SHORT
Trial question
Is short antibiotic treatment noninferior to extended antibiotic treatment with carbapenems in patients with high-risk fever of unknown origin during chemotherapy-induced neutropenia?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
39.0% female
61.0% male
N = 281
281 patients (109 female, 172 male).
Inclusion criteria: adult patients who had fever of unknown origin during high-risk neutropenia and were treated for hematological malignancy.
Key exclusion criteria: contraindication to use of imipenem-cilastatin or meropenem; corticosteroid use ≥ 10 mg/day prednisolone or equivalent for > 3 consecutive day during the previous 7 days; infection; symptoms of septic shock.
Interventions
N=144 short treatment (500 mg intravenous imipenem-cilastatin QID or 1,000 mg intravenous meropenem TID for 72 hours).
N=137 extended treatment (500 mg intravenous imipenem-cilastatin QID or 1,000 mg intravenous meropenem TID for ≥ 9 days).
Primary outcome
Carbapenem-sensitive infection or recurrent fever
19%
15%
19.0 %
14.3 %
9.5 %
4.8 %
0.0 %
Short
treatment
Extended
treatment
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in carbapenem-sensitive infection or recurrent fever (19% vs. 15%; AD 4%, 90% CI -1.7 to 9.7).
Secondary outcomes
Significant increase in the rate of death within 30 days after the end of neutropenia (3% vs. 1%; AD 2.6%, 95% CI 1.2 to 4.1).
Borderline significant increase in duration of hospital admission (24 days vs. 24 days).
Safety outcomes
Significant difference in serious adverse events (16% vs. 10%).
Conclusion
In adult patients who had fever of unknown origin during high-risk neutropenia and were treated for hematological malignancy, short treatment was noninferior to extended treatment with respect to carbapenem-sensitive infection or recurrent fever.
Reference
Nick A de Jonge, Jonne J Sikkens, Sonja Zweegman et al. Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trial. Lancet Haematol. 2022 Aug;9(8):e563-e572.
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