Point-of-care multiplex molecular diagnosis coupled with procalcitonin-guided algorithm for antibiotic stewardship in lower respiratory tract infection: a randomized controlled trial.

OBJECTIVE: We aimed to show that coupling molecular syndromic respiratory panel (RP) testing with procalcitonin (PCT) measurement in the emergency department improves antibiotic (ATB) stewardship in lower respiratory tract infection. METHODS: Open-label, prospective, randomized interventional trial, conducted from 2019 to 2022 in an adult emergency department. Patients with a suspicion of lower respiratory tract infection were randomized into an intervention arm (PCT measurement and point-of-care BIOFIRE RP2.1 plus testing, accompanied by a recommended ATB algorithm) or a standard of care (SOC) arm (PCT allowed as current practice). The primary endpoint was the duration of antibiotic exposure. RESULTS: Four hundred fifty-one patients were randomized, median age 65 years (Q1-Q3: 49-77), the hospitalization rate was 59.9% (270/451), the median length of stay 5 days (Q1-Q3: 3 - 12), and the 28-day mortality rate 5.3% (23/451). The median duration of ATB exposure was 6 days (Q1-Q3: 0-9) and 5 days (Q1-Q3: 0-9) in the SOC and interventional arm respectively (p = 0.71). ATB was started in 29.6 % (67/226) and 33.8% (76/225) respectively (p = 0.54). The BIOFIRE RP2.1 plus identified at least one viral species in 112/225 patients (49.8%) of intervention arm. Two hundred twelve out of two hundred twenty-six (93.8%) SOC patients had PCT measurement. The adherence rate to algorithm in the intervention arm was 93.3 % (210/225). CONCLUSION: Displaying PCT and real-time RP results to emergency physicians failed to significantly reduce ATB exposure in lower respiratory tract infection suspicions. However, the median ATB duration and rate of initiation were already low in the SOC arm using PCT measurement routinely.

Relevance of cortisol and copeptin blood concentration changes in an experimental pain model.

The effect of pain and analgesics on stress biomarkers is not well studied. We evaluated the effect of acute pain and analgesics on serum cortisol and copeptin in an experimental pain model in healthy volunteers. Healthy volunteers presented at 8 a.m. for an experimental pain stimulation. Cortisol and copeptin levels were measured before, during and after electrophysiological stimulation, first before and then during opioid delivery. Difference in biomarker levels compared to baseline levels was calculated, and potential influencing factors were evaluated by linear regression analysis. Cortisol decreased by 13% during the 10 min of rest at baseline, but copeptin did not change significantly. Cortisol had a median decrease of -24% or -83 nmol/l (-44 to -124 nmol/l, p = 0.0002) during the electrophysiological stimulation training session, while the median difference for copeptin was -22% or -1.01 pmol/l (-2.35 to 0.08 pmol/l, p = 0.0003). After administration of opioids, cortisol did not decrease but increased by 3% (p = 0.043), indicating an increasing opioids effect on cortisol. This effect was not visible for copeptin (median change -0.003 pmol/l (-0.50 to 0.24), p = 0.45). In this experimental pain model performed in the morning, moderate pain did not have a relevant effect on cortisol or copeptin levels, whereas opioids led to a discrete peak of cortisol.Clinicaltrials.gov identifier: NCT01975753 (registered on November 5, 2013, before start of recruitment).

Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study.

BACKGROUND: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP). RESULTS: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI]. CONCLUSIONS: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).

Optimal combination of early biomarkers for infection and sepsis diagnosis in the emergency department: The BIPS study.

OBJECTIVE: To define the best combination of biomarkers for the diagnosis of infection and sepsis in the emergency room. METHODS: In this prospective study, consecutive patients with a suspicion of infection in the emergency room were included. Eighteen different biomarkers measured in plasma, and twelve biomarkers measured on monocytes, neutrophils, B and T-lymphocytes were studied and the best combinations determined by a gradient tree boosting approach. RESULTS: Overall, 291 patients were included and analysed, 148 with bacterial infection, and 47 with viral infection. The best biomarker combination which first allowed the diagnosis of bacterial infection, included HLA-DR (human leukocyte antigen DR) on monocytes, MerTk (Myeloid-epithelial-reproductive tyrosine kinase) on neutrophils and plasma metaloproteinase-8 (MMP8) with an area under the curve (AUC) = 0.94 [95% confidence interval (IC95): 0.91;0.97]. Among patients in whom a bacterial infection was excluded, the combination of CD64 expression, and CD24 on neutrophils and CX3CR1 on monocytes ended to an AUC = 0.98 [0.96;1] to define those with a viral infection. CONCLUSION: In a convenient cohort of patients admitted with a suspicion of infection, two different combinations of plasma and cell surface biomarkers were performant to identify bacterial and viral infection.