title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bucaneve
authors.forename: Alessandra
authors.initials: A
authors.lastname: Micozzi
authors.forename: Marco
authors.initials: M
authors.lastname: Picardi
authors.forename: Stelvio
authors.initials: S
authors.lastname: Ballanti
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascavilla
authors.forename: Prassede
authors.initials: P
authors.lastname: Salutari
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Rosa
authors.initials: R
authors.lastname: Fanci
authors.forename: Mario
authors.initials: M
authors.lastname: Luppi
authors.forename: Laura
authors.initials: L
authors.lastname: Cudillo
authors.forename: Renato
authors.initials: R
authors.lastname: Cantaffa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Milone
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Anna
authors.initials: A
authors.lastname: Chierichini
authors.forename: Francesco
authors.initials: F
authors.lastname: Fabbiano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarta
authors.forename: Valeria
authors.initials: V
authors.lastname: Primon
authors.forename: Bruno
authors.initials: B
authors.lastname: Martino
authors.forename: Annunziata
authors.initials: A
authors.lastname: Manna
authors.forename: Eliana
authors.initials: E
authors.lastname: Zuffa
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferrari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gentile
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Albano
authors.initials: A
authors.lastname: Del Favero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects; D016470:Bacteremia / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000188:drug therapy* / Q000401:mortality; D004338:Drug Combinations; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage; D000077725:Piperacillin, Tazobactam Drug Combination; D012307:Risk Factors; D000078304:Tigecycline; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004338:Drug Combinations; D000077725:Piperacillin, Tazobactam Drug Combination; D000078304:Tigecycline; D010397:Penicillanic Acid; D008911:Minocycline; D010878:Piperacillin