Background: Staphylococcus aureus (SA) is the most common invasive bacterial pathogen, and the prevalence of antibiotic resistance in SA continues to increase. Currently licensed serologic diagnostics, which target alpha hemolysin (Hla), have limited utility due to low predictive value. We recently showed that children with invasive SA disease mount an early, high-titer antibody response to the SA leukotoxin LukAB. The primary aim of this study was to evaluate the potential use of anti-LukAB antibody titers as a diagnostic test for invasive SA disease.
Methods: Data were analyzed from three independent datasets in order to evaluate the use of this diagnostic test in relevant populations: children with culture-proven invasive SA disease (n=50) vs. healthy controls; children with SA pneumonia vs. pneumonia from a proven alternate cause (n=89); and children with cystic fibrosis-related pulmonary exacerbations who grew SA vs. an alternate etiologic pathogen (n=40). LukAB and Hla titers were measured by ELISA. Assays were performed by blinded personnel and results were subsequently correlated with culture results.
Results: In all three independent datasets evaluated, LukAB antibody titers strongly predicted the presence or absence of SA as the causative pathogen (Fig. 1A-C). For children with invasive SA disease, LukAB antibody titers exhibited 94% sensitivity and 96% specificity for the prediction of SA as the etiologic pathogen, with a 96% positive predictive value. Similarly, the test diagnosed SA in acute pneumonia (obtained during the first 3 days of hospitalization) with 88% sensitivity and 95% specificity and was capable of ruling out SA as the etiology with 96% negative predictive value. Hla antibody titers were also predictive of SA infection, but with test characteristics that were inferior to LukAB titers (Fig. 2).
Conclusion: A serologic assay measuring the antibody response to the cytotoxin LukAB predicted S. aureus as the causative pathogen of invasive disease with high accuracy. Test parameters universally outperformed Hla antibody titers, the only currently licensed SA serologic diagnostic target. Larger scale validation, including determination of the optimal timing of diagnostic utility, is warranted and these studies are underway.
M. Nagarsheth, None
V. Torres, None
C. B. Creech, None