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Table 4 Biomarkers and initiation or discontinuation of antibiotic therapy in adult ICU patients with sepsis

From: Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy

Biomarker Study 1st author, year [ref] Study design, patient selection (objective) Nb of patients n Level of evidence Primary endpoint and protocol Main results PCT-guided vs. controls (ARR, absolute risk reduction)
PCT Layios N, [34] Open, randomised controlled trial, 5 ICUs 509 High Total antibiotic use in ICU patients when using a PCT-based algorithm for initiating antibiotics (lower PCT threshold for not initiating therapy: 0.25 ng/mL) Percent days on antibiotics or overall DDD did not differ between the two groups. Withholding or withdrawing antibiotics similar overall (ARR = 3%) and with low PCT levels (PCT: 46.3%; controls: 32.7%; p = NS), or higher levels.
   Patients suspected of infection on admission or during the ICU stay (initiation of therapy) PCT: 353    
    Ctr: 314    
PCT Nobre V, [35] Single-centre, open RCT; 79 Moderate Total antibiotic days. ARR antibiotic days: 3.5 (6 vs. 9.5 days; p = 0.15),
   PCT-guided withdrawing antibiotics vs. “standard care” (duration)ICU patients with severe sepsis/shock on admission or during ICU stay (excl. immunosuppressed patient or requiring prolonged therapy) PCT: 39 (31 assessed)*   Recommend stopping antibiotics if PCT levels ≤ 90% of initial value but not before Day 3 (if baseline PCT level <1 ng/mL) or Day 5 (if baseline level ≥ 1 ng/mL). Less overall ab exposure (504 vs. 655 ab days; p = 0.28); days alive without antibiotics at 28 days (15.3 vs. 13.3 days; p = 0.28). 28-d mortality: 20.5% vs. 20%
    Ctr: 40 (37 assessed)*    
    70% CA infections    *4 and 2 secondary exclusions for complicated infections (empyema, mastoiditis, abscess)
PCT Bouadma L, [33] Multicenter randomised open trial, 7 ICUs 630 High Number of days alive and without antibiotics; noninferiority in terms of mortality by using a PCT-based algorithm for initiating or withdrawing antibiotics in those suspected of infection on admission or during the ICU stay (lower PCT threshold for not initiating or stopping therapy: 0.25 ng/mL) ARR: 5% for initiating antibiotics (PCT: 91% vs. 96% in Ctr group).
   Sepsis in ICU patients, on admission or ICU-acquired (Initiation and duration) PCT: 311    
    Ctr: 319    ARR for nb of antibiotic days: 2.7 days [1.4–4.1]
       Ab-free days by 28 d: 11.6 vs. 14.3 days
       28-d mortality : 21.2% vs. 20.4%; ARR = 0.8% [-4.6 to 6.2]
PCT Stolz D, [69] Multicentre open randomised trial, 7 ICUs (duration of therapy for VAP) 101 Moderate Ab-free days alive at 28 days Ab-free days at 28 d: 13 vs. 9.5 days
    PCT: 51   Discontinue ab if PCT <0.25 or <0.5 ng/ml and decrease by >80% from initial level Ab duration: 10 vs. 15 days
    Ctr: 50    28-d mortality: 20% vs. 28%
PCT Hochreiter M, [70] Single-centre open randomised trial 110 Moderate Reduction in ab duration Mean Ab duration: 5.9 vs. 7.9 d
   Postoperative sepsis (duration) PCT: 57   Discontinue ab if PCT <1.0 and clinical improvement, or sustained decrease to 25-35% initial value for 3 days Mean ICU LOS:
    Ctr: 53    28-dMortality: 26.3% vs. 26.4%
PCT Kopterides P, [71] Meta-analysis of RCT in ICU patients (7 studies) 1131 patients High Various algorithms for discontinuation of Ab therapy Duration ab : -2.1 [-2.5 to – 1.8] d
       Total Ab exposure: -4.2 [-5 to -3.4] days
       Ab free-days: 2.9 [1.9–3.9] days
       28-d mortality: OR = 0.93 [0.69-1.26]
Summary table: Sepsis in ICU patients
  Total number of patients, n Highest level of evidence Directness* Consistency** Overall strength of evidence Number of studies, n
  1010 High Yes Yes Initiation of therapy: low 7
      Discontinuation of therapy: high  
  1. *Directness: studies provide evidence of a direct association between a treatment or a given risk factor and a judgment criterion.
  2. **Consistency: results from studies of similar level of evidence are not contradictory.