Description of Procedure or Service

Description

Infectious diseases can be caused by a wide range of pathogens. Conventional diagnostic methods like culture, microscopy with or without stains and immunofluorescence, and immunoassay often lack sensitivity and specificity and have long turnaround times. Panels for pathogens using multiplex amplified probe techniques and multiplex reverse transcription can detect and identify multiple pathogens in one test using a single sample.

Related Policies

Diagnosis Of Vaginitis AHS – M2057
Identification Of Microorganisms Using Nucleic Acid Probes AHS – M2097
Onychomycosis Testing AHS – M2172

***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.

Policy

BCBSNC will provide coverage for pathogen panel testing when it is determined the medical criteria or reimbursement guidelines below are met.

Note: The coverage criteria outlined in this policy are not applicable to diagnostic COVID-19 testing.

Benefits Application

This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore, member benefit language should be reviewed before applying the terms of this medical policy.

When Pathogen Panel Testing is covered

This policy is specific to testing in the outpatient setting. Criteria below do not apply to testing allowances in situations other than the outpatient setting.

1. Reimbursement is allowed for multiplex PCR-based panel testing (up to 11 gastrointestinal pathogens [GIPs]) no more often than once every 7 days for individuals with persistent diarrhea or diarrhea with signs or risk factors for severe disease (i.e., fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain).
2. Reimbursement is allowed for panel testing of up to 5 respiratory pathogens (antigen panel testing or multiplex PCR-based panel testing) for individuals who are displaying signs and symptoms of a respiratory tract infection (see Note 1). 

NOTES:

Note 1: Signs and symptoms of a respiratory tract infection include fever, chills, fatigue, cough, rhinorrhea, anorexia, pharyngitis, vomiting, new ageusia or anosmia, headaches, myalgia, diarrhea, and weakness. Additional signs and symptoms of a respiratory tract infection may be seen in individuals who are less than 18 years of age. These include irritability, decreased activity, nausea, rash, stomach pain, ear tugging/otalgia, vomiting after coughing, tachypnea, chest retractions/nasal flaring, grunting, wheezing, crackles, dehydration, cyanosis, apnea episodes, drooling, or refusal to eat. For infants, non-specific signs such as poor feeding, lethargy, and fussiness may present over clear localizing symptoms.

When Pathogen Panel Testing is not covered

1. Reimbursement is not allowed for multiplex PCR-based panel testing of 12 or more GIPs.
2. Reimbursement is not allowed for antigen panel testing or multiplex PCR-based panel testing of 6 or more respiratory pathogens.
3. Reimbursement is not allowed for multiplex PCR-based panel testing of pathogens in cerebrospinal fluid (CSF).
4. Reimbursement is not allowed for molecular detection-based panel testing of pathogens in the blood.
5. Reimbursement is not allowed for the molecular detection-based panel testing of urine pathogens for the diagnosis of urinary tract infections (e.g., GENETWORx Molecular PCR UTI Test).
6. Reimbursement is not allowed for molecular-based panel testing to screen for or diagnose wound infections (e.g., GENETWORx PCR Wound Testing).
7. Reimbursement is not allowed for molecular-based panel testing for general screening of microorganisms (e.g., MicroGenDX qPCR+ NGS).

Policy Guidelines

Background

There has been a move in recent years towards employing molecular tests that use multiplex polymerase chain reaction (PCR) to simultaneously detect multiple pathogens associated with an infectious disease rather than one organism. These tests are usually offered as a panel for a particular infectious condition, such as sepsis and blood stream infections, central nervous system infections (for example, meningitis and encephalitis), respiratory tract infections, urinary tract infections or gastrointestinal infections. These assays are often more sensitive than conventional culture-based or antigen detection. The high diagnostic yield is particularly important when clinical samples are difficult to collect or are limited in volume (e.g., CSF). Multiplex PCR assays are also particularly beneficial when different pathogens can cause the same clinical presentation, thus making it difficult to narrow down the causative pathogen. Access to comprehensive and rapid diagnostic results may lead to more effective early treatment and infection-control measures. Disadvantages of multiplex PCR assays include high cost of testing and potential false negative results due to preferential amplification of one target over another.

The Centers for Medicare and Medicaid Services report that the top target pathogens causing foodborne infections include Salmonella, Campylobacter, Shigella, Cryptosporidium, Shiga toxin producing E. coli non-O157 and Shiga toxin producing E. coli O157; these pathogens “represent the top 90-95% of foodborne infections [incidence of infection per 100,000 population].”

Beyond molecular testing, antigen panel testing has become an increasingly utilized diagnostic approach. These panels can detect multiple pathogens simultaneously through antigen detection techniques, such as lateral flow immunoassays. While generally less sensitive than multiplex PCR, antigen panels offer rapid results at a lower cost, making them effective for point-of-care testing, outbreak management, and initial screening.

Proprietary Testing

Gastrointestinal Pathogen Panel

Approximately 1.7 billion cases of childhood diarrheal disease occur worldwide every year, resulting in about 443,832 deaths in children younger than five years of age annually. The Centers for Disease Control and Prevention (CDC) has estimated that nearly 48 million cases of acute diarrheal infection occur annually in the United States, at an estimated cost upwards of $150 million. Approximately 31 major pathogens acquired in the United States caused an estimated 9.4 million episodes of diarrheal illness, 55,961 hospitalizations, and 1,351 deaths each year. Additionally, unspecified agents caused approximately 38 million episodes of foodborne illnesses and resulted in 71,878 hospitalizations and 1,686 deaths. Diarrhea can be classified as acute (lasting less than 14 days), persistent (14 and 30 days), and chronic (lasting for greater than a month). Further, healthcare and antibiotic associated diarrhea are mainly caused by toxin-producing Clostridioides difficile causing more than 300,000 cases annually. 

Acute infectious gastroenteritis is generally associated with other clinical features like fever, nausea, vomiting, severe abdominal pain and cramps, flatulence, bloody stools, tenesmus, and fecal urgency. For patients with severe gastrointestinal symptoms, the focus is on detecting the most common and clinically significant pathogens likely to cause serious illness, including bacterial, viral, and parasitic agents. Clinically a targeted panel of gastrointestinal pathogens (GIPs) effectively covers the primary pathogens associated with severe gastrointestinal infections, such as Salmonella spp., Shigella spp., Campylobacter jejuni, and Escherichia coli for bacterial causes; Norovirus, Rotavirus, and Adenovirus for viral causes; and Giardia, Entamoeba histolytica, and Cryptosporidium for parasitic infections.

Infectious disease of the gastrointestinal (GI) tract represent a heterogenous group of conditions caused by a wide array of viral, bacterial, protozoal, and parasitic pathogens. Clinical presentation varies significantly, ranging from self-limited, non-inflammatory diarrhea to severe, persistent, or febrile dysenteric illness. Most acute, self-limited diarrheal illnesses – particularly those of short duration and non-inflammatory nature – do not require laboratory testing, as they are typically viral in origin and resolve without specific treatment or intervention.

When it comes to gastrointestinal panels of 11+ targets, many of the studies available are not randomized controlled trials and rely on retrospective data or observational design, limiting their ability to establish causation. Additionally, the detection of certain pathogens, particularly viruses, does not necessarily correlate with active infection. This can lead to inappropriate treatment decisions, unnecessary antibiotic use and potential harm to patients. Major professional societies recommend limiting broad multiplex testing in outpatient settings.

