Print Identification of Microorganisms Using Nucleic Acid Probes

Identification of Microorganisms Using Nucleic Acid Probes

 

POLICY NUMBER

A.2.04.10

 

DESCRIPTION

Nucleic acid probes are available for the identification of a wide variety of microorganisms, offering more rapid identification than standard cultures. Nucleic acid probes can also be used to quantitate the number of microorganisms present. This technology offers advantages over standard techniques when rapid identification is clinically important, when microbial identification using standard culture is difficult or impossible, and/or when treatment decisions are based on quantitative results.

Standard Microorganism Detection Techniques
Classically, identification of microorganisms relied either on culture of body fluids or tissues or identification of antigens, using a variety of techniques including direct fluorescent antibody technique and qualitative or quantitative immunoassays. These techniques are problematic when the microorganism exists in very small numbers or is technically difficult to culture. Indirect identification of microorganisms by immunoassays for specific antibodies reactive with the microorganism is limited by difficulties in distinguishing between past exposure and current infection.

Nucleic Acid Probe Techniques
The availability of nucleic acid probes has permitted the rapid direct identification of microorganisms' DNA or RNA. Amplification techniques result in exponential increases in copy numbers of a targeted strand of microorganism-specific DNA. The most commonly used amplification technique is polymerase chain reaction (PCR) or reverse transcriptase (RT)-PCR. In addition to PCR, other nucleic acid amplification techniques have been developed such as transcription-mediated amplification, loop-mediated isothermal DNA amplification (LAMP), strand displacement amplification, nucleic acid sequence-based amplification, and branched chain DNA signal amplification. After amplification, target DNA can be readily detected using a variety of techniques. The amplified product can also be quantified to give an assessment of how many microorganisms are present. Quantification of the amount of nucleic acids permits serial assessments of response to treatment; the most common clinical application of quantification is the serial measurement of HIV RNA (called viral load), which serves as a prognostic factor.

In 1998, the CPT codes were revised to include a series of new codes that describe the direct probe technique, amplified probe technique, and quantification for 22 different microorganisms. These series of CPT codes were introduced as a group. In addition, CPT codes have been added for additional microorganisms, such as Staphylococcus aureus.

Comparison of Probe Techniques
The direct probe technique, amplified probe technique, and probe with quantification methods vary in terms of the degree to which the nucleic acid is amplified and the method for measurement of the signal.

The “direct probe” technique refers to detection methods in which nucleic acids are detected without an initial amplification step.

The “amplified probe” technique refers to detection methods in which either target, probe, or signal amplification is used to improve the sensitivity of the assay over direct probe techniques, without quantification of nucleic acid amounts.

  • Target amplification methods include PCR (including PCR using specific probes, nested or multiplex PCR), nucleic acid-based sequence amplification (NASBA), transcription-mediated amplification (TMA), and strand displacement amplification (SDA). NASBA and TMA involve amplification of an RNA (rather than a DNA) target.

  • Probe amplification methods include ligase chain reaction (LCR).

  • Signal amplification methods include branched DNA probes (bDNA) and hybrid capture methods using an anti-DNA/RNA hybrid antibody.

The “probe with quantification” techniques refer to quantitative PCR (qPCR) or real-time PCR (rt-PCR) methods that use a reporter at each stage of the PCR to generate absolute or relative amounts of a known nucleic acid sequence in the original sample. These methods may use DNA-specific dyes (ethidium bromide or SYBR green), hybridization probes (cleavage-based [TaqMan] or displaceable), or primer incorporated probes.

For reference, examples of some commercially available probe methods are outlined in the table below.

Example Probe Methods

Probe Method

Sample Commercially Available Products

Microorganism(s)

Direct probeBD Affirm™ VPIII Microbial Identification
System (Becton, Dickinson, Franklin Lakes, NJ)
Candida, Gardnerella, Trichomonas
species
 GasDirect (Hologic, Bedford, MA)Group A Streptococcus
Amplified probeAmplified MTD test (Hologic, Bedford, MA)Mycobacterium tuberculosis
Probe with quantificationCobas® Amplicor HIV-1 Monitor Test (Roche
Molecular Diagnostics, Pleasanton, CA)
Human immunodeficiency virus-1

Direct assays will generally have lower sensitivity than amplified probes. In practice, most commercially available probes are amplified, with a few exceptions. For the purposes of this policy, indications for direct and/or amplified probes without quantification are considered together, while indications for a probe with quantification are considered separately.

