Clinical significance: Actinomyces israelii is a filamentous anaerobic gram-positive bacteria. The infection begins as an inflammatory soft tissue mass, which can enlarge into an abscess-like swelling. All species of Actinomyces are normal commensal inhabitants of the oral and buccal cavities in humans and certain other mammals. The anaerobic actinomycetes are not transmitted sexually and are not generally considered as part of the normal vaginal flora. Colonization in the female genital tract is stimulated greatly by the presence of a foreign body such as intrauterine contraceptive devices (IUCDs), hairpins, and even surgical sutures. Colonization may be asymptomatic or minimally symptomatic, presenting only as shedding of actinomycotic granules into the vaginal fluid. The clinical presentation includes foul-smelling vaginal discharge, intermittent pelvic pain, abnormal bleeding and one or more pelvic masses. In the acute phase, pelvic abscesses are often unilateral, involving a single fallopian tube and ovary. Single or multiple abscesses may form in the uterine wall, usually surrounding an embedded IUCD. The most extensive disease may present with a frozen or “woody” pelvis demonstrating extensive adhesions and scarring as part of the inflammatory response. A subset of genital actinomyces cases will present with some abnormalities of vaginal fluids on PAP smear. Anaerobic actinomycetes are successfully cultured in only about 10% of those cases investigated, which makes molecular amplification techniques an attractive option for the clinical diagnosis of vaginal actinomyces. The anaerobic actinomycetes are considered universally susceptible to penicillin, which is the drug of choice if antibiotic therapy is needed.

Clinical significance: Adenoviruses cause a number of self-limiting but often highly infectious diseases that affect multiple organs, most commonly those associated with the respiratory and genitourinary tracts. They are non-enveloped icosahedral particles that contain double-stranded DNA. Adenovirus is a relatively harmless pathogen in healthy individuals, but can cause a variety of symptoms in young children and the immunocompromised. Transmission can occur from direct person-to-person contact, or through contact with a contaminated surface or object. Adenovirus is usually asymptomatic, and may cause a variety of symptoms including respiratory problems, gastroenteritis, pink eye, pharyngoconjunctival fever, skin rashes, and genitourinary tract infections including cervicitis, urethritis and hemorrhagic cystitis. The most severe cases of adenovirus infection may result in pneumonia, croup, and bronchitis. In this assay DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: Bacterial vaginosis (BV) is a polymicrobial syndrome that represents a disturbance of the vaginal ecosystem through a shift in the microflora. Several adverse medical outcomes have been associated with BV. While the cause of BV is not understood, some strong associations have been made between the syndrome and the presence of particular bacterial species, such as Gardnerella vaginalis. Atopobium vaginae, an anaerobic bacteria, has also been implicated in BV. A recent study by Bradshaw et al., (2006) stated that A. vaginae is more specific for BV and abnormal vaginal flora than G. vaginalis (n=358). In addition, G. vaginalis was common in women with normal vaginal flora (60%), whereas, A. vaginae was uncommon (12%) in the normal population (p<0.001). The population with confirmed BV had both organisms present (96%), compared to women with normal vaginal flora (10%) (p<0.001). High levels of G. vaginalis (>4x10⁵ copies/ml) and A. vaginae (>4x10⁶ copies/ml) were significantly more common in women with BV.

132 Gardnerella vaginalis by Real-Time PCR
124 Mobiluncus mulieris and M. curtisii by Real-Time PCR
125 Bacteroides fragilis by Real-Time PCR