Stool culture is the primary diagnostic tool for a suspected bacterial infection, but it is time-consuming and labor-intensive. Stool samples are collected and analyzed for various bacteria present in the lower digestive tract via cell culture; these bacteria may be normal or pathogenic. By identifying the type of bacteria present in a stool sample, a physician will be able to determine if the bacteria are causing gastrointestinal problems in an individual. However, stool culture has a low positive yield. Similarly, methods like electron microscopic examination and immunoassay that are used to diagnose viruses are labor-intensive and need significant expertise. Multiplex PCR-based assays have shown superior sensitivity to conventional methods for detection of enteric pathogens and are increasingly used in the diagnosis of infectious gastroenteritis. These assays have significantly improved workflow and diagnostic output in the diagnosis of gastrointestinal infections. Several FDA-approved multiplex PCR assays are now commercially available. Some assays can detect only bacterial pathogens in stool, whereas others can detect bacterial, viral, and parasitic pathogens. The Strong-LAMP assay is a technique which uses PCR to detect Strongyloides stercoralis in stool and urine samples, although it is not yet widely available. 

Several proprietary panels are available for detecting gastrointestinal pathogens. The BioFire FilmArray Gastrointestinal Panel is an FDA-approved 22-target test that detects bacterial, viral, and parasitic pathogens, including Campylobacter, Clostridioides difficile, Norovirus, Rotavirus A, and Giardia lamblia. The manufacturer reports a sensitivity of 98.5% and specificity of 99.2%, with results available within one hour; however, the test has not been evaluated for immunocompromised patients. The xTAG Gastrointestinal Pathogen Panel by Luminex is another FDA-approved multiplex test that identifies bacterial, viral, and parasitic nucleic acids in fresh and frozen stool samples. It is capable of detecting over 90% of gastroenteritis-causing agents, including Salmonella, Shigella, Vibrio cholerae, Norovirus GI/GII, and Cryptosporidium, with results available in as little as five hours. Similarly, the Biocode Gastrointestinal Pathogen Panel is an FDA-approved test that utilizes a 96-well microplate to detect 17 diarrhea-causing pathogens, such as Clostridioides difficile toxins A/B, Enterotoxigenic E. coli, Vibrio/Vibrio parahaemolyticus, Adenovirus 40/41, and Entamoeba histolytica. This rapid multiplex assay is considered cost-effective and may aid in infection control.

Respiratory Pathogen Panel

Upper respiratory tract infections (involving the nose, sinuses, larynx, pharynx, and large airways) can be caused by a variety of viruses and bacteria. These infections may lead to several different patient ailments such as the common cold, acute bronchitis, influenza, and respiratory distress syndromes. Pediatric patients may have different signs and symptoms of respiratory tract infections. Signs and symptoms of upper respiratory tract infections for children are: nasal congestion (rhinorrhea), fever, cough, irritability (poor feeding in infants), decreased activity, headache, nausea, rash (less common), stomach pain, ear tugging/otalgia, and vomiting after coughing. For pharyngitis, CDC highlights sore throat, but notes that young children may not be able to verbalize this and present with drooling, refusal to eat, or irritability. For lower respiratory tract infections, signs and symptoms for children can include: tachypnea, chest retractions/nasal flaring, grunting, wheezing, crackles, fever, dehydration, cyanosis (occasionally), and apnea episodes. Infants and toddlers often present with non-specific signs (such as poor feeding, lethargy, and fussiness) rather than clear localizing symptoms. Regarding the common cold, the most common virus is rhinovirus; the bacteria that most commonly causes a sore throat (pharyngitis) is Streptococcus pyogenes. Lower respiratory tract infections occur in the lungs and any airways below the larynx. Lower respiratory infections include pneumonia, bronchitis, tuberculosis and bronchiolitis. 

Traditional methods used for the diagnosis of viral respiratory tract infections are direct antigen testing (non-immunofluorescent and immunofluorescent methods) and conventional and rapid cell culture. These tests have several limitations including a slow turnaround time, low sensitivity, and labor-intensive processes.

Acute respiratory infections may also be diagnosed by a simple respiratory exam, where the physician focuses on the patient’s breathing and checks for fluid and inflammation in the lungs. Symptoms of a respiratory tract infection may include a stuffed nose, cough, fever, sore throat, headache, and difficulty breathing. Chest X-rays may be used to check for pneumonia, and blood/mucus samples may be used to confirm the presence of certain bacteria and/or viruses via cell culture. The doctor may also check the ears, nose, and throat. Treatment typically incorporates over the counter medications, rest, fluids, and antibiotics (if a bacterial infection is identified).

Considerable progress has been made in the development of molecular methods to detect multiple respiratory pathogens simultaneously. Molecular detection, including multiplex PCR assays, is currently the gold standard for viral respiratory diagnosis. Multiplex PCR-based assays are now commercially available to detect several viral pathogens like adenovirus, influenza A and respiratory syncytial virus as well as bacterial pathogens like Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. These tests are rapid, sensitive, specific, and the preferred testing method to identify most respiratory pathogens. These tests may be a more reliable diagnostic test as they can be performed in just hours, do not require as large a volume of blood, and are not affected by antepartum antibiotics. 

While multiplex nucleic acid amplification testing (NAAT) panels for respiratory pathogens offer rapid detection of a broad range of viral and bacterial targets—sometimes up to 33 pathogens—the clinical utility of these expanded panels remains limited in many patient populations. Although some studies have associated multiplex respiratory panel testing with decreased hospital length of stay, reduced admissions, and lower antibiotic use, these benefits appear to be driven largely by the detection of influenza alone. In most cases, results for non–influenza pathogens do not alter clinical decision-making, particularly in immunocompetent patients with mild or moderate illness. Point-of-care influenza testing—whether antigen- or PCR-based—has shown a greater impact on clinical outcomes than broad multiplex testing.

In addition, the interpretation of expanded panel results is complicated by several factors, including the detection of colonizing or non-pathogenic organisms, prolonged viral shedding, and co-infections of uncertain clinical relevance. These findings may not change treatment plans, leading to low clinical actionability despite high analytic sensitivity. Studies have also noted that multiplex panels can contribute to over-testing and high healthcare costs, with some assays priced in the hundreds to thousands of dollars. Smaller, targeted panels or limited NAATs focused on high-impact pathogens (e.g., influenza A/B, RSV, SARS-CoV-2) are increasingly favored for their balance of diagnostic efficiency, clinical relevance, and cost-effectiveness. Expanded multiplex testing may still have a role in specific populations, such as immunocompromised or critically ill patients, especially when limited panels yield negative results and clinical suspicion remains high.

The BioFire FilmArray RP2.1 Panel is an FDA-approved test that detects 18 viral and 4 bacterial respiratory pathogens, including Influenza A, Respiratory Syncytial Virus (RSV), Human Metapneumovirus, Bordetella pertussis, and Mycoplasma pneumoniae. The updated version includes SARS-CoV-2 and provides results in 45 minutes with a reported sensitivity of 97.1% and specificity of 99.3%. The GenMark ePlex^® Respiratory Pathogen Panel and RP2 Panel are FDA-approved tests that identify bacterial and viral pathogens responsible for upper respiratory infections. The RP test detects pathogens such as Adenovirus, Parainfluenza, RSV A/B, and Chlamydia pneumoniae, while the RP2 panel includes SARS-CoV-2.