Microorganisms and Clinical Disease
Various bacteria, viruses, and fungi that can cause clinical disease and can be detected with various nucleic acid probe techniques are briefly outlined below.

Bartonella henselae or quintana
Bartonella henselae is responsible for cat-scratch disease
. In most patients (90%-95%), the infection is a localized skin and lymph node disorder that occurs close to the site of inoculation, and is characterized by chronic regional lymphadenopathy that develops about 2 weeks after contact with a cat. Less commonly, Bartonella henselae infection may lead to disseminated infection, which can manifest as visceral organ involvement, often with fever and hepatosplenomegaly, a variety of ocular manifestations, and neurological manifestations (most commonly, encephalopathy). 

Bartonella may also cause an opportunistic infection in HIV-infected patients, in whom it is characterized by an acute febrile bacteremic illness, evolving to an asymptomatic bacteremia and finally indolent vascular skin lesions. The organism is typically detected using culture techniques, although an incubation period of 5 to more than 30 days is required. DNA probe technology has been investigated as a diagnostic technique.

Bartonella quintana has classically been associated with “trench fever,” which is characterized by systemic symptoms (bone pain, malaise, headache), along with recurring fevers of varying durations. Among HIV-infected patients, B. quintana has been associated with bacillary angiomatosis.

Bartonella are fastidious organisms, making culture difficult. Histology of lesions affected by bacillary angiomatosis may be characteristic. Histology of affected lymph nodes or other tissue with B. henselae may demonstrate findings that are suggestive of cat-scratch disease, but which may be seen in other conditions. Two antigenic methods are available, one using indirect fluorescence assay (IFA) and one using enzyme immunosorbent assay (EIA), for both B. henselae and B. quintana infections. A positive serologic test is generally considered supportive, but not definitive, for Bartonella infection. Serologic methods may have limited yield in immunosuppressed patients.

Candida Species
A commonly occurring yeast, Candida species can be normally found on diseased skin, throughout the entire GI tract, expectorated sputum, the female genitalia, and in urine of patients with indwelling Foley catheters. Clinically significant Candida infections are typically diagnosed by clinical observation or by identification of the yeast forms on biopsy specimens. Candida species are a common cause of vaginitis.

Chlamydophila pneumoniae
Chlamydophila pneumoniae is an important cause of pneumonia, bronchitis, and sinusitis. Culture and isolation of the microorganism is difficult; a micro-immunofluorescence serum test may be used. The use of PCR amplification now offers a rapid diagnosis.

Chlamydia trachomatis
Chlamydia trachomatis is a significant intracellular pathogen causing, most prominently, urogenital disease (including pelvic inflammatory disease) and perinatal infections.

Chlamydia trachomatis is also responsible for lymphogranuloma venereum. Due to its prevalence and association with pelvic inflammatory disease and perinatal disease, widespread testing of chlamydia is recommended; routine chlamydia testing has been adopted as a quality measure by Healthcare Effectiveness Data and Information Set. This microoganism can be diagnosed by: 1) identifying the typical intracytoplasmic inclusions in cytology specimens; 2) isolation in tissue culture; 3) demonstration of chlamydial antigen by enzyme-linked immunosorbent assay or by immunofluorescent staining; or 4) demonstration of DNA using a direct probe or amplification technique.

Clostridium difficile
Clostridium difficile is an anaerobic, toxin-producing bacteria present in the intestinal tract. It causes clinical colitis when the normal intestinal flora is altered and overgrowth of C. difficile occurs. The common precipitant that disrupts the normal intestinal flora is previous treatment with antibiotics. The disorder has varying severity but can be severe and in extreme cases, life-threatening. C. difficile is easily spread from person-to-person contact and is a common cause of hospital-acquired outbreaks. Hospital infection control measures, such as wearing gloves and handwashing with soap and water, are effective methods of reducing the spread of C. difficile. The standard diagnosis is made by an assay for the C. difficile cytotoxin or by routine culture methods.

Cytomegalovirus
Cytomegalovirus (CMV) is a common virus that infects many, but rarely causes clinical disease in healthy individuals. However, this virus can cause protean disease syndromes, most prominently in immunosuppressed patients, including transplant recipients or those infected with the HIV virus. CMV can also remain latent in tissues after recovery of the host from an acute infection. Diagnosis depends on demonstration of the virus or viral components or demonstration of a serologic rise. DNA probe techniques, including amplification, have also been used to identify patients at risk for developing CMV disease as a technique to triage antiviral therapy.

