Piperacillin/tazobactam plus amikacin vs. piperacilin/tazobactam: treatment for children with febrile neutropenia
Keywords:
Neoplasms, Febrile Neutropenia, Piperacillin, Tazobactam, AmikacinAbstract
Background: Pediatric patients with febrile neutropenia usually receive a combination of broad spectrum antimicrobials. Treatment without aminoglycoside seems to have advantages.
Objective: To compare the efficacy of piperacillin/tazobactam plus amikacin versus piperacillin/tazobactam.
Methods: Randomized, open label, controlled clinical trial. Sample size for an efficacy of 55%, and delta of 25%; 80 episodes were required for each group. Selection criteria were patients with febrile neutropenia, candidates to receive parenteral antimicrobial treatment; they were randomized to one of two groups, piperacillin/tazobactam plus amikacin (Group A), or piperacillin/tazobactam (Group B). The outcomes were failure, adverse events and death. Mantel-Haenszel chi square test and exact Fisher test were used. Reduction of relative and absolute risk (RRR and ARR), 95% confidence intervals (CI 95%) and number needed to treat (NNT) were calculated.
Results: 88 Episodes were analyzed in group A and 76 in group B. There was no statistical difference in general characteristics of patients or type of infections. There was not significant statistical difference in: failure 31.8% group A, 30.2% group B (RR 1.05, CI 95% 0.66-1.66, p = 0.86), or adverse events (one in each group). The RRR was 1.5%, and ARR 2%, with a NNT of 67.
Conclusion: piperacillin/tazobactam without amikacin was as effective as combination therapy in pediatric patients with febrile neutropenia.
Downloads
References
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):e56-e93. DOI: 10.1093/cid/cir073
Forde C, Scullin P. Chasing the golden hour-lessons learned from improving initial neutropenic sepsis management. BMJ Quality Improvement Reports. 2017;6:u204420.w6531. DOI: 10.1136/bmjquality.u204420.w6531. eCollection 2017
Lehrnbecher T, Robinson P, Fisher B, Alexander S, Ammann RA, Beauchemin M et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 Update. J Clin Oncol. 2017;35(18):2082-94. DOI: 10.1200/JCO.2016.71.7017
Downes KJ, Zaoutis TE, Shah SS. Guidelines for management of children with fever and neutropenia. J Pediatr Infect Dis Soc. 2013;2(3):281-5. DOI: 10.1093/jpids/pit035
Santolaya ME, Álvarez AM, Avilés CL, Becker A, Cofré J, Enríquez M, et al. Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever and neutropenia. Clin Infect Dis. 2002;35(6):678-83. DOI: 10.1086/342064
Santolaya ME, Alvarez AM, Avilés CL, Becker A, Venegas M, O’Ryan M et al. Prospective validation of a risk prediction model for severe sepsis in children with cancer and high-risk febrile neutropenia. Pediatr Infect Dis J. 2013;32(12):1318-23. DOI: 10.1097/01.inf.0000436128.49972.16
Delebarre M, Tiphaine A, Martinot A, Dubos F. Risk-stratification management of febrile neutropenia in pediatric hematology-oncology patients: Results of a French nationwide survey. Pediatr Blood Cancer. 2016;63(12):2167-72. DOI: 10.1002/pbc.26121
Livadiotti S, Milano GM, Serra A, Folgori L, Jenkner A, Castagnola E, et al. Infectious Diseases Working Group of the Associazione Italiana Ematologia Oncologia Pediatrica. A survey on hematology-oncology pediatric AIEOP centers: prophylaxis, empirical therapy and nursing prevention procedures of infectious complications. Haematologica. 2012;97(1):147-50. DOI: 10.3324/haematol.2011.048918
Rivas‐Ruiz R, Villasis‐Keever M, Miranda‐Novales G, Castelán‐Martínez OD, Rivas‐Contreras S. Outpatient treatment for people with cancer who develop a low‐risk febrile neutropaenic event. Cochrane Database of Systematic Reviews. 2019, Issue 3. Art. No.: CD009031. DOI: 10.1002/14651858.CD009031.pub2
Paul M, Dickstein Y, Schlesinger A, Grozinsky-Glasberg S, Soares-Weiser K, Leibovici L. Beta-lactam versus beta-lactam aminoglycoside combination therapy in cancer patients with neutropenia. Cochrane Database Syst Rev. 2013;6: CD003038. DOI:10.1002/14651858.CD003038.pub2
Miranda-Novales MG, Belmont-Martínez L, Villasís-Keever MA, Penagos-Paniagua M, Bernaldez-Ríos R, Solórzano Santos F. Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factors for treatment failure. Arch Med Res. 1998:29(4):331-35.