The BioCode Respiratory Pathogen Panel is an FDA-approved, low-cost test that uses a 96-well microplate format to detect 17 respiratory pathogens, including coronavirus (229E, OC43, HKU1, NL63), Influenza A/B, Rhinovirus/Enterovirus, and Bordetella pertussis. NxTAG Respiratory Pathogen Panel v2, is an updated test that received FDA clearance in 2024 and includes SARS-CoV-2 among 19 viral and 2 bacterial targets. The QIAGEN QIAstat-Dx Respiratory SARS-CoV-2 Panel, authorized under an FDA Emergency Use Authorization (EUA), identifies SARS-CoV-2 along with 20 other respiratory pathogens. It provides qualitative results within an hour and demonstrated a 97% agreement with WHO-recommended RT-PCR, with a sensitivity of 100% and specificity of 93%.

Antigen-based respiratory panels provide a rapid method for detecting respiratory pathogens by identifying viral or bacterial proteins rather than genetic material. These tests are generally faster than PCR-based methods, delivering results in minutes to hours. While antigen tests may have lower sensitivity than molecular assays, they are highly specific and useful for point-of-care and outbreak settings.

The FDA-approved BD Veritor^™ Plus System, offers rapid antigen detection for influenza, RSV, and SARS-CoV-2 with results in under 30 minutes. This test is widely used in clinical and point-of-care settings due to its speed and ease of use, though its sensitivity may vary depending on viral load and timing of specimen collection. At-home antigen tests offer a rapid, low-cost and convenient method for detecting respiratory pathogens in symptomatic individuals. These at-home test include the QuickFinder COVID-19/Flu Antigen Self-Test, developed by OSANG Healthcare, has received FDA 510(k) clearance and is designed to detect both COVID-19 and influenza antigens. It is intended for home use, delivers rapid results within 15 minutes and demonstrates a sensitivity of 90.6% for SARS-CoV-2, 89.7% for influenza A, and 86.0% for influenza B, with a specificity of 99.4% for SARS-CoV-2, 98.8% for influenza A, and 99.7% for influenza B. Similarly, the Quidel Corporation’s Quidel QuickVue^® At-Home OTC COVID-19 Test is designed for the qualitative detection of SARS-CoV-2 antigens. This test provides results within 10 minutes and is authorized for non-prescription home use with self-collected nasal swab samples from individuals aged two years and older.

Central Nervous System Panel

The brain is well protected from microbial invasion via the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Nonetheless, bacteria, fungi, viruses, and amoebae can infect the brain and the consequences are often fatal. Points of entry include the BBB, BCSFB, and the olfactory and trigeminal nerves. Meningitis, which is when the brain and/or spinal cord become inflamed, is typically caused by viral infections due to enteroviruses; other neurotropic viruses include herpes simplex viruses, human cytomegalovirus, varicella zoster virus, and rabies virus. In the United States, bacterial meningitis is most commonly caused by Streptococcus pneumoniae, group B Streptococcus, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, and Escherichia coli. Fungal meningoencephalitis, which is described as inflammation of the brain and surrounding membranes, is often caused by Cryptococcus, Histoplasma, Blastomyces, Coccidioides, and Candida. Meningococcal meningitis is typically caused by Neisseria meningitidis. Other types of pathogens may enter the central nervous system. The increasing use of molecular tests for the detection of pathogens in cerebrospinal fluid (CSF) has redefined the diagnosis and management of central nervous system (CNS) infections such as meningitis and encephalitis. However, it is important that test results correlate to the probability of infection. According to Petti and Polage (2023), the number of false-positive test results increase when the multiplex PCR tests are ordered in the absence of an elevated leukocyte count or elevated protein level in the CSF. Hence, the predictive value of the test increases when the tests are ordered only for those patients with a moderate to high pre-test probability of having CNS infections based on clinical presentation and CSF findings. 

The evaluation of meningitis routinely includes molecular testing, particularly when the patient is suspected of having viral meningitis. Although use of gram stain and culture is the gold standard for diagnosis of bacterial meningitis, multiplex PCR assays may be useful as an adjunct, especially in patients who have already received antibiotic treatment. Other lab findings (for example, CSF cell count, glucose, and protein analyses) should be used as a screening method prior to the performance of molecular testing. Molecular assays for meningitis caused by fungi, parasites, rickettsia, and spirochetes are in development at this time. 

Similarly, molecular testing of CSF is recommended when viral encephalitis, especially encephalitis due to Herpesviridae, is suspected. For other viral encephalitis, the clinical sensitivity and predictive value of multiplex PCR assays is unknown. Therefore, a negative result does not exclude infection, and a combined diagnostic approach, including other methods like serology, may be necessary to confirm the diagnosis. Multiplex PCR-based assays may be useful in certain cases of bacterial meningitis, especially when a slow-growing or uncultivable bacterium like Coxiella burnetti is involved. Molecular assays for encephalitis caused by fungi, parasites, rickettsia, and spirochetes need to be investigated further and are not routinely available at this time. 

The FDA-approved BioFire FilmArray meningitis/encephalitis panel can provide information on 14 different pathogens in one hour. This test uses 0.2 mL of cerebrospinal fluid, and is able to detect bacteria (Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, and Streptococcus pneumoniae), viruses (Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, and Varicella zoster virus) and yeast (Cryptococcus neoformans/gattii). BioFire states that this panel has an overall sensitivity of 94.2% and a specificity of 99.8%. 

Sepsis Panel

Sepsis, also known as blood poisoning, is the body’s systemic immunological response to an infection. Sepsis occurs when an infection (in the lungs, skin, urinary tract or another area of the body) triggers a chain reaction in an individual. Sepsis can lead to end-stage organ failure and death. Septic shock occurs when sepsis results in extremely low blood pressure and abnormalities in cellular metabolism. The annual incidence of severe sepsis and septic shock in the United States is 300 per 100,000 people; sepsis is “the most expensive healthcare problem in the United States.”

Sepsis-related mortality remains high, and inappropriate antimicrobial and anti-fungal treatment is a major factor contributing to increased mortality. Blood culture is the standard of care for detecting bloodstream infections, but the method has several limitations. Fastidious, slow-growing, and uncultivable organisms are difficult to detect by blood culture, and the test sensitivity decreases greatly when antibiotics have been given prior to culture. Additionally, culture and susceptibility testing may require up to 72 hours to produce results. Multiplex PCR assays of positive blood culture bottles have a more rapid turnaround time and are not affected by the administration of antibiotics. Faster identification and resistance characterization of pathogens may lead to earlier administration of the appropriate antibiotic, resulting in better outcomes, and may lessen the emergence of antibiotic-resistant organisms. 

The T2Bacteria Panel is the first FDA-cleared test capable of identifying sepsis-causing bacteria directly from whole blood without requiring blood culture, detecting 50% of bloodstream infections and 90% of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) with 95% sensitivity and 98% specificity. Roche Diagnostics offer the Cobas ePlex^® Blood Culture Identification (BCID) Panels. These FDA-cleared panels provide rapid pathogen identification directly from positive blood cultures. The system includes the BCID-GP Panel (detecting 20 gram-positive bacteria and four resistance genes), the BCID-GN Panel (identifying 21 gram-negative bacteria and six resistance genes), and the BCID-FP Panel (targeting 15 fungal organisms). BioFire's FDA-cleared FilmArray BCID has expanded from detecting 24 targets to 43 in the BCID2 version, covering gram-positive bacteria (e.g., Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae), gram-negative bacteria (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa), yeast (e.g., Candida albicans, Candida auris, Cryptococcus neoformans), and antimicrobial resistance genes.

