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Chlamydia trachomatis Testing
Carin E. Reust, MD
From the Department of Family and Community Medicine, Center for Family Medicine Science, University of Missouri, Columbia.
Arch Fam Med. 2000;9:885-886.
QUESTION
How soon after treatment of Chlamydia trachomatis infection do the results of the Chlamydia test become negative?
SOLUTION
SEARCH STRATEGY
A MEDLINE search of the English medical literature was performed (1966 to present) using the following keywords: Chlamydia trachomatis, urethritis, adnexitis, and cervicitis. The literature review was further limited to the outpatient setting. Three categories of patients with chlamydial infections were identified: asymptomatic males and females; males with urethritis; and females with cervicitis or pelvic inflammatory disease who were not pregnant.
BACKGROUND
A patient presents with symptoms of urethritis, cervicitis, or pelvic inflammatory disease or is tested for Chlamydia during screening and is found to have a positive test result for Chlamydia. Treatment is initiated. When should the test for Chlamydia be repeated?
Before this question can be answered, 2 considerations must be kept in mind. Before treatment, with what certainty do positive and negative test results truly indicate the presence or absence of chlamydial infection (positive and negative predictive value of the test)? After treatment, with what certainty does a negative test result indicate that the infection has been cured (efficacy of treatment)?
Chlamydia trachomatis infection can be diagnosed by cell culture, direct fluorescent antibody (DFA), enzyme immunoassay (EIA), polymerase chain reaction (PCR), and ligase chain reaction (LCR). Specimens for testing can include urethral swabs, cervical swabs, and, increasingly, urine samples. Table 1 is a summary comparison of sensitivity, specificity, positive predictive value, and negative predictive value of each type of testing. For this clinical question, a positive test result indicates the need for treatment. The first line of treatment of asymptomatic, urethral, endocervical, or rectal chlamydial infections is doxycycline hyclate, 100 mg twice daily for 7 days, or azithromycin dihydrate, 1 g orally in a single dose. Alternative treatment regimens include ofloxacin and erythromycin base or ethylsuccinate. Children and pregnant women should receive erythromycin or azithromycin.1
Once a patient has been treated, the Centers for Disease Control and Prevention recommends that a Chlamydia test be performed after treatment to document eradication of the infection.1 The recommendation for repeated testing is based on the increasing prevalence of Chlamydia, the tendency of the infection to be asymptomatic, and the long-term consequences (primarily infertility) of chlamydial infections. Testing for cure is routinely checked up to 5 weeks posttreatment. Based on the type of test, test-for-cure can be done earlier (Table 1). For culture, viable organisms are usually not found shortly after treatment, whereas antigen and antibody (DFA, EIA) will persist longer, and nucleic acid (PCR, LCR) even longer still. Poor sampling, incomplete treatment, and reinfection due to lack of sexual abstinence complicate an accurate test-for-cure. The clinical significance of persistent antigen, antibody, or nucleic acid is uncertain.2, 6 In a study of cervicitis and urethritis using DFA and EIA testing, of the 34 patients with a positive DFA or EIA test result at 1 week, only 1 was symptomatic.12 In a small study of symptomatic cervicitis using PCR testing, all patients were asymptomatic (vaginal discharge or pruritis, and/or intermenstrual bleeding) and cervical signs (friability, erythema, ectropy) had resolved after 1 week of treatment. All of the PCR test results were positive at 1 week, but had become negative between 2 and 4 weeks.6
In addition to looking at the time interval to test-for-cure, it is necessary to look at the properties of the antibiotics used and their success and failure rates to determine the efficacy of treatment. Minimum inhibitory concentration is the lowest concentration of antibiotic required to inhibit growth of an agent and correlates with clinical activity.13 Low in vitro minimum inhibitory concentrations, or high activity against Chlamydia has been demonstrated for the tetracyclines (tetracycline, doxycycline, minocycline), erythromycins (base and salts), and the floxins (ofloxacin and ciprofloxacin).13-14 For Chlamydia urethritis, tetracyclines have a 0% to 3% failure rate and erythromycins a 0% to 37% failure rate.13 For Chlamydia cervicitis, tetracyclines have a 0% to 8% failure rate and erythromycins, a 0% to 34% failure rate.13-14 Ofloxacin has a 0% to 18% failure rate for either urethritis or cervicitis while ciprofloxacin has a 0% to 100% failure rate for urethritis or cervicitis. One dose of azithromycin for the treatment of urethritis gives a cure rate of 95% (confidence interval, 75%-99%).15 Similar cure rates are found for cervicitis.12 For pelvic inflammatory disease, guidelines for management that include treatment for Chlamydia as a possible causative agent result in a 90% to 95% cure rate.16-17
BOTTOM LINE
A test for cure can be reliably performed in 1 week if using culture, and in 2 weeks for tests that use antigen and antibody (DFA, EIA) techniques. For nucleic acid–based tests (LCR, PCR), test-for-cure should be delayed until after 3 weeks. A positive test result after appropriate treatment and the necessary interval for clearing of antigen or nucleic acid is a sign of incomplete treatment or reinfection.