Clinical significance: Bacterial Vaginosis (BV) is a leading cause of abnormal vaginal discharge and odor. It constitutes a massive microecologic alteration of the vaginal flora. BV is characterized by: (1) decreased or absent Lactobacillus spp., (2) a logarithmically increased concentration of Gardnerella vaginalis (>10^8 to 10^11 CFU/g) (3) logarithmically increased concentrations of a set of potentially pathogenic bacteria, including Bacteroides spp. and Mobiluncus spp., along with Ureaplasma urealyticum and Mycoplasma spp. BV is related to considerable, and possibly preventable, infectious morbidity in non-pregnant women. The sequelae of BV now includes endometritis, pelvic inflammatory disease, post-surgical abortion infections, post-hysterectomy infections, an increased risk of HIV acquisition and, possibly, cervical intraepithelial neoplasia. The diagnosis of BV is complicated by the polymicrobial nature of the condition. Fifty percent of patients diagnosed with BV show no symptoms. Furthermore, patients in the intermediate and the normal categories are generally not considered for treatment according to the Nugent criteria. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Bacteroides fragilis is an anaerobic bacteria that is commonly associated with Bacterial Vaginosis. BV is a leading cause of abnormal vaginal discharge and odor. BV constitutes a massive microecologic alteration of the vaginal flora. It is characterized by: (1) decreased or absent Lactobacillus spp. (2) a logarithmically increased concentration of Gardnerella vaginalis (> 10^8 to 10^11 CFU/g) (3) logarithmically increased concentrations of a set of potentially pathogenic bacteria, including Bacteroides spp. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Bacteroides ureolyticus is an obligate, aneareobic, gram-negative rod that was first described in clinical specimens in 1948. It is the most frequently isolated Bacteroides species, after Bacteroides fragilis. It has been isolated from mixed cultures of infections involving nearly every organ system in humans. It is associated with ulcerative lesions of both the external and internal genitalia including  the perineal area, and abscesses. It is also a pathogen of the urinary tract. It has been implicated in non-gonoccocal urethritis (NGU).  One study detected B. ureolyticus in 50% of men with NGU. It is thought to cause damage to the urethral mucosa via an endotoxin. In this assay, DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: Between 85% to 90% of yeast strains isolated from the vagina belong to the species of Candida albicans. Candida albicans is one of the major causes of Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By the age of 25, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Candida dubliniensis is associated with oral candidiasis and has been recovered from the vaginal tract of women. Although it is closely related to C. albicans, its differences in virluence and its ability to rapidly develop resistance to traditional anti-fungal agents makes it very clinically relevant. The use of molecular techniques, such as Real-Time PCR, enables the clinician to differentiate C. dubliniensis from other species of Candida to facilitate diagnosis and proper treatment.

Clinical significance: C. glabrata accounts for 7% of all vaginal fungal infections and about 10% of vaginal yeast isolates. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. glabrata is associated with Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By age 25 years, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Candida kefyr is one of the six strains of Candida, of approximately 154 species, that is commonly associated with infections of humans. This species, previously reported in the literature by the obsolete name of Candida pseudotropicalis, has been reported as an emerging pathogen. Candidiasis has a wide clinical spectrum, capable of affecting almost any organ or system in the body. Infections range from localized, superficial infections to dissemination in the blood stream. Considered to be a relatively rare infection, found in approximately 1% of fungal isolates, reported infections include burn wounds, blood and vaginal infections. More recently, the frequency of C. kefyr infections has increased within oncohematologic patients, particularly those with neutropenic, myeloid and lymphoblastoid leukemias.

Clinical significance: Candida krusei, which has traditionally been implicated in urinary tract infections, has recently been associated with certain instances of fungal vaginitis, particularly recurrent fungal vaginitis. The use of molecular techniques, such as Real-Time PCR, enables the clinician to differentiate C. krusei from other species of Candida to facilitate diagnosis and proper treatment.

Clinical significance: Candida lusitaniae is considered a nosocomial bloodstream pathogen that is becoming increasingly associated with Candidemia. It is also quite resistant to amphotericin B, a common antifungal treatment.

Clinical significance: C. parapsilosis accounts for 1% of vaginal yeast isolates. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. parapsilosis is associated with Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By the age of 25, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Candida tropicalis is isolated from 1% to 5% of vaginal yeast isolates and may be associated with a higher rate of recurrence after standard treatment. It is thought that the widespread use of topical antifungals, especially in short courses, may contribute to selection for non-albicans yeasts, which are less susceptible to these agents than C. albicans. C. tropicalis is associated with Candida Vaginitis (CV). CV affects most females at least once during their lives, at an estimated rate of 70% to 75%, of whom 40% to 50% will experience a recurrence. In the United States CV is currently the second most common cause of vaginal infections, with bacterial vaginosis the most common diagnostic entity. Most studies indicate that CV is a frequent diagnosis among young women, affecting as many as 15% to 30% of symptomatic women visiting a clinician. By the age of 25, half of all college women will have experienced at least one episode of CV. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Candida utilis has traditionally been described as an industrially significant yeast. However, it was recently implicated in a case of recurrent urinary tract infection and candidemia. It has also been associated with fungal keratitis. The use of molecular techniques, such as Real-Time PCR, enables the clinician to differentiate C. utilis from other species of Candida to facilitate diagnosis and proper treatment.

