Anda di halaman 1dari 9

Treatment of Chlamydia trachomatis infection Author Jeanne Marrazzo, MD, MPH Section Editor Noreen A Hynes, MD, MPH,

DTM&H Deputy Editor Barbara H McGovern, MD Disclosures Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last updated: Fri Sep 09 00:00:00 GMT 2011 (More) INTRODUCTION Chlamydia trachomatis, a small gram-negative bacterium, is the most common cause of bacterial sexually transmitted disease (STD) in both men and women [1]. A significant proportion of patients are asymptomatic, thereby providing an ongoing reservoir for infection. The most frequent clinical manifestation of chlamydial infection in men is urethritis, while the most common finding in women is cervicitis. The treatment of urethritis, cervicitis, proctitis and epididymitis secondary to C. trachomatis infection will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of these diseases are discussed elsewhere. Other types of C. trachomatisrelated diseases, such as pelvic inflammatory disease, reactive arthritis, lymphogranuloma venereum, and endemic trachoma, (an ocular infection seen commonly in the developing world), are discussed separately. (See "Genital Chlamydia trachomatis infections in women" and "Clinical features and diagnosis of pelvic inflammatory disease" and "Lymphogranuloma venereum" and "Epidemiology, diagnosis, and management of trachoma" and "Reactive arthritis (formerly Reiter syndrome)" and "Screening for Chlamydia trachomatis" and "Infectious causes of dysuria in adult men".) GENERAL TREATMENT PRINCIPLES Goals of treatment The goals of treatment are to: Prevent complicated infections related to chlamydia (eg, pelvic inflammatory disease, infertility, ectopic pregnancy) Decrease the risk of transmission to others Attain resolution of symptoms; between 83 and 86 percent of symptomatic patients with cervicitis or urethritis improve clinically within two weeks of starting treatment with doxycycline or azithromycin [2].

Eradication rates For any antibiotic agent to be considered "effective" for a sexually transmitted disease, a microbiologic cure should be achieved in more than 95 percent of treated patients. Eradication of infection decreases the risk of transmission to others. This includes sexual partners and infants at delivery, who are at risk of acquiring chlamydia ocular infection from an infected mother. (See "Chlamydia trachomatis infections in the newborn".) Impact of life cycle on antibiotic selection The treatment of Chlamydia trachomatis infection requires special consideration, largely due to its rather unique life cycle [1]. The infectious form of the organism, the extracellular elementary body, is metabolically inert and resistant to killing. Thus, antibiotics must target the sequestered intracellular and intravacuolar phases of the life cycle of this pathogen. For this reason, antibiotics with good intracellular penetration must be used. In addition, antibiotic concentrations must be present throughout the entire life cycle, which takes an average of 36 to 48 hours to complete. Thus, either a prolonged course of therapy or selection of an antibiotic with a long half-life is required to ensure adequate levels of the antibiotic agent. Antibiotic resistance appears to be exceedingly rare. The intracellular nature of the pathogen eliminates the opportunity for rapid evolution of cell surface components that could contribute to drug resistance. Furthermore, the elementary body is relatively inert, which limits opportunities for replication and the generation of antibiotic-resistant mutations. These features may also explain the paucity of inflammatory responses and the asymptomatic nature of most chlamydial infections. (See 'Drug resistance' below and "Genital Chlamydia trachomatis infections in men" and "Genital Chlamydia trachomatis infections in women".) Coinfection with gonorrhea Chlamydia and gonococcal infections may coexist in a significant percentage of community patients, which has a direct impact on treatment since first-line agents for chlamydia, in the dosage forms recommended, do not have adequate activity against gonococci. (See 'Empiric therapy for uncomplicated genital infection' below.)

