False PCR Results with Positive Culture for Chlamydia Trachomatis in Urine
Understanding the Paradox
A positive culture with a negative PCR for Chlamydia trachomatis in urine is extremely rare and suggests PCR inhibition rather than a false-positive culture, as culture specificity approaches 100% when proper visualization techniques are used. 1
Primary Cause: PCR Inhibition
The most likely explanation for this discordant result is PCR inhibition caused by substances in the urine specimen that interfere with the polymerase enzyme 1, 2:
- Blood, mucus, or other biological materials commonly found in urine can inhibit the PCR reaction 1
- Urinary inhibitors affect PCR more frequently than other amplification methods, with studies demonstrating that inhibitors can be identified through dilution and "spiking" experiments 2
- When inhibitors are present, they typically disappear with specimen dilution, confirming their presence 2
Technical and Procedural Issues
Additional factors that can contribute to false-negative PCR results include 1:
- Inadequate specimen collection for the PCR test specifically
- Laboratory processing errors during PCR handling or interpretation
- PCR primer mismatch with the specific Chlamydia strain present
Why Culture Remains Positive
Culture specificity for C. trachomatis approaches 100% when proper technique is employed with visualization of characteristic inclusions using species-specific monoclonal fluorescent antibody staining 1. This makes false-positive cultures exceptionally unlikely when proper methodology is followed 1.
Sensitivity Considerations
It's important to note that PCR typically has higher sensitivity than culture (PCR sensitivity ~88-98% vs culture sensitivity 50-70%), making the reverse scenario (PCR positive, culture negative) far more common 3, 4, 5. Culture sensitivity ranges from only 70-90% even with optimal technique 1.
Clinical Management Approach
When faced with this discordant result 1:
- Treat the patient based on the positive culture result, as this represents definitive diagnosis with nearly 100% specificity
- Treat sex partners presumptively and ensure partner notification proceeds
- Consider the positive culture as confirmation of sexually transmitted infection requiring full epidemiologic intervention
Common Pitfalls to Avoid
- Do not dismiss a positive culture result simply because PCR is negative—culture with proper visualization is the gold standard for specificity 1
- Recognize that urine specimens are particularly prone to PCR inhibitors compared to urethral or endocervical swabs 2
- The presence of inhibitors may necessitate internal positive controls, especially when testing urine by PCR 2