Urinary Tract Infection Panel

Urinary tract infections (UTIs) occur in the urinary system and can be either symptomatic or asymptomatic. UTIs can include cystitis, an infection of the bladder or lower urinary tract, pyelonephritis, an infection of the upper urinary tract or kidney, urosepsis, urethritis, and conditions such as bacterial prostatitis and epididymitis. Typically, in an infected person, bacteriuria and pyuria (the presence of pus in the urine) are present and can be present in both symptomatic and asymptomatic UTIs. A urine culture can be performed to determine the presence of bacteria and to characterize the bacterial infection.

Several molecular diagnostic tests are available for detecting UTIs. MicroGenDX's UroKEY UTI panel utilizes next-generation sequencing (NGS) to identify a wide range of over 57,000 bacteria and fungi, offering comprehensive detection in as little as five days. Pathnostics' Guidance^® UTI test combines PCR and Pooled Antibiotic Susceptibility Testing (P-AST^™) to identify 27 bacterial and yeast organisms as well as 32 antibiotic-resistance genes with a 95% sensitivity.

Wound Panel

Wounds (acute or chronic) are almost always colonized by microbes, thereby leading to a significant rate of infection. Panel testing many pathogens have been proposed as a method to quickly identify and therefore treat a wound infection. These panels may be culture-based or nucleic acid-based; nucleic acid panels are typically touted for their speed compared to culture panels.

Firms such as GenetWorx, Viracor, and MicroGenDX offer comprehensive wound pathogen panels that detect a variety of bacterial, fungal, and viral targets, as well as resistance genes.  These panels frequently include common wound pathogens such as Streptococcus, Enterococcus, and Staphylococcus. The GenetWorx Wound Pathogen Panel identifies 30 targets, including MRSA, MSSA, Streptococcus species, Pseudomonas aeruginosa, Candida species, and Herpes Simplex Virus. The Viracor Skin and Soft Tissue Infection Panel uses TEM-PCR^™ to detect 19 bacterial targets, including Acinetobacter baumannii, Enterococcus faecalis, Klebsiella spp., Proteus mirabilis, MRSA, and Pseudomonas aeruginosa, though it is not FDA-approved and has a two to three-day turnaround time. MicroGenDX also offers molecular-based wound infection panels utilizing qPCR and NGS for expanded pathogen identification and antimicrobial resistance profiling.

A comprehensive list of the main commercial pathogen panel tests mentioned above can also be found in the table below. 

Commercial Pathogen Panel Tests

Clinical Utility and Validity

Several studies demonstrated the overall sensitivity and specificity of the gastroenterology pathogen panels. Several studies have also indicated that gastrointestinal pathogen panels are more sensitive than culture, microscopy, or antigen detection. Zhang, et al. (2015) concluded that using multiplex PCR assays in the workup of infectious gastroenteritis had the potential to improve the diagnosis. However, Xie and colleagues, in a randomized controlled trial, found no differences between groups related to administration of patient care (intravenous fluid, antibiotic treatment, hospitalization, or diagnostic imaging) with use of the assay. The BioFire FilmArray test was not correlated with clinically significant reductions in the usage of health care resources or improved patient care outcomes.

Cybulski, et al. (2018) found that the FilmArray GI Panel detected pathogens at a higher rate than culture and at a faster time (35.3% in 18 hours versus 6.0% in 47 hours). This rapidity and accuracy also allowed patients to receive targeted therapy and facilitated quicker discontinuation of empirical antimicrobial therapy, demonstrating an improved clinical sensitivity with the FilmArray GI Panel when compared to culture. Beal, et al. (2018) investigated the impact of submitting patient stool specimen for testing by the FilmArray GI panel (“cases”) and compared overall findings with control patients from the year prior. The researchers concluded that this panel contributed to reducing the number of days on antibiotics (1.73 days among cases versus 2.12 days among controls), reducing “average length of time from stool culture collection to discharge” slightly (3.4 days among cases vs 3.9 days among controls), and reducing overall health care cost by $293.61.

Zhan, et al. (2020) performed a comparison of the BioFire FilmArray gastrointestinal panel and the Luminex xTAG Gastrointestinal Pathogen Panel for detecting diarrheal pathogens in China in a total of 243 diarrhea specimens. These two panels were highly consistent in detecting norovirus, rotavirus, and Campylobacter, but had low consistency in detecting Cryptosporidium, Salmonella, Shiga toxin producing Escherichia coli (ETEC) and enterotoxigenic Escherichia coli. The BioFire FilmArray panel was found to be more sensitive, but the Luminex xTAG Gastrointesinal Pathogen Panel was more specific. There appeared to be additional concern for how the Luminex xTAG Gastrointesinal Pathogen Panel yielded more false negatives when detecting ETEC as well.

van Asten, et al. (2021) evaluated the performance of the GenMark Diagnostics ePlex Respiratory Pathogen panel and the QIAGEN Sciences QIAstat-Dx Respiratory Pathogen panel. The authors specifically studied the detection of three bacterial targets: Legionella pneumophila, Mycoplasma pneumoniae and Bordetella pertussis. The study included 56 specimens taken from the lower respiratory tract, five of which were negative and the other 51 had previously tested positive on real-time PCR assays for the targets. “The QIAstat-Dx Respiratory Panel V2 assay detected all of the L. pneumophila and B. pertussis positive samples but only 11/15 (73.3%) of the M. pneumoniae targets. The ePlex Respiratory Pathogen Panel (RPP) assay detected 10/14 (71.4%) of the L. pneumophila targets, 8/12 (66.7%) of the B. pertussis positive samples and 13/15 (86.7%) of the M. pneumoniae targets.” The authors concluded that the clinical performance of both panels depend on the bacterial lode and sample type.

Mormeneo Bayo et al. (2022) compared real-time PCR with microscopy in detecting intestinal protozoa in children. The study used the Seegene Allplex Gastrointestinal panel for the real-time PCR. Five hundred stool samples were analyzed from children, 15 years of age and under, and grouped into two classifications based on if the children had or had not had clinical parasitosis. Based on microscopy, 6.2% of samples were positive. Based on real-time PCR, 51.2% of samples were positive. The authors concluded that “real-time PCR increases the detection of intestinal protozoa, being underdiagnosed by microscopy, especially D. fragilis, in which PCR is considered the most appropriate method for its detection.”

The use of multiplex PCR assays to identify pathogens following positive blood culture can be faster than standard techniques involving phenotypic identification and antimicrobial susceptibility testing that is required up to 72 hours after the blood culture became positive. A prospective randomized controlled trial evaluating outcomes associated with multiplex PCR detection of bacteria, fungi, and resistance genes directly from positive blood culture bottles concluded that the testing led to more judicious antibiotic use. A study by Ward, et al. (2015) compared the accuracy and speed of organism and resistance gene identification of two commercially available multiplex PCR sepsis panels to conventional culture-based methods for 173 positive blood cultures. The researchers discovered that both the assays accurately identified organisms and significantly reduced the time to definitive results (on average, between 27.95 and 29.17 hours earlier than conventional method). Another study assessed the diagnostic accuracy of a commercially available multiplex PCR-based assay for detecting infections among patients suspected of sepsis. They concluded that the test had high specificity with a modest sensitivity and had higher rule-in value than the rule-out value. If the patient had a positive result, a clinician can diagnose sepsis and begin appropriate antimicrobial therapy while avoiding unwanted additional testing. 