In certain high-risk populations, such as adolescents entering juvenile detention centers, coinfection rates as high as 50 percent have been documented [3,4]. However, in a study of more than 14,000 young adults aged 18 to 26 years in the general community, the overall prevalence of chlamydia was 4.1 percent; the rates of concomitant gonococcal infection among those with chlamydia were 7.3 percent [5]. Thus, while it is important to confirm if Neisseria gonorrhoeae may coexist in patients with a diagnosis of chlamydia infection, presumptive therapy for gonorrhea is not routinely indicated for all patients. The most sensitive diagnostic method for detection of chlamydia and gonococcal infections is nucleic acid amplification testing (NAAT) on either urine samples or swabs from urethral, vaginal, or cervical discharge. (See "Genital Chlamydia trachomatis infections in women", section on 'Diagnosis'.) AVAILABLE AGENTS FOR CHLAMYDIA First-line agents In general, C. trachomatis is highly susceptible to tetracyclines and macrolides [6]. Within these two classes, first-line agents include doxycycline and azithromycin, respectively. The efficacy of these two agents in the treatment of uncomplicated genital infection is discussed below. (See 'Treatment of uncomplicated genital chlamydia infection' below.) Advantages of azithromycin Azithromycin has excellent intracellular and tissue penetration [7]. Due to its half-life of five to seven days, azithromycin can be administered as single-dose therapy (1 gram orally) under direct observation. Providing single-dose azithromycin on-site at the time of diagnosis, if possible, is strongly recommended to ensure compliance and to decrease the risk of complicated infection, such as pelvic inflammatory disease. This is particularly important when asymptomatic chlamydial infection is detected as part of routine screening, since it is unclear how long the patient may have been infected. In one study of 4158 women with positive screening tests for chlamydia, only 24 percent were treated presumptively on the day of their visit, the vast majority in STD clinics; treatment was ultimately administered in 96 percent of the remaining patients but at a median interval of 21 days [8]. Advantages of doxycycline The advantage of doxycycline is its lower cost per treatment course compared with azithromycin. Whether patients will be compliant with seven full days of twice-daily dosing is a relevant concern (see 'Patient counseling' below). However, whether seven full days of twice-daily dosing is required for clinical cure is unclear since microbiologic cures have been attained in patients with suboptimal adherence to a seven-day regimen [9]. Alternative therapies Quinolones Quinolones, ofloxacin (400 mg PO once daily for seven days), and levofloxacin (500 mg PO once daily for seven days), are both highly effective against chlamydia, but require a full week of therapy and are considerably more costly than either doxycycline or azithromycin. Furthermore, these drugs cannot be used in pregnancy or lactation and should not be administered to adolescents younger than 18 years of age due to concerns regarding bone abnormalities. Other quinolones, including ciprofloxacin, are either less effective or have not been tested against chlamydia [10]. For these reasons, ofloxacin and levofloxacin are recognized as alternative therapies in the fluoroquinolone class by the Centers for Disease Control and Prevention (CDC); dosing is as follows [10]: Ofloxacin 300 mg orally twice daily for seven days Levofloxacin 500 mg orally once daily for seven days

These medications played a more important therapeutic role in the past when they were used to provide concomitant coverage for both Neisseria gonorrhoeae and chlamydia infections, which can coexist. However, due to the emergence of quinolone drug resistance, these drugs can no longer be considered adequate coverage for Neisseria gonorrhoeae. (See 'Available agents for Neisseria gonorrhoeae' below.) Erythromycins and penicillins Alternative regimens are notably inferior in their ability to affect microbial cure, with cure rates in the range of 85 to 89 percent [6,10]. Their primary use is in pregnant women who cannot tolerate either of the first-line recommended drugs. (See 'Treatment during pregnancy' below.) Agents with limited activity Sulfonamides and cephalosporins have limited activity, and should not be used. AVAILABLE AGENTS FOR NEISSERIA GONORRHOEAE As noted above, sometimes gonorrhoeae and chlamydia infections can coexist and the therapeutic agents listed above for chlamydia are not effective in eradicating gonococci. A single injection of ceftriaxone (125 mg) cures the majority of uncomplicated urogenital, anorectal, and pharyngeal infections.

