CAM 181

Pathogen Panel Testing

Category:Laboratory   Last Reviewed:December 2018
Department(s):Medical Affairs   Next Review:July 2019
Original Date:December 2017    

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.

Background 
There has been a move in recent years toward employing molecular tests that use multiplex polymerase chain reaction (PCR) to simultaneously detect multiple pathogens associated with an infectious disease rather than one particular organism (Palavecino, 2015). They are usually offered as a panel for a particular infectious condition, such as sepsis and bloodstream infections, central nervous system infections (for example, meningitis and encephalitis), respiratory 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 (Palavecino, 2015). 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 (Palavecino, 2015).

There are about 2 billion cases of diarrheal disease worldwide every year that result in 1.9 million deaths in children younger than 5 years of age each year (Farthing et al., 2013). The Centers for Disease Control and Prevention has estimated that there are nearly 48 million cases of acute diarrheal infection occurring annually in the United States, at an estimated cost upward of $150 million (Scallan et al., 2011). Thirty-one 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 (Riddle et al., 2016). Additionally, unspecified agents caused approximately 38 million episodes of foodborne illnesses and resulted in 71,878 hospitalizations and 1,686 deaths (Riddle et al., 2016). Diarrhea can be classified as acute (lasting less than 14 days), persistent (14 and 30 days), and chronic (lasting for greater than a month).

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. A wide spectrum of enteric pathogens can cause infectious gastroenteritis, including bacteria such as Campylobacter, Clostridium difficile, Salmonella, Shigella, Vibrio and Yersinia; viruses such as Norovirus, Rotavirus, Astrovirus and Adenovirus; and parasites such as Giardia, Entamoeba histolytica and Cryptosporidium.

Stool culture is the primary diagnostic tool for suspected bacterial infection, but it is time-consuming, labor intensive, and has a low culture positive yield (Zhang et al., 2015). Similarly, methods like electron microscopic examination and immunoassay that are used to diagnose viruses are labor intensive and need significant expertise (Zhang et al., 2015). Multiplex PCR based assays have shown superior sensitivity to conventional methods for detection of enteric pathogens, and are increasingly being used in the diagnosis of infectious gastroenteritis. These assays have significantly improved workflow and diagnostic output in diagnosis of GI infections (Zhang et al., 2015). Several FDA-approved multiplex PCR assays are now commercially available. Some assays can detect only bacterial pathogens in stool, whereas others are more comprehensive and detect bacterial, viral and parasitic pathogens.

Respiratory Pathogen Panel
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 (Ginocchio, 2007). These tests had several limitations like being labor-intensive, slow turnaround time, and low sensitivity.

There has been considerable progress 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 (Bonnin et al., 2016). 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. They are rapid, sensitive, specific, and the preferred tests for most of the respiratory pathogens (Weisman & Pammi, 2017; Caliendo, 2011; Yan et al., 2011). These tests can be performed in two to three hours in hospital laboratories and can aid in the rapid diagnosis of respiratory tract infections, thus reducing the unnecessary use of antibacterial agents (Weisman & Pammi, 2017).

CNS Pathogen Panel
The increasing use of molecular tests for the detection of pathogens in cerebrospinal fluid (CSF) has redefined the diagnosis and management of CNS infections such as meningitis and encephalitis. However, it is important that test results correlate to the probability of infection. According to Petti & Polage (2017), the number of false-positive test results increases 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 pretest probability of having CNS infections, based on clinical presentation and CSF findings (Petti & Polage, 2017).

The evaluation of meningitis routinely includes molecular testing, particularly when the patient is suspected to have 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 (Petti & Polage, 2017). Other lab findings (for example, CSF cell count, glucose, and protein analyses) should be used to as a screening method prior to the performance of molecular testing (Petti & Polage, 2017). Molecular assays for meningitis caused by fungi, parasites, rickettsia and spirochetes need to be investigated further and are not recommended 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 (Petti & Polage, 2017). 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 (Petti & Polage, 2017). Multiplex PCR-based assays may be useful in certain cases of bacterial meningitis, especially when a slow-growing or uncultivable bacteria like Coxiella Burnetti is involved (Petti & Polage, 2017). Molecular assays for encephalitis caused by fungi, parasites, rickettsia and spirochetes need to be investigated further and are not routinely available or recommended at this time.

Sepsis Panel
Sepsis-related mortality remains high and inappropriate antimicrobial and anti-fungal treatment is a major factor contributing to the increased mortality (Liesenfeld, 2014). 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 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, result in better outcomes, and lessen the emergence of antibiotic-resistant organisms (Banerjee et al., 2015). The disadvantages include high cost and lack of availability in most hospital laboratories, which mitigate the more rapid turnaround time (UpToDate, 2017).

