Molecular Diagnostics: A Trusted Option for Hospitalized Patient Care

Secondary bacterial and fungal infections have threatened hospitalized patients for decades and become more urgent as pathogens develop resistance to common antibiotics. Recently, the Centers for Disease Control and Prevention confirmed what many frontline workers and epidemiologists already suspected: the COVID-19 pandemic has led to "alarming" setbacks in the global fight against antimicrobial resistance (AMR). Drug-resistant infections in hospitalized patients rose by 15% from 2019 to 2020.

Whenever a patient is hospitalized for an extended period, they become increasingly vulnerable to hospital-acquired infections. Highly infectious pathogenic exposure can occur following standard surgical procedures performed with a catheter or ventilator or via transmission spread in the intensive care unit (ICU).

The situation becomes more complicated when medical professionals cannot reliably diagnose the potential for secondary threats–antibiotics may be administered unnecessarily or for longer than needed–exacerbating drug-resistant pathogens. With advances in molecular diagnostic testing methods, relying on culture results alone to make decisions regarding antibiotic use and patient care is no longer an adequate approach.

Where Culture Falls Short

Conventional culture testing methods demonstrated sensitivity challenges when used on patients taking antibiotics (The Lancet, DOI: 10.1016/S2213-2600(22)00086-8). Even with established documentation warning of its pitfalls, culture tests are widely accepted as the standard of care for identifying the presence of pathogens and their susceptibility to antibiotics.

The typical approach for testing a patient undergoing a long-term hospital or ICU stay involves performing culture tests at multiple intervals during hospitalization. Clinicians use these results to identify bacterial and fungal pathogens and inform antibiotic use. These results may take several days, prompting the empirical administration of broad-spectrum antibiotics before reaching an official diagnosis.

When culture tests are performed later in the patient's hospital stay, clinicians look for the continued presence or emergence of pathogens to assess if the current antibiotic treatment course is working. However, the sensitivity challenges inherent with culture should call these results into question, particularly for patients who have been on antibiotics for an extended time.

When clinicians order molecular diagnostic testing for the same patient samples, the results are often stacked against culture results. For example, if molecular diagnostics detect a pathogen not seen in a culture sample, the results are seen as a false positive. Alternatively, if molecular diagnostics did not recognize a pathogen detected in the culture, this would constitute a false negative.

Therein lies the dilemma for healthcare workers: Can molecular diagnostic testing results–often delivered significantly faster than culture–be trusted to provide reliable diagnostic information and inform changes in antibiotic decisions?

Finding Confidence in Molecular Diagnostics

Numerous studies have confirmed the reliability and clinical value of rapid, comprehensive molecular diagnostic panels for identifying pathogens and AMR markers from respiratory, urinary tract, and bloodstream samples.

A recent study at the Karolinska University Hospital analyzed serial microbiological culture samples taken from hospitalized COVID pneumonia patients (European Journal of Clinical Microbiology & Infectious Diseases, DOI: 10.1007/s10096-022-04466-9). Each respiratory sample sent for culture was also tested using a multiplex molecular polymerase chain reaction (PCR) diagnostic panel to compare the progression of pathogen detection across both methods.

Taking serial samples from a patient on different days offers a more comprehensive approach than comparing a single culture and corresponding molecular sample from one day. Using serial samples, the multiplex PCR panel detected pathogens, including Staphylococcus aureus and Streptococcus pneumoniae, better than culture in most cases. Therefore, researchers concluded that the PCR panel results should be considered true positives when these same pathogens were confirmed in subsequent cultures. These findings should boost confidence in the reliability of rapid molecular diagnostics.

Relying on multiplex diagnostic panels for early and comprehensive patient results also has implications for antibiotic stewardship and lowering the burden of AMR infections across healthcare facilities. Of the Karolinska patients for whom PCR detected an additional pathogen, 71.4% were exposed to antibiotics before the sample collection. We must acknowledge the known adverse impact of these therapeutics on microbiological culture results and encourage clinicians to turn to molecular diagnostic panels as a new standard of care.

PCR testing should occur earlier in a patient's hospital stay. Increased confidence in and access to these panels will reduce unnecessary antibiotic use and, by extension, lower infection and transmission rates for severely ill patients undergoing extended hospitalizations. It will also help improve antibiotic stewardship over time.