Other treatment options for gonorrhoeae are discussed in detail elsewhere. (See "Treatment of urogenital gonococcal infections".) TREATMENT OF UNCOMPLICATED GENITAL CHLAMYDIA INFECTION General background Uncomplicated genital chlamydia infections include urethritis in men and urethritis and cervicitis in women. Urethritis may present as dysuria in men and women; men may also complain of a clear scant penile discharge, though this may be purulent on occasion. Symptoms of cervicitis include vaginal discharge and intermenstrual vaginal bleeding (ie, after sexual intercourse). Since women with cervicitis may also have pelvic inflammatory disease, it is important that all women undergo a physical examination to exclude signs of upper tract disease (eg, cervical motion, uterine or adnexal tenderness). The clinical manifestations and signs of cervicitis, as well as upper tract disease, are discussed in detail separately. (See "Genital Chlamydia trachomatis infections in men" and "Genital Chlamydia trachomatis infections in women" and "Clinical features and diagnosis of pelvic inflammatory disease" and "Treatment of pelvic inflammatory disease".) The majority of uncomplicated genital chlamydial infections are asymptomatic in men and women; these infections may only be found after screening, but should be treated promptly as suggested below. (See "Screening for Chlamydia trachomatis".) The clinical significance of oropharyngeal chlamydia and the transmissibility of this infection are unclear. The optimal treatment regimen is also unknown [10]. In the absence of available data, most experts recommend that a positive test result be treated with a regimen active against genital chlamydial infection. Efficacy and safety of directed therapy A meta-analysis was performed to compare the efficacy and safety of doxycycline and azithromycin for the treatment of uncomplicated genital chlamydial infections in men and women [11]. Criteria for study inclusion included a randomized trial design with evaluation of microbial cure at follow-up. Twelve trials including 1543 patients with chlamydia infection were evaluated; cure rates were similar between both agents (97 percent for azithromycin and 98 percent for doxycycline, respectively). Microbial cure is a more reliable parameter for drug efficacy than clinical cure, since a significant proportion of patients may have other coinfections that will not respond to the administered drug, and other patients have no clinical manifestations at baseline. However, it should be noted that microbiological cure in these earlier studies was documented with culture or enzyme immunoassay testing rather than the more sensitive nucleic acid amplification technique (NAAT) assay, which is preferred today. In this meta-analysis, adverse events occurred in approximately one-quarter of the patient population in both treatment arms. The most frequently reported adverse events were gastrointestinal in nature and included diarrhea, abdominal pain, nausea and vomiting, and dyspepsia; no serious adverse events were reported. Based on these data, the Centers for Disease Control and Prevention recommend either agent as first-line therapy for the treatment of chlamydial infection [10]. When cost is not a factor, we prefer the use of azithromycin (1 gram single-dose therapy) with observed therapy when possible. If cost is an issue, then we use doxycycline (100 mg twice daily) for seven days with patient counseling on the need for adherence for optimal outcome. Women should also have pregnancy testing (see 'Patient counseling' below). If Neisseria gonorrhoeae infection is subsequently documented on NAAT testing, additional directed therapy for gonococcal infection must be given as well, even if the patient is asymptomatic. If diagnostic testing with a NAAT is negative, no additional therapy is necessary. EMPIRIC THERAPY FOR UNCOMPLICATED GENITAL INFECTION Chlamydia Empiric therapy for chlamydia infection should be offered to persons who present with symptoms suggestive of infection (cervicitis, PID, urethritis). This is especially true if follow-up cannot be ensured and if relatively insensitive diagnostic testing is being used (eg, culture rather than nucleic acid amplification testing). Gonorrhea Additional treatment for gonorrhea should be based on the following criteria: In men, treatment should be initiated if the clinician detects intracellular Gram-negative diplococci on a Gram stain of urethral discharge, which has a high degree of sensitivity and specificity for gonococci. The Gram stain is less helpful in women since nonpathogenic Neisseria species may be present in vaginal flora. The decision to empirically treat N. gonorrhoeae in women should be based upon significant concern for gonococcal

