Meta-analysis: combination of meropenem vs ceftazidime and amikacin for empirical treatment of cancer patients with febrile neutropenia

Ying Wang, Zhichao Du, Yongdong Chen, Yugang Liu, Zhitang Yang, Ying Wang, Zhichao Du, Yongdong Chen, Yugang Liu, Zhitang Yang

Abstract

Background: Meropenem monotherapy vs ceftazidime plus amikacin have been approved for use against febrile neutropenia. To assess the effectiveness and safety of them for empirical treatment of cancer patients with febrile neutropenia, we conducted a meta-analysis of randomized controlled trial.

Methods: Randomized controlled trials on ceftazidime plus amikacin, or/and monotherapy with meropenem for the treatment of cancer patients with febrile neutropenia were identified by searching Cochrane Library, PubMed, Science Direct, Wiley Online, Science Citation Index, Google (scholar), National Center for Biotechnology Information, and China National Knowledge Infrastructure. Data on interventions, participants' characteristics and the outcomes of therapy, were extracted for statistical analysis. Seven trials fulfilled the inclusion criteria.

Result: The treatment with ceftazidime plus amikacin was more effective than meropenem (OR = 1.17; 95% CI 0.93-1.46; 1270 participants). However, the treatment effects of the 2 therapy methods were almost parallel in adults (OR = 1.15; 95% CI 0.91-1.46; 1130 participants older than 16). Drug-related adverse effects afflicted more patients treated with ceftazidime plus amikacin (OR = 0.78; 95% CI 0.52-1.15; 1445 participants). The common responses were nausea, diarrhea, rash, and increased in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin.

Conclusion: Ceftazidime plus amikacin should be the first choice for empirical treatment of cancer patients with febrile neutropenia, and meropenem may be chosen as a last defense against pathogenic bacteria.

Conflict of interest statement

The authors have no conflicts of interests to disclose.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1
Figure 1
Risk of bias graph.
Figure 2
Figure 2
Flow diagram demonstrating studies processed for inclusion in the meta-analysis.
Figure 3
Figure 3
Comparison on the success rate of meropenem vs combined therapy with ceftazidime plus amikacin. The size of each square denotes the proportion of information given by each trial. Vertical line, “no difference” point in emergence of success cases treated by meropenem and ceftazidime plus amikacin; horizontal lines, 95% CIs = squares, ORs = diamond, pooled OR for all studies.
Figure 4
Figure 4
Failure rate of meropenem vs ceftazidime plus amikacin. The size of each square denotes the proportion of information given by each trial. Vertical line, “no difference” point in emergence of failure cases treated by meropenem and ceftazidime plus amikacin; horizontal lines, 95% CIs = squares, ORs = diamond, pooled OR for all studies.
Figure 5
Figure 5
Outcomes of drug-related adverse effects from the 2 treatments. The size of each square denotes the proportion of information given by each trial. Vertical line, “no difference” point in emergence of adverse effects treated by meropenem and ceftazidime plus amikacin; horizontal lines, 95% CIs = squares, ORs = diamond, pooled OR for all studies.
Figure 6
Figure 6
Sub-grouped outcome of the success cases. The size of each square denotes the proportion of information given by each trial. Vertical line, “no difference” point in emergence of success cases treated by meropenem and ceftazidime plus amikacin; horizontal lines, 95% CIs = squares, ORs = diamond, pooled OR for all studies. Grouped by age, adult, and children.
Figure 7
Figure 7
Subgroup analysis of failure cases. The size of each square denotes the proportion of information given by each trial. Vertical line, “no difference” point in emergence of failure cases treated by meropenem and ceftazidime plus amikacin; horizontal lines, 95% CIs = squares, ORs = diamond, pooled OR for all studies. Grouped by age, adult, and children.
Figure 8
Figure 8
Publication bias was analysis only in funnel plot with Review Manager.