Enterovirus
Enteroviruses are single-stranded RNA viruses. This group of viruses includes the polioviruses, coxsackieviruses, echoviruses, and other enteroviruses. In addition to 3 polioviruses, there are more than 60 types of non-polio enteroviruses that can cause disease in humans. Most people who are infected with a non-polio enterovirus have no disease symptoms at all. Infected persons who develop illness usually develop either mild upper respiratory symptoms, flu-like symptoms with fever and muscle aches, or an illness with rash. Less commonly, enteroviruses can cause "aseptic" or viral meningitis, encephalitis, acute paralysis, and/or myocarditis. Enteroviral infections can cause life-threatening systemic infections in neonates, which are often associated with myocarditis or fulminant hepatitis. The use of amplified probe DNA test(s) can be used to detect enteroviruses.

Gardnerella vaginalis
A common microorganism, Gardnerella vaginalis is typically found in the human vagina and is usually asymptomatic. However, G. vaginalis is found in virtually all women with bacterial vaginosis and is characterized by inflammation and perivaginal irritation. The microorganism is typically identified by culture. The role of G. vaginalis in premature rupture of membranes and preterm labor is also under investigation.

Hepatitis B, C, and G
Hepatitis is typically diagnosed by a pattern of antigen and antibody positivity. However, the use of probe technology permits the direct identification of hepatitis DNA or RNA, which may also provide prognostic information. Quantification techniques are used to monitor the response to direct-acting antiviral, interferon, and/or ribavarin therapy in patients with hepatitis C.

Herpes Simplex Virus
Herpes simplex infection of the skin and mucous membranes is characterized by a thin-walled vesicle on an inflammatory base typically in the perioral, ocular, or genital areas, although any skin site may be involved. The diagnosis may depend on pathologic examination of cells scraped from a vesicle base or by tissue culture techniques. Herpes simplex encephalitis is one of the most common and serious sporadic encephalitides in immunocompetent adults. The PCR technique to detect HSV in the cerebrospinal fluid has been used to provide a rapid diagnosis of herpes virus encephalitis.

Human Herpesvirus 6
Human herpesvirus 6 (HHV-6) is the common collective name for HHV-6A and HHV-6B. These closely related viruses are 2 of the 9 herpesviruses known to have humans as their primary host. HHV-6 is widespread in the general population.
In immunocompetent hosts, HHV-6 primary infection typically causes a mild, self-limited illness in childhood, often roseola. HHV-6 may also cause meningitis and encephalitis in children and adults. Diagnosis is typically based on rising serologic titers.

In immunosuppressed patients, HHV-6 reactivation may cause meningitis, encephalitis, pneumonitis, and/or bone marrow suppression.

HIV-1, HIV-2
DNA probe technology for HIV-1 is widely disseminated, and HIV-1 quantification has become a standard laboratory test in HIV-1 infected patients. HIV-2 can result in severe immunosuppression and the development of serious opportunistic diseases. Although HIV-2 has been reported in the United States, it is most commonly found in Western Africa. Blood donations are routinely tested for HIV-2, but due to its rarity in this country, clinical testing for HIV-2 is typically limited to those in contact with persons in a country where HIV-2 is endemic, or when the clinical picture suggests HIV infection, but testing for HIV-1 is negative.

Influenza virus
Influenza virus is a very common pathogen that accounts for a high burden of morbidity and mortality, especially in elderly and immunocompromised patients. The most common means of identifying influenza is by viral culture, which takes 48-72 hours to complete. Influenza is highly contagious and has been the etiology of numerous epidemics and pandemics. Identification of outbreaks is important so that isolation measures may be undertaken to control the spread of disease. Anti-viral treatment can be effective if instituted early in the course of disease. Therefore, rapid identification of influenza virus is important in making treatment decisions for high-risk patients and in instituting infection control practices.

Legionella pneumophila
Legionella pneumophila is among the most common microbial etiologies of community-acquired pneumonia. Laboratory diagnosis depends on culture, direct fluorescent antibody tests, urinary antigens, or DNA probe. DNA probe techniques have also been used in epidemiologic investigations to identify the source of a Legionella outbreak.

Mycobacteria Species
Although mycobacterium can be directly identified in sputum samples (i.e. acid fast bacilli), these organisms may take 9 to 16 days to culture. DNA probes have also been used to identify specific mycobacterial groups (i.e., mycobacterial tuberculosis, avian complex, or intracellulare) after culture. In addition, amplification techniques for Mycobacterium tuberculosis may be used in patients who have a positive smear. The rapid identification of M. tuberculosis permits prompt isolation of the patient and identification of the patient's contacts for further testing.