Policy  

  1. Multiplex PCR-based panel testing of gastrointestinal pathogens is considered MEDICALLY NECESSARY in any of the following situations: 
    • Community-acquired diarrhea of ≥7 days duration; or
    • Travel-related diarrhea; or
    • Diarrhea with signs or risk factors for severe disease (fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain, hospitalization and/or immunocompromised state).
  2. Multiplex PCR-based panel testing of pathogens in CSF is considered MEDICALLY NECESSARY for patients with clinical features and laboratory findings consistent with a CNS infection.
  3. Molecular detection-based panel testing of bloodstream pathogens is considered MEDICALLY NECESSARY for patients who have clinical findings consistent with sepsis and have a positive blood culture result.
  4. Multiplex PCR-based panel testing of respiratory pathogens is considered MEDICALLY NECESSARY for patients displaying signs and symptoms of a respiratory tract infection, as evidenced by a compatible clinical syndrome including at least one of the following: temperature of 102 or greater, pronounced dyspnea, tachypnea, or tachycardia.
  5. Using molecular-based panel testing, including, but not limited to, testing such as SmartGut™ and SmartJane™, for general screening of microorganisms is considered INVESTIGATIONAL.

Rationale 
Buss et al. (2015), Claas et al. (2013) and Onori et al. (2013) demonstrated the overall high sensitivity and specificity of the gastroenterology pathogen panels. Several studies have indicated that gastrointestinal pathogen panels are more sensitive than culture, microscopy or antigen detection, thus illustrating the potential of panels as a diagnostic tool for gastrointestinal infections (Humphrey et al., 2016; Buss et al., 2015; Liu et al., 2014; Operario and Houpt, 2011; Couturier et al., 2011). Zhang el al. (2015) concluded that using multiplex PCR assays in the work-up of infectious gastroenteritis has the potential to improve the diagnosis. However, the clinical utility of these assays and impact on patient management need to be further evaluated.

Mahony et al. (2009) concluded that multiplex PCR-based testing was the most cost-effective strategy for the diagnosis of respiratory virus infections in children and resulted in better patient outcomes (shorter hospital stays) at lower costs. Ginocchio et al. (2009) compared the sensitivities, specificities, positive predictive value and negative predictive value of four different Influenza A diagnostic test including rapid antigen, direct immunofluorescence, viral culture and PCR panel. The authors inferred that the PCR panel test provided the best diagnostic option with the highest sensitivity for the detection of all influenza strains and identified a significant number of additional respiratory pathogens. Subramony (2016) reported the use of multiple PCR-based assays for respiratory viruses in hospitalized patients resulted in decreased health care resource utilization, including decreased use of antibiotics and chest radiographs. Brittain-Long et al. (2011) concluded that use of multiplex-PCR testing for the etiologic diagnosis of ARTIs reduces antibiotic prescription rates at the initial visit in an outpatient setting. 

The Infectious Diseases Society of America (IDSA) stated that CSF RT-PCR can be one of the methods used for the diagnosis of rabies virus and enteroviral encephalitis (Tunkel et al., 2008). Several studies have evaluated the clinical impact of RT-PCR for the detection of enterovirus in the CSF of patients with aseptic meningitis (Ramers et al., 2000; Stellrecht et al., 2002; Robinson et al., 2002). These studies showed a reduction in unnecessary diagnostic and therapeutic intervention (for example, antibiotic use, ancillary tests, etc.), length of hospital stay, and hospital costs. Tzanakaki et al. (2005) evaluated a multiplex PCR assay for detection of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b, and concluded that the test had high sensitivity (between 88 percent and 93.9 percent), an overall specificity and positive predictive value of 100 percent, and a negative predictive value >99 percent. Leber et al. (2016) evaluated the performance of a commercially available multiplex PCR-based panel for meningitis and encephalitis and concluded that the test was a sensitive and specific aid in diagnosis of CNS infections and leads to improved patient outcomes.

The use of multiplex PCR assays to identify pathogens following positive blood culture can be faster than the standard techniques involving phenotypic identification and antimicrobial susceptibility testing that required up to 72 hours after the blood culture became positive (Liesenfeld et al., 2014). 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 (Banerjee et al., 2015). 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. They 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). Chang et al. (2013) 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 could confidently diagnose sepsis and begin appropriate antimicrobial therapy while avoiding unwanted additional testing.

Practice Guidelines and Position Statements
American College of Gastroenterology 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" (Riddle et al., 2016). 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)" (Riddle et al., 2016).