551 Candida albicans by Real-Time PCR
557 Candida tropicalis by Real-Time PCR
558 Candida parapsilosis by Real-Time PCR
559 Candida glabrata by Real-Time PCR

Clinical significance: The incidence of Candida Vaginitis (CV) is poorly documented, particularly since CV is not a reportable entity. Regrettably, without laboratory confirmation, CV is misdiagnosed in as much as 50% of cases. Ninety-one percent of yeast strains isolated from the vagina belong to the species of Candida albicans. Other vaginal yeast strains isolated include C. glabrata, C. parapsilosis, and C. tropicalis, accounting for the remaining CV cases in the United States. Vulvovaginal candidiasis accounts for about one-third of all the vaginitis cases seen in private practices. Patients with CV generally complain of perivaginal pruritus, often with little or no discharge. Currently, CV diagnosis is based on the addition of 10% potassium hydroxide to vaginal discharge on a slide (the “whiff” test). However, the whiff test fails to elicit a confirmatory odor in most women with CV. Direct microscopic examination of wet mount vaginal discharge fails to reveal the fungi in 30% to 50% of infected women. A commercially available latex agglutination test has a limited sensitivity of 60%. MDL has developed a highly sensitive and specific PCR based assay that can differentiate among the four CV-causing pathogens.

Clinical significance: Chlamydia trachomatis is the causative agent of the disease Chlamydia. It is the most common sexually transmitted bacterial agent. In women it causes cervicitis, urethritis, endometritis and salpingitis. In more complicated cases it may result in tubal scarring, infertility, and ectopic pregnancy. In men it causes urethritis and proctatitis. If left untreated, Chlamydia may develop into lymphogranuloma venereum. Other forms of infection also seen are trachoma, the most preventable form of blindness, and conjunctivitis in neonates. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Cytomegalovirus (CMV) infects 50-80% of Americans by the age of 40. It is known to cause mild or asymptomatic infection in most healthy individuals. The virus is spread from person-to-person through most bodily fluids. Congential infection, which occurs when an infected mother passes the infection along to the fetus, may result in hearing, vision, neurologic and developmental problems shortly after birth. CMV viral shedding can be detected in the vaginal secretions of infected women. The use of molecular techniques, such as Real-Time PCR, enables the clinician to detect this viral shedding thus enabling diagnosis and treatment prior to conception.

Clinical significance: Escherichia coli (E. coli) is the head of the large bacterial family, Enterobacteriaceae, the entericbacteria, which are facultatively anaerobic gram-negative rods that live in the intestinal tracts of animals and humans during both health and disease. The urinary tract is the most common site of infection by E coli. E coli accounts for more than 90% of all uncomplicated UTIs. The recurrence rate after a first E coli infection is 44% over 12 months. E coli UTIs are caused by the uropathogenic strains of E coli. E coli causes a wide range of UTIs, including uncomplicated urethritis/cystitis, symptomatic cystitis, pyelonephritis, acute prostatitis, prostatic abscess, or urosepsis. Uncomplicated cystitis occurs primarily in females who are sexually active and are colonized by a uropathogenic strain of E coli. Subsequently, the periurethral region is colonized from colon contamination, and the organism reaches the bladder during sexual intercourse.

Clinical significance: G. vaginalis can be found as normal vaginal flora in some women. However, significant increases in numbers can cause bacterial vaginosis and urinary tract infections. G. vaginalis infection is a risk factor for premature labor, chorioamionitis, and postpartum endometritis.

110 Treponema pallidum by Real-Time PCR
122 Haemophilus ducreyi by Real-Time PCR
126 Herpes subtype (HSV-1 & HSV-2) by Real-Time PCR

Clinical significance: The three major causes of Genital Ulcer Disease (GUD) in the United States are Herpes simplex virus, Treponema pallidum (syphilis), and Haemophilus ducreyi (chancroid). Currently, the diagnosis of GUD is based primarily on the clinical presentation of the ulcer itself. However, agent-specific diagnosis based solely on clinical evaluations are often obscured by multiple and mixed infections. As treatment options vary, it is medically necessary to identify the causative agent of GUD. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: H. ducreyi is the causative agent of the sexually transmitted disease soft chancre or chancroid. It is most commonly diagnosed in males, probably due to the asymptomatic or inapparent infection that often occurs in females. It typically takes 5-7 days after exposure for symptoms to present, but may take as long as several weeks. A tender, small, solid, raised skin lesion will develop with a red base that may develop into a raised sore containing pus. It may then become an open ulcer within 2 days. These lesions are generally limited to the genitalia or perianal area. The lesion erodes to form a painful ulcer and swelling of lymph nodes in the groin area (bubo) in approximately 50% of patients. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Only performed after a #126 is positive.
Charges will be the total of tests #126 + #113.

