Interventional antimicrobial therapy in febrile neutropenic patients

Abstract

In this prospective multicenter trial, treatment strategies for 1573 patients with neutropenia < 1000/microliters and fever > or = 38.5 degrees C after cytotoxic chemotherapy were compared. Patients with unexplained fever were randomized to a three-phase sequential study for different established drug regimens. If an infection could be defined microbiologically or clinically, treatment modifications were determined. In phase I, treatment for all patients consisted of acylaminopenicillin (PEN) plus aminoglycoside (AMG); or third-generation cephalosporin (CEPH) plus AMG; or PEN plus CEPH. In 800 patients with unexplained fever the response rates were: PEN/AMG (n = 258): 74.4%, CEPH/AMG (n = 252): 73.4%; PEN/CEPH (n = 290): 70.0%. Total response rate was 72.5%. In phase II, patients not responding after 3 days received PEN/CEPH/vancomycin (n = 70) or PEN/CEPH/AMG (n = 74). The respective response rates were 52.9% and 55.4%, total 54.2%. If fever did not resolve, the patients received either PEN/CEPH (n = 40) or imipenem/cilastatin (n = 59) both in combination with amphotericin-B/5-flucytosin/rifampin. The response rates were 62.5% and 79.7%, respectively (p = 0.07), total 72.7%. No significant differences between the treatment modalities compared were found. Analyzing all three phases together, 91.3% of patients with unexplained fever were cured. The response rate was also analyzed according to patients with gram-positive bacteremia (n = 183), response rate = 82.5%; gram-negative organisms (n = 145) 78.6%; fungemia (n = 51) 43.1% (p < 0.001); lung infiltrates (n = 269) 61.3% (p < 0.001); clinically documented infections (n = 198) 84.4%; and clinically and microbiologically documented infections (n = 84) 82.1%. If infections were diagnosed after at least 5 febrile days, more lung infiltrates and fungal infections occurred (p < 0.001). Leukocytes rising above 500/mu during the infection predicted better response rates (p < 0.001): in unexplained fever 97.8% vs 86.5% and lower death rates 1.5% vs 8.5%. In documented infections the response rates were then 89.9% vs 62.3% and the death rates 7.0% vs 20.5%. Therapy of neutropenic fever and infections must be adapted according to risk factors and should include early empiric antifungal therapy. The therapeutic and prophylactic use of hematopoietic growth factors to overcome neutropenia should be evaluated.

Comparison of infectious complications during induction/consolidation chemotherapy versus allogeneic hematopoietic stem cell transplantation

“…Published rates of BSIs in patients undergoing HSCT are reported to be higher than rates from studies including patients receiving induction/consolidation chemotherapies (29-39% versus 10-30%, respectively). 10,13,[25][26][27] In our analysis, there was a trend toward more BSIs in the allogeneic HSCTs, without a statistically significant difference in the McNemar model, which may be explained by the small number of patients available for this analysis.…”

European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia

“…58 A later report maintained the empirical therapy for at least two afebrile days in patients with increasing neutrophil count or seven days in patients with persistent neutropenia. 59 Two more recent prospective studies in children found that discontinuation of antibiotics before marrow recovery did not increase fatality due to bacterial infections. In the first study, children considered to be at low risk for bacterial infections (no identifiable focus, hemodynamic stability, negative admission cultures, and serum C-reactive protein (CRP) < 40 mg/L on Days 1 and 2; normal <10) were randomized on Day 3 of empirical antibiotic therapy to stop antibiotic therapy (n=36) or to continue (n=39) until the resolution of fever and neutropenia.…”

Responsiveness to G-CSF before leukopenia predicts defense to infection in high-dose chemotherapy recipients

“…8 The success of antibiotic treatment in leukopenic patients depends on the leukocyte recovery. 9 The transplantation of autologous hematopoietic stem cells can rescue the host hematopoietic functions after high-dose chemotherapy. High-dose chemotherapy showed favorable disease control and survival in patients with multiple myeloma or lymphoma.…”