Chlamydia Screening and Treatment Guideline Prevention Screening Recommendations and Tests Treatment Goals Lifestyle/Non-Pharmacologic Options Pharmacologic Options Follow-up/Monitoring Reporting Comorbidity Prevention Evidence Summary References Guideline Team and Development Process Appendix 1. Recommendation Grade Labels 2 2 3 3 3 4 4 4 5 6 7 8 Last guideline approval: September 2011 Guidelines are systematically developed statements to assist patients and providers in choosing appropriate health care for specific clinical conditions. While guidelines are useful aids to assist providers in determining appropriate practices for many patients with specific clinical problems or prevention issues, guidelines are not meant to replace the clinical judgment of the individual provider or establish a standard of care. The recommendations contained in the guidelines may not be appropriate for use in all circumstances. The inclusion of a recommendation in a guideline does not imply coverage. A decision to adopt any particular recommendation must be made by the provider in light of the circumstances presented by the individual patient. Chlamydia Screening and Treatment Guideline Copyright © 2001–2013 Group Health Cooperative. All rights reserved. 1 Prevention Risk reduction counseling should be tailored to each patient's individual risk factors, needs, and abilities. Effective measures to reduce risk include:  Abstaining from sex.  Maintaining a mutually monogamous relationship with a partner known to be uninfected with STDs.  Regular and proper use of latex condoms or female condoms.  Avoiding contact with casual partners and high-risk individuals (e.g., intravenous drug users, commercial sex workers, and persons with numerous sex partners).  Avoiding high-risk sexual practices (such as anal intercourse with a person who may have an STD). Screening Recommendations and Tests Table 1. Recommendations for screening for chlamydia Population eligible for screening Test(s) Frequency Sexually active women  16 through 24 years of age Grade A  25 years or older and at increased risk Nucleic acid amplification 2, 3, 4 tests Annually and when patient reports a new partner 1 Expert Opinion Grade A Pregnant women  Through 24 years of age Grade B  25 years or older and at increased risk Grade B 1 2 3 4 1 Nucleic acid amplification 2, 3, 4 tests At the first prenatal visit and during the third trimester if the first test was positive or she has a new sexual partner Patients at risk for chlamydia infection include:  All sexually active women and adolescents through 24 years of age  Women 25 years or older with - History of previous chlamydia infection or other sexually transmitted infection - New or multiple partners - Inconsistent condom use - History of exchanging sex for money Vaginal self-swab is the preferred collection method due to higher sensitivity than cervical swab or urine testing. For women who require a pelvic examination for other reasons, a vaginal swab may be collected by the provider. Urine testing is an acceptable option if the patient prefers this over vaginal self-swab. Cervical swabs are no longer recommended. Individuals undergoing evaluation following sexual assault need cervical, rectal, or urethral cultures. Special media are required. Contact the Lab. The chlamydia screening test used in the GH Laboratory tests for both chlamydia and gonorrhea. Chlamydia Screening and Treatment Guideline 2 Treatment Goals Eradication of infection in patient and her partner(s). Lifestyle Modifications/Non-Pharmacologic Options Patients who have tested positive should abstain from sex until they and their partner(s) have completed a course of antibiotic treatment. Pharmacologic Options For information on side effects, contraindications, and other pharmacy-related issues, see the Group Health Formulary, the Healthwise® Knowledgebase, or other resources. Table 2. Recommended pharmacologic options for chlamydia treatment Eligible population Line Medication Non-pregnant women with uncomplicated infections 1st Azithromycin 2nd Doxycycline 100 mg PO b.i.d.. x 7 days Erythromycin base 500 mg PO q.i.d. x 7 days Levofloxacin 500 mg PO daily x 7 days Pregnant women with 1st uncomplicated infections 2nd Partners 1 1 Grade B 1st Azithromycin Regimen Grade A Grade A 1 g PO (single dose) 1 g PO (single dose) Amoxicillin 500 mg PO t.i.d. x 7 days Erythromycin base 500 mg PO q.i.d. x 7 days Azithromycin 1 g PO (single dose) Effective clinical management of patients with treatable sexually transmitted diseases (STDs) requires treatment of the patients’ current sex partners to prevent reinfection and curtail further transmission. With expedited partner therapy (EPT), partners are treated without an intervening clinical assessment; the kit is provided at no charge to the partner. Within Group Health, see the Pharmacy EPT page at http://incontext.ghc.org/rx/med/ept.html . More information is available through the Washington State Department of Health, at http://www.doh.wa.gov/YouandYourFamily/IllnessandDisease/SexuallyTransmittedDisease/ExpeditedPa rtnerTherapy.aspx. Chlamydia Screening and Treatment Guideline 3 Follow-up/Monitoring Table 3. Recommended testing for reinfection vs. test-of-cure Population eligible for testing Test(s) Sexually active, non-pregnant women Nucleic acid amplification tests Pregnant women Nucleic acid amplification tests 1 2 3 Timing 1, 2 3–6 months after initial treatment 3 Grade B 1, 2 3–4 weeks after initial treatment and 3 during the third trimester Vaginal self-swab is the preferred