• Leukemia Clinical Trials
• Bacterial Infections

Tigecycline, first in a new class of glycylcyclines, in combination with piperacillin/tazobactam, is effective, safe, and well tolerated in high-risk febrile neutropenic oncohematologic patients. Giampaolo Bucaneve, MD, University of Perugia, Perugia, Italy, believes that tigecycline in combination should be considered one of the “first-line” empiric antibiotic therapies (particularly in a specific epidemiological setting (eg, high rate of extended-spectrum β-lactamase-producing gram-negatives and/or methicillin-resistant Staphylococci). This combination therapy may aid in reducing the increase and extensive use of carbapenems, which have been associated with an increase in multidrug-resistant bacteria.

This prospective, randomized, multicenter study included 364 cancer patients from 28 Italian oncohematological departments with profound (<500 neutrophils/mmc) chemotherapy-induced neutropenia and fever (>38.5°C once or >38°C on at least two occasions during a period of 12 hours) due to presumed infection. Patients were randomized centrally and stratified according to center and underlying disease (acute leukemia vs lymphoma and solid tumors). Patients received either IV (n=174) piperacillin/tazobactam (4.5 g 3× daily) plus tigecycline (50 mg twice daily) or IV (n=190) piperacillin/tazobactam (4.5 g 3× daily) as monotherapy. All other antibiotic therapy was stopped at randomization.

Successful treatment was defined as resolution of fever (maintained for at least 4 days) or any clinical sign of infection whenever present and eradication of the infecting microorganism whenever isolated, without change in the initial allocated treatment. Failure was defined as one of the following: death from primary infection, persistence of bacteremia beyond the first 24 hours of therapy, breakthrough bacteremia, documented pathogen resistant to assigned antibiotic(s), lack of response that required antibacterial therapy modification, development of shock or acute respiratory distress syndrome or disseminated intravascular coagulation or multiple organ failure, relapse of infection within 7 days of treatment discontinuation, or toxicity requiring treatment discontinuation.

Overall response to therapy was significantly (p<0.01) more effective following piperacillin/tazobactam plus tigecycline (72%) compared with monotherapy (47%; Table 1). Piperacillin/tazobactam plus tigecycline treatment success rates were significantly (p≤0.01) greater for microbiologically (with bacteremia) and clinically documented infections compared with monotherapy. Single gram-positive and -negative (E. coli) bacteremias and coagulase-negative Staphylococcus species were more successfully treated with combination therapy than monotherapy (Table 2).

Treatment success rates were significantly (p≤0.01) higher with combination therapy for infections that were associated with skin and soft tissues and for bacteremias of unknown origin. Overall treatment failures were greater for monotherapy. Overall mortality rates, deaths due to bacteremia, and treatment-related adverse events were similar between the two arms.

Tigecycline in combination with piperacillin/tazobactam, compared with the standard regimen of piperacillin/tazobactam, is more effective overall in bacteremias and clinically documented infections as well.

• © 2011 MD Conference Express