infection based on individual risk (eg, partner with new diagnosis of gonorrhoeae) or high local prevalence rates of gonorrhea (eg, greater than 5 percent) [10]. This type of information is obtained by calling your local public health department. Other etiologic agents Other etiologic agents to consider include Ureaplasma and Mycoplasma genitalium. Several studies have examined the outcome of therapy for NGU depending upon the etiologic agent and the antibiotic regimen. In one randomized double-blind trial, single-dose azithromycin was compared with a seven-day course of doxycycline for empiric treatment of NGU; cultures were performed for N. gonorrhoeae, C. trachomatis, and U. urealyticum [12]. The clinical cure rates were comparable between the azithromycin and doxycycline groups (90 versus 89 percent), regardless of whether C. trachomatis or U. urealyticum were isolated. NGU may also be caused by Mycoplasma genitalium, which appears to respond better to azithromycin than doxycycline, although overall clinical eradication rates with azithromycin are low (66 to 89 percent) [13,14]. COMPLICATED CHLAMYDIA INFECTIONS IN MEN C. trachomatis infects susceptible columnar epithelium present in male urethra, rectum, and epididymis and can cause proctitis and epididymitis in addition to uncomplicated urethritis. Gonorrhea may also coexist in a subset of patients. Proctitis Chlamydial proctitis, defined as inflammation of the distal rectal mucosa, is relatively uncommon and occurs almost exclusively in men who have sex with men (MSM) who have had receptive rectal intercourse [15,16]. Clinical manifestations include anorectal pain, rectal discharge, or tenesmus [17]. The clinical manifestations and the differential diagnosis of this clinical entity are found elsewhere. (See "Genital Chlamydia trachomatis infections in men".) Chlamydial proctitis may be caused by either the common genital strains of chlamydia (serovars D-K) that typically cause uncomplicated genital infection in men and women, or the lymphogranuloma venereum (LGV) strains (serovars L1, L2, L3), which can cause severe disease (eg, abundant bloody or mucopurulent discharge, severe pain with defecation, fever) [18]. (See "Lymphogranuloma venereum".) Treatment There are few data regarding the best treatment approach for acute proctitis. The largest randomized trial, published in 1988, randomly assigned 129 MSM to either empirical therapy for both chlamydia and gonorrhea compared with directed treatment after laboratory testing [17]. Patients assigned to the empiric therapy arm had more rapid resolution of symptoms; however, the findings of the study were limited by patient attrition and the use of antibiotics, which are not currently administered for these indications due to high rates of drug resistance. Another issue is that sensitive NAAT testing is not approved by the FDA for use on rectal specimens; thus, culture is the most commonly used method, which may lead to underdiagnosis of N. gonorrhoeae. Thus, empiric therapy for both chlamydia and gonorrhea is indicated for the treatment of patients with acute proctitis. An empiric regimen of doxycycline (100 mg twice daily) plus a single intramuscular dose of ceftriaxone (125 mg) are recommended. The duration of doxycycline therapy will depend on the severity of symptoms. For patients with mild proctitis, seven days of therapy is adequate. Patients with severe proctitis may have lymphogranuloma venereum infection, which requires a full threeweek course of doxycycline. Epididymitis N. gonorrhoeae or C. trachomatis are the most frequent pathogens in epididymitis among sexually active men <35 years of age. Symptoms include unilateral testicular pain; signs include tenderness and palpable swelling of the epididymis. (See "Infectious causes of dysuria in adult men".) Treatment Because symptoms of epididymitis are often severe and improve rapidly with timely antibiotic treatment, empiric therapy for both gonococcal and chlamydial infection is indicated before diagnostic studies are available. The CDC guidelines recommend the combination of ceftriaxone (250 mg IM as a single dose) plus doxycycline (100 mg PO BID) for 10 days for the treatment of acute epididymitis [10]. Ofloxacin (300 mg PO BID for 10 days) or levofloxacin (500 mg daily for 10 days) should be administered for patients with epididymitis who are allergic to cephalosporins and/or tetracyclines. Outpatient treatment is usually sufficient except for patients who appear toxic with a high fever or in those in whom severe pain necessitates the exclusion of another diagnosis such as testicular torsion or infarction. COMPLICATED INFECTIONS IN WOMEN

Pelvic inflammatory disease When cervical infection is untreated, C. trachomatis ascends to the upper genital tract at least 20 percent of the time, leading to pelvic inflammatory disease, which may manifest as either silent infection ("subclinical" PID, or silent endometritis) or overt PID [19,20]. Apart from direct involvement of the pelvic organs, PID can also include peritonitis and inflammation of the liver capsule (Fitzhugh-Curtis syndrome). Treatment The evaluation and treatment of PID is discussed in detail elsewhere. (See "Treatment of pelvic inflammatory disease".) TREATMENT DURING PREGNANCY Treatment of chlamydia during pregnancy prevents transmission of C. trachomatis to infants through the birth canal. The recommended regimens for treatment of the pregnant female are azithromycin (1 gram PO given as a single dose) or amoxicillin (500 mg PO tid for seven days) [10]. Women who cannot tolerate either of these regimens should be treated with one of four erythromycin regimens, as follows. In general, erythromycins are associated with a high degree of gastrointestinal complaints (primarily nausea). The lower dose 14day regimens may be helpful for women who cannot tolerate higher doses of erythromycin. Erythromycin base 500 mg PO four times daily for 7 days Erythromycin base 250 mg PO four times daily for 14 days Erythromycin ethylsuccinate 800 mg PO four times daily for 7 days Erythromycin ethylsuccinate 400 mg PO four times daily for 14 days