Mycoplasma pneumoniae
Mycoplasma pneumoniae is an atypical bacterium that is a common cause of pneumonia. It is most prevalent in younger patients below age 40 years and in individuals who live or work in crowded areas such as schools or medical facilities. The infection is generally responsive to antibiotics of the macrolide or quinolone class. Most patients with M. pneumonia recover completely, although the course is sometimes prolonged for up to 4 weeks or more. Extrapulmonary complications of M. pneumonia occur uncommonly, including hemolytic anemia and the rash of erythema multiforme.

Neisseria gonorrhoeae
Isolation by culture is the conventional form of diagnosis for this common pathogen, but culture requires specific sampling and plating techniques. Direct DNA probes and amplification techniques have also
 been used. Neisseria is often tested for at the same time as chlamydia.

Papillomavirus
Papillomavirus species are common pathogens that produce epithelial tumors of the skin and mucous membranes, most prominently the genital tract. Physical examination is the first diagnostic technique. Direct probe and amplification procedures have been actively investigated in the setting of cervical lesions. The ViraPap test is an example of a commercially available direct probe technique for identifying papillomavirus. There has also been interest in evaluating the use of viral load tests of human papillo
mavirus to identify patients at highest risk of progressing to invasive cervical carcinoma.

Streptococcus, Group A
Also referred to as Streptococcus pyogenes, this pathogen is the most frequent cause of acute bacterial pharyngitis. It can also give rise to a variety of cutaneous and systemic conditions, including rheumatic fever and post-streptococcal glomerulonephritis. Throat culture is the preferred method for diagnosing streptococcal pharyngitis. In addition, a variety of commercial kits are now available that use antibodies for the rapid detection of group A carbohydrate antigen directly from throat swabs. While very specific, these kits are less sensitive than throat cultures, so a negative test may require confirmation from a subsequent throat culture. DNA probes have also been used for direct identification of streptococcus, and can be used as an alternative to a throat culture as a back-up test to a rapid, office-based strep test.

Streptococcus, Group B
Also referred to as Streptococcus agalactiae, group B streptococcus (GBS) is the most common cause of sepsis, meningitis, or death among newborns. Early-onset disease, within 7 days of birth, is related to exposure to GBS colonizing the mother's anogenital tract during birth. The Centers for Disease Control and Prevention (CDC), the American College of Obstetrics and Gynecology (ACOG), and the American Academy of Pediatricians (AAP) recommend either maternal risk assessment or screening for GBS in the perinatal period. Screening consists of obtaining vaginal and anal specimens for culture at 35 to 37 weeks of gestation. The conventional culture and identification process requires 48 hours. Therefore there has been great interest in developing rapid assays using DNA probes to shorten the screening process, so that screening could be performed in the intrapartum period with institution of antibiotics during labor.

Trichomonas Vaginalis
Trichomonas is a single-cell protozoan that is a common cause of vaginitis. The organism is sexually transmitted and can infect the urethra or vagina. The most common way of diagnosing Trichomonas is by clinical signs and by directly visualizing the organism by microscopy in a wet prep vaginal smear. Culture of Trichimonas is limited by poor sensitivity. Treatment with metronidazole results in a high rate of eradication. The disease is usually self-limited without sequelae, although infection has been associated with premature birth and higher rates of HIV transmission, cervical cancer, and prostate cancer.

 

POLICY

The use of nucleic acid testing using a direct or amplified probe technique (without quantification of viral load) may be considered medically necessary for the following microorganisms (See Policy Guidelines):

  • Bartonella henselae or quintana
  • Candida species
  • Chlamydia trachomatis
  • Clostridium difficile
  • Enterococcus, vancomycin-resistant (eg, enterococcus vanA, vanB)
  • Enterovirus
  • Gardnerella vaginalis
  • Herpes simplex virus
  • Human papillomavirus
  • Legionella pneumophila
  • Mycobacterium species
  • Mycobacterium tuberculosis
  • Mycobacterium avium intracellulare
  • Mycoplasma pneumoniae
  • Neisseria gonorrhoeae
  • Respiratory virus panel
  • Staphylococcus aureus
  • Staphylococcus aureus, methicillin resistant
  • Streptococcus, group A
  • Streptococcus, group B
  • Trichomonas vaginalis

The use of nucleic acid testing using a direct or amplified probe technique (with or without quantification of viral load) may be considered medically necessary for the following microorganisms:

  • Cytomegalovirus
  • Hepatitis B virus
  • Hepatitis C virus
  • HIV-1
  • HIV-2
  • Human herpesvirus 6
  • Influenza virus

The use of nucleic acid testing with quantification of viral load is considered investigational for microorganisms that are not included in the list of microorganisms for which probes with or without quantification are considered medically necessary.

