Pneumococcal Urinary Antigen

The pneumococcal urinary antigen test detects the C-polysaccharide cell wall antigen common to all Streptococcus pneumoniae serotypes, in urine, by immunochromatographic membrane assay (results in 15 minutes) and, less often, in CSF, pleural fluid and other sterile fluids.

In adults with pneumococcal pneumonia sensitivity is 60 to 80% (higher in bacteraemic disease, 80 to 90%, and lower in non-bacteraemic disease, 55 to 70%) and specificity is 90 to 97%. Results are available when culture is still pending and are not suppressed by prior antibiotic therapy (antigen persists for days after the start of treatment).

Streptococcus pneumoniae is the commonest bacterial cause of community acquired pneumonia (30 to 50% of identified cases), otitis media, sinusitis and bacterial meningitis in adults, and causes about 300 000 deaths yearly in children under 5 years, mostly in sub-Saharan Africa and South Asia. Conjugate vaccination has reduced invasive disease, with serotype replacement.

Antigen testing allows narrowing of empirical therapy to penicillin or amoxicillin in non-severe pneumonia, which reduces broad spectrum antibiotic use.

Indications. Hospitalised adults with community acquired pneumonia, particularly severe pneumonia, as part of a diagnostic bundle. Pneumonia with antibiotic pre-treatment and a negative culture. Pleural effusion or empyema of unknown cause. Meningitis (CSF antigen) when Gram stain and culture are negative or delayed. Narrowing of therapy when pneumococcus is probable. Not for children under 5 years (nasopharyngeal carriage causes false positives), and not for monitoring.

Specimen. Fresh random urine 0.1 to 1 mL, tested at once or refrigerated for up to 24 hours (frozen for longer). CSF 0.1 mL, pleural fluid or other sterile body fluids. Send blood cultures, sputum Gram stain and culture, and, in severe disease, a Legionella urinary antigen at the same time.

Reference values. Negative (no test line). In children colonised with pneumococcus, positive tests are common (up to 20 to 40%) without disease.

Interpretation.

• Positive result in an adult with pneumonia: pneumococcal pneumonia is probable, and treatment can be narrowed to penicillin or amoxicillin if the isolate is susceptible and the patient is stable.
• Negative result: does not exclude pneumococcal pneumonia (negative predictive value is about 85 to 90%), and other tests and clinical judgement decide.
• Positive antigen in a patient with recent pneumococcal pneumonia in the past 3 months: may reflect persistent excretion (up to several months in some adults), not a new episode.
• Positive CSF antigen with consistent CSF findings: pneumococcal meningitis (sensitivity 95% to 100%, specificity 99%), supporting treatment even if culture is negative.
• Positive pleural fluid antigen: pneumococcal empyema (sensitivity over 90%), valuable when culture is negative after antibiotics.
• Antigen positive in an adult who recently received a pneumococcal conjugate vaccine: false positives rarely reported in the days after vaccination, particularly in children.
• Antigen testing does not provide serotype or susceptibility, so cultures and molecular serotyping remain necessary in invasive disease.
• Severity tools combine antigen with clinical scores to select outpatient or inpatient management.

Critical values and findings needing immediate action.

• Positive CSF antigen: bacterial meningitis is present, so start treatment immediately (high dose third generation cephalosporin with vancomycin, with dexamethasone started before or with the first antibiotic dose).
• Positive urinary antigen with sepsis, hypotension or respiratory failure: intensive care, resuscitation, and bactericidal therapy within an hour.
• Positive antigen with empyema or parapneumonic effusion: drainage and prolonged therapy.
• Positive antigen with penicillin resistant pneumococcus risk (high local resistance): choose cover on susceptibility results.
• Positive antigen in an asplenic or hyposplenic patient: overwhelming post-splenectomy infection is likely, so give immediate antibiotics and critical care.

Interferences and pitfalls.

• False positives in children from nasopharyngeal carriage, and in adults after recent pneumococcal infection or vaccination, and with cross-reacting streptococci (S. mitis and S. oralis share antigenic components).
• False negatives with low bacterial load, early disease, non-bacteraemic pneumonia, and mixed infections, and if the urine is very dilute.
• Sensitivity is lower in patients without bacteraemia, so a negative test should not lead to withholding pneumococcal cover in a compatible illness.
• The test does not distinguish susceptible from resistant pneumococcus or give the serotype, and use of the result to narrow therapy needs confirmation of low local resistance.
• Antigen positivity can persist for weeks after infection, limiting use in recurrent infection.
• Antigen testing complements culture, and does not replace sputum Gram stain, blood culture and molecular tests in severe disease.
• Respiratory viral co-infection (influenza, SARS-CoV-2) is common, and viral tests are done in winter.
• Cost effectiveness depends on local pneumococcal prevalence and antimicrobial stewardship policy.

Special groups.

• Children: nasal carriage makes the test unreliable, and it is not used for pneumonia in children under 5 years. CSF antigen retains value.
• Older adults and patients with chronic disease: highest burden, with atypical and severe presentations.
• Asplenia, sickle cell disease, HIV, nephrotic syndrome, cirrhosis, and immunoglobulin deficiency: higher risk of invasive disease, and vaccination is a priority.
• Pregnancy: pneumonia carries maternal and foetal risks, and penicillins are safe.
• Regions: pneumococcal disease burden is highest in sub-Saharan Africa and South Asia, with increasing penicillin and macrolide resistance in many regions.

Follow up tests. Blood cultures, sputum Gram stain and culture, pleural fluid analysis and culture, CSF analysis, pneumococcal PCR and serotyping, Legionella urinary antigen, respiratory viral PCR, HIV test, C-reactive protein and procalcitonin, chest radiograph or CT, pulse oximetry or arterial blood gas, antimicrobial susceptibility (penicillin minimum inhibitory concentration),

spleen function and immunoglobulin levels in recurrent invasive disease, and vaccination status review.