In 2013, the ACG made the following recommendations on diagnostic tests used for Clostridium difficile infections (Surawicz et al, 2013):

  • "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)"
  • "Glutamate dehydrogenase (GDH) screening tests for C. difficile can be used in two- or three-step screening algorithms with subsequent toxin A and B EIA testing, but the sensitivity of such strategies is lower than NAATs. (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)"

The World Gastroenterology Organization guidelines (Farthing et al., 2013) on acute diarrhea in adults and children have no recommendations for multiplex PCR testing.

In 2013, Infectious Diseases Society of America (IDSA) stated that "molecular diagnostics that detect microbial DNA directly in blood have achieved a modest level of success, but several limitations still exist. Based on available data, well-designed multiplex PCRs appear to have value as sepsis diagnostics when used in conjunction with conventional culture and routine antibiotic susceptibility testing" (Caliendo et al., 2013).

A joint 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 (Rhodes et al., 2017). 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" (Rhodes et al., 2017).

References 

  1. Banerjee, R., Teng, C.B., Cunningham, S.A., et al. (2015). Randomized Trial of Rapid Multiplex Polymerase Chain Reaction–Based Blood Culture Identification and Susceptibility Testing. Clin Infect Dis, 61(7): 1071-1080.
  2. Bartlett, J. (2017). Diagnostic approach to community-acquired pneumonia in adults. Accessed online on February 7, 2017 from https://www.uptodate.com/contents/diagnostic-approach-to-community-acquired-pneumonia-in-adults
  3. Bonnin, P., Miszczak, F., Kin, N., Resa, C., Dina, J., Gouarin, S., … Vabret, A. (2016). Study and interest of cellular load in respiratory samples for the optimization of molecular virological diagnosis in clinical practice. BMC Infectious Diseases, 16, 384.
  4. Brittain-Long, R., Westin, J., Olofsson, S., Lindh, M., & Andersson, L.-M. (2011). Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial. BMC Medicine, 9, 44. http://doi.org/10.1186/1741-7015-9-44
  5. Buss, S.N., Leber, A., Chapin, K., et al. (2015). Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for the Etiologic Diagnosis of Infectious Gastroenteritis. J Clin Microbiol., 53(3):915-25. doi: 10.1128/JCM.02674-14.   
  6. Caliendo, A. M., Gilbert, D. N., Ginocchio, C. C., Hanson, K. E., May, L., Quinn, T. C., … for the Infectious Diseases Society of America (IDSA). (2013). Better Tests, Better Care: Improved Diagnostics for Infectious Diseases. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 57(Suppl 3), S139–S170. http://doi.org/10.1093/cid/cit578
  7. Caliendo, A.M. (2011). Multiplex PCR and Emerging Technologies for the Detection of Respiratory Pathogens. Clin Infect Dis, 52(suppl_4): S326-S330. doi: 10.1093/cid/cir047
  8. Chang, S.-S., Hsieh, W.-H., Liu, T.-S., Lee, S.-H., Wang, C.-H., Chou, H.-C., … Lee, C.-C. (2013). Multiplex PCR System for Rapid Detection of Pathogens in Patients with Presumed Sepsis – A Systemic Review and Meta-Analysis. PLoS ONE, 8(5), e62323.
  9. Couturier, M.R., Lee, B., Zelyas, N. et al. (2011). Shiga-toxigenic Escherichia coli detection in stool samples screened for viral gastroenteritis in Alberta, Canada. J Clin Microbiol, 49: 574– 578
  10. Claas, E.C., Burnham, C.A., Mazzulli, T., et al. (2013). Performance of the xTAG(R) gastrointestinal pathogen panel, a multiplex molecular assay for simultaneous detection of bacterial, viral, and parasitic causes of infectious gastroenteritis. J Microbiol Biotechnol, 23(7):1041-1045
  11. Farthing, M., Salam, M.A., Lindberg, G. et al. (2013). Acute diarrhea in adults and children: a global perspective. J Clin Gastroenterol, 47:12-20
  12. Ginocchio, C. C. (2007). Detection of respiratory viruses using non-molecular based methods. J. Clin. Virol., 40(Suppl. 1): S11-S14
  13. Ginocchio, C.C., Zhang, F., Manji, R. et al. (2009). Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak. J Clin Virol., 45(3):191-5. doi: 10.1016/j.jcv.2009.06.005.
  14. Humphrey, J. M., Ranbhise, S., Ibrahim, E., Al-Romaihi, H. E., Farag, E., Abu-Raddad, L. J., & Glesby, M. J. (2016). Multiplex Polymerase Chain Reaction for Detection of Gastrointestinal Pathogens in Migrant Workers in Qatar. The American Journal of Tropical Medicine and Hygiene, 95(6), 1330-1337. http://doi.org/10.4269/ajtmh.16-0464
