A Randomized, Open-Label, Multicenter Comparative Study of the Efficacy and Safety of Piperacillin-Tazobactam and Cefepime for the Empirical Treatment of Febrile Neutropenic Episodes in Patients with Hematologic Malignancies

Abstract

This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

“…In the present study, the overall efficacy rate was 57.0% in the 4th Cephs group and 59.2% in the P/T group. Similar to our findings, the efficacy rates of 4th Cephs ± aminoglycoside and PIPC/TAZ ± aminoglycoside in cases of FN reported from previous controlled studies varied at 21-62% and 27%-61%, respectively [12][13][14][15]. This variability in the efficacy rates noted in these studies is likely related to differences in the definition of efficacy, which was variously set as 2-or 3-day defervescence, microbiological eradication, test of cure, and so on.…”

“…The third limitation of this study is that the antimicrobials were given to the patients at 9:00, 15:00, and 21:00 hours, taking into account the patients' sleeping times and the nursing shifts. As reported elsewhere, intravenous antimicrobial infusion should desirably be given at 8-hour intervals according to the antimicrobial pharmacokinetics/pharmacodynamics [12][13][14][15].…”

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].…”

“…These rates are higher than in a very similar study conducted by Sanz et al [18] in 867 episodes comparing piperacillin/tazobactam (4 g/6 h) vs. cefepime (2 g/8 h) in combination with amikacin; in that trial, the rate of response without any change in the antibiotic was 49% in the C-A group and 51% in the PT-A group. Another recently published study [30] conducted in a very similar population also had lower response rates with monotherapy with cefepime (2 g/8 h) or piperacillin/tazobactam (4.5 g/6 h) (20.5 and 26.8% success rate, respectively). These results would indicate that the addition of an aminoglycoside to a low dose of piperacillin/tazobactam or cefepime favors better rates of response; even in patients with microbiologically documented infection (where the response rate is usually lower), our patients had a~50% chance of response without changing the therapy.…”

“…Most published trials have evaluated the standard doses of piperacillin/tazobactam or cefepime [6,[17][18][19][20][27][28][29][30] side, although some studies with lower doses [21,31] have been conducted with good response rates. A synergistic effect against gram-negative bacteria and a lower incidence of bacterial resistance has been argued, favoring the classical combination therapy [26].…”