The use of nucleic acid testing using a direct or amplified probe technique with or without quantification of viral load is considered investigational for the following microorganisms:

  • Chlamydophila pneumoniae
  • Hepatitis G virus
  • Gastrointestinal pathogen panel

  

POLICY EXCEPTIONS

None

 

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

The use of molecular diagnostics for the diagnosis and management of Borrelia burgdorferi infection (Lyme disease) is addressed in the Intravenous Antibiotic Therapy and Associated Diagnostic Testing for Lyme Disease medical policy.

It should be noted that the technique for quantification includes both amplification and direct probes; therefore, simultaneous coding for both quantification with either amplification or direct probes, is not warranted.

Antibiotic sensitivity of streptococcus A cultures is generally not performed for throat cultures. However, if an antibiotic sensitivity is considered, then the most efficient method of diagnosis would be a combined culture and antibiotic sensitivity.

For uncomplicated infections, testing for only 1 candida species, C. albicans, may be considered medically necessary. For complicated infections, testing for multiple candida subspecies may be considered medically necessary. The Centers for Disease Control and Prevention classifies uncomplicated vulvovaginal candidiasis as being sporadic or infrequent; or mild to moderate; or likely to be C. albicans; or in nonimmunocompromised women. Complicated vulvovaginal candidiasis is classified as being recurrent or severe; or not a C. albicans species; or in women with uncontrolled diabetes, debilitation, or immunosuppression.

In the evaluation of group B streptococcus, the primary advantage of a DNA probe technique compared to traditional culture techniques is the rapidity of results. This advantage suggests that the most appropriate use of the DNA probe technique is in the setting of impending labor, for which prompt results could permit the initiation of intrapartum antibiotic therapy.

Many probes have been combined into panels of tests. For the purposes of this policy, other than the gastrointestinal pathogen panel and the respiratory virus panel, only individual probes are reviewed.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Nervous/Mental Conditions, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

 

POLICY HISTORY

10/26/2006: Policy added 

1/2/2007: Code reference section updated per the 2007 CPT/HCPCS revisions. Added CPT 87797 and 87798 to covered table. Added CPT 87799 to non-covered table with see policy note.

5/14/2007: Policy reviewed; updated to include enterovirus, staphylococcus aureus, and MRSA. CPT codes 87640-87641 added to covered table. CPT code 87948 added to non-covered table. Added ICD-9 codes 041.01, 041.02, 041.11, and V09.0 to covered table.

9/7/2007: Code reference section updated per annual ICD-9 code updates.

6/25/2008: Vancomycin resistance (eg., enterococcus vanA, vanB) amplified probe added as medically necessary. CPT 87500 added to covered

8/26/2008: Code reference section reviewed. CPT codes 87797, 87798, and 87799 removed

9/10/2008: Annual ICD-9 updates applied

03/11/2010: Code reference section updated. New CPT code 87493 added to non-covered table.

12/13/2011:  Policy description updated.  Medically necessary indications added for clostridium difficile, influenza virus, and trichomoniasis vaginalis.  Moved 87493 from the Non-Covered Codes table to the Covered Codes table. Added CPT codes 87501, 87502,  87503, and 87660 and ICD-9 codes 008.45, 131.00 - 131.09, and 487.0 - 488.19 to the Covered Codes table.

01/09/2013:  Added coverage guidelines for respiratory syncytial virus (RSV). Added ICD-9 code 079.6 and CPT codes 87631 , 87632 , and 87632 to the Code Reference section.

01/21/2014: Policy statement revised to change Candida species amplified probe from investigational to medically necessary. Added medically necessary indication for Trichomonas vaginalis amplified probe. Moved CPT code 87481 from non-covered to covered. Added the following new 2014 CPT code(s) to the Code Reference section: 87761.

12/31/2014: Policy description updated to add information regarding amplification techniques, Enterovirus, and Mycoplasma pneumoniae. Policy statement updated to add investigational indications for Gastrointestinal Pathogen Panel amplified probe, Mycobacterium tuberculosis quantification, and Mycoplasma pneumoniae direct probe, amplified probe, and quantification. Added medically necessary indications for Mycobacterium tuberculosis direct probe and amplified probe. Policy guidelines updated regarding quantification and probe techniques. Made the following correction in the Code Reference section: changed "87761" to "87661." Code Reference section updated to revise the description of the following CPT codes: 87504, 87502, 87503, 87631, 87632, and 87633. Added the following new 2015 CPT codes: 87623, 87624, 87625, 87806, 87505, 87506, and 87507.