Doxycycline, levofloxacin, ofloxacin, and erythromycin estolate are contraindicated in pregnancy and lactation. Test of cure Cure rates of chlamydia in women who are pregnant are generally lower than in nonpregnant females, particularly with the alternative agent amoxicillin. For this reason, a test of cure is recommended for all pregnant women and should be performed no earlier than three weeks after treatment is initiated. (See 'Patient follow-up' below.) TREATMENT OF HIV-INFECTED PATIENTS The treatment of HIV-infected patients with chlamydia infections is the same as in HIV-seronegative patients. PATIENT FOLLOW-UP Patient follow-up is important to determine symptom resolution. Persistent symptoms Persistent symptoms in patients with confirmed chlamydial infection after appropriate therapy with good adherence are usually not due to primary treatment failure: A detailed prospective evaluation of 20 women with culture-proven and polymerase chain reaction (PCR)-proven C. trachomatis urogenital infections was performed to assess the incidence of persistent infection after treatment with doxycycline [21]. After five months of serial sampling with PCR, culture, and serial measurements of local and systemic antibody to C. trachomatis, no evidence of persistent infection was documented. One longitudinal prospective study of adolescent females with chlamydia infection used DNA genotyping and behavioral histories to assess whether repeated Chlamydia infections may be related to reinfection versus treatment failure with azithromycin [22]. Of 79 matched-paired Chlamydia samples, 10 were classified as "probable" treatment failures. Antibiotic efficacy was estimated to be 92 percent; although this is somewhat lower than the 95 percent target for STD eradication, the study illustrates that the vast majority of patients respond to treatment.

Persistent symptoms related to chlamydial infection may be due to recurrent infection, or to infection with another pathogen not optimally treated with the initial antibiotic regimen (for example, Mycoplasma genitalium is more effectively treated with azithromycin than doxycycline). Clinicians should inquire about possible reinfection, including whether sex partners were treated. (See 'Management of sex partners' below.) The medical history should also assess whether the patient is using vaginal douches or other chemical irritants; such products can provoke a local inflammatory response with subsequent vaginal symptoms that can be confused with infection. Males with chronic prostatitis may also have evidence of chronic urethral inflammation (ie, >5 WBCs per high-powered field), which may be confused with NGU [10]. Recurrence of symptoms Recurrence of symptoms after initial resolution should lead to a repeat evaluation for chlamydia and other sexually transmitted diseases that cause urethritis or cervicitis, including gonorrhea, bacterial vaginosis, and other pathogens. Objective signs of urethritis should be present before consideration of re-initiation of antimicrobial therapy [10]. Retreatment should be considered if the patient was not adherent to the course of antibiotics and was re-exposed to an untreated partner. A repeat diagnosis of chlamydia in a previously treated patient usually indicates reinfection, as noted above.

If the patient has been adherent, and has no history of re-exposure, persistent urethritis after doxycycline may indicate infection with a pathogen that is resistant to doxycycline (eg, Ureaplasma urealyticum or Mycoplasma genitalium). Trichomonas vaginalis can occasionally cause urethritis in males and females. While awaiting a diagnostic work-up, the 2010 CDC STD guidelines recommend [10]: Metronidazole 2 grams orally in a single dose OR Tinidazole 2 gram orally in a single dose PLUS Azithromycin I gram orally in a single dose (if not used for the initial episode)

Drug resistance Persistence or recurrence of symptoms should not be attributed to chlamydia drug resistance; drug resistance to azithromycin or doxycycline has not been demonstrated to date. Although the swine pathogen, Chlamydia suis, is commonly tetracycline resistant, there are no examples of stable tetracycline resistance in clinical strains of Chlamydia trachomatis. One in vitro study was able to demonstrate that a clinical strain of C. trachomatis was able to acquire a resistance element from a C. suis strain within coculture experiments [23]. Testing for chlamydia after treatment There are two different strategies for testing for chlamydia after treatment including test of cure, which is performed usually within four to six weeks of treatment, or retesting, which is performed approximately three to six months after treatment of infection. Test of cure A test of cure is defined as diagnostic testing performed for the express purpose of assessing whether the administered antibiotic regimen eradicated the pathogen. Since cure rates of lower genital tract infection are generally high (>95 percent) in compliant, nonpregnant patients who are treated with azithromycin, doxycycline, levofloxacin, or ofloxacin, a test of cure is not indicated. Indications for test of cure include: Pregnancy Persistent symptoms Use of a regimen with inferior cure rates, such as erythromycin and amoxicillin.