REFERENCES
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1. Centers for Disease Control and Prevention. Recommendations for the prevention and management of Chlamydia trachomatis infections, 1993. MMWR Morb Mortal Wkly Rep. 1993;42(RR-12):1-39.
2. Gaydos CA, Crotchfelt KA, Howell MR, Kralian S, Hauptman P, Quinn TC. Molecular amplification assays to detect chlamydial infections in urine specimens from high school female students and to monitor the persistence of chlamydial DNA after therapy. J Infect Dis. 1998;177:417-424.
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3. Buimer M, van Doornum GJ, Ching S, et al. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by ligase chain reaction–based assays with clinical specimens from various sites: implications for diagnostic testing and screening. J Clin Microbiol. 1996;34:2395-2400.
ABSTRACT
4. Tan HH, Chan RK, Teo AS, Boey LP. Use of ligase chain reaction and polymerase chain reaction on urine specimens to detect Chlamydia trachomatis infections in a sexually transmitted diseases clinic in Singapore. Ann Acad Med Singapore. 1999;28:245-251.
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5. Lee HH, Chernesky MA, Schachter J, et al. Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase chain reaction assay of urine. Lancet. 1995;345:213-216.
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6. Workowski KA, Lampe MF, Wong KG, Watts MB, Stamm WE. Long-term eradication of Chlamydia trachomatis genital infection after antimicrobial therapy: evidence against persistent infection. JAMA. 1993;270:2071-2075. [published erratum appears in JAMA. 1994;271:348].
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7. Chan EL, Brandt K, Horsman GB. A 1-year evaluation of Syva MicroTrak Chlamydia enzyme immunoassay with selective confirmation by direct fluorescent-antibody assay in a high-volume laboratory. J Clin Microbiol. 1994;32:2208-2211.
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8. Mahony JB, Luinstra KE, Sellors JW, Jang D, Chernesky MA. Confirmatory polymerase chain reaction testing for Chlamydia trachomatis in first-void urine from asymptomatic and symptomatic men. J Clin Microbiol. 1992;30:2241-2245.
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9. Cerin A, Grillner L, Persson E. Chlamydia test monitoring during therapy. Int J STD AIDS. 1991;2(3):176-179.
10. Ferris DG, Lawler FH, Horner RD, Jernigan JC, Crout FV. Test of cure for genital Chlamydia trachomatis infection in women. J Fam Pract. 1990;31:36-41.
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11. Worm AM, Petersen CS. Chlamydia trachomatis sampling during erythromycin treatment. Dan Med Bull. 1984;31:500-501.
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12. Thorpe EM Jr, Stamm WE, Hook III EW, et al. Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises. Genitourin Med. 1996;72:93-97.
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13. Sanders LL Jr, Harrison HR, Washington AE. Treatment of sexually transmitted chlamydial infections. JAMA. 1986;255:1750-1756.
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14. Toomey KE, Barnes RC. Treatment of Chlamydia trachomatis genital infection. Rev Infect Dis. 1990;12(suppl 6):S645-S655.
15. Stamm WE, Hicks CB, Martin DH, et al. Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men: a randomized double-blind study. JAMA. 1995;274:545-549.
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16. Walker CK, Kahn JG, Washington AE, Peterson HB, Sweet RL. Pelvic inflammatory disease: metaanalysis of antimicrobial regimen efficacy. J Infect Dis. 1993;168:969-978.
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17. Washington E, Berg AO. Preventing and managing pelvic inflammatory disease: key questions, practices, and evidence. J Fam Pract. 1996;43:283-293.
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SECTION EDITOR: M. LEE CHAMBLISS, MD, MSPH
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