08/31/2015: Medical policy revised to add ICD-10 codes.

12/31/2015: Policy guidelines updated to add medically necessary and investigative definitions. Code Reference section updated to revise code descriptions for the following CPT codes: 87502 and 87503.

02/15/2016: Policy description updated regarding probe methods and microorganisms. Removed information regarding Borrelia burgdorferi from policy. Policy section revised to remove probe techniques table and group direct and amplified probe techniques (without quantification) into medically necessary policy statements. Enterovirus, Legionella pneumophila, Mycoplasma pneumoniae, and Bartonella added as medically necessary for nonquantifed nucleic acid-based testing. Human herpesvirus 6 added as medically necessary for quantified testing. Policy guidelines updated regarding antibiotic sensitivity of streptococcus A cultures and testing for infections. The following CPT codes moved from the Investigational Codes table to the Covered Codes table: 87470, 87471, 87498, 87511, 87531, 87532, 87533, 87540, 87541, 87551, 87561, and 87651. Added CPT codes 87580 and 87581 to the Covered Codes table and CPT code 87582 to the Investigational Codes table. Removed deleted CPT codes 87620, 87621, and 87622 from the Code Reference section.

06/06/2016: Policy number added.

08/12/2016: Medically necessary policy statement regarding probes without quantification of viral load updated to add Clostridium difficile. Added investigational statement for probes with quantification of viral load that do not meet criteria for quantification.

 

SOURCE(S)

Blue Cross Blue Shield Association Policy # 2.04.10 

 

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes 

Code Number

Description

CPT-4

87470

Infectious agent detection by nucleic acid (DNA or RNA); Bartonella henselae and Bartonella quintana, direct probe technique

87471Bartonella henselae and Bartonella quintana, amplified probe technique

87480

Candida species, direct probe technique

87481

Candida species, amplified probe technique

87490

Chlamydia trachomatis, direct probe technique

87491

Chlamydia trachomatis, amplified probe technique

87493

Infectious agent detection by nucleic acid (DNA or RNA); Clostridium difficile, toxin gene(s), amplified probe technique

87495

Cytomegalovirus, direct probe technique

87496

Cytomegalovirus, amplified probe technique

87497

Cytomegalovirus, quantification

87498

Enterovirus, amplified probe technique

87500

Infectious agent detection by nucleic acid (DNA or RNA); vancomycin resistance (eg, enterococcus species van A, van B), amplified probe technique

87501

Infectious agent detection by nucleic acid (DNA or RNA); influenza virus; includes reverse transcription, when performed, and amplified probe technique, each type or subtype

87502

Infectious agent detection by nucleic acid (DNA or RNA); influenza virus, for multiple types or sub-types, includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, first 2 types or sub-types  (Revised 01/01/2016)

87503

Infectious agent detection by nucleic acid (DNA or RNA); influenza virus, for multiple types or sub-types, includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, each additional influenza virus type or sub-type beyond 2 (List separately in addition to code for primary procedure)  (Revised 01/01/2016)

87510

Gardnerella vaginalis, direct probe technique

87511Gardnerella vaginalis, amplified probe technique

87515

Hepatitis B virus, direct probe technique

87516

Hepatitis B virus, amplified probe technique

87517

Hepatitis B virus, quantification

87520

Hepatitis C virus, direct probe technique

87521

Hepatitis C virus, amplified probe technique

87522

Hepatitis C virus, quantification

87528

Herpes simplex virus, direct probe technique

87529

Herpes simplex virus, amplified probe technique

87531Herpes virus-6, direct probe technique
87532Herpes virus-6, amplified probe technique
87533Herpes virus-6, quantification

87534

HIV-1, direct probe technique

87535

HIV-1, amplified probe technique

87536

HIV-1, quantification

87537

HIV-2, direct probe technique

87538

HIV-2, amplified probe technique

87539

HIV-2, quantification

87540Legionella pneumophila, direct probe technique
87541Legionella pneumophila, amplified probe technique

87550

Mycobacterium species, direct probe technique

87551Mycobacterium species, amplified probe technique

87555

Mycobacterium tuberculosis, direct probe technique

87556

Mycobacterium tuberculosis, amplified probe technique

87560

Mycobacterium avium intracellulare, direct probe technique

87561Mycobacterium avium intracellulare, amplified probe technique
87580Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, direct probe technique
87581Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, amplified probe technique