In these situations, test of cure should be performed no earlier than three weeks after treatment is completed. This is especially important when nucleic acid amplification tests (NAAT) are used, as they may be positive in the presence of dead organisms. Retesting Retesting is performed for the express purpose of evaluating whether a patient has been reinfected. Epidemiologic studies have documented that persons with chlamydial infection often have a history of recent treated infection in the preceding months [24,25]. Retesting is particularly important in the pregnant woman since recurrent infection could put the infant at risk of C. trachomatis ocular infection at birth [10]. The majority of these chlamydia infections result from resumption of unprotected sex with an untreated sex partner, though some do result from sex with a new sex partner. In women, repeat infections confer an increased risk of developing complicated genital infections, such as pelvic inflammatory disease. Thus, recently infected persons should have repeat testing for C. trachomatis infection approximately three to six months after treatment, regardless of whether patients believe their sex partners were treated [10]. PATIENT COUNSELING Medication adherence It is important to educate the patient regarding treatment adherence, particularly if doxycycline is prescribed. One study of men and women with uncomplicated genital chlamydia infection evaluated medication compliance with doxycycline by administering medications through an electronic medication system where all pill box openings were electronically recorded [26]. Eighty percent of 223 patients returned their pill bottles for assessment. Patients were considered strictly compliant if they had opened their bottles for at least 12 of 14 doses; only 25 percent of the patients demonstrated this level of adherence. Sexual activity Patients should be counseled to avoid sexual activity until seven days after initiating treatment; they may subsequently resume having sex provided that their symptoms have resolved and their sex partner(s) have been treated.

Persistence of symptoms may indicate infection with an additional pathogen (eg, Trichomonas vaginalis), reinfection, or incomplete adherence to the therapeutic regimen. (See "Trichomonas vaginalis".) HIV counseling and testing Patients with sexually transmitted diseases are at increased risk of acquiring HIV infection and should be offered HIV testing [27]. (See "Diagnostic assays for HIV infection".) MANAGEMENT OF SEX PARTNERS Issues of reinfection Sex partners are typically asymptomatic and, unless treated, will reinfect the index patient or spread infection to other partners. In fact, rates of reinfection among index cases of women with C. trachomatis range from 15 to 30 percent, and are typically associated with resumption of sex with previously established partners (not new partners) [28]. Low rates of partner assessment Ideally, sex partners of persons with chlamydial infection should be examined, tested for C. trachomatis and N. gonorrhoeae, treated, and counseled on prevention. Unfortunately, this approach is infrequently successful. The alternative traditional approach of using public health field workers to notify exposed sex partners can be useful, but is costly and is not available in most areas. In lieu of public health advocacy, patients are asked to notify their partners of the need for medical evaluation and treatment. This approach has been deemed a public health failure [29]. Expedited partner therapy A strategy termed "expedited partner therapy" (EPT) has been proposed as an alternative way to increase the proportion of sex partners receiving treatment and to decrease rates of reinfection in the index patient. With EPT, treatment (without examination), is facilitated by giving an antibiotic or a prescription to the index patient, or by calling in a prescription directly for the partner [29,30]. EPT for chlamydia can be accomplished with single-dose oral therapy (azithromycin) [30]. Patients and sexual partners should be counseled to abstain from sexual activity until the therapeutic course of antibiotics is completed, or in the case of azithromycin, for seven days after the single-dose treatment was administered. In one randomized controlled trial, 2751 patients (23 percent male) with diagnosed gonococcal infection, chlamydial infection, or both were assigned either to an "expedited treatment group" or a standard referral group. Patients in the expedited treatment group were given "partner packets" of cefixime and/or azithromycin to distribute to their partners, without requiring a formal medical evaluation of the partners. In the standard referral arm, patients simply notified their sex partners of the need for evaluation and treatment. Patients assigned to expedited treatment of sexual partners were significantly more likely to report that all of their partners had been treated compared with those assigned to the standard referral arm (61 versus 49 percent) [31]. The trial also demonstrated a significant benefit in lowering the number of recurrent infections among those assigned to expedited treatment. The limitations of this approach include lost opportunities for screening and counseling [32] and a risk of adverse events related to antibiotic administration. However, the CDC consensus is that EPT offers a valuable means to control STDs and is an option for partner management, although ongoing evaluation of this approach is needed [33]. Legal issues Clinicians should routinely employ EPT for the partners of persons with chlamydial infection, to the extent permitted by regional laws and regulations, when follow-up is in question. The legal status of EPT is state specific, although surveys indicate that many clinicians frequently pursue the practice in managing their patients with sexually transmitted infections. The legal status of EPT options can be found at SCREENING FOR CHLAMYDIA Screening for C. trachomatis is a critically important tool in the control of this infection, and is discussed in a separate section. (See "Screening for Chlamydia trachomatis".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient information: Chlamydia and gonorrhea (The Basics)") Beyond the Basics topics (see "Patient information: Chlamydia")


