Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia.

J Clin Oncol 2014 May 14;32(14):1463-71. Epub 2014 Apr 14.

Giampaolo Bucaneve, Stelvio Ballanti, and Albano Del Favero, Ospedale S. Maria della Misericordia, Perugia, Italy; Alessandra Micozzi, Giuseppe Gentile, and Robin Foà, "Sapienza" Università di Roma, Roma; Marco Picardi, A. O. Universitaria "Federico II," Napoli; Nicola Cascavilla, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo; Prassede Salutari, Ospedale Civile "Spirito Santo," Pescara; Giorgina Specchia, Università di Bari, Bari; Rosa Fanci, A. O. Universitaria "Careggi," Firenze; Mario Luppi, A. O. Universitaria Policlinico, Modena; Laura Cudillo, Policlinico Tor Vergata, Roma; Renato Cantaffa, A. O. "Pugliese Ciaccio," Catanzaro; Giuseppe Milone, Policlinico "Vittorio Emanuele," Catania; Monica Bocchia, Policlinico "S. Maria alle Scotte," Siena; Giovanni Martinelli, Istituto Europeo Oncologico, Milano; Massimo Offidani, A. O. Universitaria-Ospedali Riuniti, Ancona; Anna Chierichini, Ospedale S. Giovanni Addolorata, Roma; Francesco Fabbiano, Ospedali Riuniti, Palermo; Giovanni Quarta, Ospedale "A. Perrino," Brindisi; Valeria Primon, Ospedale SS Antonio e Biagio, Alessandria; Bruno Martino, A. O. "Bianchi-Melacrino-Morelli," Reggio Calabria; Annunziata Manna, ASL5, La Spezia; Eliana Zuffa, Ospedale S. Maria delle Croci, Ravenna; and Antonella Ferrari, A. O. Sant'Andrea, Roma.

Purpose: Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria.

Patients And Methods: In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment.

Results: Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups.

Conclusion: 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 MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.

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http://dx.doi.org/10.1200/JCO.2013.51.6963DOI Listing
May 2014
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