F. Marra et al., PIPERACILLIN TAZOBACTAM VERSUS IMIPENEM - A DOUBLE-BLIND, RANDOMIZED FORMULARY FEASIBILITY STUDY AT A MAJOR TEACHING HOSPITAL/, Diagnostic microbiology and infectious disease, 31(2), 1998, pp. 355-368
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.