Multicentre randomised controlled trial to investigate usefulness of the rapid diagnostic βLACTA test performed directly on bacterial cell pellets from respiratory, urinary or blood samples for the early de-escalation of carbapenems in septic intensive care unit patients: the BLUE-CarbA protocol

Abstract

IntroductionThe dramatic increase of the incidence of infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) has led to an increase of 50% of carbapenem consumption all around Europe in only 5 years. This favours the spread of carbapenem-resistant Gram-negative bacilli (GNB), causing life-threatening infections. In order to limit use of carbapenems for infections actually due to ESBL-PE, health authorities promote the use of rapid diagnostic tests of bacterial resistance. The objective of this work conducted in the intensive care unit (ICU) is to determine whether an early de-escalation of empirical carbapenems guided by the result of the βLACTA test is not inferior to the reference strategy of de-escalating carbapenems after the antibiogram result has been rendered.Methods and analysisThis multicentre randomised controlled open-label non-inferiority clinical trial will include patients suffering from respiratory and/or urinary and/or bloodstream infections documented with GNB on direct examination and empirically treated with carbapenems. Empirical carbapenems will be adapted before the second dose depending on the results of the βLACTA test performed directly on the microbiological sample (intervention group) or after 48–72 hours depending on the definite antibiogram (control group). The primary outcome will combine 90-day mortality and percentage of infection recurrence during the ICU stay. The secondary outcomes will include the number of carbapenems defined daily doses and carbapenem-free days after inclusion, the proportion of new infections during ICU stay, new colonisation of patients’ digestive tractus with multidrug-resistant GNB, ICU and hospital length of stay and cost-effectiveness ratio.Ethics and disseminationThis protocol has been approved by the ethics committee of Paris-Ile-de-France IV, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.Trial registration numberNCT03147807.

Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial

“…According to previous published studies evaluating diagnostic accuracy of ddPCR in patients with suspected sepsis, expected test sensitivity (SN) and specificity compared with blood culture are 85% and 75%, respectively according to our pre-test and the previous studies [ 11 , 14 ]. And the estimated disease prevalence (P), which is the blood culture positive rate in this case, is around 3% to 15% [ 5 , 21 , 22 ]. Therefore, based on the sample size calculation statistical methodology incorporating in the prevalence of disease [ 23 , 24 ], with a significance ( ) level of 0.05, a 95%CI width of 10% and a prevalence of 3%, the sample size for the experimental group is: …”

Antibiotic stewardship in the ICU: time to shift into overdrive

“…If cultures retrieve Enterobacteriaceae with a negative ESBL-chromogenic test, physicians may safely discontinue carbapenems [ 52 ]. A randomized-controlled trial is underway to evaluate the benefit of a rapid antibiotic de-escalation strategy based on this test (NCT03147807 [ 53 ]). On the contrary, the performance of mPCR tests in the ICU is disappointing: the detection of the resistance mechanism of identified germs is not always reliable, and these tests do not yet allow correct guidance of empirical antibiotic therapy, particularly for Pseudomonas aeruginosa and ESBL-producing Enterobacteriaceae [ 38 , 39 ].…”

Hospital-Acquired Pneumonia

“…The test detects GNB resistance via a colorimetric indicator and can quickly be used for antibiotic deescalation [43]. It is currently being evaluated for its clinical efficaciousness in France's multicenter randomized controlled trial (RCT) called BLUE-CarbA [44].…”