collection method due to higher sensitivity than cervical swab or urine testing. For women who require a pelvic examination for other reasons, a vaginal swab may be collected by the provider. Urine testing is an acceptable option if the patient prefers this over vaginal self-swab. Cervical swabs are no longer recommended. Individuals undergoing evaluation following sexual assault need cervical, rectal, or urethral cultures. Special media are required. Contact the Lab. The majority of post-treatment infections result from reinfection, frequently occurring because the patient’s sex partners were not treated or because the patient resumed sex with a new partner infected with C. trachomatis. Except in pregnant women, test-of-cure (repeat testing 3–4 weeks after completing therapy) is not recommended. Nucleic acid amplification tests conducted < 3 weeks after completion of therapy in persons who were treated successfully could yield false-positive results because of the continued presence of dead organisms. See the CDC Web site for more information: http://www.cdc.gov/std/treatment/2006/urethritis-and-cervicitis.htm#uc4 Reporting For information regarding reporting notifiable conditions such as chlamydia and gonorrhea, see Group Health Infection Control, the Washington State Department of Health, the Washington State Legislature, and the Idaho Department of Health and Welfare. Comorbidity Prevention Within Group Health, see recommendations for human papillomavirus (HPV) immunization on the Immunizations page of Connection: http://incontext.ghc.org/clinical/clin_topics/immunization/imm_poc.html Chlamydia Screening and Treatment Guideline 4 Evidence Summary Accuracy and reliability of screening and diagnostic tests There is fair evidence that nucleic acid amplification tests (NAATs) can identify chlamydial infection in asymptomatic men and women with high test specificity. In low-prevalence populations, however, a positive test result is more likely to be false-positive than true-positive, even with the most accurate tests available. Cook and colleagues' (2005) meta-analysis of 14 studies showed that the NAATs had high sensitivity and excellent specificity in detecting chlamydial infection in both men and women. There was only a minor difference in the sensitivities and specificities for the test results of specimens obtained from urine (PCR pooled sensitivity and specificity 83.3% and 99.5% respectively) vs. cervical (PCR pooled sensitivity and specificity 85.5% and 99.6% respectively). No tests of significance were reported. Effectiveness of screening There is no direct evidence from randomized controlled trials (RCTs) that screening for chlamydia reduces adverse outcomes. The rationale for the recommendation is based on indirect evidence that 1) the history of the condition is well known, 2) screening can identify early disease, and 3) treatment of disease has been shown to improve health outcomes. Effectiveness of treatment Non-pregnant women and adolescents The pooled results of 12 RCTs showed that the microbial cure rates were 96.5% with azithromycin and 97.9% with doxycycline (Lau 2002). Adverse events were reported in 25.0% and 22.9%, respectively. In an earlier study with 597 men and women, Thorpe found similar rates of cure and side effects for doxycycline 100 mg twice daily for 7 days (99%) and 1 g single dose of azithromycin (97%) (Thorpe 1997). Decision analysis studies showed that single-dose azithromycin was just as or more cost-effective than a 7-day course of doxycycline. There is insufficient published evidence on the efficacy and safety of azithromycin in adolescents. The CDC and Group Health recommendations that adolescents receive azithromycin at a dose equivalent to that given to adults are based on expert opinion. There is insufficient published evidence on the efficacy of alternative regimens of doxycycline or different formulations of azithromycin. Pregnant women The published studies reviewed for the CDC guideline showed that erythromycin and azithromycin were similar in efficacy in pregnant women with chlamydial infection, but azithromycin was better tolerated. There is no direct evidence on the effect of azithromycin on neonatal outcomes. An observational study of 277 women showed no significant difference in preterm labor among women receiving azithromycin versus amoxicillin. A recent meta-analysis (Pitsouni 2007) published after the CDC review showed that azithromycin was associated with similar effectiveness but fewer adverse events compared with erythromycin or amoxicillin in the treatment of pregnant women with chlamydial infection. Expedited Partner Therapy (EPT)/Patient Delivered Partner Therapy (PDPT) There is evidence from published trials (Schillinger 2003, Golden 2005, and Kissinger 2005) that EPT is at least as effective as the current practice of partner referral. In the Schillinger et al (2003) and Golden et al (2005) studies, there were no statistically significant differences in persistent and/or recurrent infections in groups of women who were given partner therapy versus women told to refer their partners for therapy. The Kissinger et al (2005) study found that, among those who were tested, men whose partner had received treatment for them had significantly lower positive test results for Chlamydia Screening and Treatment Guideline 5 chlamydia or gonorrhea than those in the standard referral group. In this study, men had nongonococcal urethritis at baseline. Potential harms of screening/treatment There is insufficient evidence on the harms of screening for chlamydial infection. The USPSTF concluded that these are no greater than small. Potential harms include anxiety and relationship problems arising from false-positive results and overtreatment. References Cook RL, Hutchison SL, Ostergaard L, et al. Systematic review: Noninvasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med. 2005;142:914–925. Golden MR, Whittington WLH, Hansfield HH, et al. Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydia infection. N Engl J Med. 2005;352:676–685. Kissinger P, Mohammed H, Richardson-Alston G, et al. Patient-delivered partner treatment for male urethritis: a randomized controlled trial. Clin Infect Dis. 2005;41:623–629. Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydia infections. A meta-analysis of randomized clinical trial. Sex Transm Dis. 2002;29:497–502. Pitsouni E, Iavazzo C, Athanasiou S, et al. Single-dose azithromycin versus erythromycin or amoxicillin for Chlamydia trachomatis infection during pregnancy: a meta-analysis of randomized controlled trials. Int J Antimicrob Agents. 2007;30:213–221. Schillinger JA, Kissinger P, Calvet H, et al. Patient-delivered partner treatment with azithromycin to prevent repeated Chlamydia trachomatis infection among women: a randomized controlled trial. Sex Transm Dis. 2003;30:49–56. Thorpe EM Jr., Stamm WE, Hook EW III, et al. Chlamydia cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practices. Genitourin Med. 1997;72:93– 97. Chlamydia Screening and Treatment Guideline 6 Guideline Team and Development Process Clinician lead Paula Lozano, MD, MPH, Assistant Medical Director of Preventive Care [email protected] Guideline coordinator Avra Cohen, MN, Clinical Improvement & Prevention [email protected] Guideline team members Jim Carlson, PharmD, Pharmacy Administration Chris Coppeans, MD, Resident, Family Medicine Rebecca Doheny, MPH, Epidemiologist, Clinical Improvement & Prevention Robyn Mayfield, Patient Health Education Resources, Clinical Improvement & Prevention Jim Ramsey, RPh, Pharmacy Administration Terry Richardson, PharmD, Pharmacy Peggy Rogers, MT (ASCP) SM, Microbiology Manager Molly Skinner, PharmD, Resident, Pharmacy Services Ann Stedronsky, Clinical Web Team, Clinical Improvement & Prevention Last guideline approval: September 2011 Process of Development This evidence-based guideline was developed using an explicit evidence-based process, including systematic literature search, critical appraisal with evidence grading, and evidence synthesis. The following specialties were represented on the development and/or update teams: epidemiology, family medicine, microbiology, pediatrics, pharmacy. Chlamydia Screening and Treatment Guideline 7 Appendix 1. Recommendation Grade Labels About the Labeling System This labeling system is adapted from the U.S. Preventive Services Task Force (USPSTF). The label is based on the degree to which the evidence supports the specific clinical recommendation as written by the Group Health guideline team. In this system, certainty refers to the likelihood that the guideline team’s assessment of net benefit (i.e., the benefit minus harm of the service as implemented in a general primary care population) is correct, based on the nature of the overall evidence available. While the grades are useful tools in assessing recommendations, they are not meant to replace the clinical judgment of the individual provider or to establish a standard of care. Recommendation Grade Definitions Label Definition Grade A The service is recommended. There is high certainty that the net benefit (i.e., benefits minus harms) is substantial. Grade B The service is recommended. There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial. Grade C The recommendation is against routinely providing the service. There may be considerations that support providing the service to an individual patient. There is at least moderate certainty that the net benefit is small. Grade D The recommendation is against providing the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. I statement The current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms. Expert opinion Expert opinion refers to the collective opinion of the Group Health guideline team. The language of the recommendation is at the team's discretion. The evidence is assumed to be insufficient unless otherwise stated. In the rare case there is fair or good evidence, the evidence does not support the expert opinion recommendation put forth by the team. Levels of Certainty Regarding Net Benefit Level of certainty Description High The available evidence usually includes consistent results from well-designed, wellconducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies. Moderate The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by such factors as:  The number, size, or quality of individual studies  Inconsistency of findings across individual studies  Limited generalizability of findings to routine primary care practice  Lack of coherence in the chain of evidence As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion. Low The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:  The limited number or size of studies  Important flaws in study design or methods  Inconsistency of findings across individual studies  Gaps in the chain of evidence  Findings that are not generalizable to routine primary care practice  A lack of information on important health outcomes More information may allow an estimation of effects on health outcomes. Chlamydia Screening and Treatment Guideline 8