Cervicitis: Balancing the Goals of Empiric Therapy and Antimicrobial Stewardship to Improve Women's Health

Cervicitis is a well-described inflammatory syndrome in women. It is characterized by mucopurulent cervical discharge or friability on examination although many women have few or no symptoms. Common infectious etiologies include Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in 30% to 50%.^1-4 Adverse outcomes of untreated cervicitis include the extension of infection to the upper genital tract with endometritis, and pelvic inflammatory disease as a result. For this reason, the US Centers for Disease Control and Prevention (CDC) has recommended routine diagnostic nucleic acid amplification testing (NAAT) to detect gonorrhea and chlamydia in women with cervicitis since 2006.^5,6

In their commentary in this issue of STD, Nsuami and colleagues question the role of presumptive ceftriaxone treatment in women with suspected gonococcal cervicitis. The crux of their argument is that we should limit the use of empiric antibiotics with efficacy against gonorrhea in the setting of limited treatment options and increasing antimicrobial resistance. They cite data demonstrating high follow-up rates after sexually transmitted infection (STI) diagnostic testing in women, and they calculate that loss to follow-up in the absence of presumptive ceftriaxone therapy rarely leads to a missed opportunity to prevent pelvic inflammatory disease. The authors also note the rare incidence of adverse events associated with ceftriaxone administration and the cost associated with providing presumptive intramuscular antibiotic therapy for cervicitis in clinic.

A brief review of current CDC guidelines for the diagnosis and management of cervicitis in women provides useful context. Based on national surveillance data, presumptive cervicitis treatment with oral azithromycin is recommended to treat chlamydia in women who are at increased risk (defined as age <25 years, new sex partner, nonmonogamous sex partner or sex partner with an STI), “especially if follow-up cannot be ensured or if testing with NAAT is not possible.” The recommendation for presumptive gonorrhea therapy is provided as a footnote to the cervicitis table with the following wording: “consider concurrent treatment for gonococcal infection if patient is at risk for gonorrhea or lives in a community where the prevalence of gonorrhea is high.”⁷

Fortunately, NAAT testing for gonorrhea and chlamydia to guide the clinical management of cervicitis in women is now widely available in clinic and emergency room settings in the United States.⁸ More than 580,000 cases of gonorrhea were reported to the CDC in 2018. This represents an 83% increase in cases since 2009 with rates rising among women and men in every region of the country.⁹ The highest case rates for gonorrhea in women occur in younger age groups (15–29 years). Black women residing in the Southeastern US also have a disproportionate burden of infection compared with other groups. Since regional gonorrhea rates in women vary widely, universal presumptive gonococcal therapy in all US women with cervicitis may not be indicated or cost-effective. Nonetheless, the benefit of presumptive eftriaxone therapy increases as gonorrhea prevalence and the pretest probability of infection rise.

It is reasonable to consider whether or not presumptive ceftriaxone therapy for suspected gonococcal cervicitis is consistent with the principles of antimicrobial stewardship. The Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America have outlined evidence-based antimicrobial stewardship goals to optimize clinical outcomes and minimize the unintended consequences of antimicrobial use.¹⁰ Many of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America–specific benchmarks for stewardship goals are met by current CDC guidance for cervicitis: (a) targeting patients with specific infectious disease syndromes, (b) reducing therapy to the shortest effective duration, (c) use of targeted high-quality diagnostic testing, (d) preference to select antibiotics that have been proven to improve infection outcomes in the population, and (e) efforts to support local antimicrobial resistance testing.¹⁰

In terms of resistance testing, gonococcal isolates have been collected from men with urethritis and cultured at laboratories across the country since 1986 as part of a CDC-supported national sentinel surveillance project (GISP) to track emerging gonococcal resistance.⁹ In 2018, 0.2% of gonococcal isolates sampled in GISP had evidence of emerging resistance to ceftriaxone with an elevated minimum inhibitory concentration defined as 0.125 μg/mL or greater. It is clear that ceftriaxone-resistant gonorrhea has spread between countries, and new antibiotics are needed.^11,12

Although data about antibiotic utilization and prescribing patterns for the treatment of cervicitis in the United States are limited, it is not clear that changes to the clinical management of women with cervicitis will change the trajectory of emerging gonococcal resistance at a population level. Potential factors that support the emergence and dissemination of antimicrobial-resistant gonorrhea include selective pressure caused by antimicrobial use, genetic resistance mechanisms, and sexual networks.^13-16 Current data suggest that the 2015 CDC guidelines are appropriate in recommending targeted therapies based on NAAT NG/CT testing in women with cervicitis. In the setting of increasing gonorrhea rates among US women, it remains reasonable and consistent with antimicrobial stewardship principles for providers to consider presumptive ceftriaxone therapy for gonorrhea for women who are at particular risk of infection based on trends in regional epidemiology.

If we are serious about improving women's health and reducing STI rates in the United States, we must improve access to high-quality health care that includes sexual health and gonorrhea testing and treatment. Access to STI testing is particularly important in an era where women may have fewer provider visits scheduled for routine cervical cancer screening.¹⁷ The NAAT testing for gonorrhea in women with cervicitis reduces the need to rely on empiric or presumptive therapy. Even more exciting is the possibility that point-of-care NAAT testing will bring additional improvements to treatment rates and health outcomes in women.¹⁸ Public health officials and STI training programs should continue to share local epidemiology with regional health care providers to inform clinical decision making. The CDC Division of STD Prevention should consider expanding the eligibility criteria for gonococcal surveillance programs to include women because findings in men may be inadequate to guide management in women. Finally, ensuring support for gonorrhea surveillance programs and maintaining culture capacity in regional microbiology laboratories for antimicrobial testing is necessary to inform our understanding of national epidemiology and future treatment options for gonorrhea in women. If not now, when?