eMedicine Specialties > Infectious Diseases > Sexually Transmitted Diseases

Chlamydial Genitourinary Infections

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Renuka Heddurshetti, MD, Fellow in Infectious Diseases, Department of Internal Medicine, State University of New York at Brooklyn; Jeffrey Blitstein, MD, Staff Physician, Department of Internal Medicine, Division of Infectious Disease, VA New York Harbor Health Care System at Brooklyn

Updated: Apr 20, 2009

Introduction

Background

Chlamydiae are small gram-negative obligate intracellular microorganisms that preferentially infect squamocolumnar epithelial cells.

Chlamydia trachomatis is one of the 4 species (also including Chlamydia puerorum, Chlamydia psittaci, and Chlamydia pneumoniae) in the genus Chlamydia. C trachomatis can be differentiated into 18 serovars (serologically variant strains) based on monoclonal antibody–based typing assays. Serovars A, B, Ba, and C are associated with trachoma (a serious eye disease that can lead to blindness), serovars D-K are associated with genital tract infections, and L1-L3 are associated with lymphogranuloma venereum ([LGV] see Lymphogranuloma Venereum).

Pathophysiology

The pathophysiologic mechanisms of chlamydiae are poorly understood at best. The initial response to infected epithelial cells is a neutrophilic infiltration followed by lymphocytes, macrophages, plasma cells, and eosinophilic invasion. The release of cytokines and interferons by the infected epithelial cell initializes this inflammatory cascade.

Infection with chlamydial organisms invokes a humoral cell response, resulting in secretory immunoglobulin A (IgA) and circulatory immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies and a cellular immune response. Recent studies have implicated a 40-kd major outer membrane protein (MOMP) and a 60-kd heat-shock protein (Chsp60) in the immunopathologic response, but further studies are needed to better understand these cell-mediated immune responses.

Chlamydiae have a unique biphasic life cycle that is adaptable to both intracellular and extracellular environments. In the extracellular milieu, the so-called elementary body (EB) is found. EBs are metabolically inactive infectious particles; functionally, they are spore-type structures. Once inside a susceptible host cell, the EB prevents phagosome-lysozyme fusion and then undergoes reorganization to form a reticulate body (RB).

The RB synthesizes its own DNA, RNA, and proteins but requires energy in the form of adenosine triphosphate (ATP) from the host cell. After a sufficient amount of RBs have formed, some transform back into EBs, exiting the cell to infect others.

Frequency

United States

Chlamydia is the most commonly reported infectious disease in the United States—estimated at 4 million infections annually with prevalence rates of higher than 10% in sexually active adolescent females.

International

In 1995, the World Health Organization (WHO) estimated 89 million cases of C trachomatis infection worldwide.

Mortality/Morbidity

Although urogenital carriage of chlamydiae often is asymptomatic, the most common manifestation of disease is local mucosal inflammation associated with a discharge, urethritis in the male, and urethritis/vaginitis/cervicitis in the female.

• Chlamydia is one of the leading causes of pelvic inflammatory disease (PID) and infertility in women. The risk of ectopic pregnancy in women who have had PID is 7-10 times greater than that for women without a history of PID. In 15% of women who have contracted PID, chronic abdominal pain is a long-term manifestation that most likely is related to pelvic adhesions in the ovaries and fallopian tubes.
• Chlamydial infections increase the risk for acquiring HIV infection by increasing genital mucosal inflammation.
• Pregnant women infected with chlamydia can pass the infection on to their infants during delivery, which may develop into chlamydial pneumonia or chlamydial conjunctivitis.

Race

The incidence of chlamydial infection is not related to race per se but rather to the sexual histories of the individuals and, particularly, to the frequency and use (or nonuse) of barrier protection.

Sex

Although the presence of asymptomatic infection with genitourinary chlamydiae can differ, acquisition is similar for both sexes.

Age

Age factors in chlamydial genitourinary infection relate to the age of first sexual exposure and the frequency of exposure.

Clinical

History

C trachomatis is a sexually transmitted microorganism responsible for a wide spectrum of diseases that include cervicitis, salpingitis, endometritis, urethritis, epididymitis, conjunctivitis, and neonatal pneumonia. In contrast to gonorrhea infection, most men and women who are infected are asymptomatic, and, therefore, diagnosis is delayed until a positive screening result or upon discovering a symptomatic partner. In July 2007, The US Preventive Services Task Force Screening released a new recommendation statement for chlamydial infections.