Clinical significance: HSV quantitative DNA based assay is performed by quantitative Real-Time PCR. Real-Time PCR is an ultra sensitive assay that utilizes intermolecular controls that coincide with the tested specimen. Evaluation of viral load is essential for patient stratification, predicting clinical outcome, and evaluating disease progression.

Clinical significance: HSV infection is epidemic in the United States. Genital herpes is the most common cause of genital ulcer disease in the developed world. HSV-1 classically presents as herpes gingivostomatitis, an infection of the oral mucosa. It can also cause conjunctivitis, keratitis, and herpetic whitlow. HSV-2 is the most common cause of genital ulcers in the United States. More than 95% of recurrent disease is due to HSV-2. The main application for HSV subtyping is with regard to the clinical issue of recurrent infection. Most painful and annoying recurrent genital herpes is due to HSV-2, and almost all recurrent cold sores or fever blisters are due to HSV-1. However, genital herpes also can be caused by HSV-1. This type of genital herpes is much less frequently recurrent and each recurrence usually lasts only a few days. It has been documented that as many as one third of herpes infections are due to HSV-1, particularly in adolescents and young adults.

Antigen detection systems for HSV are specific and sensitive when applied to the evaluation of genital lesions, but the titer of HSV present during asymptomatic reactivation is 10- to 100-fold less than the titer present during symptomatic episodes. Therefore, methods based on the detection of viral proteins are not likely to be as sensitive as DNA amplification assays. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Human Papillomavirus (HPV) type is a well established risk factor determinant for progression to cervical cancer. To date, over 115 different HPV subtypes have been reported. HPV-16 and HPV-18 are the most common “high risk” HPV types associated with cervical cancer. Together, they only account for about 70% of all cases, a value which is highly variable between clinical studies. While other diagnostic procedures report the HPV infections as either “high risk” or “low risk” for the development of cervical cancer, HPV Type-Detect specifically identifies which actual HPV subtypes are contained within the biological specimen. Additionally, combinations of HPV types are detectable within single specimens, a phenomenon that occurs with significant frequency. Designed using an automated system capable of robotic precision, this highly specific assay can be readily incorporated into diagnostic screening and epidemiological evaluations.

This test has been replaced by Test 140: HPV Type-Detect by PCR. (Oct. 4, 2006)

Clinical significance: Klebsiella pneumoniae is a gram-negative rod-shaped bacterium that belongs to the family Enterobacteriaceae.  It is among the most common bacteria encountered by physicians worldwide and has become a well-recognized cause of nosocomial infections such as pneumonia, urinary tract infections, wound infections and bacteremia in immunocompromised patients. It is a common cause of human urinary tract infection when there are structural abnormalities or urethral medical instrumentation.

105 Chlamydia trachomatis by Real-Time PCR
145 Neisseria gonorrhoeae by Real-Time PCR with reflex to Ciprofloxacin Resistance by Pyrosequencing
111 Trichomonas vaginalis by Real-Time PCR

Clinical significance: Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis are the major causes of leukorrhea. C. trachomatis is the most common sexually transmitted bacterial agent. In women, C. trachomatis causes cervicitis, urethritis, endometritis, and salpingitis. Prolonged C. trachomatis infection may result in tubal scarring, infertility, and ectopic pregnancy. Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease gonorrhea. In women, the most common symptom of N. gonorrhoeae infection is endocervical infection and, if left untreated, may develop into vulvovaginitis and pelvic inflammatory disease. As a protozoan parasite, Trichomonas vaginalis is the causative agent of the sexually transmitted disease trichomoniasis. T. vaginalis infection is the primary cause of vaginitis, cervicitis and urethritis in women. Routine clinical diagnosis usually depends on microscopic identification of the parasite in wet mount preparations, which are only 60% sensitive as compared to culture-positive women. The sensitivity and specificity of PCR testing for C. trachomatis and N. gonorrhoeae are superior to the HCII (probe-based) assay which has a sensitivity/specificity of 75% / 97%, and 90.8% / 99.3%, respectively. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Lymphogranuloma venereum (LGV) is a sexually transmitted Chlamydial disease that should be part of the differential diagnosis for any patient presenting with a genital ulcer and / or inguinal lymphadenopathy. Treatment involves the use of antibiotics to clear the infection and to prevent tertiary sequelae. LGV is caused by C. trachomatis, serotypes L₁, L₂, and L₃. C. trachomatis serovars B and D-K are associated with causing non-gonococcal urethritis and cervicitis. While these other serotypes of C. trachomatis are limited to superficial infection of mucus membranes, serotypes L₁, L₂, and L₃ are more invasive and virulent, and tend to result in systemic disease.

