Impact of Real-time MIC (Minimum Inhibitory Concentration) Reporting (<6 Hours) on β-lactam Prescription in Cases of Gram-negative Bacilli Bacteremia in ICU Patients in Real-life Settings (CMIBActRéa)

Assistance Publique - Hôpitaux de Paris

Status: Not yet enrolling

Conditions: Gram-negative Bacteremia; Intensive Care Patients

Treatments: Diagnostic Test: SPECIFIC REVEAL® Rapid AST system; Diagnostic Test: antibiotic susceptibility testing on agar medium

Study type: Interventional

Funder types: Other

Identifiers

NCT07202377

APHP240793

Details and patient eligibility

About

Evaluate the impact of rapid, real-time (4 to 6 h) MIC reporting compared with the standard method (=diffusion antibiotic susceptibility testing) (18 to 24 h) on β-lactam prescribing in terms of the choice of molecule by the resuscitating clinician in the event of real-life Gram-negative Bacilli GNB bacteremia in the ICU.

Full description

In the microbiology laboratory, antibiotic susceptibility is traditionally determined using the disk diffusion method on agar medium, directly from a positive blood culture bottle, which requires 18 to 24 hours of incubation. Over the past decade, the turnaround time for antibiotic susceptibility testing has been shortened (down to 7 hours) thanks to rapid diagnostic tools. However, to date, there is no rapid (within 4 to 6 hours) and accurate method for determining the Minimum Inhibitory Concentration (MIC) that would allow for optimized antibiotic treatment beyond the basic susceptibility to a tested drug. This level of precision would be particularly useful in critically ill septic patients, especially in cases of bacteremia caused by Gram-negative bacilli (GNB).

Recent intensive care guidelines have suggested that for β-lactam antibiotics, the therapeutic target in these patients should be a plasma antibiotic concentration between 4 to 8 times the MIC of the administered antibiotic, depending on the bacterium and the drug. MIC thus represents a key determinant for optimizing antibiotic therapy by increasing the likelihood of achieving the pharmacodynamic efficacy targets of β-lactams.

The use of a new instrument, the SPECIFIC REVEAL® Rapid AST system (bioMérieux), which provides not only a full antibiogram but also MIC values for 23 different antibiotics as early as 4 hours after a positive GNB blood culture (Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii), could represent a potential benefit for ICU patients by enabling rapid optimization of antibiotic therapy. This technique was validated by comparison with two reference methods: a precise MIC determination method (broth microdilution, Sensititre, ThermoFisher) and an approximate method (Vitek2, bioMérieux). A 96% correlation was observed across the 23 antibiotics tested. Furthermore, a recent study conducted outside the ICU suggested a clinical impact, with earlier re-evaluation of antibiotic choices in 58% of cases.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients aged over 18 years
• Patients with a positive blood culture for Gram-negative bacilli (Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii) with results reported on weekdays before 11:00 ante meridiem (AM)
• Patients clinically suspected of infection
• Treated with empirical antibiotic therapy including a β-lactam, among the standard list of antibiotics to be tested recommended by CASFM-EUCAST (European Committee on Antimicrobial Susceptibility Testing) for Enterobacterales/Pseudomonas and included in the Reveal Rapid AST System panel
• Hospitalized in intensive care unit (ICU) for at least the next 24 hours
• Written informed consent obtained from the patient or a relative for study participation (emergency consent)
• Affiliated with the French social security system

Exclusion criteria

• Patients receiving withdrawal or limitation of care
• Patients with an expected survival prognosis of less than 72 hours
• Patients with bloodstream infections caused by Gram-negative bacilli other than Acinetobacter baumannii, Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa
• Patients treated with antibiotic therapy not including a β-lactam
• Polymicrobial bloodstream infections
• Pregnant or breastfeeding women
• Patients under legal protection (guardianship or conservatorship)
• Participation in another interventional research study

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Performance of an antibiotic susceptibility test on agar medium

Active Comparator group

Description:

Performance of an antibiotic susceptibility test on agar medium, with results expected between H18 and H24

Treatment:

Diagnostic Test: antibiotic susceptibility testing on agar medium

Antibiotic susceptibility testing performed using the Reveal technique

Experimental group

Description:

Antibiotic susceptibility testing performed using the Reveal technique, with results available between the 4th and 6th hour (H4-H6) after blood culture positivity, allowing for rapid clinical categorization for the 23 antibiotics tested, along with their corresponding MICs.

Treatment:

Diagnostic Test: SPECIFIC REVEAL® Rapid AST system