Combined use of respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in sickle-cell adult patients with acute chest syndrome (The ANTIBIO-STA study): a randomised, controlled, open-label trial

Abstract

Background

Respiratory infection may account for 30% of acute chest syndrome (ACS) aetiologies. However, antimicrobials are routinely prescribed, and de-escalation and/or discontinuation are challenging. Multiplex Polymerase Chain Reaction (mPCR) with an enlarged respiratory panel might support antimicrobial stewardship, and procalcitonin (PCT) measurements help reduce duration of antibiotic therapy. We hypothesized that a strategy combining the use of mPCR with repeated PCT measurements would reduce antibiotic exposure during ACS.

Methods

We conducted a randomised, controlled, parallel group, open-label study in two French hospitals. Consecutive adult patients with ACS were randomly assigned to the conventional or interventional strategy, where antibiotic therapy was targeted on the results of mPCR performed on lower respiratory tract secretions (LRTS) samples, and antibiotic discontinuation based on PCT values and kinetics at Day 1 (D1), D3 and D7. The primary outcome was the number of days of antibiotic exposure at D28 after randomisation. This trial was registered on ClinicalTrial.gov (NCT03919266) and is closed to recruitment.

Findings

From June 2020 to September 2022, 72 patients were assigned to the interventional (n = 37) or conventional strategy (n = 35). Despite a higher rate of microbiological documentation with the intervention (n = 25; 67.6% versus n = 13; 37.1%; difference, 30.4%; 95% CI 6.7%–51.5%), antibiotic exposure at D28 was similar between the two strategies (6 days [4.0–8.0] versus 6 days [5.0–9.0], respectively; difference, 0.0 day; 95% CI, −2.1 to 2.1). The time to clinical stability, and ICU and hospital lengths of stay did not differ.

Interpretation

As compared with conventional tests, an enlarged respiratory panel mPCR combined with a PCT-guided algorithm did not reduce antibiotic exposure at D28 in adults with ACS.

Funding

Assistance Publique—Hôpitaux de Paris, AP-HP (CRC180159). A financial support for the multiplex PCR kits used in this study was partially provided by bioMérieux.