Routine chlamydia screening in sexually active young women is recommended to prevent consequences of untreated chlamydial infection (eg, pelvic inflammatory disease, infertility, ectopic pregnancy, chronic pelvic pain). Fewer than half of young, sexually active females in the United States are screened for chlamydia, reports Morbidity and Mortality Weekly Report. Nationally, the annual screening rate increased from 25.3% in 2000 to 43.6% in 2006 and then decreased slightly to 41.6% in 2007.¹

• Risk factors
  • Nonwhite race
  • Multiple sexual partners
  • Age younger than 19 years
  • Poor socioeconomic conditions
  • Single marital status
  • Nonbarrier contraceptive use
• Neonatal risk
  • Conjunctivitis
  • Neonatal pneumonia

Physical

• Women
  • Easily induced endocervical bleeding
  • Mucopurulent endocervical discharge
  • Intermenstrual bleeding
  • Cervical discharge
  • Dysuria
  • Abdominal pain
• Men
  • Urethral discharge
  • Urinary frequency and/or urgency
  • Dysuria
  • Scrotal pain/tenderness
  • Perineal fullness (related to prostatitis)

Differential Diagnoses

Herpes Simplex

Other Problems to Be Considered

Gonorrhea
Ureaplasma infection
Trichomonas infection
Foreign body
Periurethral abscess
Mycoplasma genitalium infection
Prostatitis

Workup

Laboratory Studies

• Because of the possibility of multiple sexually transmitted infections, all patients with any sexually transmitted disease (STD) should be evaluated for chlamydial infection because chlamydial treatment is included in the Centers for Disease Control and Prevention (CDC) STD treatment regimens.
• Cytologic diagnosis
  • This is used mainly for the diagnosis of infant inclusion conjunctivitis and in ocular trachoma by the demonstration of intracytoplasmic C trachomatis inclusions in HeLa cells (ie, continuously cultured carcinoma cell line used for tissue cultures).
  • Cytologic diagnosis also is used to evaluate endocervical scrapings, but interpretation is difficult and sensitivity and specificity have been low.
• Isolation in cell culture
  • C trachomatis grows well in a variety of cell lines (eg, McCoy, HeLa cells) that can be maintained in tissue culture.
  • Incubation in tissue culture is 40-72 hours, depending on the cell type and specific biovar.
  • Intracytoplasmic inclusions can be detected either by Giemsa stains or by immunofluorescent staining with monoclonal antibodies.
  • Because of its high specificity (100%) and sensitivity, cell culture is the only test that should be used to establish the presence or absence of infections in cases with legal implications such as rape or sexual abuse.
• Antigen detection and nucleic acid hybridization
  • By direct fluorescent antibody (DFA)
  • By enzyme-linked immunosorbent assay
  • Detection of chlamydial ribosomal RNA (rRNA) by hybridization with a DNA probe
    • Advantage: This is simpler and less expensive. Most studies report sensitivities greater than 70% and specificities of 97-99% in populations of men and women with a prevalence of infection of 5% or more. Antigen detection may well be the most appropriate diagnostic test for a primary care setting in the United States if a definitive diagnostic test is required.
    • Disadvantage: It is less sensitive when compared to tissue culture. In low-prevalence populations (ie, <5% infected), a highly significant proportion of positive test results are false-positive results. Therefore, verification of a positive test result is desirable in certain cases. Such verification can be by culture (eg, a second nonculture test that identifies a different chlamydial antigen or nucleic acid sequence than the first test), a blocking antibody, or competitive probe.
• Detection of chlamydial genes by DNA amplification tests
  • Polymerase chain reaction (PCR)
  • Ligase chain reaction (LCR)
  • Specific chlamydial rRNA using transcription-mediated amplification
  • Both PCR and LCR detect C trachomatis in urine or self-administered vaginal swab specimens with sensitivity comparable to that with urogenital swab specimens.
• Serology
  • Complement fixation test
    • All patients with LGV or psittacosis have complement-fixing antibody titers of greater than 1:16.
    • Fifteen percent of men with urethritis and 45% of women with endocervical infection have titers 1:16 or greater.
  • Microimmunofluorescence test
    • This is more sensitive than complement fixation test.
    • Results are positive in 99% or more of women with cervicitis and in 80-90% of men with urethritis.
• Antibody classes
  • Antichlamydia IgM is uncommon in adults with genital tract infection.
  • The prevalence of antichlamydia IgG is high in sexually active adults, even in those who do not have an active infection, and it likely is due to past infection.
  • A statistically significant association exists between chlamydia-specific serum IgA and active disease.
  • The sensitivity, specificity, and predictive values are not high enough to make any serology clinically useful in the diagnosis of active disease. Therefore, chlamydial serologies are not recommended for diagnosis of genital tract disease.
• The choice of the most appropriate test depends on the clinical setting, the facilities available, and the relative cost.