References

    1. Yao JC, Lombard-Bohas C, Baudin E, et al. . Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 2010;28:69–76.
    1. Chawla SP, Blay J, Ray-Coquard IL, et al. . Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus (R) as maintenance therapy in advanced sarcoma patients (pts) following clinical benefit from prior standard cytotoxic chemotherapy (CT [ASCO Meeting Abstracts]. J Clin Oncol 2011;29S.
    1. Patel K, West HJ. Febrile neutropenia. JAMA Oncol 2017;3:1751.
    1. Serefhanoglu K, Ersoy Y, Serefhanoglu S, et al. . Clinical experience with three combination regimens for the treatment of high-risk febrile neutropenia. Ann Acad Med Singapore 2006;35:11–6.
    1. Kuderer NM, Dale DC, Crawford J, et al. . Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 2006;106:2258–66.
    1. Perucca E. Pharmacologic advantages of antiepileptic drug monotherapy. Epilepsia 1997;38:S6–8.
    1. Anolik R. Mometasone Furoate Nasal Spray with Loratadine Study G.Clinical benefits of combination treatment with mometasone furoate nasal spray and loratadine vs monotherapy with mometasone furoate in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2008;100:264–71.
    1. Faught E. Monotherapy in adults and elderly persons. Neurology 2007;69:S3–9.
    1. Raad II, Escalante C, Hachem RY, et al. . Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime. Cancer 2003;98:1039–47.
    1. Paul M, Yahav D, Fraser A, et al. . Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 2006;57:176–89.
    1. Yildirim I, Aytac S, Ceyhan M, et al. . Piperacillin/tazobactam plus amikacin versus carbapenem monotherapy as empirical treatment of febrile neutropenia in childhood hematological malignancies. Pediatr Hematol Oncol 2008;25:291–9.
    1. Feld R, DePauw B, Berman S, et al. . Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial. J Clin Oncol 2000;18:3690–8.
    1. Owens RC, Owens CA, Holloway W, et al. . Reduction in vancomycin (VANC) consumption in patients with fever and neutropenia. Clin Infectious Dis 2000;31:291.
    1. Kebudi R, Gorgun O, Ayan I, et al. . Randomized comparison of cefepime versus ceftazidime monotherapy for fever and neutropenia in children with solid tumors. Med Pediatr Oncol 2001;36:434–41.
    1. Edwards JR. Meropenem: a microbiological overview. J Antimicrob Chemother 1995;36: Suppl A: 1–7.
    1. Schulz KF, Altman DG, Moher D, et al. . CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med 2010;8:18.
    1. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med 1997;127:820–6.
    1. Thompson SG. The merits of matching in community intervention trials: a cautionary tale. Stat Med 1998;17:2149–52.
    1. Mantel NHW. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 2004;1:533–53.
    1. Kobayashi S, Ito M, Sano H, et al. . Clinical analysis of combination therapy for febrile neutropenic patients in childhood cancer. Pediatr Int 2013;55:65–71.
    1. Aksoylar S, Cetingul N, Kantar M, et al. . Meropenem plus amikacin versus piperacillin-tazobactam plus netilmicin as empiric therapy for high-risk febrile neutropenia in children. Pediatr Hematol Oncol 2004;21:115–23.
    1. Erbey F, Bayram I, Yilmaz S, et al. . Meropenem monotherapy as an empirical treatment of febrile neutropenia in childhood cancer patients. Asian Pac J Cancer Prev 2010;11:123–6.
    1. Muller J, Garami M, Constantin T, et al. . Meropenem in the treatment of febrile neutropenic children. Pediatr Hematol Oncol 2005;22:277–84.
    1. Pancharoen C, Mekmullica J, Buranachonapa J, et al. . Efficacy and safety of meropenem as an empirical treatment for febrile neutropenia in children with cancer. J Med Assoc Thai 2003;86: Suppl 2: S174–8.
    1. Fleischhack G, Hartmann C, Simon A, et al. . Meropenem versus ceftazidime as empirical monotherapy in febrile neutropenia of paediatric patients with cancer. J Antimicrob Chemother 2001;47:841–53.
    1. Oguz A, Karadeniz C, Citak EC, et al. . Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors. Pediatr Hematol Oncol 2006;23:245–53.
    1. Solberg CO, Sjursen H. Safety and efficacy of meropenem in patients with septicaemia: a randomised comparison with ceftazidime, alone or combined with amikacin. J Antimicrob Chemother 1995;36: Suppl A: 157–66.
    1. Agaoglu L, Devecioglu O, Anak S, et al. . Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey. J Chemother 2001;13:281–7.
    1. Akova M, Akan H, Korten V, et al. . Comparison of meropenem with amikacin plus ceftazidime in the empirical treatment of febrile neutropenia: a prospective randomised multicentre trial in patients without previous prophylactic antibiotics. Int J Antimicrob Agents 1999;13:15–9.
    1. Behre G, Link H, Maschmeyer G, et al. . Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Ann Hematol 1998;76:73–80.
    1. Cometta A, Calandra T, Gaya H, et al. . Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto Infection Program. Antimicrob Agents Chemother 1996;40:1108–15.
    1. de la Camara R, Figuera A, Sureda A, et al. . Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes in neutropenic patients: a randomized study. Haematologica 1997;82:668–75.
    1. Hung KC, Chiu HH, Tseng YC, et al. . Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empirical therapy for neutropenic fever in children with malignancy. J Microbiol Immunol Infect 2003;36:254–9.
    1. Aapro MS, Bohlius J, Cameron DA, et al. . 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011;47:8–32.
    1. Freifeld AG, Bow EJ, Sepkowitz KA, 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:e56–93.
    1. de Naurois J, Novitzky-Basso I, Gill MJ, et al. . Management of febrile neutropenia: ESMO clinical practice guidelines. Ann Oncol 2010;21: Suppl 5: 252–6.
    1. Furno P, Bucaneve G, Del Favero AD. Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis. Lancet Infect Dis 2002;2:231–42.
    1. Sipsas NV, Bodey GP, Kontoyiannis DP. Perspectives for the management of febrile neutropenic patients with cancer in the 21st century. Cancer 2005;103:1103–13.

Source: PubMed

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