There are a few limitations with this type of testing. First, the level—detection or non-detection—of a microorganism does not necessarily imply a diagnosis. The tests can only describe the levels of microorganisms found in the environment, but additional information is required to make a diagnosis. Second, the scope of the 16S rRNA sequencing used in testing may be limited. Differences in regions more specific than rRNA (such as surface antigens or individual toxin genes) cannot be resolved with this test. For example, the test cannot distinguish between a pathogenic C. difficile strain and a non-pathogenic one. Moreover, the tests report some of their targets at a genus level only, which means that these targets cannot be differentiated at the species level. 

UroSwab is a urine-based proprietary test from Medical Diagnostics LLC. UroSwab is a real-time PCR test intended to detect numerous pathogens potentially involved in sexually transmitted and urological infections. This test uses a patient’s urine, and the turnaround time is estimated at 24-72 hours. The results include whether a pathogen’s presence was normal or abnormal and includes comments on what the pathogen’s presence means.

McCarty et al. (2023) tested the performance and clinical utility of the GenMark ePlex BCID Gram-Negative Panel. The authors used “matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry on bacterial isolates” as a reference to compare results. In total, 98.1% (106/108) of the bacteria identified by MALDI were on the GenMark panel, and “valid tests (107/108, 99.1%) yielded results on average 26.7 h earlier.”

Guidelines and Recommendations

American College of Gastroenterology (ACG)

The ACG stated that “diarrheal disease by definition has a broad range of potential pathogens particularly well suited for multiplex molecular testing. Several well-designed studies show that molecular testing now surpasses all other approaches for the routine diagnosis of diarrhea. Molecular diagnostic tests can provide a more comprehensive assessment of disease etiology by increasing the diagnostic yield compared with conventional diagnostic tests.” Furthermore, the ACG recommended that “traditional methods of diagnosis (bacterial culture, microscopy with and without special stains and immunofluorescence, and antigen testing) fail to reveal the etiology of the majority of cases of acute diarrheal infection. If available, the use of Food and Drug Administration-approved culture independent methods of diagnosis can be recommended at least as an adjunct to traditional methods. (Strong recommendation, low level of evidence)” 

The ACG also notes:

• “Diagnostic evaluation using stool culture and culture-independent methods if available should be used in situations where the individual patient is at high risk of spreading disease to others, and during known or suspected outbreaks.” 
• “Stool diagnostic studies may be used if available in cases of dysentery, moderate–severe disease, and symptoms lasting >7 days to clarify the etiology of the patient’s illness and enable specific directed therapy.”

In 2013, the ACG made the following recommendations on diagnostic tests used for Clostridioides difficile (C. difficile) infections:

• “Only stools from patients with diarrhea should be tested for Clostridium difficile. (Strong recommendation, high-quality evidence)” 
• “Nucleic acid amplification tests (NAAT) for C. difficile toxin genes such as PCR are superior to toxins A + B EIA testing as a standard diagnostic test for CDI. (Strong recommendation, moderate-quality evidence)” 
• “Repeat testing should be discouraged. (Strong recommendation, moderate-quality evidence)” 
• “Testing for cure should not be done. (Strong recommendation, moderate-quality evidence).”

In 2021, the ACG reaffirmed the above recommendations with a note that the bacterium was reclassified from Clostridium difficile to Clostridioides difficile based on updated genetic analysis in 2016. AGP also updated their C. difficile guidelines to include the following recommendations:

• “Only individuals with symptoms suggestive of active CDI should be tested (3 or more unformed stools in 24 hours).
• CDI testing algorithms should include both a highly sensitive and a highly specific testing modality to help distinguish colonization from active infection (conditional recommendation, low quality of evidence)."

The ACG states that “no single test is suitable to be used as a stand-alone test; use of a 2-step testing algorithm … is our preferred testing method for optimal diagnostic accuracy,” recommending that a multistep approach is necessary because NAAT testing alone or GDH alone is not considered sufficient; it must be paired with either a toxin test or a multistep algorithm to ensure accurate diagnosis. “In this approach, stool is first tested using a highly sensitive NAAT or GDH test, and the second test is the more specific toxin EIA.”

Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)

The IDSA and the ASM have issued a comprehensive guideline for the utilizing the microbiology laboratory in the diagnosis of infectious diseases. While multiplex molecular panels improve diagnostic speed and accuracy, the IDSA caution that careful validation and clinical experience are needed for effective integration. Below are their panel testing recommendations organized by body system:

Gastrointestinal System

According to the 2024 IDSA Clinical Practice Guideline, laboratory testing to determine the cause of infectious gastroenteritis is considered medically necessary only in specific clinical contexts. Testing is indicated for individuals presenting with moderate to severe diarrhea, including cases that are bloody, febrile, dysenteric, persistent in duration, or associated with a nosocomial setting. Testing is also appropriate for individuals who are immunocompromised, as they are at greater risk for complications and may require tailored clinical management. Outside of these scenarios, laboratory testing is not routinely recommended. Patients with non-inflammatory, self-limited diarrhea or acute gastroenteritis or short duration typically do not benefit from diagnostic testing, as the condition is most often viral and self-resolving.

When testing is clinically appropriate, the use of culture independent diagnostic tests—such as multiplex molecular panels—is supported by IDSA for the detection of bacterial pathogens. However, for patients without risk factors or for those with likely viral etiology, such tests may not influence clinical decision-making and may result in unnecessary downstream interventions. Multiplex panels that include viral targets generally offer limited clinical utility in immunocompetent individuals, as viral gastroenteritis frequently resolves without specific treatment. The use of multiplex panels to detect parasitic pathogens may be considered medically appropriate in patients with diarrhea lasting more than seven days, particularly when initial workup is inconclusive and the patient is at risk for parasitic exposure. The guideline also notes that highly multiplexed assays can identify mixed infections and organisms of uncertain clinical significance, including enteroaggregative or enteropathogenic Escherichia coli and certain viral agents, where the role is pathogenesis and need for treatment remain unclear. In such cases, test results should be interpreted in the context of the patient’s clinical presentation and risk profile.

Stool cultures are designed to detect specific pathogens. “Routine stool culture in most laboratories is designed to detect Salmonella spp., Shigella spp., and Campylobacter spp.” More comprehensive syndromic panel tests are recommended for patients with diarrhea of unknown etiology, particularly those with relevant exposure risks. “Cryptosporidium and Giardia lamblia testing is often offered and performed together as the primary parasitology examination. Additional parasite examinations should follow if a travel history, risk factors or clinical symptoms suggest parasitic disease."

Furthermore, NAATs and multiplex molecular panels are recommended for detecting bacterial, viral, and parasitic causes of gastroenteritis. These methods are more sensitive than culture and provide rapid results. For Clostridioides difficile, NAATs are recommended as part of a multistep algorithm to improve diagnostic accuracy and reduce the identification of colonized patients.

