Fri, May 29, 2026
[Archive]
Volume 17, Issue 4 (December-2025 2025)
Iranian Journal of Blood and Cancer 2025, 17(4): 20-26 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Alfaqaih S, Ghlio N, Assadi A. Clinical efficacy of Empirical (Piperacillin/tazobactam plus Amikacin) Combined Therapy of Febrile Neutropenia Among Pediatric Patients with Cancer: A Cohort Observational Study. Iranian Journal of Blood and Cancer 2025; 17 (4) :20-26
URL: http://ijbc.ir/article-1-1863-en.html
URL: http://ijbc.ir/article-1-1863-en.html
1- Department of Pediatrics, Faculty of Medicine, Misurata University, Misurata, Libya. , sarah.alfaqaih@med.misuratau.edu.ly
2- Department of Pediatric Oncology, National Cancer Institute, Misurata, Libya.
3- Department of Pediatrics, Faculty of Medicine, Misurata University, Misurata, Libya.
2- Department of Pediatric Oncology, National Cancer Institute, Misurata, Libya.
3- Department of Pediatrics, Faculty of Medicine, Misurata University, Misurata, Libya.
Abstract: (240 Views)
Background: Febrile neutropenia (FN) is a life-threatening complication in pediatric oncology patients that requires prompt and effective empirical antibiotic treatment. Local data on the success of these regimens are essential for guiding clinical practice. This study assesses the effectiveness and safety of the local empirical combined therapy of Piperacillin/tazobactam plus Amikacin for FN in pediatric cancer patients.
Methods: A prospective observational cohort study was conducted on 68 FN episodes in 34 pediatric cancer patients between August 2022 and December 2023. The first-line regimen included intravenous Piperacillin/tazobactam and Amikacin, with Amikacin de-escalated after 72 hours of fever resolution. The primary outcome was the success rate of the first-line regimen, defined as fever resolution and clinical clearance without modification or switch. Safety was evaluated by monitoring creatinine levels.
Results: The overall success rate of the empirical regimen without modification was 63.2%, with a failure rate of 22%. The success rate increased to 77.9% when Vancomycin was added (14.7% of cases). Microbiologically documented infections (MDI) were mostly Gram-positive (62.5%), including MRSA isolates resistant to Piperacillin/tazobactam. No treatment-related mortality or significant nephrotoxicity was observed (mean creatinine difference: -0.0107, p=0.338). Additionally, the duration of neutropenia was strongly correlated with the length of hospital stay (r=0.7, p<0.00001).
Conclusion: The combined Piperacillin/tazobactam and Amikacin regimen shows a reasonable success rate and a good safety profile in the local setting, supporting its continued use as a first-line option. However, the high prevalence of Gram-positive MDI and the frequent need for Vancomycin addition highlight the importance of ongoing local resistance monitoring and maintaining a low threshold for early Vancomycin use in high-risk patients.
Methods: A prospective observational cohort study was conducted on 68 FN episodes in 34 pediatric cancer patients between August 2022 and December 2023. The first-line regimen included intravenous Piperacillin/tazobactam and Amikacin, with Amikacin de-escalated after 72 hours of fever resolution. The primary outcome was the success rate of the first-line regimen, defined as fever resolution and clinical clearance without modification or switch. Safety was evaluated by monitoring creatinine levels.
Results: The overall success rate of the empirical regimen without modification was 63.2%, with a failure rate of 22%. The success rate increased to 77.9% when Vancomycin was added (14.7% of cases). Microbiologically documented infections (MDI) were mostly Gram-positive (62.5%), including MRSA isolates resistant to Piperacillin/tazobactam. No treatment-related mortality or significant nephrotoxicity was observed (mean creatinine difference: -0.0107, p=0.338). Additionally, the duration of neutropenia was strongly correlated with the length of hospital stay (r=0.7, p<0.00001).
Conclusion: The combined Piperacillin/tazobactam and Amikacin regimen shows a reasonable success rate and a good safety profile in the local setting, supporting its continued use as a first-line option. However, the high prevalence of Gram-positive MDI and the frequent need for Vancomycin addition highlight the importance of ongoing local resistance monitoring and maintaining a low threshold for early Vancomycin use in high-risk patients.
: Original Article |
Subject:
Pediatric Hematology & Oncology
Received: 2025/10/3 | Accepted: 2025/12/7 | Published: 2025/12/30
Received: 2025/10/3 | Accepted: 2025/12/7 | Published: 2025/12/30
References
1. Sultan I, Alfaar AS, Sultan Y, Salman Z, Qaddoumi I. Trends in childhood cancer: Incidence and survival analysis over 45 years of SEER data. PLOS ONE. 2025;20(1):e0314592. [DOI:10.1371/journal.pone.0314592]
2. Punnapuzha S, Edemobi PK, Elmoheen A. Febrile Neutropenia. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Paul Edemobi declares no relevant financial relationships with ineligible companies. Disclosure: Amr Elmoheen declares no relevant financial relationships with ineligible companies.: StatPearls Publishing
3. Zimmer AJ, Freifeld AG. Optimal Management of Neutropenic Fever in Patients With Cancer. J Oncol Pract. 2019;15(1):19-24. [DOI:10.1200/JOP.18.00269]
