The BinaxNOW pneumococcal antigen test: An adjunct for diagnosis of pneumococcal bacteraemia

Abstract

Background: Culture remains the diagnostic standard for Streptococcus pneumoniae bacteraemia but is limited by time to identification, prior antibiotics and bacterial autolysis. Culture-independent methods for detecting S. pneumoniae include PCR and antigen tests. We evaluated an antigen test on blood culture broth for the rapid detection of S. pneumoniae bacteraemia.

Method: We collected 212 signal-positive blood cultures, with gram-positive cocci in pairs, chains or with uncertain morphology. The BinaxNOW S. pneumoniae urinary antigen test, Gram stain, culture and lytA PCR were performed on all samples. Diagnostic accuracy of the antigen test and Gram stain with gram-positive cocci in pairs were compared with culture, polymerase chain reaction (PCR) and the composite of culture and PCR.

Results: Streptococcus pneumoniae was isolated in 26% of samples, 66% cultured other gram-positive organisms and 8% of samples had no growth. Sensitivity and negative predictive values of the antigen test were 100%, specificity and positive predictive values were 87% - 88% and 76% - 81%, but increased to 93% - 96% and 96% - 98% when applied to subsets with gram-positive cocci in pairs, or history compatible with respiratory illness or meningitis. Sensitivity (69% - 75%) and specificity (81%) of Gram stain (gram-positive cocci in pairs) were lower than the antigen test even when applied to the same subsets.

Conclusion: Accurate and rapid diagnosis of S. pneumoniae bacteraemia is challenging. Specificity of this antigen test is limited by cross-reactivity with other gram-positive organisms, but could be improved if Gram stain morphology and clinical history are available. The antigen test is a useful adjunct for rapid diagnosis of S. pneumoniae bacteraemia.

Keywords: BinaxNOW; Streptococcus pneumoniae; antigen; bacteraemia; pneumococcal diagnosis; test.

FIGURE 1

Venn diagrams representing numbers and proportions of specimens tested with (a) culture positivity versus immunochromatographic test and PCR positivity; (b) PCR positivity versus culture stratified into Streptococcus pneumoniae, non-Streptococcus pneumoniae and NG groups; (c) autolysis versus culture positivity stratified into Streptococcus pneumoniae, non-Streptococcus pneumoniae and no growth groups; (d) Gram stain with gram-positive cocci in pairs (‘Gram’) versus culture positivity stratified into Streptococcus pneumoniae, non-Streptococcus pneumoniae and no growth groups; (e) immunochromatographic test versus culture stratified into Streptococcus pneumoniae, non-Streptococcus pneumoniae and no growth groups; and (f) samples that met the study definition for hospital-acquired infection versus culture positivity stratified into Streptococcus pneumoniae, non-Streptococcus pneumoniae and no growth groups.

FIGURE 1-A1

Receiver operating characteristic (ROC) curve analysis was used to determine the optimal CT cut-off value for determining a positive PCR result. Samples culturing S. pneumoniae were regarded as true positives, and samples culturing organisms other than S. pneumoniae were regarded as true negatives for this analysis. ROC curve analysis suggested that the optimal CT cut-off value for determining a positive PCR result was between 17 and 22 (AUC 0.99), and the upper value of 22 was selected.

FIGURE 2-A1

Distribution of PCR cycle threshold (CT) values using box and whisker diagrams, in signal-positive blood culture samples that have been grouped based on culture results. Whiskers represent the minimum and maximum values of the CT-values and boxes represents the interquartile range. ‘X’ represents the mean of CT-values. For the S. pneumoniae group, there were 2 CT-values that were outliers (excluded from box and whisker diagram) and these are represented by dots in the figure.