  15. Leber, A.L., Everhart, K., Balada-Llasat, J.M. et al. (2016). Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens. J Clin Microbiol., 54(9):2251-61. doi: 10.1128/JCM.00730-16.
  16. Liesenfeld, O., Lehman, L., Hunfeld, K.-P., & Kost, G. (2014). Molecular diagnosis of sepsis: New aspects and recent developments. European Journal of Microbiology & Immunology, 4(1), 1–25. http://doi.org/10.1556/EuJMI.4.2014.1.1
  17. Liu, J., Kabir, F., Manneh, J., et al. (2014). Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea: a multicentre study. Lancet Infect Dis., 14(8):716–724
  18. Mahony, J. B., Blackhouse, G., Babwah, J., Smieja, M., Buracond, S., Chong, S., … Goeree, R. (2009). Cost Analysis of Multiplex PCR Testing for Diagnosing Respiratory Virus Infections. Journal of Clinical Microbiology, 47(9), 2812–2817.
  19. Operario, D.J. and Houpt, E. (2011). Defining the causes of diarrhea: novel approaches. Curr Opin Infect Dis, 24: 464-471
  20. Onori, M., Coltella, L., Mancinelli, L., et al. (2014). Evaluation of a multiplex PCR assay for simultaneous detection of bacterial and viral enteropathogens in stool samples of paediatric patients. Diagn Microbiol Infect Dis., 79(2):149-154
  21. Palavecino, E. (2015). One Sample, Multiple Results. Accessed online on February 15, 2017 from American Association of Clinical Chemistry website: https://www.aacc.org/publications/cln/articles/2015/april/one-sample-multiple-results
  22. Petti, C. & Polage, C. (2017). Molecular diagnosis of central nervous system infections. Accessed online on February 9, 2017 from https://www.uptodate.com/contents/molecular-diagnosis-of-central-nervous-system-infections?source=see_link&sectionName=Meningitis&anchor=H7#H7
  23. Ramers, C., Billman, G., Hartin, M., Ho, S., and Sawyer, M.H (2000). Impact of a Diagnostic Cerebrospinal Fluid Enterovirus Polymerase Chain Reaction Test on Patient Management. JAMA, 283(20): 2680-2685. doi:10.1001/jama.283.20.2680
  24. Riddle, M.S., DuPont, H.L., and Connor B.A. (2016). ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults. Am J Gastroenterol., 111(5):602-22. doi: 10.1038/ajg.2016.126
  25. Rhodes, A., Evans, L.E., Alhazzani, W. et al. (2017). Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Critical Care Medicine, 45(3) :486-552. doi: 10.1097/CCM.0000000000002255
  26. Robinson, C.C., Willis, M., Meagher, A. et al. (2002). Impact of rapid polymerase chain reaction results on management of pediatric patients with enteroviral meningitis. Pediatr Infect Dis J., 21(4):283-6
  27. Scallan, E., Griffin, P.M., Angulo, F.J., et al. (2011). Foodborne illness acquired in the United States – unspecified agents. Emerg Infect Dis, 17: 16-22  
  28.  Stellrecht, K.A., Harding, I., Woron, A.M., Lepow, M.L., and Venezia, R.A. (2002). The impact of an enteroviral RT-PCR assay on the diagnosis of aseptic meningitis and patient management. J Clin Virol., 25(suppl 1): S19–26.
  29. Subramony, A., Zachariah, P., Krones, A., et al. (2016). Impact of Multiplex Polymerase Chain Reaction Testing for Respiratory Pathogens on Healthcare Resource Utilization for Pediatric Inpatients. The Journal of Pediatrics, 173: 196-201
  30. Surawicz, C.M., Brandt, L.J., Binion, D.G. et al (2013). Guidelines for Diagnosis, Treatment, and Prevention of Clostridium diffi cile Infections. Am J Gastroenterol, 108:478–498
  31. Tzanakaki, G., Tsopanomichalou, M., Kesanopoulos. K., et al. (2005). Simultaneous single-tube PCR assay for the detection of Neisseria meningitidis, Haemophilus influenzae type b and Streptococcus pneumoniae. Clin Microbiol Infect, 11:386-90.
  32. Ward, C., Stocker, K. Begum, J. et al. (2015). Performance evaluation of the Verigene® (Nanosphere) and FilmArray® (BioFire®) molecular assays for identification of causative organisms in bacterial bloodstream infections. Eur J Clin Microbiol Infect Dis., 34(3):487-96. doi: 10.1007/s10096-014-2252-2.
  33. Weisman, L., & Pammi, M. (2017). Clinical features and diagnosis of bacterial sepsis in the preterm infant (<34 weeks gestation). Accessed online on February 10, 2017 from https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bacterial-sepsis-in-the-preterm-infant-less-than34-weeks-gestation
  34. Yan, Y., Zhang, S., and Tang, Y.W. (2011). Molecular assays for the detection and characterization of respiratory viruses. Semin Respir Crit Care Med., 32(4):512-26. doi: 10.1055/s-0031-1283288.
  35. Zhang, H., Morrison, S., & Tang, Y.-W. (2015). Multiplex PCR Tests for Detection of Pathogens Associated with Gastroenteritis. Clinics in Laboratory Medicine, 35(2), 461-486. http://doi.org/10.1016/j.cll.2015.02.006

