How PCR is Helping Medical Practices Meet Increasing Demand for Speed and Accuracy

In the world of patient care, change is the only constant. The need to provide patients with faster diagnostic results while maintaining accuracy drives the healthcare industry forward to continuously innovate. In the modern day, if you were to develop a new diagnostic tool for pathogen detection that took 3-5 days to result, you’d have a hard time getting a patient to sign onto using it!

Perhaps that’s because a technique like that already exists - in the form of bacterial and cell culture. The time to result of classic culture techniques has hampered health systems, labs, providers, and patients themselves in their ability to treat or be treated for infections in a way that is rapid and targeted. The increased use of Polymerase Chain Reaction (PCR) testing stands as a testament to the fact that modern healthcare has had enough of waiting.

There are a number of ways PCR outshines culture, with ongoing improvements to the technique that make it a progressively more compelling option for physician’s practices. Because of this, PCR has the power to reshape diagnostics and, thus, offer patients a quantum leap forward in time-to-result, clinical accuracy, and sensitivity.

The Efficiency Leap of PCR

Traditionally, culturing methods have been the de facto choice for pathogen identification. PCR takes a different approach by amplifying genetic material, a process which can be shortened from the 3-5 days that it normally takes with culture to just a few hours. So drastic is the shortened diagnostic timeframe that many physicians leverage this to choose tailored antibiotics before a patient even leaves the office! PCR’s ability to drastically reduce time-to-diagnosis in this way is renowned - it’s the main reason PCR was used when speedy response times were demanded by the COVID-19 pandemic.

One 2019 study shows the immediate practical application of PCR. After stacking up multiplex PCR pathogen panels against typical respiratory viral testing, one facility saw a notable reduction in turnaround time (3.0 hours versus 27.9 hours). This led to a decrease in the prescription of antibiotics in patients that lacked radiographic lung findings. This effect was observed even when providers were not extensively trained on PCR-related decision-making.¹

Improving on Sensitivity and Specificity

Of course, speed is important, but so is accuracy. A recent study in the journal Urology demonstrated a high level of ​​agreement between PCR and urine cultures for positive cultures (90%), clearly exceeding non-inferiority thresholds (85%).² Further, since PCR does not rely on live organisms, it may have some usefulness in situations where antibiotics have already been administered, such as in meningitis patients.³ Inherent to PCR is its ability to detect pathogens even in low concentrations, which can translate to a heightened sensitivity.

A PNAS study which used PCR to detect blood stream infections (BSIs) achieved sample-to-result time to less than 2.5 hours. But speed was not the only positive finding - the culture-free approach used in the study demonstrated a 100% sensitivity and specificity in detecting pathogens in clinical samples.⁴ The study positions PCR as being simultaneously rapid and accurate, which can be of critical importance in the context of BSIs.

The Added Advantage of Antibiotic Resistance Marker Detection

Considering the prevalence of antibiotic resistance among patients, there is an increased demand to leverage modern techniques in the fight for antibiotic stewardship. While cultures can provide antibiotic sensitivities, they cannot detect the presence of antibiotic resistance markers. PCR can not only identify organisms, but also the presence of these critical resistance markers, which allows providers to more judiciously prescribe laser-targeted antibiotics.

Ongoing Improvements to PCR

While culture has essentially remained unchanged for decades, PCR has continued to improve since its development. One of these recent developments is the ability to perform extractionless, PCR. While the details of this are intricate, the end result is that a major step in the PCR process is able to be completely removed, culminating in even faster results - one study showed extractionless PCR being used to reduce SARS-CoV-2 detection times (from collection to results) to less than an hour.⁵

Benefits for Laboratories

PCR has firmly established itself as a diagnostic tool that can provide physicians with increased speed, clinical accuracy, and sensitivity when compared to using cultures. It also has the unique ability to detect antibiotic resistance markers to help doctors make better decisions as they fight the new pandemic of antibiotic-resistant organisms, and is continually being improved as a diagnostic platform. When change is the only constant, and classic techniques no longer meet the needs of modern providers, they can be confident that PCR will help them face the future and provide the best outcomes for their patients.

References

1. Weiss ZF, Cunha CB, Chambers AB, Carr AV, Rochat C, Raglow-Defranco M, Parente DM, Angus A, Mermel LA, Sivaprasad L, Chapin K. 2019. Opportunities revealed for antimicrobial stewardship and clinical practice with implementation of a rapid respiratory multiplex assay. J Clin Microbiol 57:e00861-19. https://doi.org/10.1128/JCM.00861-19.
2. Wojno K, Baunoch D, Luke N et al. Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients. Urology. 2020;136:119-126. doi:10.1016/j.urology.2019.10.018
3. Bryant PA, Li HY, Zaia A, et al. Prospective study of a real-time PCR that is highly sensitive, specific, and clinically useful for diagnosis of meningococcal disease in children. J Clin Microbiol. 2004;42(7):2919-2925. doi:10.1128/JCM.42.7.2919-2925.2004
4. Ganguli, Anurup, et al. “A Culture-Free Biphasic Approach for Sensitive and Rapid Detection of Pathogens in Dried Whole-Blood Matrix.” Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 40, 26 Sept. 2022, https://doi.org/10.1073/pnas.2209607119. Accessed 16 Sept. 2023.
5. Marino FE, Proffitt E, Joseph E, Manoharan A. A rapid, specific, extraction-less, and cost-effective RT-LAMP test for the detection of SARS-CoV-2 in clinical specimens. PLoS One. 2022 Apr 11;17(4):e0266703. doi: 10.1371/journal.pone.0266703. PMID: 35404944; PMCID: PMC9000105.