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Addition of Tigecycline to Empiric Therapy Improves Success Rate in Febrile Neutropenic Patients With Hematologic Malignancy

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Key Points

  • The addition of tigecycline to piperacillin/tazobactam improved success rates in empiric therapy in febrile neutropenic patients.
  • The combination warrants consideration as first-line empiric therapy in settings characterized by high rates of infections due to multidrug-resistant organisms.

Antibiotic monotherapy is considered standard in empiric therapy in febrile neutropenic cancer patients, but the approach may be insufficient given the increase in infections due to multidrug-resistant microorganisms. Tigecycline (Tygacil), the first in a new class of glycylcycline antibiotics, has a broad antibacterial spectrum that includes the majority of multidrug-resistant Gram-positive and Gram-negative bacteria. In an open-label trial reported in Journal of Clinical Oncology, Bucaneve et al found that the combination of piperacillin/tazobactam plus tigecycline was more effective as empiric therapy vs piperacillin/tazobactam alone in febrile neutropenic high-risk patients with hematologic malignancies.

Study Details

In the study, 399 adult, febrile, high-risk neutropenic patients with hematologic malignancies were randomly assigned to receive intravenous piperacillin/tazobactam at 4.5 g every 8 hours with (n = 187) or without (n = 293) intravenous tigecycline at 50 mg every 12 hours after a 100 mg loading dose. The primary endpoint was resolution of febrile episodes without modifications of the initial allocated treatment.

Higher Success Rates

On intention-to-treat analysis, successful outcome occurred in 67.9% of combination patients vs 44.3% of monotherapy patients (absolute difference in risk = 23.6%, P < .001). Response rates were significantly better with combination therapy in microbiologically documented infections (n = 184; 61.4% vs 28.1%, P = .001), bacteremias (total n = 190; 60.5% vs 27.7%, P < .001), and clinically documented infections (total n = 38; 84.2% vs 47.4%, P < .01).

Death occurred in 8.5% of the combination group and 7.3% of the monotherapy group, including death from infectious causes in 5.8% and 5.4%, and death related to bacteremia in 4.2% and 3.9%.

Adverse events occurred in 6.4% of patients in each treatment group and resulted in discontinuation of treatment in 1.6% of the combination group and 2.5% of the monotherapy group.

The investigators concluded, “The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of [multidrug-resistant] microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.”

Alessandra Micozzi, MD, of “Sapienza” Università di Roma, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Wyeth and Pfizer. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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