Ceftriaxone versus β-lactams with antipseudomonal activity for empirical, combined antibiotic therapy in febrile neutropenia: a meta-analysis

Abstract

The object of this work was to compare the efficacy of antibiotic combinations including ceftriaxone with that of combinations including an antipseudomonal beta-lactam for the empirical treatment of febrile neutropenia in cancer patients. We identified all published randomised trials comparing two antibiotic combinations differing only in the beta-lactam, being ceftriaxone in one treatment group and an antipseudomonal beta-lactam in the other. The quality of individual trials was formally evaluated. A meta-analysis was performed using the Peto-modified Mantel-Haenszel method for combining binary data. Primary analysis was done, for both febrile episodes and bacteraemic episodes, using failure of empirical antibiotic treatment defined as modification of the initial allocated regimen or death during treatment. Secondary analysis was done using death from any cause in the two treatment groups. Data relating to 1,537 febrile neutropenic episodes recorded in eight randomised clinical trial were pooled s. Overall, there were 256 treatment failures out of 782 febrile episodes treated with ceftriaxone-containing combinations (32.7%), and 243 out of 755 treated with antipseudomonal beta-lactam regimens (32.1%). The pooled odds ratio of failure for ceftriaxone-containing combinations for febrile episodes was 1.04, with the 95% confidence interval ranging from 0.84 to 1.29, and that for bacteraemic episodes was 0.93 (95% confidence interval 0.58-1.49). With regard to overall mortality, there were 54 deaths among 782 febrile episodes treated with ceftriaxone-containing combinations (6.9%) and 62 deaths among 755 febrile episodes treated with antipseudomonal beta-lactam-containing regimens (8.2%). The pooled odds ratio of death for ceftriaxone regimens was 0.84 (95% confidence interval 0.57-1.24). Results of this meta-analysis show that in the empirical treatment of febrile neutropenia, antibiotic combinations containing ceftriaxone are as effective as those in which the beta-lactam has specific activity against Pseudomonas aeruginosa, such as ureidopenicillin or ceftazidime.

Case-Control Comparison of At-Home to Total Hospital Care for Autologous Stem-Cell Transplantation for Hematologic Malignancies

“…26 Moreover, despite prophylaxis with oral antibiotics most of the patients who receive myeloablative hematopoietic transplantation will develop fever. 31,32 This antibiotic is suitable for once-daily intravenous administration and facilitates patient management on an outpatient basis. Preliminary reports suggest that this approach could be effective in preventing early bacterial infections and related complications after hematopoietic transplantation and to be cost effective.…”

“…27 This observation has led some investigators to study the effectiveness of the administration of prophylactic intravenous antibiotic after hematopoietic transplantation. Of note, whereas data on the safety and efficacy of ceftriaxone in the treatment of febrile neutropenia in low-risk patients are available, 31,32 no previous studies have addressed the role of prophylactic intravenous ceftriaxone in high-risk neutropenic patients. [28][29][30] Ceftriaxone is a third-generation cephalosporin with a long elimination half-life, effective against a broad range of Gram-positive and Gram-negative bacteria but having a limited activity against Pseudomonas aeruginosa.…”

Consenso Manejo racional del paciente con cáncer, neutropenia y fiebre: Rational approach towards the patient with cancer, fever and neutropenia

“…Cobertura anti Pseudomonas. En un metaanálisis publicado por Furno y cols sobre este tema no se evidenció diferencias al comparar esquemas con y sin cobertura anti Pseudomonas sp 98 ; sin embargo, este análisis incluyó pacientes con neutropenia moderada y sin estratificación de riesgo, por lo que los resultados no se pueden extrapolar a la terminología actual de NF con clasificación de riesgo y con neutropenia severa (RAN < 500/ mm³). Una infección por Pseudomonas sp fue identificada en menos de 2% de los pacientes incluidos en el meta-análisis, constituyendo 15% de todos los bacilos gramnegativos recuperados.…”

“…Para poder catalogar la respuesta terapéutica como favorable o desfavorable, es necesario considerar que la duración habitual de la fiebre en adultos y niños con episodios de NF de alto y bajo riesgo es diferente: en adultos con episodios de NF de alto riesgo la mediana es de 10 días, y en episodios de bajo riesgo es de 6-7 días; en niños es de 5-7 días en episodios de NF de alto riesgo, y de 2-3 días en episodios de bajo riesgo 12, 65,98,109 .…”