Combined Use of a Respiratory Broad Panel Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Hospitalized Sickle-cell Adults With Acute Chest Syndrome.

Acute Chest Syndrome (ACS) is a frequent and severe acute complication of sickle-cell disease. It may affect 10 to 20% of hospitalized patients and is the leading cause of death. The symptoms combine a new pulmonary infiltrate and symptom(s) among fever, cough, dyspnea, expectoration, chest pain and crackles. The pathophysiology of ACS is complex and there are many interlinked aetiologies.

Lower respiratory tract infection (LRTI) is one of the most frequent aetiologies of ACS. Intracellular bacteria (Chlamydia, Mycoplasma), respiratory virus (especially respiratory syncytial virus) and pyogenes (Streptococcus pneumoniae and Staphylococcus aureus) are the most frequently identified microorganisms. Nevertheless, the clinical presentation of ACS is not helpful for the diagnosis of LRTI; the respiratory tract samples are not always collected, either because the patients do not expectorate or because the benefit-risk ratio of a fiberoptic bronchoscopy may be not advantageous. Moreover, usual diagnostic test are not enough performant.

The current practices rely on the systematic administration of antibiotics for 7 to 10 days. The efficacy and safety of alternative diagnostic and therapeutic strategies have never been evaluated in controlled clinical trial to cure ACS.

In this context, the optimisation of the microbiological documentation of ACS might enhance the use of antimicrobial drugs, reduce their duration, and limit the emergence of multidrug resistant bacteria.

Therefore, we speculate that an early pathogen-directed strategy (respiratory broad panel multiplex PCR and early antibiotics interruption based on the PCT values decrease) might reduce the antibiotics exposure in SCD patients with ACS who are hospitalized and for whom an antibiotic treatment is indicated, as compared with usual care.

Inclusion criteria

• Age ≥ 18 years
• Sickle Cell Disease patients with ACS with an antibiotic therapy indication
• Signed and informed consent
• Affiliated with social security

Exclusion criteria

Documented extra-pulmonary bacterial infection at the time of inclusion;

• Patients who received antibiotics for more than 24 hours before the diagnosis of ACS (during the primary hospitalization)
• Known severe immunosuppression (AIDS, neutropenia (<1000 PNN), hematology, solid tumor under chemotherapy, transplanted organ); long-term treatment with hydroxy-carbamide is not considered
• Pregnant or lactating women;
• Person deprived of liberty or under legal protection;
• Participation in another interventional study of type Jardé 1