Jones B, Jarvis P, Lewis JA, Ebbutt AF. Trials to assess equivalence: the importance of rigorous methods. BMJ. 1996;313(7048):36-9. DOI: 10.1136/bmj.313.7048.36
Sano H, Kobayashi R, Suzuki D, Kishimoto K, Yasuda K, Kobayashi K. Comparison between piperacillin/tazobactam and cefepime monotherapies as an empirical therapy for febrile neutropenia in children with hematological and malignant disorders: A prospective, randomized study. Pediatr Blood Cancer. 2015;62(2):356-58. DOI: 10.1002/pbc.25178
Sano H, Kobayashi R, Suzuki D, Kishimoto K, Hori D, Matsushima S, et al. Differential efficacy of empirical antibiotic therapy for febrile neutropenia in adolescent/young adult (AYA) and child patients. Int J Hematol. 2018;108(5):543-49. DOI: 10.1007/s12185-018-2503-6.
Proyecto de Norma Oficial Mexicana PROY-NOM-220-SSA1-2015, Instalación y operación de la farmacovigilancia. Disponible en: http://diariooficial.gob.mx/nota_detalle.php?codigo=5238160&fecha=08/03/2012
Kobayashi S, Ito M, Sano H, Mochizuki K, Akaihata M, Waragai T, et al. Clinical analysis of combination therapy for febrile neutropenic patients in childhood cancer. Pediatr Int. 2013;55(1):65-71. DOI: 10.1111/ped.12025
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
Aamir M, Abrol P, Sharma D, Punia H. A clinical evaluation of efficacy and safety of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia in a tertiary care centre of north India. Trop Doct. 2016;46(3):142-8. DOI: 10.1177/0049475515617571
Avilés-Robles M, Ojha RP, González M, Ojeda-Diezbarroso K, Dorantes-Acosta E, Jackson BE, et al. Bloodstream infections and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City. Am J Infect Control. 2014;42(11):1235-7. DOI: 10.1016/j.ajic.2014.07.021
Penagos-Paniagua M, Villasís-Keever MA, Miranda-Novales MG, Tapia-Marcial A, Rivera-Márquez H, Bernaldez-Ríos R, et al. Utilidad de la proteína C reactiva para el diagnóstico de infección bacteriana en el paciente pediátrico con cáncer fiebre y neutropenia. Bol Med Hosp Infant Mex. 2012;69(5):376-83.
Fisher BT, Robinson PD, Lehrnbecher T, Steinbach WJ, Zaoutis TE, Phillips B et al. Risk factors for invasive fungal disease in pediatric cancer and hematopoietic stem cell transplantation: A systematic review. J Pediatric Infect Dis Soc. 2018;7(3):191-8. DOI: 10.1093/jpids/pix030
Demirel A, Tabak F, Ar MC, Mete B, Öngören S, Yemisen M, et al. Secondary infections in febrile neutropenia in hematological malignances: more than another febrile neutropenic episode. Turk J Haematol. 2015;32(3):243-50. DOI: 10.4274/tjh.2013.0422
Zengin E, Sarper N, Kilic 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
Robinson PD, Lehrnbecher T, Phillips R, Dupuis LL, Sung L. Strategies for empiric management of pediatric fever and neutropenia in patients with cancer and hematopoietic stem-cell transplantation recipients: a systematic review of randomized trials. J Clin Oncol. 2016;34(17):2054-60. DOI: 10.1200/JCO.2015.65.8591
Paul M, Yahav D, Bivas A, Fraser A, Leibovici L. Anti-pseudomonal beta-lactams for the initial, empirical treatment for febrile neutropenia: comparison of beta-lactams. Cochrane Database Syst Rev. 2010;11:CD005197
Downloads
Published
Issue
Section
License
Authors retain their copyright and grant the Revista Médica del IMSS the right of first publication. Articles are distributed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows sharing as long as the author and the original source are properly credited.
