Cefepime/Amikacin Versus Ceftazidime/Amikacin as Empirical Therapy for Febrile Episodes in Neutropenic Patients: A Comparative Study

Abstract

We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.

Low-dose β-lactam plus amikacin in febrile neutropenia: cefepime vs. piperacillin/tazobactam, a randomized trial

“…The population studied in our trial was similar to that of other studies with respect to the main disease (acute leukemia in approximately half of the cases) [4,18,20,22,27,30] and the rates of granulocytopenia (>90% of episodes had <500 cells/mm 3 ). The time to defervescence was very short (a median of 3 days in both groups) and the need for changing or adding other antimicrobials was surprisingly low (39 and 33% of episodes, respectively) compared to other trials, with approximately two-thirds of the episodes (49-70%) in which the antibiotic therapy had to be modified [4,18,22].…”

“…The combination of a β-lactam with antipseudomonal activity (piperacillin, ticarcillin) plus an aminoglycoside has been used since the 1970s with good results [2], and it has been the most commonly used empirical treatment for years. More recently, other combinations with third-and fourth-generation cephalosporins plus an aminoglycoside have been validated (ceftazidime plus amikacin, cefepime plus amikacin) [3,4]. Finally, antibiotic therapy with a single agent with a broad spectrum of activity (carbapenems, ceftazidime, cefepime) has been widely used because of similar efficacy and less toxicity as compared to the classic combination therapy [5][6][7][8][9], particularly in the mid1990s, when the prevalence of Pseudomonas aeruginosa infections decreased in parallel with a progressive predominance of gram-positive coccal infections.…”

“…Thus, in the case of piperacillin/tazobactam, 4 g/500 mg q/6 h is an approved dosing regimen for fever and granulocytopenia [5,17,18], and in the case of cefepime, 2 g/8 h is the standard of care in this setting [6,[18][19][20]. However, lower doses of both antibiotics have been used in some studies [4,9,21,22]. When a combination of agents is used, it is plausible that lower dosing can be administered [23].…”

Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality

“…1,4,6,16,[38][39][40][41][42][43] It is possible that the high proportion of coagulase-negative staphylococcal BSI was due to the consideration of contaminants in blood cultures as true bacteremias. However, in this study, such an influence of contaminants is less likely since (1) our definition of BSI with common skin contaminants was rigorous (at least two positive consecutive cultures or two positive cultures within 72 h of one another) and in accordance with that used by other investigators; 1,4,6,16,[38][39][40][41][42][43] (2) the cultures were obtained in response to an indication of infection as opposed to carried out for surveillance; and (3) the common isolation of coagulase-negative staphylococcal from the blood is consistent with other studies. 2,6,44,45 It is more likely that the high proportion of coagulase-negative staphylococcal BSI was due to several factors including the presence of indwelling central venous catheters in virtually all of the patients in the early post-HSCT phase and the universal use of prophylaxis with fluoroquinolones.…”

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

“…[130][131][132][133][134][135][136][137] Others reported on 10-14 days of therapy. 138,139 Some studies required some evidence of bone marrow recovery.…”