The goals of treatment are to prevent complicated infections related to chlamydia (eg, pelvic inflammatory disease, infertility, ectopic pregnancy), decrease the risk of transmission to others, and attain resolution of symptoms. (See 'General treatment principles' above.) Chlamydia and gonococcal infections may coexist in a significant percentage of community patients, which has a direct impact on treatment since first-line agents for chlamydia do not have activity against gonococci. (See 'General treatment principles' above.) Available agents that have excellent activity against chlamydia include doxycycline (a tetracycline) and azithromycin (a macrolide). (See 'Available agents for chlamydia' above.) Uncomplicated genital chlamydia infections include urethritis in men and urethritis and cervicitis in women. We recommend single-dose azithromycin (1 gram) for patients with uncomplicated genital chlamydia infections. Observed therapy is preferred when possible. (See 'Treatment of uncomplicated genital chlamydia infection' above.) When cost is a factor, doxycycline (100 mg twice daily) for seven days is an equally effective alternative. Patients who are prescribed doxycycline should be counseled on treatment adherence. Women should also have pregnancy testing since doxycycline is not recommended for pregnant women. (See 'Treatment of uncomplicated genital chlamydia infection' above.) Empiric therapy for chlamydia infection should be offered to persons who present with symptoms suggestive of infection (cervicitis, PID, urethritis). This is especially true if follow-up cannot be ensured and if relatively insensitive diagnostic testing is being used (eg, culture rather than nucleic acid amplification testing). (See 'Empiric therapy for uncomplicated genital infection' above.) Additional empiric therapy for gonorrhoeae should be based on a high suspicion of infection (eg, a positive Gram stain in men, a sexual partner recently diagnosed with gonorrhea). (See 'Empiric therapy for uncomplicated genital infection' above.) In patients with clinical symptoms of proctitis (eg, tenesmus), we recommend empiric therapy for both chlamydia and gonorrhea. An empiric regimen of doxycycline 100 mg twice daily plus a single intramuscular dose of ceftriaxone (125 mg) have excellent activity against chlamydia and gonorrhoeae, respectively. The duration of therapy for mild proctitis is doxycycline for 7 days; patients with severe proctitis should be treated for 21 days. (See 'Complicated chlamydia infections in men' above.) In men with epididymitis, we recommend empiric therapy for both chlamydia and gonococcal infections with doxycycline (100 mg PO BID) for 10 days plus ceftriaxone (250 mg IM as a single dose). (See 'Complicated chlamydia infections in men' above.) Doxycycline is contraindicated during pregnancy; the preferred agent is azithromycin. (See 'Treatment during pregnancy' above.) The treatment of HIV-infected patients with chlamydia infection is the same as in HIV-seronegative patients. (See 'Treatment of HIV-infected patients' above.) A test of cure for assessing the adequacy of the prescribed antibiotic regimen is not routinely done except in the pregnant female or among those with persistent symptoms. In these circumstances, a test of cure may be performed approximately four to six weeks after treatment. (See 'Patient follow-up' above.) Recently infected persons should have repeat testing for chlamydia infection approximately three to six months after treatment, regardless of whether patients believe their sex partners were treated, to rule out the possibility of reinfection. (See 'Patient follow-up' above.)

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. 2. 3. 4. 5. 6. Stamm WE. Chlamydia trachomatis infections of the adult. In: Sexually Transmitted Diseases, 4th Edition, Holmes KK, Sparling PF, Mardh PA, et al (Eds), McGraw-Hill, New York 2008. p.575. Thorpe EM Jr, Stamm WE, Hook EW 3rd, et al. Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises. Genitourin Med 1996; 72:93. Kahn RH, Mosure DJ, Blank S, et al. Chlamydia trachomatis and Neisseria gonorrhoeae prevalence and coinfection in adolescents entering selected US juvenile detention centers, 1997-2002. Sex Transm Dis 2005; 32:255. Nsuami M, Cammarata CL, Brooks BN, et al. Chlamydia and gonorrhea co-occurrence in a high school population. Sex Transm Dis 2004; 31:424. Miller WC, Ford CA, Morris M, et al. Prevalence of chlamydial and gonococcal infections among young adults in the United States. JAMA 2004; 291:2229. Geisler WM. Management of uncomplicated Chlamydia trachomatis infections in adolescents and adults: evidence reviewed for the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis 2007; 44 Suppl 3:S77. Stamm WE. Azithromycin in the treatment of uncomplicated genital chlamydial infections. Am J Med 1991; 91:19S. Foglia G, Rhodes P, Goldberg M, St Louis ME. Completeness of and duration of time before treatment after screening women for Chlamydia trachomatis infections. Sex Transm Dis 1999; 26:421.

