PROTOCOLS
OB/GYN INFECTION

Uncomplicated anogenital gonorrhea

By Daniel V. Landers, MD

Antibiotic resistance can complicate the treatment of this common sexually transmitted infection. The author discusses diagnostic tests and CDC recommendations for antimicrobial therapy.

An estimated 600,000 new infections by Neisseria gonorrhoeae occur each year in the United States. Although this represents a continuing decline in the incidence of gonococcal infections in this country, the rate remains significantly higher than is the case in other developed nations.

The majority of uncomplicated anogenital gonorrheal infections occur in the 15- to 29-year-old age group. Sexually active 15- to 19-year-olds have twice the incidence seen in sexually active 20- to 24-year-olds, but the highest incidence overall is found among 20- to 24-year-olds, because of the higher proportion of sexually active individuals in this age group. There are also seasonal variations of about 20% in the incidence of gonorrhea in the US, with the peak occurring in late summer.

Many risk factors have been associated with gonococcal infections, including low socioeconomic status, urban residence, non-Asian and non-white race and ethnicity, early onset of sexual activity, unmarried marital status, illicit drug use, prostitution, and history of gonococcal infections. Contraceptive choices also affect a person's likelihood of being infected. Spermicides, diaphragms, and condoms have been found to reduce the risk.

Etiology

Transmission of gonorrhea is almost entirely by sexual contact. It has been estimated that during a single sexual encounter, the risk of transmission from male to female is 80% to 90%, compared with a risk of 20% to 25% for transmission from female to male. Although uncomplicated anogenital gonorrhea is often asymptomatic, it can also be associated with many different clinical manifestations. Most women either develop symptoms within 10 days of infection or remain asymptomatic. The primary site of urogenital gonococcal infection in women is the endocervix.

Mucopurulent cervicitis (MCP), the hallmark of clinical infection of the endocervix associated with N gonorrhoeae or Chlamydia trachomatis, is characterized by a purulent or mucopurulent endocervical exudate. You may see this exudate at the endocervical canal or in an endocervical swab specimen. Unfortunately, MCP is most often asymptomatic and, in most cases, neither N gonorrhoeae nor C trachomatis can be isolated. Moreover, it can persist even after repeated courses of antimicrobial therapy and no evidence of gonorrhea or chlamydial infection.

Some experts suggest that easily induced cervical bleeding and an increased number of polymorphonuclear (PMN) leukocytes on endocervical Gram's stain should raise the suspicion of gonococcal infection. Colonization of the urethra rarely occurs by itself, but may be common in association with endocervical infection. Occasionally, Bartholin's, Skene's, and periurethral glands may be involved in gonococcal infections.

In up to 50% of women with gonococcal cervicitis, there is concurrent gonococcal rectal infection with or without a history of acknowledged rectal sexual contact. Anal examination may frequently be normal or may reveal erythema, discharge, or both. Anoscopy may reveal mucoid or purulent exudate, edema, and mucosal friability.

Diagnosis

A definitive diagnosis of gonorrhea depends on identifying N gonorrhoeae, a gram-negative intracellular diplococcus. Isolation in culture continues to be the standard means of diagnosis. Newer DNA-based tests may improve the diagnostic process, but at present are relatively expensive and not widely available.

Culture is best accomplished by using selective media containing antibiotics. Modified Thayer­Martin medium has a diagnostic sensitivity of 96% in cultures from the endocervix. Sensitivity can be increased by duplicate endocervical swabbings or consecutive endocervical and anal swabbings. Collect specimens by first cleansing the cervix to remove external exudate and then inserting a swab 1 to 2 cm up to the internal os and rotating it gently for 5 to 10 seconds.

Gram's stain can be useful when culture is unavailable or as an adjunct to culture. Finding gram-negative diplococci with typical morphology identified or closely associated with PMN leukocytes is considered diagnostic. Gram's stain is used primarily when there is a high index of suspicion of infection.

Nucleic acid detection assays such as the nonamplification method (GenProbe) and, more recently, amplification methods such as polymerase chain reaction (PCR) and ligase chain reaction (LCR) have been developed for use in the diagnosis of N gonorrhoeae infection. These detection systems boast a high degree of sensitivity and specificity (nearly 100%) and may be accurate in identifying N gonorrhoeae from clinician- or self-collected vaginal swabs. Expense and limited availability are major disadvantages at this time, but in the future these DNA-based tests may become the test of choice where applicable.

Treatment

Antimicrobial therapy for gonococcal infections is based on in vitro resistance patterns. The rising incidence of infection due to penicillinase-producing or tetracycline-resistant N gonorrhoeae (PPNG and TRNG) or strains with chromosomally mediated resistance to multiple antibiotics has led the Centers for Disease Control and Prevention to alter treatment recommendations over the years. Quinolones are a mainstay of treatment in the presence of antibiotic resistance. As of February 1997, quinolone-resistant strains for minimum inhibitory concentration greater than 1.0 µg/mL occurred in less than 0.05% of 4,639 isolates collected by the CDC's Gonococcal Isolate Surveillance Project. Guidelines have also been influenced by the high frequency of chlamydial infections in individuals with gonorrhea and the absence of a rapid, inexpensive, and accurate test for these infections.

