A recent study based in Australia evaluated the use of scanning techniques in antimicrobial management for high-risk patients who have persistent or recurrent neutropenic fever. The study’s findings were reported in the journal Lancet Haematology.

Persistent or recurring neutropenic fevers are commonly faced by patients receiving conditioning chemotherapy prior to hematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for acute leukemia, the study investigators explained in their report. However, identifying the cause of the fever is often difficult, with conventional computed tomography (CT) scanning often used but frequently lacking in sensitivity and specificity.

“Given the substantial risk of deterioration in the setting of untreated infection, there is high reliance on empirical and often protracted antimicrobial therapy, which is not aligned with best practice antimicrobial stewardship,” the investigators wrote. They developed this study to compare conventional CT scanning with the more sensitive and specific method of 18F-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG-PET-CT) scanning in antimicrobial management.

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Patients were recruited in the phase 3 PIPPIN study (ClinicalTrials.gov Identifier: NCT03429387) who had persistent or recurrent neutropenic fever and were being treated with chemotherapy for acute leukemia or conditioning chemotherapy for HSCT. Persistent fever was defined as lasting more than 72 hours, while recurrent fever was defined as a new fever beyond 72 hours of first onset and interspersed with >48 hours of fever subsidence.

Patients were randomly assigned 1:1 to be evaluated by either [18F]FDG-PET-CT imaging or by conventional CT imaging. Imaging occurred within 3 days of being assigned to either trial arm. The composite primary study endpoint involved a change in antimicrobial management, or antimicrobial rationalization within 96 hours of being scanned. Antimicrobial rationalization could include starting, stopping, or broadening/narrowing the spectrum of antimicrobial therapy.

The trial randomly assigned 147 patients between arms. Ultimately, 65 patients were evaluated in the [18F]FDG-PET-CT cohort, and 69 patients were evaluated in the conventional CT scanning cohort. The median study follow-up time was 6 months.

Antimicrobial rationalization was reported in 82% of the patients in the [18F]FDG-PET-CT cohort and in 65% of patients in the conventional CT cohort (odds ratio [OR], 2.36; 95% CI, 1.06-5.24; P =.033).

The most common form of antimicrobial rationalization in this study was reported to be adjustments to the antimicrobial spectrum. Narrowing of the antimicrobial spectrum occurred in 43% of the patients in the [18F]FDG-PET-CT cohort, compared with 25% of patients in the conventional CT cohort (OR, 2.31; 95% CI, 1.11-4.83; P =.024).

The study investigators determined that antimicrobial rationalization occurred more often with [18F]FDG-PET-CT scanning than with conventional CT scanning in this study, with the most common consequence being a narrowing of the antimicrobial spectrum. “These findings suggest that [¹⁸F]FDG-PET-CT is a diagnostic tool that could improve antimicrobial stewardship when integrated into an algorithm for investigating persistent and recurrent neutropenic fever,” the investigators wrote in their report.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Douglas A, Thursky K, Spelman T, et al. [¹⁸F]FDG-PET-CT compared with CT for persistent or recurrent neutropenic fever in high-risk patients (PIPPIN): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Haematol. Published online June 28, 2022. doi:10.1016/S2352-3026(22)00166-1