The IDSA published guidelines for the diagnosis and management of infectious diarrhea in 2017 which state:

Stool testing should be performed for Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, and STEC in people with diarrhea accompanied by fever, bloody or mucoid stools, severe abdominal cramping or tenderness, or signs of sepsis. However, other bacterial, viral, and parasitic agents should be considered regardless of symptoms. Any specimen testing positive for bacterial pathogens by culture independent diagnostics (such as an antigen-based molecular assay) should be cultured in a clinical or public health laboratory if isolation was requested or required. Finally, clinical consideration should occur with interpretation of results of multi-pathogen NAATs as these tests only detect DNA and not necessarily pathogens.

In 2018 the IDSA and the Society for Healthcare Epidemiology of America (SHEA) released a shared Clostridioides difficile guideline stating that the best-performing method for detecting patients with a greater risk of a C. difficile infection from a stool sample is to “Use a stool toxin test as part of a multistep algorithm (ie, glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no pre-agreed institutional criteria for patient stool submission (weak recommendation, low quality of evidence).” These guidelines also state that repeat testing (within seven days) should not be performed. Panel testing is not specifically mentioned in these guidelines.

Respiratory System

The IDSA recommends that panel testing remain optional for outpatients or hospitalized patients with mild community-acquired pneumonia (CAP) with testing being more important for patients with severe illness or significant risk factors. The guidelines state “identification of a pathogen will focus the antibiotic management for a particular patient. In addition, identification of certain pathogens such as Legionella species, influenza viruses, and SARS-CoV-2 have important public health significance. Current IDSA/ATS practice guidelines consider diagnostic testing as optional for the patient who is not hospitalized or who is hospitalized with mild CAP."

Blood culture panel testing is recommended that "in those patients who require admission for severe CAP or who have strong risk factors for MRSA or Pseudomonas aeruginosa, blood culture sets should be collected before initiating antimicrobial therapy."

The IDSA advises using respiratory antigen tests for use in symptomatic patients for quick diagnosis, but caution that even negative results should be confirmed with NAAT in cases where COVID-19 is suspected. "Rapid antigen tests have been widely used in the diagnosis of COVID-19... In symptomatic patients, antigen tests have demonstrated a sensitivity of 70%–80%, but in the asymptomatic population, the sensitivity has ranged from 40% to 50%." For COVID-19, the IDSA highlights the use of panel tests that include SARS-CoV-2 as one of the targets. “Several FDA-cleared multiplex molecular panels include SARS-CoV-2 as one of the targets. These panels can detect a wide range of respiratory pathogens, including SARS-CoV-2, and provide rapid results.”

In terms of specific respiratory pathogens, the IDSA notes that “FDA-cleared NAAT platforms are available for detecting a broad range of respiratory viruses and some atypical bacteria (e.g., Mycoplasma pneumoniae, Chlamydia pneumoniae, Bordetella pertussis). These have largely replaced rapid antigen detection tests and culture in most institutions.” Additionally, for hospitalized patients with severe CAP or strong epidemiological risk factors, the IDSA recommends pathogen panels for detecting respiratory pathogens, including viruses and atypical bacteria.

Central Nervous System

The IDSA recommends "NAAT of CSF [cerebrospinal fluid] is more sensitive than viral culture for the diagnosis of enteroviral central nervous system infection... If the patient develops any signs of acute flaccid myelitis (AFM) or central nervous system involvement, testing of CSF is recommended." They caution that specific NAATs may be necessary when multiplex tests do not cover all required targets. "Parechoviruses, which can cause disease similar to enteroviruses, require a specific NAAT for detection."

Genitourinary System

The IDSA recommends that individuals at higher risk for sexually transmitted infections should get panel testing state that "Multiplex molecular assays for detection of several organisms associated with bacterial vaginosis are more specific and sensitive than syndromic assessment alone... Adding testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) identifies approximately 25% more infections in high-risk populations."

Infectious Diseases Society of America (IDSA), the American Society for Microbiology (ASM), the Association for Molecular Pathology (AMP), and the Pan American Society for Clinical Virology

In a 2023 Joint Report by the Association for Molecular Pathology, American Society for Microbiology, Infectious Diseases Society of America, and Pan American Society for Clinical Virology, multiplex PCR panel tests are described as the “preferential use of molecular approaches for pathogen detection, with many clinical laboratories discontinuing conventional methods (e.g., viral culture) because of gains in performance and operational efficiency from the molecular assays.”

The report also notes that “the availability and simplicity of multiplex molecular panels have increased their adoption in a wide range of settings (e.g., community hospitals and large reference laboratories).” However, this report emphasizes the “importance of diagnostic stewardship for the appropriate implementation of multiplex molecular panels by considering, for example, which patient population would benefit most from their use (eg, recommending use in hospitalized, immuncompromised hosts and limiting use for relatively healthy outpatient hosts).”

The report also outlines limitations of syndromic multiplex panels, including their fixed target lists, vulnerability to decreased accuracy from evolving sequences, inability to differentiate between viable and nonviable organisms, and the potential to detect clinically irrelevant pathogens. As stated, “syndromic multiplex panels do not always displace standard-of-care practices and may add laboratory cost to patient care.”

Importantly the report recommends careful consideration by medical providers and laboratories before adopting a multiplex test stating that “At a minimum, before the laboratory invests time and resources to evaluate a new test, there should be some evidence of clinical validity and utility, a clinically relevant demand for the test, and, ideally, there should be a potential cost benefit for the hospital and/or laboratory… In addition to demonstrating analytical and clinical validity, laboratories are increasingly required to demonstrate the clinical utility (medical value) of a test in their patient population”

Infectious Diseases Society of America (IDSA)

The IDSA advances infectious disease research, education, and clinical practice. The IDSA provides guidelines to support healthcare professionals in diagnosing, treating, and preventing infectious diseases. Below are recommendations from various current IDSA guidelines related to pathogen panel testing:

Respiratory System

The IDSA recommends RT-PCR or other molecular tests over other influenza tests in hospitalized patients. RT-PCR tests targeting a panel of respiratory pathogens are recommended in hospitalized, immunocompromised patients. 

In their 2020 Molecular Testing for Acute Respiratory Tract Infections guideline, the IDSA acknowledges that multiplex viral NAAT (potentially combined with bacterial NAAT) makes some clinical sense for immunocompromised and critically ill patients with pneumonia, as well as for those with exacerbations of airway disease. “These are situations where treatment of non–influenza viruses such as respiratory syncytial virus (RSV) or adenovirus may be considered (eg, in a stem-cell-transplant patient) and rapid test results are most likely to influence subsequent modifications of empiric broad-spectrum antibiotics.”

While the analytic sensitivity of multiplex NAAT decreases the likelihood that an important pathogen will be missed, enhanced detection can also complicate interpretation of results and available studies on the significance of mixed infections have reported variable results. IDSA notes that “additional studies are needed to understand whether co-infections portend poorer prognosis. . . High analytic sensitivity also translates to high negative-predictive values (i.e., generally >97%, depending on prevalence), but there may be important differences among individual panel targets or across manufacturers. It is incumbent on clinicians and laboratorians to understand the test characteristics of each individual panel target, especially if the results inform antibiotic de-escalation in high-acuity settings. Even the largest multiplex panels do not detect all potential pathogens, and the optimal multiplex panel design remains a matter of debate. As a result, current tests are not yet a replacement for bacterial and fungal culture with antimicrobial susceptibility testing. Culture also remains essential for epidemiologic studies, vaccine-related decisions, and local antibiograms.” 

