin/tazobactam than to ceftazidime, this antibiotic is the recommended alternative.


Download data is not yet available.

Abstract 297
PDF Downloads 202
HTML Downloads 43


[1] 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. Haematol. 2013;98(12):1826. https://doi.org/10.3324/haematol.2013.091025
[2] Khoo AL, Zhao YJ, Teng M, et al. Evaluation of a risk-guided strategy for empirical carbapenem use in febrile neutropenia. Ijantimicag. 2018 Sep;52(3):350-357. https://www.doi.org/10.1016/j.ijantimicag.2018.04.017
[3] Schmidt-Hieber M, Teschner D, Maschmeyer G, Schalk E. Management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation. Expert review of anti-infective therapy. 2019 Dec 02;17(12):983-995. https://doi.org/10.1080/14787210.2019.1573670
[4] Blennow O, Ljungman P. Infections in Hematology Patients. Concise Guide to Hematology Cham: Springer International Publishing; 2018. p. 503-518. https://www.doi.org/10.1007/978-3-319-97873-4_38
[5] Wang Y, Du Z, Chen Y, Liu Y, Yang Z. Meta-analysis: combination of meropenem vs ceftazidime and amikacin for empirical treatment of cancer patients with febrile neutropenia. Medicine. 2021 Feb 26;100(8):e24883. https://www.doi.org/10.1097/MD.0000000000024883
[6] Regelink JC, Godschalk PCR, Russcher M. Richtlijn infectiepreventie en antibioticabeleid hemato-oncologie MeanderMC. Personal communication.
[7] Ballo O, Kreisel E, Eladly F, et al. Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy. Ann Hematol. 2020 Sep 24;99(11):2547-2553. https://www.doi.org/10.1007/s00277-020-04274-1
[8] Cornistein W, Mora A, Orellana N, Capparelli FJ, del Castillo M. Candida: epidemiology and risk factors for non-albicans species. Enferm Infecc Microbiolog Clin. 2012;31(6):380-384. https://www.doi.org/10.1016/j.eimc.2012.09.011
[9] Ben-Ami R, Olshtain-Pops K, Krieger M, et al. Antibiotic Exposure as a Risk Factor for Fluconazole-Resistant Candida Bloodstream Infection. Antimicrob Agents Chemother. 2012 May 01;56(5):2518-2523. https://www.doi.org/10.1128/AAC.05947-11
[10] Zaoutis TE, Prasad PA, Localio AR, et al. Risk Factors and Predictors for Candidemia in Pediatric Intensive Care Unit Patients: Implications for Prevention. Clini Infect Dis. 2010 Sep 01;51(5):e38-e45. https://www.doi.org/10.1086/655698
[11] Paul M, Yahav D, Bivas A, Fraser A, Leibovici L, Paul M. Anti‐pseudomonal beta‐lactams for the initial, empirical, treatment of febrile neutropenia: comparison of beta‐lactams. Cochrane library. 2010 Nov 10;2015(2):CD005197. https://www.doi.org/10.1002/14651858.CD005197.pub3
[12] Elgarten CW, Li Y, Getz KD, et al. Broad-Spectrum Antibiotics and Risk of Graft-versus-Host Disease in Pediatric Patients Undergoing Transplantation for Acute Leukemia: Association of Carbapenem Use with the Risk of Acute Graft-versus-Host Disease. Transplant Cellular Ther. 2021 Feb;27(2):177.e1-177.e8. https://www.doi.org/10.1016/j.jtct.2020.10.012
[13] SWAB. The Dutch Working Party on Antibiotic Policy (SWAB) recommendations for the diagnosis and management of febrile neutropenia in patients with cancer Committee. [Internet]. Available at: https://swab.nl/nl/febriele-neutropenie-algemene-informatie. [Accessed February 26th, 2022].
[14] Ahn ST, Kim SW, Kim JW, Park HS, Moon DG, Oh MM. Does urinary tract infection caused by extended-spectrum β-lactamase-producing Escherichia coli show same antibiotic resistance when it recurs? J Infect Chemother. 2019 Jul;25(7):498-502. https://www.doi.org/10.1016/j.jiac.2019.02.006
[15] Karami N, Lindblom A, Yazdanshenas S, Lindén V, Åhrén C. Recurrence of urinary tract infections with extended-spectrum β-lactamase-producing Escherichia coli caused by homologous strains among which clone ST131-O25b is dominant. JGAR. 2020 Sep;22:126-132. https://www.doi.org/10.1016/j.jgar.2020.01.024
[16] P. Young, A Prisides. Antibiotic sensitivity overview. [Internet]. Available at: https://drug.wellingtonicu.com/Appendices/5/. [Accessed February 26th, 2022].
[17] Macdougall C. Beyond Susceptible and Resistant, Part I: Treatment of Infections Due to Gram-Negative Organisms With Inducible β-Lactamases. J Pediatr Pharmacol Ther. 2011-01-01;16(1):23. https://www.doi.org/10.5863/1551-6776-16.1.23
[18] Harris PN, Wei JY, Shen AW, et al. Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis. J Antimicrob Chemother 2016;71:296-306. https://doi.org/10.1093/jac/dkv346

[19] Cheng L, Nelson BC, Mehta M, et al. Piperacillin-tazobactam versus other antibacterial agents for treatment of bloodstream infections due to AmpC beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 2017;61:e00276-17. https://doi.org/10.1128/AAC.00276-17
[20] Tan SH, Ng TM, Chew KL, et al. Outcomes of treating AmpC-producing Enterobacterales bacteraemia with carbapenems vs. non-carbapenems. Int J Antimicrob Agents 2020;55:105860. https://doi.org/10.1016/j.ijantimicag.2019.105860
[21] Drozdinsky G, Neuberger A, Rakedzon S, et al. Treatment of bacteremia caused by Enterobacter spp.: should the potential for ampC induction dictate therapy? A retrospective study. Microb Drug Resist 2021;27:4104. https://doi.org/10.1089/mdr.2020.0234

[22] Choi A, Park I, Lee HS, Chung J, Kim MJ, Park YS. Usefulness of complete blood count parameters to predict poor outcomes in cancer patients with febrile neutropenia presenting to the emergency department. Annals of medicine. 2022 Dec 31;54(1):599-609. https://www.doi.org/10.1080/07853890.2022.2031271
[23] Dhanya R, Agarwal RK, Ramprakash S, et al. Do Weekly Surveillance Cultures Contribute to Antibiotic Stewardship and Correlate with Outcome of HSCT in Children? A Multicenter Real-World Experience of 5 Years from the Indian Subcontinent. Transplant Cellular Ther. 2021 Dec 20;(2021):1-7. https://www.doi.org/10.1016/j.jtct.2021.12.008