87590

Neisseria gonorrhoeae, direct probe technique

87591

Neisseria gonorrhoeae, amplified probe technique

87623

Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), low-risk types (eg, 6, 11, 42, 43, 44) (New 01-01-2015)

87624

Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), high-risk types (eg, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) (New 01-01-2015)

87625

Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), types 16 and 18 only, includes type 45, if performed (New 01-01-2015)

87631

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, 3-5 targets (Revised 01-01-2015)

87632

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, 6-11 targets (Revised 01-01-2015)

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 (Revised 01-01-2015)

87640

Staphylococcus aureus, amplified probe technique

87641

Staphylococcus aureus, methicillin resistant, amplified probe technique

87650

Streptococcus group A, direct probe technique

87651Streptococcus group A, amplified probe technique

87653

Streptococcus, group B, amplified probe technique

87660

Infectious agent detection by nucleic acid (DNA or RNA); Trichomonas vaginalis, direct probe technique

87661

Infectious agent detection by nucleic acid (DNA or RNA); Trichomonas vaginalis, amplified probe technique

87806

Infectious agent antigen detection by immunoassay with direct optical observation; HIV-1 antigen(s), with HIV-1 and HIV-2 antibodies (New 01-01-2015)

HCPCS

  

ICD-9 Procedure

ICD-10 Procedure

  

 

 

ICD-9 Diagnosis

ICD-10 Diagnosis

008.45

Clostridium difficile

A04.7

Enterocolitis due to Clostridium difficile

010.0, 010.1, 010.8, 010.9, 011.0, 011.1, 011.2, 011.3, 011.4, 011.5, 011.6, 011.7, 011.8, 011.9, 012.0, 012.1, 012.2, 012.3, 012.8, 013.0, 013.1, 013.2, 013.3, 013.4, 013.5, 013.6, 013.8, 013.9, 014.0, 014.8, 015.0, 015.1, 015.2, 015.5, 015.7, 015.8, 015.9, 016.0, 016.1, 016.2, 016.3, 016.4, 016.5, 016.6, 016.7, 016.9, 017.0, 017.1, 017.2, 017.3, 017.4, 017.5, 017.6, 017.7, 017.8, 017.9, 018.0, 018.8, 018.9

Tuberculosis, code range

A15.0 - A19.9

Tuberculosis, code range

030.0, 030.1, 030.2, 030.3, 030.8, 030.9

Diseases due to infection by Mycobacterium leprae

A30.0 - A30.9

Leprosy (Hansen's Disease)

031.0, 031.1, 031.2, 031.8, 031.9

Diseases due to other mycobacteria (includes mycobacterium avium-intracellualare)

A31.0 - A31.9

Infection due to other mycobacteria

041.01

Streptococcus Group A

B95.0

Streptococcus, group A, as the cause of diseases classified elsewhere

041.02

Streptococcus Group B

B95.1

Streptococcus, group B, as the cause of diseases classified elsewhere

041.11

Methicillin susceptible Staphylococcus aureus in conditions classified elsewhere and of unspecfied site

A49.01, B95.61

Methicillin susceptible Staphylococcus aureus in conditions classified elsewhere and of unspecfied site

041.12

Methicillin resistant Staphyloccus aureus in conditions classified elsewhere and of unspecified site

A49.02, B95.62

Methicillin susceptible Staphylococcus aureus in conditions classified elsewhere and of unspecfied site

042

Human immunodeficiency virus (HIV) disease

B20

Human immunodeficiency virus (HIV) disease

054.0, 054.1, 054.4, 054.3, 054.4, 054.5, 054.6, 054.8, 054.9

Herpes simplex, code range

A60.00 - A60.9

 

B00.0, B00.2, B00.4, B00.50 - B00.59, B00.7, B00.89, B00.9

Anogenital herpesviral infections

 

 

Herpesviral infections

058.21

Human herpes virus 6 encephalitis

B10.01

Human herpesvirus 6 encephalitis

058.29

Other human herpes virus encephalitis

B10.09

Other human herpesvirus encephalitis

058.81

Human herpes virus 6 infection

B10.81

Human herpesvirus 6 infection

058.82

Human herpes virus 7 infection

B10.82

Human herpesvirus 7 infection

058.89

Other human herpes virus infection

B10.89

Other human herpesvirus infection

070.20,
070.21, 070.22, 070.23, 070.30, 070.31, 070.32, 070.33

Viral Hepatits B, code range

B16.0 - B16.9

 