The CDC recommendations for treatment of uncomplicated anogenital gonorrhea include a single 400-mg oral dose of cefixime, a single IM dose of ceftriaxone, or a single dose of a fluoroquinolone (ciprofloxacin or ofloxacin). All of these agents should be followed either by a single 1-g oral dose of azithromycin or a 7-day course of oral doxycycline (Table 1). According to the CDC's 1998 guidelines, the antimicrobial spectrum of cefixime and ceftriaxone is similar, but the 400-mg oral dose may not provide as high (97.1% vs. 99.1%) or as sustained a bactericidal level as a 125-mg IM dose of ceftriaxone. This needs to be weighed against the obvious convenience of oral administration.

TABLE 1
Treatment of uncomplicated gonococcal infections of the cervix, urethra, and rectum

400 mg orally in a single dose

Add to any of the above regimens:

100 mg orally twice a day for 7 days

Source: Centers for Disease Control and Prevention. MMWR. 1998;47(RR-1):59-65.

Ciprofloxacin and ofloxacin are also effective against most strains of N gonorrhoeae in single doses of 500 mg and 400 mg, respectively. Other single-dose quinolone regimens—including enoxacin, 400 mg; lomefloxacin, 400 mg; and norfloxacin, 800 mg orally—appear to be safe and effective for uncomplicated gonorrhea, but data for these drugs are less extensive. None of the quinolones seems to offer a significant advantage over the others. The safety of the quinolones has not been established in women who are pregnant or lactating or under 18 years of age.

A single 2-g dose of spectinomycin has long been an alternative treatment for gonorrhea in pregnant cephalosporin-allergic patients or in those who cannot tolerate either the quinolones or cephalosporins. The effectiveness of other alternative regimens included in the CDC guidelines has been established in less extensive studies. All alternatives to ceftriaxone are also followed with a 7-day course of oral doxycycline. Although tetracycline is a possible substitute for doxycycline, compliance may be worse with this drug because it must be administered four times a day instead of twice. Also, at current prices, tetracycline costs slightly more than generic doxycycline. Doxycycline or tetracycline is added to cover coexisting chlamydial infection; neither alone is considered adequate therapy for gonococcal infection.

Follow-up

Since treatment failure after the ceftriaxone/doxycycline regimen is rare, the CDC considers follow-up cultures ("test-of-cure") nonessential. A more cost-effective strategy may be reexamination with culture 1 to 2 months after treatment ("rescreening"). This approach detects both treatment failure and reinfections. Patients treated with regimens other than ceftriaxone/doxycycline should have follow-up cultures taken 4 to 7 days after completion of therapy.

Persons exposed to gonorrhea within the preceding 60 days should be examined, cultured, and treated presumptively. All patients with gonorrhea should have a serologic test for syphilis and should be offered confidential counseling and testing for HIV infection. Most patients with incubating syphilis will be cured by a regimen containing ceftriaxone, another ß-lactam, or tetracyclines. Patients treated with other regimens (for example, spectinomycin, ciprofloxacin, or norfloxacin) should have a serologic test for syphilis in 1 month.

Treatment failure

Persistent symptoms after treatment need to be cultured for N gonorrhoeae, and any gonococcal isolate should be tested for antibiotic sensitivity. Infections occurring after treatment with one of the recommended regimens are common, primarily because of reinfection rather than treatment failure.

Prevention

As with all sexually transmitted diseases, reducing the incidence of gonorrhea depends on educating patients and raising public awareness of modes of transmission and means of prevention. Among contraceptives, condoms are the most effective means for preventing transmission of N gonorrhoeae. The diaphragm, cervical cap, and to a lesser degree topical bacteriocidal agents may reduce infection risk in women. Practices such as douching, washing, or urinating after intercourse have not been shown to reduce risk of acquiring N gonorrhoeae, however. In fact, douching may potentially harm patients.

Tracing and treating sexual contacts is an essential part of any prevention effort. This task is easier in areas where reporting gonococcal infections is mandatory, as in the US. Private physicians, as well as public health departments, should make every attempt to refer or treat partners of infected individuals.

Efforts continue toward developing a vaccine for the prevention of gonorrhea and gonococcal pelvic inflammatory disease. Thus far, however, no effective vaccine is on the immediate horizon.

SUGGESTED READING

Bassiri M, Mårdh PA, Domeika M. Multiplex AMPLICOR PCR screening for Chlamydia trachomatis and Neisseria gonorrhoeae in women attending nonsexually transmitted disease clinics. J Clin Microbiol. 1997;35:2556-2560.

Centers for Disease Control and Prevention. 1998 Guidelines for treatment of sexually transmitted diseases. MMWR. 1998;47(RR-1):59-65.

Hook EW III, Ching SF, Stephens J, et al. Diagnosis of Neisseria gonorrhoeae infections in women by using the ligase chain reaction on patient-obtained vaginal swabs. J Clin Microbiol. 1997;35:2129-2132.

Institute of Medicine (US) Committee on Prevention and Control of Sexually Transmitted Diseases. The Hidden Epidemic: Confronting Sexually Transmitted Diseases. Eng TR, Butler WT, eds. Washington, DC: National Academy Press; 1997.

Moran JS, Levine WC. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis. 1995; 20(suppl 1):S47-S65.

Dr. Landers is Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, and Director, Division of Infectious Diseases and Immunology, University of Pittsburgh/Magee­ Womens Hospital, Pittsburgh, Pa.

Adapted from Mead PB, Hager WD, Faro S, eds. Protocols for Infectious Disease in Obstetrics and Gynecology. 2nd ed. Malden, Mass: Blackwell Science Inc; 1999.

 

Daniel Landers. OB/GYN Infection: Uncomplicated anogenital gonorrhea. Contemporary Ob/Gyn 2000;7:127-132.