Use of a Computerized C-Reactive Protein (CRP) Based Sepsis Evaluation in Very Low Birth Weight (VLBW) Infants: A Five-Year Experience

<div><p>Background</p><p>Serial C-reactive protein (CRP) values may be useful for decision-making regarding duration of antibiotics in neonates. However, established standard of practice for its use in preterm very low birth weight (<1500 g, VLBW) infants are lacking.</p><p>Objective</p><p>Evaluate compliance with a CRP-guided computerized decision support (CDS) algorithm and compare characteristics and outcomes of compliant versus non-compliant cases. Measure correlation between CRPs and white blood count (WBC) indices.</p><p>Methods</p><p>We examined 3 populations: 1) all preterm VLBW infants born at Vanderbilt 2006–2011 – we assessed provider compliance with CDS algorithm and measured relevant outcomes; 2) all patients with positive blood culture results admitted to the Vanderbilt NICU 2006–2012 – we tested the correlation between CRP and WBC results within 7 days of blood culture phlebotomy; 3) 1,000 randomly selected patients out of the 7,062 patients admitted to the NICU 2006–2012 – we correlated time-associated CRP values and absolute neutrophil counts.</p><p>Results</p><p>Of 636 VLBW infants in cohort 1), 569 (89%) received empiric antibiotics for suspected early-onset sepsis. In 409 infants (72%) the CDS algorithm was followed; antibiotics were discontinued ≤48 hours in 311 (55%) with normal serial CRPs and continued in 98 (17%) with positive CRPs, resulting in significant reduction in antibiotic exposure (p<0.001) without increase in complications or subsequent infections. One hundred sixty (28%) were considered non-compliant because antibiotics were continued beyond 48 hours despite negative serial CRPs and blood cultures. Serial CRPs remained negative in 38 (12%) of 308 blood culture-positive infants from cohort 2, but only 4 patients had clinically probable sepsis with single organisms and no immunodeficiency besides extreme prematurity. Leukopenia of any cell type was not linked with CRPs in cohorts 2 and 3.</p><p>Conclusions</p><p>CDS/CRP-guided antibiotic use is safe and effective in culture-negative VLBW infants. CRP results are not affected by low WBC indices.</p></div

Organisms isolated from positive blood cultures in patients with confirmed infections (N = 38) and CRP persistently <10 mg/L.

<p>Organisms isolated from positive blood cultures in patients with confirmed infections (N = 38) and CRP persistently <10 mg/L.</p

Reasons stated by clinical providers in the clinical decision support (CDS) module for continued antibiotic therapy despite negative serial CRP values.

1<p>Providers were able to state more than one reason.</p>2<p>Included preterm premature rupture of membranes (PPROM), Group B <i>streptococcus</i> (GBS) status, chorioamnionitis, fever.</p>3<p>Included concerns for respiratory and gastrointestinal pathology.</p

Patient demographics by CRP-protocol compliance status.¹

1<p>Compliance with the CRP-protocol in the setting of negative blood cultures was defined as (1) antibiotics were discontinued ≤48 hours after 2 consecutive negative CRP results, or continued if at least one positive CRP was present [“CRP-protocol compliant” (Comp)], and (2) antibiotics were continued >48 hours despite negative serial CRP results [“CRP-protocol non-compliant” (Non-Comp)].</p>2<p>Pair-wise comparison between Comp and Non-Comp group.</p>3<p>Median (lower quartile; upper quartile).</p>4<p>Wilcoxon test.</p>5<p>Pearson test.</p>6<p>C =  Caucasian, AA  =  African American, H =  Hispanic, O =  Other, U =  Unknown.</p>7<p>Absolute neutrophil count at time of initial sepsis evaluation.</p>8<p><2,500/µL.</p>9<p>Absolute neutrophil count at 48 hours.</p

Number of cases (N) with confirmed positive blood cultures and low WBC indices with positive (>10 mg/L) CRP values versus negative (<10 mg/L) serial CRP results.¹

1<p> =  Only cases with a full set of reported WBC and differential were analyzed.</p>2<p> =  CONS  =  coagulase-negative <i>Staphylococcus</i>.</p>3<p> =  Total serial CRP pos. N = 43; total serial CRP neg. N = 17.</p>4<p> =  Total serial CRP pos. N = 54; total serial CRP neg. N = 16.</p