B18.0, B18.1

 

B19.10, B19.11

Acute Hepatitis B

 

 

Chronic viral hepatitis

 

 

Unspecified viral hepatitis B

070.41

Acute or unspecified hepatitis C with hepatic coma

B17.11

Acute hepatitis C with hepatic coma

070.44


070.54

Chronic hepatitis C with hepatic coma

Chronic hepatitic C without mention of hepatic coma

B18.2

Chronic viral hepatitis C

070.51

Acute or unspecified hepatitis C without mention of hepatic coma

B17.10

Acute hepatitis C without hepatic coma

078.5

Cytomegaloviral disease

B25.0 - B25.9

Cytomegaloviral disease

079.6

Respiratory syncytial virus (RSV)

B97.4

 

 

 

J20.5

Respiratory syncytial virus as the cause of diseases classified elsewhere

 

Acute bronchitis due to respiratory syncytial virus

079.83

Parvovirus B19

B34.3

Parvovirus B19

079.88

Other specified chlamydial infection

A74.81, A74.89

Other chlamydial diseases

079.89

Other specified viral infections     (includes papillomavirus)

B33.8

 

B34.1, B34.2, B34.4, B34.8

 

B97.19, B97.29, B97.5, B97.6, B97.81, B97.89

 

J20.4

Other viral diseases

 

Viral infection of unspecified site

 

 

 

 

Viral agents as the cause of diseases classified elsewhere

 

 

 

 

 

Acute bronchitis due to parainfluenza virus

079.98

Unspecified chlamydial infection

A74.9

Chlamydial infection, unspecified

098.0, 098.10, 098.11, 098.12, 098.13, 098.14, 098.14, 098.15, 098.16, 098.17, 098.19, 098.2, 098.30, 098.31, 098.32, 098.33, 098.34, 098.35, 098.36, 098.37, 098.39, 098.4, 098.41, 098.43, 098.49, 098.50, 098.51, 098.52, 098.53, 098.59, 098.6, 098.7, 098.8, 098.81, 098.82, 098.83, 098.84, 098.85, 098.86, 098.89

Gonococcal infections, code range

A54.00 - A54.30, A54.32 - A54.9

Gonococcal infections, code range

131.00 - 131.09

Urogenital trichomoniasis code range

A59.00 - A59.09

Urogenital trichomoniasis code range

482.84

Legionnaires' disease

A48.1

Legionnaires' disease

487.0 - 488.19

Influenza code range

J09.X1 - J12.9

Influenza code range

771.1

Congenital cytomegalovirus infection

P35.1

Congenital cytomegalovirus infection

771.2

Other congenital infections ( includes herpes simplex, tuberculosis)

P35.2 - P35.9, P37.0 - P37.9

Congenital viral diseases and other congenital diseases

V08

Human immodeficiency virus (HIV) asymptomatic

Z21

Human immodeficiency virus (HIV) asymptomatic

V09.0

Infection with microorganisms resistant to penicillins

Z16.11

Resistance to penicillins

V28.6

Antenatal screening for Streptococcus B

Z36

Encounter for antenatal screening of mother

 

Investigational Codes

Code Number

Description

CPT-4

87472

Bartonella henselae and Bartonella quintana, quantification

87475

Borrelia burgdorferi, direct probe technique

87476

Borrelia burgdorferi, amplified probe technique

87477

Borrelia burgdorferi, quantification

87482

Candida species, quantification

87485

Chlamydia pneumoniae, direct probe technique

87486

Chlamydia pneumoniae, amplified probe technique

87487

Chlamydia pneumoniae, quantification

87492

Chlamydia trachomatis, quantification

87505

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, 3-5 targets (New 01-01-2015)

87506

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, 6-11 targets (New 01-01-2015)

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, 12-25 targets (New 01-01-2015)

87512

Gardnerella vaginalis, quantification

87525

Hepatitis G, direct probe technique

87526

Hepatitis G, amplified probe technique

87527

Hepatitis G, quantification

87530

Herpes Simplex virus, quantification

87542

Legionella pneumophila, quantification

87552

Mycobacterium species, quantification

87557

Mycobacterium tuberculosis, quantification

87562

Mycobacterium avium intracellulare, quantification

87582Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, quantification

87592

Neisseria gonorrhoeae, quantification

87652

Streptococcus group A, quantification

HCPCS

  

ICD-9 Procedure

ICD-10 Procedure

  

 

 

ICD-9 Diagnosis

ICD-10 Diagnosis

  

 

 

                 

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