Coding Section 

Code Number Description
CPT  87150  Culture, typing; identification by nucleic acid (DNA or RNA) probe, amplified probe technique, per culture or isolate, each organism probed 
  87483 Infectious agent detection by nucleic acid (DNA or RNA); central nervous system pathogen (eg, Neisseria meningitidis, Streptococcus pneumoniae, Listeria, Haemophilus influenzae, E. coli, Streptococcus agalactiae, enterovirus, human parechovirus, herpes simplex virus type 1 and 2, human herpesvirus 6, cytomegalovirus, varicella zoster virus,  Cryptococcus), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes
  87486  Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia pneumoniae, amplified probe technique
  87496  Infectious agent detection by nucleic acid (DNA or RNA); cytomegalovirus, amplified probe technique 
  87498 Infectious agent detection by nucleic acid (DNA or RNA); enterovirus, amplified probe technique, includes reverse transcription when performed 
  87505-87507  Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen (eg, Clostridium difficile, E. coli, Salmonella, Shigella, norovirus, Giardia), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes  
  87529  Infectious agent detection by nucleic acid (DNA or RNA); Herpes simplex virus, amplified probe technique
  87532  Infectious agent detection by nucleic acid (DNA or RNA); Herpes virus-6, amplified probe technique 
  87581  Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, amplified probe technique 
  87633  Infectious agent detection by nucleic acid (DNA or RNA); respiratory virus (eg, adenovirus, influenza virus, coronavirus, metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 12-25 targets 
  87634  Infectious agent detection by nucleic acid (DNA or RNA); respiratory syncytial virus, amplified probe technique 
  87653  Infectious agent detection by nucleic acid (DNA or RNA); Streptococcus, group B, amplified probe technique 
  87798  Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; amplified probe technique, each organism  
ICD-10-CM  A04.0-A04.9  Other intestinal Escherichia coli infections 
  A08-A09  Viral and other specified intestinal infections 
  A39.0-A39.9  Meningococcal infection 
  B86.0 Dehydration  
  G83.9 Paralytic syndrome, unspecified 
  J02.0  Acute pharyngitis, unspecified, Sore throat (acute) NOS 
  M54.9  Dorsalgia, unspecified 
  M62.81  Muscle weakness (generalized) 
  M79.62X and M79.63X codes  Pain in arms 
  M79.65X and M79.66X codes Pain in legs 
  R00.0  Tachycardia, unspecified 
  R05  Cough 
  R06 Codes  Dyspnea 
  R09.81  Nasal congestion 
  R09.89  Other specified symptoms and signs involving the circulatory and respiratory systems 
  R10.0-R10.9  Abdominal and pelvic pain 
  R11.0-R11.2  Nausea and vomiting 
  R19.7 Diarrhea, unspecified, Diarrhea NOS 
  R20.0  Anesthesia of skin 
  R25.1  Tremor, unspecified 
  R41.0  Disorientation, unspecified 
  R41.3  Other amnesia,Amnesia NOS 
  R41.840  Attention and concentration deficit 
  R47.81  Slurred speech 
  R50.81  Fever presenting with conditions classified elsewhere 
  R50.9  Fever, unspecified 
  R51  Headache, Facial pain NOS 
  R56.9  Unspecified convulsions 
  R53.81  Other malaise, Malaise NOS 
  R68.83 Chills (without fever), Chills NOS
  R79.89 Other specified abnormal findings of blood chemistry

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2017 Forward     

01/08/2019 

Interim review adding SmartGut and SmartJane investigational statement. 

07/18/2018

Annual review, no change to policy intent. Changing month of annual review only.

12/05/2017

New Policy


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