LGV occurs in three distinct stages. The first stage is an incubation period of anywhere from three days to six weeks (10-14 days average) and is characterized by a painless genital papule which usually disappears after a few days. The onset of the second stage occurs two-six weeks later and often manifests as unilateral inguinal lymphadenopathy. Constitutional symptoms, such as fever, chills, malaise, myalgias, and arthralgias, are common in this stage of the disease. The third stage may occur years after the initial infection and is termed genitoanorectal syndrome. Women are more likely to present in this stage. Symptoms include fever, pain, tenesmus, pruritus, and purulent or bloody diarrhea. In this Real-Time PCR assay amplification with high sensitivity and specificity can differentiate between LGV and C. trachomatis serotypes.

Clinical significance: Mobiluncus species are anaerobic bacteria that are commonly associated with Bacterial Vaginosis (BV). It is a leading cause of abnormal vaginal discharge and odor. BV constitutes a massive microecologic alteration of the vaginal flora. It is characterized by: (1) decreased or absent Lactobacillus spp., (2) a logarithmically increased concentration of Gardnerella vaginalis (> 10^8 to 10^11 CFU/g), (3) logarithmically increased concentrations of a set of potentially pathogenic bacteria, including Mobiluncus spp. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Molluscum contagiosum virus (MCV) is a member of the human pox viruses which produces small raised papules or lesions with central umbilications and a white, firm, curd-like core. Infection occurs commonly in children under 5 years due to casual contact and in young adults due to skin-to-skin contact during sexual intercourse. MCV is a common infection in the United States and accounts for approximately 1% of all undiagnosed skin disorders. Many physician’s find it necessary to differentiate MCV from Human Papillomavirus (HPV) or Herpes Simplex virus (HSV) infections, which have greater mortality and mobidity. In this assay, DNA is extracted from a swab sample of lesions actively shedding the virus or biopsies of the actual lesion and subjected to Real-Time PCR amplification.

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. Mycoplasma genitalium has been associated with non-gonoccocal urethritis, acute endometritis, cervicitis, and pelvic inflammatory disease (PID). Genital mycoplasma infections are usually diagnosed by culture. However, due to it’s fastidious slow-growing nature, M. genitalium may take up to 8 weeks to culture. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. M. hominis has been linked to pyelonephritis, pelvic inflammatory disease (PID), spontaneous abortion, and postpartum septicemia and fever. Genital mycoplasma infections are usually diagnosed by culture. However, it can take 2 to 5 days to culture M. hominis. In this assay, DNA is extracted from the specimen and subjected to PCR amplification

Clinical significance: Mycoplasma penetrans, a species of Mycoplasmataceae, infects humans in the urogenital and respiratory tracts. A typical feature of M.penetrans is penetration into human cells. Long-term persistence of M.penetrans in patients has also been documented on the basis of its isolation from urine specimens collected at different times over the period of 1 year from the same children with human immunodeficiency virus (HIV) infection. In human disease, M.penetrans is associated mainly with HIV-1 infection, particularly in adults among the homosexual population in Europe and the USA, and among both homosexual and heterosexual males in South America but has also been suggested to be a primary cause of human disease in non-HIV-related urethritis and respiratory disease.

