Antibiotics are often prescribed in the emergency department (ED) to patients presenting with a suspected infection before any definitive diagnosis can be made [
1]. However, increasing antibiotic resistance and detrimental effects on the microbiota require their use to be limited to those with a high likelihood of bacterial infection or the potential for further clinical deterioration. Conversely, withheld or delayed treatment in higher severity patients may lead to increased morbidity and mortality rates [
2]. Thus, an accurate assessment of antibiotic requirement and speed of administration is crucial.
Current tools to aid clinical decision-making include the use of procalcitonin (PCT) and C-reactive protein (CRP). However, recent interventional evidence in the ED has shown few differences between conventional biomarker-guided therapy and standard practice [
1,
3], despite protocol compliance, patient selection and cut-off concerns. This post hoc analysis of a patient subset (Malmö, Sweden) from our previous investigation [
4] compared the use of PCT, CRP and lactate to the novel biomarker mid-regional proadrenomedullin (MR-proADM) in guiding antibiotic administration during treatment within the ED.
Within this subset (
N = 213), 26 (12.2%), patients were prescribed antibiotics < 48 h prior to presentation, whilst 187 (87.8%) were administered antibiotics during ED assessment. Of these patients, 164 (77.0%) were treated with intravenous (i.v.) and 23 (10.8%) with oral antibiotics. The median time to initial administration was 93 [28–160] min, with 71 (43.8%) patients receiving therapy within 60 min. Univariate and multivariate logistic regression found that MR-proADM had the strongest association with the requirement for antibiotic administration during ED treatment (Table
1). Interestingly, MR-proADM (Spearman
ρ = − 0.31,
p < 0.001) and lactate (Spearman
ρ = − 0.25,
p = 0.002) were the only parameters to be significantly negatively correlated with the time to antibiotic administration, with significant differences found at optimised MR-proADM cut-offs for antibiotic administration (1.27 nmol/L: 139 [76–211] vs 43 [26–135] min;
p < 0.001) or pre-established [
4] cut-offs for mortality prediction (1.54 nmol/L: 124 [33–199] vs 42 [26–122] min;
p = 0.002). Similar results were also found for MR-proADM within previously established PCT concentration ranges [
5] (Table
2), with an absence of ICU admission or 28-day mortality in patients with low MR-proADM concentrations, despite lower antibiotic administration rates and a significantly longer time to administration.
Table 1
Univariate and Multivariate analyses found that MR-proADM had the strongest correlation with the requirement for antibiotic administration during ED treatment
MR-proADM | 213 | 164 | < 0.001 | 0.76 | 3.1 [1.9–4.9] | 3.3 [1.9–5.9] |
PCT | 213 | 164 | < 0.001 | 0.74 | 2.7 [1.7–4.3] | 2.7 [1.7–4.5] |
CRP | 207 | 159 | < 0.001 | 0.68 | 1.8 [1.3–2.5] | 1.9 [1.4–2.8] |
Lactate | 204 | 158 | 0.002 | 0.66 | 1.8 [1.2–2.6] | 1.6 [1.1–2.5] |
Table 2
Low MR-proADM concentrations resulted in an absence of ICU admission or 28-day mortality, despite lower antibiotic administration rates and a significantly longer time to administration, irrespective of corresponding PCT concentration
Subgroup 1: PCT concentration: < 0.25 μg/L (N = 106) |
Patients (N) | 65 | 41 |
Antibiotic administration (N, %) | 35 (53.8%) | 34 (82.9%) |
Time to antibiotic administration (min) (median, Q1-Q3) | 127 [45.0–220] | 42 [25.8–116] |
Composite of 28-day mortality and ICU admission (N, %) | 0 (0.0%) | 7 (17.1%) |
Subgroup 2: PCT concentration: ≥ 0.25 and < 0.50 μg/L (N = 24) |
Patients (N) | 8 | 16 |
Antibiotic administration (N, %) | 7 (87.5%) | 15 (93.8%) |
Time to antibiotic administration (min) (median, Q1–Q3) | 165 [88–305] | 50 [19.3–186] |
Composite of 28-day mortality and ICU admission (N, %) | 0 (0.0%) | 1 (6.3%) |
Subgroup 3: PCT concentration: ≥ 0.50 μg/L (N = 83) |
Patients (N) | 21 | 62 |
Antibiotic administration (N, %) | 15 (71.4%) | 59 (95.2%) |
Time to antibiotic administration (min) (median, Q1–Q3) | 131 [92.8–166] | 45 [26–136.5] |
Composite of 28-day mortality and ICU admission (N, %) | 0 (0.0%) | 15 (24.2%) |
Results suggest that delayed antibiotic administration in patients with low MR-proADM concentrations may result in few adverse effects, potentially allowing for a more detailed clinical assessment prior to any subsequent initiation. Further studies in larger patient populations are required to confirm these initial findings.
Acknowledgements
The authors are grateful to the staff at Skåne University Hospital for their assistance in identifying eligible patients for enrollment.
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