The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis

Andreatos, Nikolaos; Flokas, Myrto Eleni; Apostolopoulou, Anna; Alevizakos, Michail; Mylonakis, Eleftherios

doi:10.1093/ofid/ofx113

Cited by 13 publications

(9 citation statements)

References 50 publications

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“…However, the mortality finding was correlated with trials utilizing low-dose cefepime therapy (2 g q12h), while high-dose cefepime therapy (2 g q8h) did not demonstrate this association. 27 These data clearly support the necessity of utilizing high-dose cefepime for the treatment of febrile neutropenia. Additionally, high-dose cefepime was found to be significantly associated with adverse effects leading to discontinuation; this was not found in the low-dose cefepime (2 g q12h) cohort.…”

Section: Discussionmentioning

confidence: 70%

Impact of a cefepime shortage on dosing regimens and outcomes in hospitalized adults with febrile neutropenia

Haiduc

Patel

Walsh

et al. 2020

J Oncol Pharm Pract

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Background Drug shortages may negatively impact outcomes in hospitalized patients. A cefepime dosing regimen of 1 gram every 6 hours (1 g q6h) has shown to provide similar exposures above target minimum inhibitory concentrations compared to the regimen of 2 g q8h approved by the United States Food and Drug Administration (FDA) for febrile neutropenia. Our objective was to determine if the dosing regimen of 1 g q6h amidst a cefepime shortage is an appropriate alternative for the treatment of febrile neutropenia. Methods A retrospective chart review of hospitalized patients who received cefepime for febrile neutropenia over a two-year period was performed. Patients were grouped based on cefepime dosing strategy: 2 g q8h vs. 1 g q6h. The primary objective was to compare time to defervescence after cefepime initiation. Secondary objectives included all-cause 30-day mortality, duration of antibiotic therapy, and inpatient length of stay. Results Seventy-five patients in each arm were included. There were no differences in baseline age or severity of illness between groups. There was no difference in the primary objective as median time to defervescence was similar between the 2 g q8h and 1 g q6h groups (69.0 vs. 65.3 h: p= 0.67). Additionally, no differences were found in the secondary objectives of all-cause 30-day mortality (10.7% vs. 9.3%: p = 0.79), duration of therapy (80.8 vs. 88.0 h: p = 0.34), or length of stay (9 vs. 7 days: p = 0.50). Conclusions Our study identified no differences in clinical outcomes with cefepime 1 g q6h compared to the traditional FDA-approved 2 g q8h regimen for the treatment of febrile neutropenia.

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Section: Discussionmentioning

confidence: 70%

Impact of a cefepime shortage on dosing regimens and outcomes in hospitalized adults with febrile neutropenia

Haiduc

Patel

Walsh

et al. 2020

J Oncol Pharm Pract

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“…Additionally, the doses of cefepime used in the study may have been subtherapeutic, whereas our doses were reviewed for therapeutic efficacy and we also took into account if renal dose adjustments had been made [ 28 ]. Lower doses of cefepime have been associated with treatment failure and higher mortality [ 28 , 32 ]. Literature suggests that higher maximal doses of cefepime, even when renally adjusted, may be more beneficial than standard cefepime dosing [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lower doses of cefepime have been associated with treatment failure and higher mortality [ 28 , 32 ]. Literature suggests that higher maximal doses of cefepime, even when renally adjusted, may be more beneficial than standard cefepime dosing [ 32 ]. Because time above MIC is critical for clinical success of cefepime dosing, our study evaluated if the dose was appropriate based on the infection type and renal function [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Infections with Susceptibilities among Levofloxacin, Cefepime, and Carbapenems

Walker

Lee

Klar

2018

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Purpose Highly resistant Gram-negative bacterial infections are associated with high mortality. Increasing resistance to standard therapy illustrates the need for alternatives when treating resistant organisms, especially extended-spectrum beta-lactamase- (ESBL-) producing Enterobacteriaceae. Methods A retrospective chart review at a community hospital was performed. Patients who developed ESBL-producing infections were included. Patients less than eighteen years old, who were pregnant, or who were incarcerated were excluded. The primary outcome was hospital mortality. The secondary outcomes included intensive care unit (ICU) mortality, ICU length of stay, and hospital length of stay. Results 113 patients with ESBL-producing infections met the criteria for review. Hospital mortality: carbapenem (16.6%), cefepime (0%), and levofloxacin (15.3%) (p=0.253). ICU mortality: carbapenem (4.5%), cefepime, (0%), and levofloxacin (3.7%) (p=0.616). Mean ICU and hospital length of stay: carbapenem (9.8 ± 16, 12.1 ± 1 days), cefepime (7.8 ± 6, 11.1 ± 10.5 days), and levofloxacin (5.4 ± 4.1, 11.1 ± 10.4 days) (p=0.805, 0.685). No predictors were clearly found between the source of infection and mortality. Conclusion Cefepime or levofloxacin can be a potential alternative agent for infections with ESBL-producing Enterobacteriaceae, and larger clinical trials investigating these outcomes are warranted.