Treatment

Medical Care

• Patients should abstain from sexual intercourse for 7 days after single-dose therapy or until the end of a longer regimen.
• Patients also should refrain from sexual intercourse until all of their sex partners have been cured.
• Follow-up culture is not recommended after azithromycin or doxycycline therapy, but it may be considered in pregnancy after erythromycin or amoxicillin therapy. Nonculture tests should be avoided in this circumstance to avoid positive results from nonviable organisms.

Medication

Treatment of genitourinary chlamydial infection clearly is indicated when the infection is diagnosed or suspected. Treatment also is indicated for sex partners of the index case if the time of the last sexual encounter was within 60 days of onset, and it should be considered for longer periods for the last sexual partner. Treatment of chlamydia is indicated for patients being treated for gonorrhea, as well.

In April 2007, the Centers for Disease Control and Prevention (CDC) updated treatment guidelines for gonococcal infection and associated conditions. Fluoroquinolone antibiotics are no longer recommended to treat gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC's Gonococcal Isolate Surveillance Project (GISP). The data from GISP showed the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone-resistant (QRNG) reached 6.7%, an 11-fold increase from 0.6% in 2001.

The data were published in the April 13, 2007, issue of the Morbidity and Mortality Weekly Report. This limits treatment of gonorrhea to drugs in the cephalosporin class (eg, ceftriaxone 125 mg IM once as a single dose). Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented.

For more information, see the CDC's Antibiotic-Resistant Gonorrhea Web site; CDC Updated Gonococcal treatment recommendations (April 2007); or Medscape Medical News on CDC Issues - New Treatment Recommendations for Gonorrhea.

Antibiotics

Therapy should cover all likely pathogens in the context of this clinical setting.

Azithromycin (Zithromax)

Relatively new member of the macrolide family of antimicrobials. Related to erythromycin, it is considered by many to be the treatment of choice of C trachomatis genitourinary infection because it may be administered as a 1-dose treatment, which improves adherence to treatment.

Dosing

Adult

1 g PO once

Pediatric

<8 years: Not established
>8 years or >45 kilograms: Administer as in adults

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine; can inhibit metabolism of disopyramide and pimozide, leading to cardiotoxicity; inhibition of rifabutin metabolism may lead to rifabutin toxicity

Contraindications

Documented hypersensitivity; hepatic impairment; do not administer with pimozide

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Generally not recommended for routine use during pregnancy but can be used as an alternative if failure occurs (by followup culture) after treatment with erythromycin or amoxicillin (neither are highly efficacious treatments); site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients; adverse effects are GI in origin, namely nausea, vomiting, diarrhea, and abdominal pain; less common effects include headache, dizziness, and hepatotoxicity

Doxycycline (Doryx, Vibramycin)

Well absorbed tetracycline antimicrobial. When administered for 1 wk, appears to be as effective as single-dose azithromycin for genitourinary chlamydial infections. Although the course is longer (7 d versus 1 dose) than azithromycin, the cost is less and it has been used in clinical practice for a much longer time.

Dosing

Adult

100 mg PO bid

Pediatric

<8 years: Not recommended
>8 years: Administer as in adults

Interactions

Bioavailability minimally decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Unsafe in pregnancy

Precautions

Photosensitivity may occur rarely; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth

Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)

Macrolide antimicrobial agent that generally is considered the recommended treatment for chlamydial genitourinary infection only during pregnancy.