This test has been replaced by Test 145: Neisseria gonorrhoeae by Real-Time PCR with reflex to Ciprofloxacin Resistance by Pyrosequencing. (Dec. 11, 2006)

Clinical significance: The incidence of drug-resistant strains of Neisseria gonorrhoeae has increased dramatically worldwide. Since 1991, when the first ciprofloxacin resistant strains were isolated, the number of resistant cases has been found to exceed 50% in some Asian countries. Fluoroquinolone-resistant strains are also on the rise in the United States and Canada (CDC STD Surveillance Report 2004). Accordingly, the number of failed treatments has risen, with 500 mg doses of ciprofloxacin demonstrating a 45% failure rate for gonorrheal strains having an MIC greater than 4.0 μg/mL (Gonococcal Isolate Surveillance Report, 2003). Therefore, the CDC currently does not recommend the use of fluoroquinolones for the treatment of gonorrhea acquired in Asia, the Pacific Islands (including Hawaii), England, Wales, California and other locales with increased quinolone-resistant prevalences. MDL is providing, at no additional charge to the client, an analysis of two codons within the DNA gyrase gene for all N. gonorrhoeae positive OneSwab^® and UroSwab^® specimens. Mutations in these regions have been associated with ciprofloxacin resistance and result in the recommendation of an alternative drug treatment. The result of this DNA-based analysis will also be available to the physician significantly faster than conventional culture based methods.

105 Chlamydia trachomatis by Real-Time PCR
145 Neisseria gonorrhoeae by Real-Time PCR with reflex to Ciprofloxacin Resistance by Pyrosequencing

Clinical significance: Genitourinary tract infections due to C. trachomatis and N. gonorrhoeae are a major cause of morbidity in sexually active individuals. In males they may cause epididymitis and urethritis. In females, they can cause pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. If left untreated, Chlamydia may develop into lymphogranuloma venereum and N. gonorrhoeae may develop into a disseminated gonococcal infection (DGI). DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Polyomavirus BK is a member of the Papovavirus family and infects up to 90% of the general population. After primary infection, generally occurring in childhood without evident symptoms, the virus can remain latent in the urinary tract. Reactivation can be enhanced by immunosuppressive conditions, leading to overt clinical disease. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Polyomavirus JC is a double-stranded DNA virus belonging to the Papovavirus family and it is estimated that 60-80% of adults in Europe and the United States have antibodies to JC virus. It is proposed that JC virus establishes a latent infection in the kidney after a primary infection. JC virus has been linked to the development of hemorrhagic cystitis, ureteral stenosis and allograft dysfunction in renal transplant recipients. It is also believed to be the primary causative agent of both nephropathies after transplantation and progressive multifocal leukoencephalopathy. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Proteus mirabilis, a gram-negative enteric bacterium, is one of the most common gram-negative pathogens encountered in clinical specimens and can cause a variety of community or hospital-acquired illnesses, including urinary tract, wound, and bloodstream infections. P. mirabilis is one of the most common causes of urinary tract infections (UTI) in individuals with long-term indwelling catheters, complicated UTI, and bacteremia among the elderly.   Individuals suffering from UTIs caused by P. mirabilis often develop bacteriuria, kidney and bladder stones, catheter obstruction due to stone encrustation, acute pyelonephritis, and fever. In this assay, DNA is extracted from the patient specimen and subjected to PCR amplification.

Clinical significance: T. pallidum is the causative agent of the sexually transmitted disease syphilis. The diagnosis of syphilis is complicated because T. pallidum is one of the few major bacterial pathogens of humans that cannot be cultivated on artificial medium. In this assay, we utilize a sensitive technique for T. pallidum identification that is based upon the amplification of the gene encoding the pathogen-specific and highly conserved 47-kDa membrane immunogen (tpp 47). In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Trichomonas vaginalis is a protozoan parasite. It is the causative agent of the sexually transmitted disease trichomoniasis. It is a major cause of vaginitis, cervicitis, and urethritis in women and may cause nongonococcal urethritis, prostatitis, and perhaps other genitourinary tract syndromes in men. Routine clinical diagnosis usually depends on microscopic identification of the parasite in wet mount preparations. Unfortunately, wet mount examination detects only 60% of culture-positive cases in women. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

Clinical significance: Ureaplasma, of the family Mycoplasmataceae, are among the smallest free-living bacteria. Colonization, the presence and multiplication of microorganisms without tissue invasion or damage, usually begins at birth with passage through an infected mother’s birth canal. Ureaplasmas have been isolated from the genital tract of 1/3 of infant girls and from the noses and throats of 15% of infant boys and girls. Carriage of these organisms does not usually persist beyond the age of 2. However, a small portion of pre-pubertal children will remain colonized and asymptomatic. As a result of sexual contact, the incidence of genital Ureaplasmas increases after puberty. In some pregnant women, Ureaplasma infections are considered to be the cause of chorioamnionitis and premature delivery. They are frequently transmitted from mothers to their infants, which may cause a variety of disorders including pneumonia, persistent pulmonary hypertension, and chronic infection of the central nervous system. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

