PIPERACILLIN TAZOBACTAM VERSUS IMIPENEM - A DOUBLE-BLIND, RANDOMIZED FORMULARY FEASIBILITY STUDY AT A MAJOR TEACHING HOSPITAL/

With the introduction of piperacillin/tazobactam to the North American market, hospitals have been faced with the task of making a decision regarding its formulary role. In view of its broad spectrum of activit y, piperacillin/tazobactam could be considered as a formulary alternat ive to imipenem. To evaluate the formulary feasibility of substituting piperacillin/tazobactam for imipenem, a comparative assessment of the se agents in the empiric treatment of serious bacterial infections was undertaken at this tertiary care hospital. This trial was conducted a s a randomized, double-blind, single-center study. Consenting adult pa tients (>16 years of age) who were prescribed imipenem were randomized to receive either 4 g of i.v. piperacillin/tazobactam or imipenem 500 mg of i.v. Q6H with or without concurrent antibiotics. Doses were adj usted according to renal function. There were no restrictions regardin g the use of nonstudy antibiotics before and during the study period. Patients with beta-lactam allergies or meningitis or who had received greater than 72 h of previous imipenem therapy were excluded. Patients were evaluated at the end of treatment, at discharge, and at 30 days postdischarge. Endpoints included both clinical and microbiologic effi cacy as well as drug toxicity. Over the 433-day study period, 360 imip enem treatment courses were initiated. Of these, 150 treatment courses (75 piperacillin/tazobactam courses and 75 imipenem courses) met stud y criteria and were subsequently randomized. The distribution of presc riber services for enrolled patients runs similar to that for all pati ents receiving imipenem during the study period (p = 0.15). Also, ther e were no statistically significant differences in demographic paramet ers between enrolled and excluded patients. For those patients enrolle d in the study, demographic characteristics, treatment course indicati on(s), and accompanying antibiotics were similar across treatment arms . The mean duration of study drug therapy was 7.7 days (SD, 6.2) for i mipenem and 7.5 days (SD, 6.7) for piperacillin/tazobactam (p = 0.84). In the majority of cases, treatment discontinuation occurred as a res ult of a favorable treatment course outcome, stepdown to a narrower sp ectrum parenteral agent, or stepdown to an oral agent and did not diff er between study drugs (p = 0.73). Clinical and microbiologic treatmen t course outcomes were also similar across treatment arms. Clinical ou tcome was deemed successful or improved for 68% of imipenem and 70% of the piperacillin/tazobactam treatment courses (p = 0.54). Fifty-three percent of treatment courses were microbiologically confirmed. Of the 58 courses that were assessed for microbiological outcome, 93% demons trated successful eradication of the causative pathogens. There was no difference between study drugs (96% imipenem; 90% piperacillin/tazoba ctam; p = 0.61). The proportion of treatment courses with at least one adverse event was similar between the study drugs (p = 1.0). Nausea a nd/or vomiting were/was observed move commonly in the imipenem arm (p = 0.03). Discontinuation of therapy due to drug toxicity occurred in 1 6% of imipenem and 5% of piperacillin/tazobactam treatment courses (p = 0.06). There was no statistically significant difference between the mean treatment course cost for imipenem ($762; range, $55-$3192) vers us piperacillin/tazobactam ($696; range, $79-$2967; p = 0.59). In summ ary, piperacillin/tazobactam seems to represent a suitable alternative to imipenem for several clinical indications including intraabdominal infections, pneumonia, febrile neutropenia, and skin/soft tissue infe ctions in which the causative pathogens are susceptible. However, in v iew of the prevalence of multiresistant Gram-negative aerobic pathogen s at this institution, we do not believe that imipenem can be removed from the drug formulary. In addition, at the currently studied dosing regimen, there seems to be no evidence of a direct cost advantage asso ciated with the use of piperacillin/tazobactam as an alternative to im ipenem. (C) Elsevier Science Inc.