Dosing

Adult

500 mg erythromycin base PO qid for 7 d; alternatively, 250 mg erythromycin base PO qid for 14 d or 800 mg erythromycin ethylsuccinate PO qid for 7 d or 400 mg qid for 14 d

Pediatric

<45 kilograms: 50 mg/kg/d erythromycin base divided PO qid for 10-14 d; this regimen also should be used for ophthalmia neonatorum and/or infant pneumonia due to chlamydia

Interactions

As an inhibitor of the cytochrome oxidase P-450 3A4 system, can increase serum levels of atorvastatin, buspirone, carbamazepine, cerivastatin (removed from US market 8/8/01), cilostazol, cisapride, clozapine, cyclosporine, diazepam, dicumarol, dihydroergotamine, disopyramide, felodipine, fexofenadine, lovastatin, midazolam, pimozide, pravastatin, quinidine, sildenafil, triazolam, valproic acid, vinblastine, and warfarin; similar effects as doxycycline can occur with concomitant use of digoxin and oral contraceptives

Contraindications

Documented hypersensitivity; hepatic impairment

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur; efficacy of treatment is not as high as the standard regimens in adults; test of cure at 3 wk after completion of therapy should be considered and re-treatment may be needed

Ampicillin (Principen, Omnipen, Marcillin)

Like erythromycin, amoxicillin is considered a recommended treatment for genitourinary chlamydial infection only in pregnant women.

Dosing

Adult

500 mg PO tid for 7 d

Pediatric

Not recommended

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives; coadministration with PO typhoid vaccine can affect the immunogenicity of the vaccine by inhibiting replication; methotrexate levels may be increased by penicillins

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Retesting 3 wk after therapy completion should be considered; major adverse effects include diarrhea, rash, nausea, and vomiting; Clostridium difficile infection and/or colitis may occur

Follow-up

Deterrence/Prevention

Individuals who are sexually active should be aware of the risk not only of genitourinary chlamydia infection but also of the whole gamut of STDs and that the best way of avoiding infection is to practice safe sex. This means using appropriate barrier protection (ie, latex condoms).

Complications

• Reiter syndrome, a reactive arthritis secondary to an immune-mediated response has been associated (among other things) with a primary chlamydial infection.
  • It may present as asymmetric polyarthritis, urethritis, inflammatory eye disease, mouth ulcers, circinate balanitis, and keratoderma blennorrhagica.
  • While the etiology of Reiter syndrome may not be completely clear, 2 clear associations are observed. It usually follows an infectious episode, and 80% of affected patients are human leucocyte antigen-B27 (HLA-B27)–positive.
• Deeper pelvic complications in the female
  • PID
  • Potential infertility
  • Spread to the newborn during parturition

Prognosis

Treatment failures with primary therapies are quite rare.

Relapse may occur with alternative therapies.

Reinfection is very common and is related to nontreatment of infected sexual partners or acquisition from a new partner.

Patient Education

Appropriate counseling of infected individuals must be performed.

• Counsel patients to avoid reinfection from the sexual partner by facilitating treatment of the contact prior to sexual reexposure.
• Counsel patients to use latex condoms to prevent reinfection.

For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center. Also, see eMedicine's patient education articles Sexually Transmitted Diseases and Chlamydia.

Miscellaneous

Medicolegal Pitfalls

• Remembering to treat patients for chlamydial genitourinary infection even when gonococcal infection is clearly diagnosed is important.
• Consider testing the cure when treatment with amoxicillin or erythromycin is used instead of the standard doxycycline or azithromycin regimens.

References

1. Centers for Disease Control and Prevention. Chlamydia screening among sexually active young females enrollees of health plans - United States, 2000-2007. MMWR Weekly. April 17, 2009;58(14):362-365. [Full Text].

2. Quinn TC, Gaydos C, Shepherd M. Epidemiologic and microbiologic correlates of Chlamydia trachomatis infection in sexual partnerships. JAMA. Dec 4 1996;276(21):1737-42. [Medline].

3. Bell TA, Sandstrom IK, Eschenbach DA. Treatment of Chlamydia trachomatis in pregnancy with amoxicillin. In: Mardh PA, Holmes KK, Oriel JD, Piot P, Schachter J, eds. Chlamydial Infections. New York, NY: Elsevier Biomedical; 1982:221-4.

