Prospective randomized study to compare imipenem 1.5 grams per day vs. 3.0 grams per day in infections of
1Med. Clinic III, Department of Medical Hematology, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Abstract:
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.
Insights
This study found no significant difference in efficacy between two imipenem dosages for neutropenic infections. However, the higher imipenem dose (3.0 g/day) resulted in more frequent side effects, particularly nausea and vomiting.
Area of Science:
- Infectious Diseases
- Pharmacology
- Hematology
Background:
- Neutropenic patients are highly susceptible to severe infections.
- Empirical antimicrobial therapy is crucial for managing febrile episodes in neutropenia.
- Imipenem is a broad-spectrum carbapenem antibiotic used for serious infections.
Purpose of the Study:
- To compare the efficacy of two empirical antimicrobial monotherapy dosages of imipenem (3 x 0.5 g/day vs. 3 x 1.0 g/day).
- To evaluate treatment outcomes in neutropenic patients with febrile episodes.
Main Methods:
- Prospective randomized study design.
- Evaluated 192 febrile episodes in neutropenic patients.
- Compared clinical efficacy, response rates, and adverse events between imipenem dosage groups.
Main Results:
- Overall clinical efficacy was similar: 57% vs. 58% response rates.
- Fever of unknown origin showed good response (71% vs. 86%), while pneumonia had poor outcomes (25% vs. 17%).
- The higher imipenem dose (3.0 g/day) was associated with significantly more side effects (20.6% vs. 4.2%), including severe nausea/vomiting (11.8% vs. 2.1%).
Conclusions:
- No significant difference in efficacy was observed between imipenem 1.5 g/day and 3.0 g/day for empirical monotherapy in neutropenic patients.
- The lower imipenem dosage was better tolerated, with fewer adverse events.
- Therapy modification led to successful outcomes in most initial non-responders across both groups.
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