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