4. Bowie WR. Nongonococcal urethritis. Urol Clin North Am. Feb 1984;11(1):55-64. [Medline].

5. CDC. Diseases characterized by urethritis and cervicitis (see update from April 13, 2007). MMWR Morb Mortal Wkly Rep [serial online]. Aug 4 2006;55(RR-11):35-49. Available at http://www.cdc.gov/std/treatment/2006/urethritis-and-cervicitis.htm#uc4.

6. CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. Apr 13 2007;56(14):332-6. [Medline]. [Full Text].

7. CDC, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. Aug 4 2006;55(RR-11):1-94. [Medline]. [Full Text].

8. Cook RL, Hutchison SL, Østergaard L, et al. Systematic review: noninvasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med. Jun 7 2005;142(11):914-25. [Medline].

9. Donders GG. Management of genital infections in pregnant women. Curr Opin Infect Dis. Feb 2006;19(1):55-61. [Medline].

10. Donovan B. Sexually transmissible infections other than HIV. Lancet. Feb 14 2004;363(9408):545-56. [Medline].

11. Dorman SA, Danos LM, Wilson DJ. Detection of chlamydial cervicitis by Papanicolaou stained smears and culture. Am J Clin Pathol. Apr 1983;79(4):421-5. [Medline].

12. Ehret JM, Judson FN. Susceptibility testing of Chlamydia trachomatis: from eggs to monoclonal antibodies. Antimicrob Agents Chemother. Sep 1988;32(9):1295-9. [Medline].

13. Hook EW 3rd, Smith K, Mullen C. Diagnosis of genitourinary Chlamydia trachomatis infections by using the ligase chain reaction on patient-obtained vaginal swabs. J Clin Microbiol. Aug 1997;35(8):2133-5. [Medline].

14. Katz BP, Fortenberry D, Orr DP. Factors affecting chlamydial persistence or recurrence one and three months after treatment. In: Stephens RS, Byrne GI, Christiansen G, et al, eds. Chlamydial Infections, Proceedings of the Ninth International Symposium on Human Chlamydial Infection. San Francisco, Calif: International Chlamydial Symposium; 1998:35-8.

15. Magat AH, Alger LS, Nagey DA. Double-blind randomized study comparing amoxicillin and erythromycin for the treatment of Chlamydia trachomatis in pregnancy. Obstet Gynecol. May 1993;81(5 ( Pt 1)):745-9. [Medline].

16. Martin DH, Mroczkowski TF, Dalu ZA. A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group. N Engl J Med. Sep 24 1992;327(13):921-5. [Medline].

17. Rahman MU, Hudson AP, Schumacher HR Jr. Chlamydia and Reiter's syndrome (reactive arthritis). Rheum Dis Clin North Am. Feb 1992;18(1):67-79. [Medline].

18. Stamm WE. Chlamydia trachomatis infections: progress and problems. J Infect Dis. Mar 1999;179 Suppl 2:S380-3. [Medline].

19. Wehbeh HA, Ruggeirio RM, Shahem S. Single-dose azithromycin for Chlamydia in pregnant women. J Reprod Med. Jun 1998;43(6):509-14. [Medline].

Keywords

nongonococcal urethritis, nonspecific urethritis, postgonococcal urethritis, Chlamydia trachomatis, Chlamydia puerorum, Chlamydia psittaci, Chlamydia pneumoniae, C trachomatis, C puerorum, C psittaci, C pneumoniae, sexually transmitted diseases, STDs

Contributor Information and Disclosures

Author

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Renuka Heddurshetti, MD, Fellow in Infectious Diseases, Department of Internal Medicine, State University of New York at Brooklyn
Renuka Heddurshetti, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Jeffrey Blitstein, MD, Staff Physician, Department of Internal Medicine, Division of Infectious Disease, VA New York Harbor Health Care System at Brooklyn
Disclosure: Nothing to disclose.

Medical Editor

John M Leedom, MD, Professor of Medicine, Keck School of Medicine, University of Southern California; Chief, Division of Infectious Diseases, Department of Internal Medicine, Los Angeles County, University of Southern California Medical Center
John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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