Prospective randomized study to compare imipenem 1.5 grams per day vs. 3.0 grams per day in infections of granulocytopenic patients.
The objective of this presented prospective randomized study was to compare the efficacy of empirical antimicrobial monotherapy with imipenem 3 x 0.5 g per day to 3 x 1.0 g per day for treatment of infections in neutropenic patients. A total of 192/220 febrile episodes were evaluable for clinical efficacy. The overall response rate was 53/93 (57%) vs. 57/99 (58%). Of the different infection types, fever of unknown origin (FUO) showed the best response, with defervescence in 29/41 (71%) and 36/42 (86%) cases, respectively (not significant). Unfavourable results were found in pneumonias [5/20 (25%) vs. 4/23 (17%)]. The median time until persistent defervescence was equal in both groups (2 days), likewise the median duration of imipenem therapy in responders (7 days). The most frequent micro-organisms were Gram-negative, documented in 22% of the febrile episodes in the lower dosage group vs. 17% of all episodes in the patients with imipenem 3.0 g per day (Gram-positives 17% vs. 14%, fungal 5% vs. 8%). In the lower dosage group, fever with abdominal symptoms occurred less frequently (8% vs. 15%), and significantly more patients tolerated imipenem without any side-effects (95.8% vs. 79.4%), especially regarding severe nausea/vomiting (2.1% vs. 11.8%). Of the initial non-responders, 35/40 (88%) vs. 41/42 (98%) were cured after therapy modification. There was no significant difference in the use of further antibiotics such as aminoglycosides, glycopeptides, ceftazidime or amphotericin B, except a marginally higher use of metronidazole in patients with imipenem 3.0 g per day (3% vs. 10%). Overall, we found no significant differences in efficacy between the two study groups, but more frequent side-effects with imipenem 3.0 g per day.
Böhme
A
A
Med. Clinic III, Department of Medical Hematology, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Shah
P M
PM
Stille
W
W
Hoelzer
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000145:classification / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D016896:Treatment Outcome
D013845:Thienamycins; D015378:Imipenem