The IDSA published guidelines on the diagnosis of COVID-19, recommending the use of multiplex molecular panel tests that include SARS-CoV-2 for rapid and accurate diagnosis in symptomatic individuals and those with known exposure. However, standard NAATs (like RT-PCR) are preferred over rapid antigen tests for higher accuracy. Panel testing should be carefully validated and used alongside clinical judgment.

American Society for Microbiology/Association for Molecular Pathology/Association of Public Health Laboratories/College of American Pathologists/Infectious Diseases Society of America/Pan American Society for Clinical Virology

These societies made a joint statement regarding respiratory viral panels and noted three populations in which multiplex panels would be beneficial. Those populations were “immunocompromised hosts, adult patients appearing acutely ill who are potential hospital admissions, and critically-ill adult patients, particularly ICU patients.”

Global Wound Biofilm Expert Panel Consensus Guidelines

A Global Wound Biofilm Expert Panel have strongly agreed that “there are currently no routine diagnostic tests available to confirm biofilm presence” and that “the most important measure for future diagnostic tests to consider is indication of where the biofilm is located within the wound.”

Society of Critical Care Medicine and the European Society of Intensive Care Medicine (SCCM)

A collaboration of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine issued international guidelines for management of sepsis and septic shock. It states “in the near future, molecular diagnostic methods may offer the potential to diagnose infections more quickly and more accurately than current techniques. However, varying technologies have been described, clinical experience remains limited, and additional validation is needed before recommending these methods as an adjunct to or replacement for standard blood culture techniques.”

A 2020 update regarding “Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children” was published by the Society of Critical Care Medicine (SCCM), European Society of Intensive Care Medicine (ESICM), and the International Sepsis Forum. In it, they acknowledge the presence of new molecular technologies, but remark that they are “currently relatively expensive, are not sufficient for all pathogens and antibiotic sensitivities, and are not universally available.”

In 2023 the SCCM and The IDSA co-published a guideline update on evaluating new fevers in critically ill adult patients. They discussed the use of panel testing, particularly in respiratory infections, while acknowledging limitations in evidence for routine viral blood testing. Below are their recommendations:

• “For critically ill patients with new fever and suspected pneumonia, or new upper respiratory infection symptoms (e.g., cough), we suggest testing for viral pathogens using viral NAAT panels (weak recommendation, very low-quality evidence).
• The panel found insufficient evidence to issue a recommendation on performing routine blood testing for viral pathogens (e.g., herpesviruses, adenovirus) in immunocompetent patients in the ICU.
• For critically ill patients with a new fever, we recommend testing for SARS-CoV-2 by PCR based on levels of community transmission.”

American College of Chest Physicians (CHEST)

The CHEST has recommended that outpatient adults with an acute cough and suspected pneumonia should not undergo routine microbiological testing because there is no need for such testing. However, testing may be considered if the results would change the therapeutic approach. Microbiological tests may include culture, serologic, and PCR testing. 

Centers for Disease Control and Prevention

Regarding molecular tests that are commonly used for a C. difficile diagnosis, the CDC states that “FDA-approved PCR assays are same-day tests that are highly sensitive and specific for the presence of a toxin-producing C. diff organism. . . Molecular assays can be positive for C. diff in asymptomatic individuals and those who do not have an infection. Patients with other causes of diarrhea might be positive, which leads to over-diagnosis and treatment. . . When using multi-pathogen (multiplex) molecular methods, read the results with caution as the pre-test probability of C. diff infection might be less.”

For hospitalized patients with acute respiratory illness, the CDC recommends ordering “multiplex nucleic acid detection assay for influenza A/B/SARS-CoV-2.23 If not available, order SARS-CoV-2 nucleic acid detection assay or antigen detection assay and influenza nucleic acid detection assay.”

The European Association of Urology

The EAU published urological infections guidelines. For uncomplicated UTIs (recurrent UTIs, cystitis, pyelonephritis), the EAU does not mention molecular testing at any point of the treatment algorithm; instead, they recommend bacterial culture or dipstick testing for diagnosis and recommending against extensive workup. The EAU notes that antimicrobial susceptibility testing should be performed in all cases of pyelonephritis, but their guidelines do not suggest any methods over another. In complicated UTIs, the EAU recommends urine culture to identify cases of clinically significant bacteriuria.

American Society of Transplantation Infectious Diseases Community of Practice

These guidelines focus on identifying infections in transplant patients. Their recommendations are as follows:

“For the diagnosis of SOT [solid organ transplant] recipients with suspected gastrointestinal infections,” gastrointestinal multiplex molecular assays are recommended to identify Cryptosporidium, Cyclospora, and Giardia. 

American Society for Clinical Pathology (ASCP, through ChoosingWisely)

The ASCP states “do not routinely order broad respiratory pathogen panels unless the result will affect patient management.” They further state that patient management may include “provid [ing] immediate diagnosis and potentially expedite management decisions” and list “rapid molecular or point of care tests for RSV, Influenza A/B, or Group A pharyngitis” as examples. 

State and Federal Regulations, as applicable

Food and Drug Administration (FDA)

There are numerous FDA-approved pathogen panels. Additionally, many labs have developed specific tests that they must validate and perform in house. These laboratory-developed tests (LDTs) are regulated by the Centers for Medicare and Medicaid (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). LDTs are not approved or cleared by the U. S. Food and Drug Administration; however, FDA clearance or approval is not currently required for clinical use. 

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes:  87154, 87428, 87483, 87505, 87506, 87507, 87631, 87632, 87633, 87636, 87637, 0068U, 0086U, 0109U, 0112U, 0115U, 0140U, 0141U, 0142U, 0152U, 0202U, 0223U, 0225U, 0321U, 0323U, 0371U,  0441U, 0442U, 0480U, 0504U, 0528U, 0531U, 0556U, 0563U, 0564U, 0590U, 0593U.

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included. 

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Xie J, Kim K, Berenger BM, et al. Comparison of a Rapid Multiplex Gastrointestinal Panel with Standard Laboratory Testing in the Management of Children with Hematochezia in a Pediatric Emergency Department: Randomized Controlled Trial. Microbiol Spectr. Jun 15 2023;11(3):e0026823. doi:10.1128/spectrum.00268-23

Cybulski RJ, Jr., Bateman AC, Bourassa L, et al. Clinical Impact of a Multiplex Gastrointestinal Polymerase Chain Reaction Panel in Patients With Acute Gastroenteritis. Clin Infect Dis. Nov 13 2018;67(11):1688-1696. doi:10.1093/cid/ciy357

Beal SG, Tremblay EE, Toffel S, Velez L, Rand KH. A Gastrointestinal PCR Panel Improves Clinical Management and Lowers Health Care Costs. J Clin Microbiol. Jan 2018;56(1)doi:10.1128/jcm.01457-17

Zhan Z, Guo J, Xiao Y, et al. Comparison of BioFire FilmArray gastrointestinal panel versus Luminex xTAG Gastrointestinal Pathogen Panel (xTAG GPP) for diarrheal pathogen detection in China. Int J Infect Dis. Oct 2020;99:414-420. doi:10.1016/j.ijid.2020.08.020

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Specialty Matched Consultant Advisory Panel review 3/2020

Medical Director review 3/2020

Specialty Matched Consultant Advisory Panel review 3/2021

Medical Director review 3/2021

Medical Director review 7/2022

Medical Director review 7/2023

Medical Director review 10/2024

Medical Director review 7/2025

Policy Implementation/Update Information

1/1/2019 New policy developed. BCBSNC will provide coverage for Multiplex PCR-based panel testing when it is considered to be medically necessary because criteria and guidelines are met. Medical Director review 1/1/2019. Policy noticed 1/1/2019 for effective date 4/1/2019.