7. 8.


10. 11. 12. 13. 14. 15.

16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29.

30. 31. 32. 33.

Bachmann LH, Stephens J, Richey CM, Hook EW 3rd. Measured versus self-reported compliance with doxycycline therapy for chlamydia-associated syndromes: high therapeutic success rates despite poor compliance. Sex Transm Dis 1999; 26:272. file:// (Accessed on January 11, 2011). Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Sex Transm Dis 2002; 29:497. 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. Mena LA, Mroczkowski TF, Nsuami M, Martin DH. A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitalium-positive urethritis in men. Clin Infect Dis 2009; 48:1649. Schwebke JR, Rompalo A, Taylor S, et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens--a randomized clinical trial. Clin Infect Dis 2011; 52:163. Geisler WM, Morrison SG, Bachmann LH. Absence of lymphogranuloma venereum strains among rectal Chlamydia trachomatis outer membrane protein A genotypes infecting women and men who have sex with men in Birmingham, Alabama. Sex Transm Dis 2008; 35:856. Manavi K, McMillan A, Young H. The prevalence of rectal chlamydial infection amongst men who have sex with men attending the genitourinary medicine clinic in Edinburgh. Int J STD AIDS 2004; 15:162. Rompalo AM, Roberts P, Johnson K, Stamm WE. Empirical therapy for the management of acute proctitis in homosexual men. JAMA 1988; 260:348. Ward H, Alexander S, Carder C, et al. The prevalence of lymphogranuloma venereum infection in men who have sex with men: results of a multicentre case finding study. Sex Transm Infect 2009; 85:173. Wiesenfeld HC, Hillier SL, Krohn MA, et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol 2002; 100:456. Wiesenfeld HC, Sweet RL, Ness RB, et al. Comparison of acute and subclinical pelvic inflammatory disease. Sex Transm Dis 2005; 32:400. Workowski KA, Lampe MF, Wong KG, et al. Long-term eradication of Chlamydia trachomatis genital infection after antimicrobial therapy. Evidence against persistent infection. JAMA 1993; 270:2071. Batteiger BE, Tu W, Ofner S, et al. Repeated Chlamydia trachomatis genital infections in adolescent women. J Infect Dis 2010; 201:42. Suchland RJ, Sandoz KM, Jeffrey BM, et al. Horizontal transfer of tetracycline resistance among Chlamydia spp. in vitro. Antimicrob Agents Chemother 2009; 53:4604. Whittington WL, Kent C, Kissinger P, et al. Determinants of persistent and recurrent Chlamydia trachomatis infection in young women: results of a multicenter cohort study. Sex Transm Dis 2001; 28:117. Fung M, Scott KC, Kent CK, Klausner JD. Chlamydial and gonococcal reinfection among men: a systematic review of data to evaluate the need for retesting. Sex Transm Infect 2007; 83:304. Augenbraun M, Bachmann L, Wallace T, et al. Compliance with doxycycline therapy in sexually transmitted diseases clinics. Sex Transm Dis 1998; 25:1. Centers for Disease Control and Prevention (CDC). Recommendations for partner services programs for HIV infection, syphilis, gonorrhea, and chlamydial infection. MMWR Recomm Rep 2008; 57:1. Gaydos CA, Wright C, Wood BJ, et al. Chlamydia trachomatis reinfection rates among female adolescents seeking rescreening in school-based health centers. Sex Transm Dis 2008; 35:233. Murphy TV, Slade BA, Broder KR, et al. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008; 57:1. Hogben M. Partner notification for sexually transmitted diseases. Clin Infect Dis 2007; 44 Suppl 3:S160. Golden MR, Whittington WL, Handsfield HH, et al. Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection. N Engl J Med 2005; 352:676. Khan A, Fortenberry JD, Juliar BE, et al. The prevalence of chlamydia, gonorrhea, and trichomonas in sexual partnerships: implications for partner notification and treatment. Sex Transm Dis 2005; 32:260. Centers for Disease Control and Prevention. Expedited partner therapy in the management of sexually transmitted diseases. Atlanta, GA: US Department of Health and Human Services, 2006.