4. Lucas AJ, Olin JL, Coleman MD. Management and Preventive Measures for Febrile Neutropenia. P t. 2018;43(4):228-32.
5. El Assaad N, Azzi A, Haddad F, Lebbos J, Haddad E, Chehata N, et al. Febrile neutropenia in the Middle East and North Africa Region: trends, management, and outcomes (2000-2024)-A systematic review. IJID Regions. 2025;16:100682. [DOI:10.1016/j.ijregi.2025.100682]
6. Lehrnbecher T, Robinson PD, Ammann RA, Fisher B, Patel P, Phillips R, et al. Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update. J Clin Oncol. 2023;41(9):1774-85. [DOI:10.1200/JCO.22.02224]
7. Rosa RG, Goldani LZ. Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother. 2014;58(7):3799-803. [DOI:10.1128/AAC.02561-14]
8. Monroe K, Cohen CT, Whelan K, King A, Maloney L, Deason J, et al. Quality Initiative to Improve time to Antibiotics for Febrile Pediatric Patients with Potential Neutropenia. Pediatr Qual Saf. 2018;3(4):e095. [DOI:10.1097/pq9.0000000000000095]
9. 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 Leukemia. Haematologica. 2013;98(12):1826-35. [DOI:10.3324/haematol.2013.091025]
10. Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(suppl 5):v111-v8. [DOI:10.1093/annonc/mdw325]
11. Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2024. [DOI:10.1093/cid/ciae403]
12. Keck JM, Wingler MJB, Cretella DA, Vijayvargiya P, Wagner JL, Barber KE, et al. Approach to fever in patients with neutropenia: a review of diagnosis and management. Ther Adv Infect Dis. 2022;9:20499361221138346. [DOI:10.1177/20499361221138346]
13. Zengin E, Sarper N, Kılıç SC. Piperacillin/tazobactam monotherapy versus piperacillin/tazobactam plus amikacin as initial empirical therapy for febrile neutropenia in children with acute leukemia. Pediatr Hematol Oncol. 2011;28(4):311-20. [DOI:10.3109/08880018.2011.557144]
14. Yildirim I, Aytac S, Ceyhan M, Cetin M, Tuncer M, Cengiz AB, et al. Piperacillin/tazobactam plus amikacin versus carbapenem monotherapy as empirical treatment of febrile neutropenia in childhood hematological malignancies. Pediatr Hematol Oncol. 2008;25(4):291-9. [DOI:10.1080/08880010802016847]
15. Demirkaya M, Celebi S, Sevinir B, Hacımustafaoglu M. Randomized comparison of piperacillin-tazobactam plus amikacin versus cefoperazone-sulbactam plus amikacin for management of febrile neutropenia in children with lymphoma and solid tumors. Pediatr Hematol Oncol. 2013;30(2):141-8. [DOI:10.3109/08880018.2012.756565]
16. Hamidah A, Rizal AM, Nordiah AJ, Jamal R. Piperacillin-tazobactam plus amikacin as an initial empirical therapy of febrile neutropenia in paediatric cancer patients. Singapore Med J. 2008;49(1):26-30.
17. Libuit J, Whitman A, Wolfe R, Washington CS. Empiric vancomycin use in febrile neutropenic oncology patients. Open Forum Infect Dis. 2014;1(1):ofu006. [DOI:10.1093/ofid/ofu006]
18. Maertens J, Lodewyck T, Donnelly JP, Chantepie S, Robin C, Blijlevens N, et al. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clin Infect Dis. 2023;76(4):674-82. [DOI:10.1093/cid/ciac623]
19. Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019;13(Suppl 1):S31-s4. [DOI:10.4103/sja.SJA_543_18]
20. Paul M, Soares-Weiser K, Leibovici L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis. Bmj. 2003;326(7399):1111. [DOI:10.1136/bmj.326.7399.1111]
21. Alfaqaih S, Ghlio N. A Three-Year Retrospective Analysis of the Common Isolated Microorganisms and the Sensitivity Pattern of Blood Culture in Children with Cancer. Jordan Medical Journal. 2025;59(5). [DOI:10.35516/jmj.v59i5.4383]
22. Carmona-Bayonas A, Gómez J, González-Billalabeitia E, Canteras M, Navarrete A, Gonzálvez ML, et al. Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients. Br J Cancer. 2011;105(5):612-7. [DOI:10.1038/bjc.2011.284]
23. Nattamol H, Saranapoom K, Supannee R, Grerk S, Lukman T, Saba R. Prognostic factors for mortality with febrile neutropenia in hospitalized patients. The Southwest Respiratory and Critical Care Chronicles. 2015;3(9). [DOI:10.12746/swrccc2015.0309.112]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
- Iranian Journal of Blood and Cancer
- Journal Tel: +989369936116
- Publisher Tel: +982122275917
- Mail: Info@ijbc.ir