551 Candida albicans by Real-Time PCR
557 Candida tropicalis by Real-Time PCR
558 Candida parapsilosis by Real-Time PCR
559 Candida glabrata by Real-Time PCR

Clinical significance: The incidence of Urogenital Candidiasis in men is poorly documented, particularly since it is not a reportable entity. Four major causes of Urogenital Candidiasis in men are Candida albicans. C. glabrata, C. parapsilosis, and C. tropicalis. Candida infection in men can cause urethritis and balanitis, an inflammation of the foreskin and glans of the penis in uncircumcised men. Prostatic infection with Candida has also been reported. Candidosis of the penis can be transmitted during sexual contact with partners with chronic vaginal or anal carriage. MDL has developed a highly sensitive and specific PCR based assay that can differentiate among these four pathogens.

129 Mycoplasma genitalium by Real-Time PCR
130 Mycoplasma hominis by Real-Time PCR

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm), membrane-bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. After puberty, colonization with mycoplasmas occurs primarily through sexual contact. Genital mycoplasmas are commonly isolated from gravid women at approximately the same recovery rate as in nonpregnant women with the same degree of sexual activity. Mycoplasmas and Ureaplasmas are strongly associated with infertility, intraamnionic infection, postpartum infection, pelvic inflammatory disease (PID), and histologic chorioamnionitis. Genital mycoplasma infections are usually diagnosed by culture. However, it can take from 2 to 5 days or up to 8 weeks to culture. Subspeciation of human urogenital mycoplasma infections is paramount for successful antimicrobial therapy due to differential antimicrobial susceptibilities. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

129 Mycoplasma genitalium by Real-Time PCR
130 Mycoplasma hominis by Real-Time PCR
320 Ureaplasma urealyticum by Real-Time PCR

Clinical significance: Mycoplasmas are small (0.2 – 0.3 nm) membrane bound organisms capable of independent self-replication. The most prevalent strains recoverable from the genital tract are Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. Infants can become colonized with genital mycoplasmas during birth. After puberty, colonization with mycoplasmas occurs primarily through sexual contact. Genital mycoplasmas are commonly isolated from gravid women at approximately the same recovery rate as in nonpregnant women with the same degree of sexual activity. Mycoplasmas and Ureaplasmas are strongly associated with infertility, intraamnionic infection, postpartum infection, pelvic inflammatory disease (PID), and histologic chorioamnionitis. Genital mycoplasma infections are usually diagnosed by culture. However, it can take from 2 to 5 days or up to 8 weeks to culture. Subspeciation of human urogenital mycoplasma infections is paramount for successful antimicrobial therapy due to differential antimicrobial susceptibilities. In this assay, DNA is extracted from the specimen and subjected to PCR amplification.

This test is for patients that are penicillin-allergic and sensitivities are required.

Only performed after a #127 is positive.
Charges will be the total of tests #127 + #137.

Clinical significance: The typical treatment for these patients is penicillin G of which there is no known resistance. However, up to 12% of the population reports allergies to penicillin. Therefore the macrolide (erythromycin) or lincosamide (clindamycin) classes of drugs need to be administered, particularly for those patients who are at high risk for anaphylactic shock. Previous reports cite an increase in resistance of GBS to erythromycin and clindamycin. For instance, in 2003, resistance to erythromycin and clindamycin was reported as high as 37% and 17%, respectively.

The antibiotic resistance mechanisms are most commonly caused by three genes: ermB, ermTR, and mefA. MDL concluded a study where both the Clinical and Laboratory Standards Institute (formerly NCCLS) 2003 “Performance Standards for Antimicrobial Susceptibility Testing” protocols and a multiplex PCR assay were used to screen for the prevalence of these genes in 222 GBS clinical isolates.

These isolates were obtained from MDL’s clinical swab samples. Of the 222 GBS clinical isolates, 84 strains (38%) were resistant to erythromycin and 46 strains (21%) were resistant to clindamycin. The multiplex PCR proved to be an efficient method to identify the three major antibiotic resistance genes in GBS. With the presence of these genes on mobile genetic elements, such as plasmids and/or transposons, the passing of these genes from bacteria to bacteria is likely and should be monitored to provide the physician with the vital information needed for proper patient treatment.

MDL has developed a highly sensitive and specific multiplex polymerase chain reaction to identify GBS antibiotic resistance genes from GBS clinical isolates.