EFFICACY AND TOXICITY OF SINGLE DAILY DOSES OF AMIKACIN AND CEFTRIAXONE VERSUS MULTIPLE DAILY DOSES OF AMIKACIN AND CEFTAZIDIME FOR INFECTION IN PATIENTS WITH CANCER AND GRANULOCYTOPENIA
T. Calandra et al., EFFICACY AND TOXICITY OF SINGLE DAILY DOSES OF AMIKACIN AND CEFTRIAXONE VERSUS MULTIPLE DAILY DOSES OF AMIKACIN AND CEFTAZIDIME FOR INFECTION IN PATIENTS WITH CANCER AND GRANULOCYTOPENIA, Annals of internal medicine, 119(7), 1993, pp. 584-593
Objective. To compare the efficacy and toxicity of single daily dosing
of amikacin and ceftriaxone with that of multiple daily dosing of ami
kacin and ceftazidime for febrile episodes in patients with cancer and
granulocytopenia. Design: A prospective, randomized, unblinded, multi
center trial. Setting: Twenty-one tertiary care or university medical
centers. Patients: Six hundred seventy-seven patients with cancer and
granulocytopenia (858 febrile episodes). Interventions: Random assignm
ent to empiric therapy with a single daily dose of amikacin (20 mg/kg)
and ceftriaxone (adults, 30 mg/kg; children, 80 mg/kg) (24-hour group
) or with multiple daily doses of amikacin (6.5 mg/kg every 8 hours) a
nd ceftazidime (33 mg/kg every 8 hours) (8-hour group). Measurements:
Percentage response to each regimen and occurrence of nephrotoxicity a
nd ototoxicity. Results. Single daity dosing of amikacin and ceftriaxo
ne was as effective as multiple daily dosing of amikacin and ceftazidi
me (71% compared with 74%; difference, -3%; 95% CI, -10% to 3%; P > 0.
2). Equivalent responses also were noted for each category of infectio
n. Median peak (30 minutes after a 60-minute infusion) serum concentra
tions of amikacin were higher in the 24-hour group than in the 8-hour
group (45.6 compared with 21 mug/mL, P < 0.001), whereas trough (prein
fusion) levels were lower (0.9 compared with 2 mug/mL, P < 0.001). Nep
hrotoxicity was 3% in the 24-hour group and 2% in the 8-hour group (di
fference, 1%; CI, -1% to 4%). Increases in serum creatinine, however,
were delayed (P = 0.048) and smaller (P = 0.06) in the 24-hour group t
han in the 8-hour group and occurred almost exclusively after other ne
phrotoxic drugs were added. Audiometry was only done in 144 patients (
21%). Ototoxicity was 9% in the 24-hour group and 7% in the 8-hour gro
up (difference, 2%; CI, -7% to 11 %; P > 0.2). Further infections deve
loped in 15% and 12% of patients, respectively (difference, 3%; CI, -2
% to 9%). The overall mortality rate was 11% in both treatment groups
(difference, 0%; CI, -5% to 5%). Conclusions: Single daily dosing of a
mikacin and ceftriaxone was as effective and no more toxic than multip
le daily dosing of amikacin and ceftazidime for the empiric therapy of
infection in patients with cancer and granulocytopenia.