and not all NAATs are approved for vaginal swabs. A major disadvantage for some NAATs is decreased specificity compared with culture, particularly for N. gonorrhoeae. Depending on the target amplified by the NAAT, there is cross-reactivity with nonpathogenic Neisseria species. As a result, when screening for gonorrhea in a low-prevalence population, it would be expected that a large fraction of the unconfirmed positive results are false positives, which may be associated with adverse medical, social, or psychological consequences for these patients. It is recommended not to use off-label specimens (i.e., rectal/oral swabs or specimens from children) when using NAATs with decreased specificity. Other disadvantages of these assays include their higher cost, the potential for contamination resulting in a positive result in a patient without an infection, and in some assays the possible nonspecific inhibition of the assays by blood or other components of cervical secretions and by compounds present in urine. Additionally, the use of NAATs has limited the availability of isolates for antimicrobial resistance surveillance. This is a particular concern with N. gonorrhoeae. Nonetheless, the increased sensitivity and ease of screening large numbers of patients simultaneously for both chlamydia and gonorrhea by NAAT outweigh the potential limitations.
3. C. trachomatis was the organism identified in this patient’s infection. C. trachomatis is the most common bacterial cause of sexually transmitted infections (N. gonorrhoeae is the second most common). It is one of the causes of PID, which is often a polymicrobial infection (see answer 1, above). Only a subset of women infected with C. trachomatis subsequently develop PID. The pathogenesis of the development of PID in cases of C. trachomatis infections is an active area of research. Following the infection of epithelial cells by C. trachomatis, proinflammatory cytokines are secreted. It may be that the pathogenesis of PID is the result of an inappropriately increased host inflammatory response, causing tissue injury. A small number of published investigations have looked at the possibility that the variability in the response to C. trachomatis genital infection is the result of variations in human innate immune receptor genes such as members of the Toll-like receptor family.
Complications of PID include infertility, chronic pelvic pain, and ectopic pregnancy.
4. Chlamydia was once incorrectly classified as a virus because it is an obligate intracellular pathogen and as such cannot be cultured on enriched agar media like most bacteria. McCoy cells are used to culture C. trachomatis. After the infectious elementary body infects the McCoy cells, the organism is taken into the cell by a process called receptor-mediated endocytosis. The bacterium develops into a reticulate body within a membrane-bound structure called an inclusion. Reticulate bodies, the reproductive form of the organism, multiply by binary fission. The reticulate bodies then condense to form elementary bodies. Elementary bodies are released from the cell by lysis, release of intact inclusions, or exocytosis. The presence of chlamydial inclusions is demonstrated by staining these cells with a fluorescein-tagged monoclonal antibody that binds specifically to the chlamydial antigens present within the infected McCoy cells. These can then be viewed with a fluorescent microscope, where they will give a characteristic apple-green fluorescence, and the etiologic diagnosis can be established. Chlamydia culture is now only rarely used in clinical laboratories as a result of the availability of the less labor-intensive and more sensitive molecular methods (see answer 2, above).
5. C. trachomatis, the most common sexually transmitted bacterial pathogen in the United States, is also an etiologic agent of both nongonococcal urethritis and epididymitis in males and cervicitis, endometritis, and salpingitis in women, and it can cause pneumonia and conjunctival disease in neonates if they have passed through an infected birth canal. It is worth noting that many patients are minimally symptomatic or asymptomatic with genital infection due to C. trachomatis and may not seek medical attention. Other serotypes of C. trachomatis, found rarely in the United States, cause lymphogranuloma venereum. Lymphogranuloma venereum is a genital tract infection characterized by enlarged, tender, and erythematous inguinal lymph nodes and is frequently accompanied by systemic symptoms of fever, headache, and malaise. Still other serotypes of C. trachomatis cause trachoma, a leading cause of blindness in the developing world.
6. The CDC notes that “all regimens used to treat PID should also be effective against N. gonorrhoeae and C. trachomatis because negative endocervical screening for these organisms does not rule out upper-reproductive-tract infection.”
Empiric therapy for sexually active women in whom PID is clinically suspected includes, most commonly, a β-lactam antimicrobial agent to treat N. gonorrhoeae and anaerobes, plus doxycycline to treat C. trachomatis. The combination is necessary because of the poor activity of β-lactams against C. trachomatis. β-Lactams characteristically have poor intracellular penetration. The intracellular location of the replicative phase of C. trachomatis (the reticulate bodies) protects it from the activity of β-lactam antibiotics. Other combinations of antibiotics have been used with success in the treatment of PID, including intravenous clindamycin and gentamicin. Oral treatment of PID can be used in those patients who are able to be managed as outpatients. However, fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin) are no longer recommended in the oral treatment of PID as a result of an increase in the resistance of N. gonorrhoeae to these antibiotics. Resistance to antibiotics in N. gonorrhoeae has become more of a problem in the past decade. The first isolate with high-level resistance to azithromycin was identified in 2011 in Hawaii, and resistance to the oral cephalosporin cefixime has increased in the United States to the point that it is no longer a recommended treatment for gonococcal infections. The 2010 CDC recommendations note that when considering alternative regimens, the addition of metronidazole should be considered because anaerobic organisms are suspected in the etiology of PID. As a result, it has become more difficult in recent years to determine an efficacious oral antibiotic regimen for PID.
In addition, it is important for sex partners of women who have PID to be evaluated because of the high risk of infection with C. trachomatis and N. gonorrhoeae even if these pathogens have not been isolated from the affected woman. The 2010 CDC guidelines state:
Male sex partners of women with PID should be examined and treated if they had sexual contact with the patient during the 60 days preceding the patient’s onset of symptoms … Patients should be instructed to abstain from sexual intercourse until therapy is completed and until they and their sex partners no longer have symptoms. Evaluation and treatment are imperative because of the risk for reinfection of the patient and the strong likelihood of urethral gonococcal or chlamydial infection in the sex partner. Male partners of women who have PID caused by C. trachomatis and/or N. gonorrhoeae frequently are asymptomatic. Sex partners should be treated empirically with regimens effective against both of these infections, regardless of the etiology of PID or pathogens isolated from the infected woman.
In non-PID cases of genital infection by C. trachomatis, the two oral antibiotics that are options in the current recommendations are doxycycline (a tetracycline) and azithromycin. Of note, in patients who are likely to have poor treatment compliance or are unlikely to return for follow-up, azithromycin, which is given as a single dose, is preferred to doxycycline, which is taken twice daily for 7 days. In addition, tetracyclines should be avoided in pregnancy.
7. The use of criteria to identify women among a low-prevalence population who are at increased risk for chlamydial infections, to test these women for cervical chlamydial infections, and to treat those who are found to be infected has significantly reduced the incidence of PID in a low-prevalence population. Adolescent inner-city females are a very high-prevalence population for C. trachomatis, and on the basis of a prospective longitudinal study, the screening of all sexually active adolescent females every 6 months has been advocated. Similarly, the high prevalence of both chlamydial and gonococcal infection in women entering jails and adolescents entering juvenile detention centers suggests that screening of these women may be worthwhile.
Untreated lower genital tract infections in women may lead not only to PID but to complications of PID, including infertility, ectopic pregnancy, and chronic pelvic pain, as noted above.
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