PIPERACILLIN-TAZOBACTAM PLUS AMIKACIN VERSUS CEFTAZIDIME PLUS AMIKACIN AS EMPIRIC THERAPY FOR FEVER IN GRANULOCYTOPENIC PATIENTS WITH CANCER

Gram-positive bacteria have become-the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum ce phalosporin, but the response to therapy in gram-positive coccal bacte remia has been unsatisfactory. Thus, new antibiotics with better activ ity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compa re the efficacy and tolerance of piperacillin-tazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the I nternational Antimicrobial Therapy Cooperative Group of the European O rganization for Research and Treatment of Cancer, in the empiric treat ment of febrile granulocytopenic cancer patients. A total of 858 episo des were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the pip eracillin-tazobactam-amikacin group. A significant difference in respo nse to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 epis odes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the pro bability of failure was significantly greater with ceftazidime plus am ikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). Tox icity was assessed in 854 episodes, and no significant difference in t he overall occurrence of unwanted effects was found between the two tr eatment groups. However, rash or urticaria did occur more frequently i n the piperacillin-tazobactam-amikacin group (12 of 421 episodes compa red with 3 of 433 episodes in the ceftazidime-amikacin group; P = 0.02 ). This trial suggests that piperacillin-tazobactam plus amikacin is m ore effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-t azobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.