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

Abstract

Patients with fever and granulocytopenia are at risk of developing severe infection. We performed a prospective, randomized trial to evaluate the efficacy of low-dose cefepime plus amikacin (C-A) compared to lowdose piperacillin/tazobactam plus amikacin (PT-A). Patients received cefepime (2 g/12 h) plus amikacin (15 mg/kg/day) or piperacillin/tazobactam (4 g/500 mg/8 h) plus amikacin. A total of 317 episodes of febrile granulocytopenia in 190 patients were studied (152 in the C-A group, 165 in the PT-A group). A microbiologically documented infection was present in 53 (35%) episodes in the C-A group and 41 (25%) episodes in the PT-A group (p=ns); a clinically documented infection was observed in 39 (26%) and 47 (28%) episodes, respectively. Toxicity was observed in 6 (4%) episodes in the C-A group and in 5 (3%) episodes in the PT-A group. The antibiotic success rate (no change or addition of antibiotics) was recorded in 89 (59%) and 105 (64%) cases, respectively (p=ns). Mortality related to infection was similar in each arm (3.9% vs. 3.6%). Combination therapy of low-dose β-lactam with an aminoglycoside achieves very good response rates and low rates of toxicity. It might be an attractive option in an environment of increasing resistance among gram-negative bacteria.

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

“…However, additional subanalyses yielded nonsignificant findings (Supplemental Results). It is interesting to note that the incidence of treatment failure in microbiologically documented infections (23 trials, reporting on 455 cefepime-treated infections vs 420 infections treated with other antibiotics [ 12 , 20–25 , 27 , 28 , 32 , 35–43 , 45–48 ]) was similar across study arms (Supplemental Results). Furthermore, the occurrence of superinfections (12 trials, reporting on 174 vs 161 superinfections in the cefepime and comparator study arms, respectively [ 23 , 25 , 27 , 29 , 32 , 36 , 39 , 41–43 , 46 , 48 ]) was not significantly different in the cefepime arm (Supplemental Results).…”

“…It is interesting to note that the incidence of treatment failure in microbiologically documented infections (23 trials, reporting on 455 cefepime-treated infections vs 420 infections treated with other antibiotics [ 12 , 20–25 , 27 , 28 , 32 , 35–43 , 45–48 ]) was similar across study arms (Supplemental Results). Furthermore, the occurrence of superinfections (12 trials, reporting on 174 vs 161 superinfections in the cefepime and comparator study arms, respectively [ 23 , 25 , 27 , 29 , 32 , 36 , 39 , 41–43 , 46 , 48 ]) was not significantly different in the cefepime arm (Supplemental Results). Finally, infection-specific mortality (18 trials, 4007 patients [ 20 , 22–25 , 27 , 28 , 30 , 32 , 34 , 35 , 37 , 40–42 , 45 , 46 , 48 ]) was similar in patients treated with cefepime or other antibiotics (Supplemental Results).…”

“…Treatment failure among patients with clinically documented infections was significantly more common with cefepime therapy (RR = 1.143; 95% CI, 1.004–1.300; P = .043) (16 trials, reporting on 355 cefepime-treated infections vs 384 infections treated with other antibiotics [ 12 , 20–22 , 24 , 25 , 27 , 28 , 32 , 35–39 , 42 , 46 ]). However, additional subanalyses yielded nonsignificant findings (Supplemental Results).…”

Connexins and pannexins in the skeleton: gap junctions, hemichannels and more

“…A few in vitro studies highlight the context dependence of the role of Cx43 in osteoblast/osteocyte function. Loss of Cx43 has been shown to reduce the inhibitory effects of endothelin-1 on osteoblasts [82,83], perhaps by disrupting calcium-dependent signaling events [84]. Similarly, loss of Cx43 increases β-catenin levels in cultured osteocytes, enhancing their mechano-responsiveness [85].…”

Toxicity of β-Lactam Antibiotics: Pathophysiology, Molecular Biology and Possible Recovery Strategies

“…This strategy has been able to increase the eiciency of the β-lactam antibiotics [91][92][93][94]. But clinicians should be aware that, because of a possibility of unexpected adverse efects, dialysis facilities should be available [95].…”