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“…Meta analisis dari Cochrane 20 menyebutkan bahwa sefepim dan seftazidim memiliki efikasi dan efektifitas yang serupa. Penelitian IDSA dalam metaanalisis mereka menemukan bahwa administrasi sefepim mungkin berhubungan dengan peningkatan mortalitas di antara pasien ALL dengan demam neutropenia, 21 tetapi penelitian Food and Drug Administration Amerika Serikat menunjukkan bahwa peningkatan mortalitas tidak berkaitan dengan sefepim. 22 Penelitian lain juga menemukan sefepim sama efektif dan amannya dengan piperasilin/ tazobaktam, dan sefozopran pada anak-anak dengan demam neutropenia.…”

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Perbandingan Efektifitas Antara Monoterapi Empiris Seftazidime dan Sefepim Pada Anak Leukemia Limfoblastik Akut dengan Demam Neutropenia

Suryaningrat

Primadi

Chairulfatah

2019

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Latar belakang. Demam neutropenia pada leukemia limfoblastik akut (LLA) termasuk kegawatan onkologi yang harus mendapatkan tatalaksana segera berupa pemberian antibiotik tanpa menunggu hasil kultur. Saat ini, seftazidim dan sefepim digunakan sebagai monoterapi empiris demam neutropenia di Divisi Hemato-Onkologi Rumah Sakit Hasan Sadikin. Namun, hingga saat ini, efektifitas kedua antibiotik tersebut tidak pernah dinilai.Tujuan. Studi ini bermaksud untuk membandingkan efektifitas seftazidim dan sefepim sebagai monoterapi empiris pada pasien demam neutropenia anak dengan LLA.Metode. Uji acak terkendali dilakukan terhadap pasien LLA anak dengan demam neutropenia pada bulan Maret 2017 hingga Maret 2018 di Rumah sakit Dr Hasan Sadikin Bandung. Seftazidim dan sefepim diberikan secara konsekutif sebagai monoterapi empiris. Turunnya demam, peningkatan absolute neutophyl count (ANC) dan penurunan C-reactive protein (CRP) pada hari ke-3,5, dan 7 digunakan sebagai parameter efektivitas terapi.Hasil. Sebanyak 48 pasien mengikuti penelitian hingga selesai. Seftazidim dan sefepim diberikan masing-masing pada 28 dan 20 pasien. Tidak didapatkan perbedaan bermakna secara statistik pada usia, jenis kelamin dan keparahan penyakit pada kedua grup (p=0,908, p=0,251, p=0,507). Pada kelompok seftazidim terjadi penurunan demam pada hari ke-2, 3-4, 5-6 and >7 ditemukan sebanyak 15 (53,6%), 4 (14,3%), 1 (3,6%), 8 (28,6%) pasien, sedangkan pada kelompok sefepim masing-masing ditemukan pada 12 (60%), 4 (20%), 0, dan 4 (20%) pasien (p=0,638, p=0,442, p=0,583 p=0,449). Nilai rata-rata ANC pada awal 315,4 (154,2) pada grup seftazidim dan 276,2 (292,3) pada grup sefepim (p=0,778). Sebagian besar pasien pada kedua grup mencapai ANC>500 pada hari 5 (x=773 (1603,8) dan x=840 (979,8), (p=0,664). Nilai CRP awal mengalami sedikit peningkatan dari nilai normal, tidak berbeda signifikan secara statistik (x=8,80 (6,28) CI 0,3−28,1 dan 13,62 (10,57) CI 0,5−35,3; p=0,193). Nilai CRP menurun pada kedua grup pada hari ke-7 (x=7,84 (6,82), CI 0,5−25 dan 8,15 (9,39) CI 0,1−36,7; p=0,618)Kesimpulan. Penelitian ini menunjukan bahwa seftazidim dan sefepim memiliki efektifitas yang sama sebagai monoterapi empiris pada pasien LLA anak dengan demam neutropenia. Pemilihan antibiotik dengan mempertimbangkan ketersediaan obat, biaya, dan efek samping.

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The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis

Cited by 13 publications

References 50 publications

Impact of a cefepime shortage on dosing regimens and outcomes in hospitalized adults with febrile neutropenia

Impact of a cefepime shortage on dosing regimens and outcomes in hospitalized adults with febrile neutropenia

Clinical Outcomes of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Infections with Susceptibilities among Levofloxacin, Cefepime, and Carbapenems

Perbandingan Efektifitas Antara Monoterapi Empiris Seftazidime dan Sefepim Pada Anak Leukemia Limfoblastik Akut dengan Demam Neutropenia

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