4/16/2019 Removed item B that concerns “travel-related diarrhea” from the When Covered section and added second paragraph stating that genetic panel sequencing testing methods such as SmartGut^™ and SmartJane^™, to identify microbes is investigational to the When Not Covered sectiUpdated policy guidelines and references. Medical Director review 4/2019. (jd)

10/1/2019 Reviewed by Avalon 2^nd Quarter 2019 CAB. Related Policies added to Description section. Revised the indications under the When Not Covered section to include the nature of the sample as well as UroSwab^®. The following codes were added to the Billing/Coding section: 0068U, 0086U, 0097U, 0098U, 0099U, 0100U, and code table removed. References updated. Medical Director review 8/2019. (jd)

10/29/19 Wording in the Policy, When Covered, and/or Not Covered section(s) changed from Medical Necessity to Reimbursement language, where needed. (gm)

2/11/20 Annual review by Avalon 4^th Quarter 2019 CAB. Added items 2 and 3 to the When Not Covered section. Billing/Coding section: added the following codes 0107U, 0112U, 0140U, 0141U, 0142U, 0151U, 0152U. Medical Director review 12/2019. (jd)

3/31/20 Specialty Matched Consultant Advisory Panel review 3/2020. Medical Director review 3/2020. (jd)

5/12/20 Reviewed by Avalon 1^st Quarter 2020 CAB. Related Policies section updated, added Diagnosis Of Vaginitis Including Multi-Target PCR Testing AHS – M2057 and Onychomycosis Testing AHS – M2172. Revised the When Covered section as follows: item #1: revised reimbursement statement and added “(GIP) up to 5 pathogens”, along with “*(See Note 1)”; item #2: added “In the outpatient setting before the reimbursement statement, along with “gastrointestinal”, “up to 11 pathogens”, “immunosuppressed or HIV positive patients AND any of the following situations *(See Note 1)” along with corresponding criteria noted in items a. and b. Revised item #3 to allow for “up to 5” respiratory pathogens”, added “Note 1”. Revised the When Not Covered section as follows: added items 1-4. Policy guidelines and references updated. Removed codes 87150, 87486, 87496, 87498, 87529, 87532, 87581, 87634, 87653, 87798 and 0107U. Added CPT codes 87631 and 87632. Medical Director reviewed 4/2020. (jd)

7/28/20 Reviewed by Avalon 2^nd Quarter 2020 CAB. Note added to the policy statement as follows: “The coverage criteria outlined in this policy are not applicable to diagnostic COVID-19 testing.” Policy guidelines and references updated. The following codes were added to the Billing/Coding section: 87631, 87632. Medical Director review 7/2020. (jd)

3/31/21 Specialty Matched Consultant Advisory Panel review 3/2021. Medical Director review 3/2021. (jd)

5/4/21 Off-cycle review by Avalon 1^st Quarter 2021 CAB. The following codes were deleted from the Billing/Coding section: 0098U, 0099U, 0100U. Medical Director review 4/2021. (jd)

8/24/21 Reviewed by Avalon 2^nd Quarter 2021 CAB. Background, policy guidelines and references updated. Medical Director review 7/2021. (jd)

12/30/21 The following codes were added to the Billing/Coding section: 87154, 87636, 87637 effective 1/1/22. (jd)

5/17/22 Off-cycle code review by Avalon 1^st Quarter 2022 CAB. The following codes were deleted from the Billing/Coding section: 0097U and 0151U and code 0321U was added to this section. (jd)

7/1/22 The following PLA codes were added to the Billing/Coding section: 0323U, 0330U. (jd)

9/13/22 Reviewed by Avalon 2^nd Quarter 2022 CAB. Background, policy guidelines and references updated. Updated Billing/Coding section. No changes to policy statement. Medical Director review 7/2022. (tm)

3/31/23 Updated Billing/Coding section to add codes 0369U, 0370U, 0371U, 0373U, and 0374U effective 4/1/2023. (tm)

8/15/23 Reviewed by Avalon 2^nd Quarter 2023 CAB. Background, Policy Guidelines and References updated. When Covered and Not Covered sections edited for clarity, no changes to policy statement. Removed previous Note 1. Removed PLA code 0330U from Billing/Coding section. Medical Director review 7/2023. (tm)

9/29/23 Updated Billing/Coding section to add code 0416U, effective 10/1/2023. (tm)

4/17/24 Codes 0441U and 0442U added to Billing/Coding section, effective 4/1/24. (tm)

10/1/24 Codes 0480U and 0504U added to Billing/Coding section, effective 10/1/24. (tm)

12/17/24 Reviewed by Avalon 3^rd Quarter 2024 CAB. Description, Policy Guidelines and References updated. Removed phrase “in the outpatient setting” from coverage criteria in the When Covered and Not Covered sections. Additional changes made to the When Covered section: added statement “This policy is specific to testing in the outpatient setting. Criteria below do not apply to testing allowances in situations other than the outpatient setting”, removed previous coverage criteria 2 as up to 11 GIPs on a PCR-panel are now allowed for all individuals. Criteria 1 now reads “Reimbursement is allowed for multiplex PCR-based panel testing (up to 11 gastrointestinal pathogens [GIPs]) no more often than once every 7 days for individuals with persistent diarrhea or diarrhea with signs or risk factors for severe disease (i.e., fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain).” Criteria 2 (previously criteria 3) edited to now read “Reimbursement is allowed for multiplex PCR-based panel testing (up to 5 respiratory pathogens) for individuals who are displaying signs and symptoms of a respiratory tract infection (i.e., temperature ≥ 102°F, pronounced dyspnea, tachypnea, tachycardia).” Added CPT code 0528U to Billing/Coding section, effective 1/1/2025. Medical Director review 10/2024. Notification given 12/17/2024 for effective date 2/12/2025. (tm)

2/26/25 Reviewed by Avalon 4^th Quarter CAB 2024 for code updates only. Added codes 0202U, 0223U and 0225U to Billing/Coding section. (tm)

4/1/25 Code 0531U added to Billing/Coding section, effective 4/1/2025. (tm)

7/1/25 Codes 0556U, 0563U, 0564U added to Billing/Coding section, effective 7/1/25. (tm)

10/15/25 Reviewed by Avalon 3rd Quarter 2025 CAB. Description, Policy Guidelines and References updated.  Updates to the When Covered section: coverage criteria 2 edited to add antigen panel testing and moved respiratory infection signs/symptoms to new Note 1 and now reads "Reimbursement is allowed for panel testing of up to 5 respiratory pathogens (antigen panel testing or multiplex PCR-based panel testing) for individuals who are displaying signs and symptoms of a respiratory tract infection (see Note 1)." Updates to Not Covered section: coverage criteria 2 edited to add antigen panel testing and now reads "2. Reimbursement is not allowed for antigen panel testing or multiplex PCR-based panel testing of 6 or more respiratory pathogens." Updates to Billing/Coding section: added code 87428 and removed codes 0240U, 0241U, 0369U, 0370U, 0373U and 0374U. Added codes 0590U and 0593U, effective 10/1/25. Medical Director review 7/2025. (tm)