Bacterial Antigen Testing: The Good, the Not-so-Bad, and the Ugly

Christina Wojewoda, MD
Community acquired pneumonia (CAP) and meningitis are serious infections, and patients benefit
from prompt initiation of appropriate antibiotic therapy. Determination of the specific cause by bacterial
antigen testing is an appealing approach due to the rapid availability of results compared to culture,
the broader choice of specimens to test, and their relative simplicity to perform. But these tests only
perform well if there is a high pre-test likelihood of disease.
Legionella urinary antigen assays stand out as an example of tests that perform well. 1 Culture
diagnosis of Legionella sp. requires special media used only upon clinical suspicion2 and takes three
to five days. Test specificity reportedly ranges from 96.6% to 100%.1,3 Garbino et al reported that
Legionella urinary antigen tests had a positive impact on two thirds of the studied patients due to
either the addition of a Legionella active antibiotic or the withdrawal of ineffective ones.1 Also,
definitive identification led to fewer relapses since the recommended length of treatment for Legionella
pneumonia is longer than that for other bacteria.4
Streptococcus pneumoniae, a more common cause of CAP, presents a different dilemma due to the
low sensitivity and specificity of sputum culture. Tests to detect S. pneumoniae antigen in the urine
have been available for some time, and a recent review reported sensitivity of 80 to 86% and
specificity of 97%.5 The author concluded that antigen testing was as effective as Gram stain or
culture, with the advantages of rapid results, diagnostic usefulness even after initiation of antibiotic
treatment, and specimen availability in patients who cannot produce sputum. Disadvantages include
decreased sensitivity in children due to higher colonization rates and the lack of an isolate for
susceptibility testing, important in these days of increasing antibiotic resistance.5 Some recommend a
sequential approach, performing the urinary antigen test if the Gram stain is negative or not
adequate.6
A real disappointment in the use of antigen detection tests lays in their lack of utility in the diagnosis of
bacterial meningitis using either cerebrospinal fluid (CSF) or urine samples. In one study, antigen
detection testing was deemed unnecessary on CSF samples because all true-positive samples were
detected by Gram stain.7 The number of bacterial agents that can be detected are limited to the most
common causes of community acquired meningitis, so they are not useful in nosocomially acquired
meningitis. The success of vaccination to prevent invasive disease due to Haemophilus influenzae
type B (Hib) and S. pneumoniae has made the application of these tests even less useful. Imperfect
specificity for Hib and detection of the antigen up to seven days after vaccination can lead to more
false positives than true positives.7,8 Some recommend that bacterial antigen testing should only be
performed on CSF if the cell count is abnormal, the Gram stain is negative, and cultures remain
negative for 48 hours.7 In children, urine collected by a perineal bag is likely to contain skin and fecal
contamination, leading to high false positive rates,9 and cross-reactivity between common causes of
meningitis and with normal flora can make the tests difficult to interpret. In a review of 111 cases of a
positive antigen detection test for Neisseria meningitidis/E. coli, none had proven N. meningitidis
meningitis.9
While these assays have their appeal, their clinical utility in most cases is unfortunately limited; and
culture is still the gold standard.

References
1. Garbino J, Bornand JE, Ukay I, et al. Impact of positive legionella urinary antigen test on patient
management and improvement of antibiotic use. J Clin Pathol. 2004;57(12):13025.
2. Waterer GW, Baselski VS, Wunderink RG. Legionella and community acquired pneumonia: a
review of current diagnostic tests from a clinicians viewpoint. Am J Med. 2001;110(1):4148.
3. Diederen BM, Peeters MF. Evaluation of two new immunochromatographic assays (Rapid U
Legionella antigen test and SD Bioline Legionella antigen test) for detection of Legionella pneumophila
serogroup 1 antigen in urine. J Clin Microbiol. 2006;44(8):29912993.
4. Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of
community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37(11):14051433.
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6. Roson B, Fernandez-Sabe N, Carratala J, et al. Contribution of a urinary antigen assay (Binax
NOW) to early diagnosis of pneumococcal pneumonia. Clin Infect Dis. 2004;38(2):222226.
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Microbiol. 1995;33(6):14861491.
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cerebrospinal fluid after immunization. Pediatr Infect Dis J. 1992;11(3):243244.
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Neisseria meningitidis/Escherchia coli antigens in the urine. Pediatr Infect Dis J. 1993;12(9):779780.